This chapter deals with a number of conditions that do not fit easily into the major categories of movement disorders. Some, such as stereotypies, can be seen in a variety of the diseases that have been covered in the preceding chapters, while others are again mentioned to put them into a broader context. Thus, neuroleptic malignant syndrome can be considered as a drug-induced akinetic–rigid syndrome, and hence has been covered in Chapter 13, but also has features of catatonia, and is thus also briefly mentioned here.
By its very nature, this chapter deals with a number of unrelated disorders. Some are very important because of their frequency, e.g. drop attacks and hemifacial spasm.
The term ‘drop attack’ was introduced into the medical literature by Sheldon in 1948 in an investigation into the impact of old age. It has now become an ‘umbrella label’ for a wide range of aetiological different attacks, many of which were well described in the medical literature well prior to that date (see Table 1 in the Introduction to Episodic Movement Disorders – Section 11). For example, Hunt called epileptic drop attacks ‘static seizures’ as early as 1922. Not only are the causes heterogeneous but also there is no universally accepted definition of a drop attack and what are called such in the literature are frequently not clearly described. This makes any review of the topic imprecise.
Table 52.1 Causes of drop attacks due to neuromuscular and neurodegenerative disorders.
Neuromuscular diseases associated with weak legs
Inclusion body myositis
Idiopathic Parkinson's disease
Multiple system atrophy
Progressive supranuclear palsy
One of the major points of disagreement relates to the retention of consciousness. Some authors exclude attacks in which there is loss of consciousness (Brust et al. 1979, Meissner et al. 1986) whereas others not only accept this but include bouts of unconscious for 1–2 minutes followed by brief confusion (Pazzaglia et al. 1985). If loss of consciousness is disallowed this would eliminate some epileptic seizures, cardiac dysrhythmias, and faints due to orthostatic hypotension, which have been called drop attacks (Pfammater et al. 1995). There is no clear answer to this dilemma, which is perhaps best exemplified by epilepsy. Suspension of awareness may momentarily occur during a burst of generalized spike and wave activity in the electroencephalography (EEG) associated with a fall. In most cases, such as during a large generalized myoclonic jerk, it is impossible to determine whether the patient has lost consciousness for such a brief period. On the other hand, an atonic epileptic seizure associated with falling and prolonged unconsciousness would not generally be regarded as a drop attack. Similarly, fainting due to a simple vasovagal syncope would normally not be included. For the purposes of our discussion, we will generally exclude bouts in which the patient is aware of loss of consciousness or it has been prolonged for more than a few seconds.
We will also disregard patients who have prolonged signs following a drop attack, unless these are the result of injuries sustained in the fall. Thus, a brainstem transient ischaemic attack followed by motor or sensory signs that gradually resolve over an hour or so would not qualify. The question is to what extent falls resulting from pre-existing physical disability, such as weak limbs or impaired balance mechanisms, should be included. Neuromuscular disorders, spinal cord lesions, and the like may result in collapse due to reduced lower limb power, and a variety of neurodegenerative disorders may interfere with postural control. For example, quadriceps myopathy and progressive supranuclear palsy may present with unexplained falls. While accepting they may have a legitimate claim to be considered as drop attacks we have not discussed them in detail here, although they are outlined in Table 52.1. Occasionally drop attacks have been secondary to a metabolic disturbance, such as hypothyroidism (Kramer and Achiron 1993), but in such cases weakness or myopathy may have been the underlying reason for the collapse. In addition, a significant proportion of what have been called ‘drop attacks’ in the geriatric literature really consists of falls due to a variety of mechanisms (Table 52.2). These are not reviewed extensively, although they need to be kept in mind.
Table 52.2 Falls in old age
Causes of falls
Extension of neck
Falls out of bed or chair
Based on 500 falls in 202 people aged 50–90 years: 59 falls resulted in a fractured femur; drop attacks (125 of the 500 falls) occurred in 58 individuals; 26 of these 58 patients sustained fractures or dislocations; 51 of the 58 patients had more than one fall.
CNS= central nervous system.
Reproduced with permission from Sheldon JH. On the natural history of falls in old age. Br Med J 1960; 2:1685–1690. © BMJ Publishing Group.
We will thus define drop attacks as sudden falls that occur without warning or post-ictal symptoms in which the subject is unaware of losing consciousness or such loss of consciousness is brief, and it is possible to get up straight away unless injury prevents this. In our discussion, however, we have included some cases that do not completely fulfil these criteria and we have attempted to make it clear where we have done this.
Most drop attacks are caused by a sudden brief disturbance of postural mechanisms, without vertigo or dizziness. This can have many different aetiologies, which are very age dependent. Thus, drop attacks starting in young children are particularly likely to be epileptic whereas this is less often the case in adults. In the elderly cardiovascular causes tend to predominate. In a retrospective computerized search of drop attacks seen at the Mayo Clinic between 1976 and 1983, 108 cases were identified. Patients with loss of awareness or consciousness were excluded (Table 52.3). From subsequent examinations, patient questionnaires, telephone interviews, and death certificates it was felt the cause was established in 39. The likely aetiology was cardiac in 12%, cerebrovascular insufficiency in 8%, combined cardiac and cerebrovascular disease in 7%, seizures in 5%, vestibular disturbance in 3%, and psychogenic in 1%. In all the patients who were under 40 years of age epileptic seizures were felt to be the cause. In 64% no cause could be established but there were a number of associated medical conditions, which may have been relevant. Cardiovascular problems predominated, including hypertension and heart disease.
Table 52.3 The causes and associations of drop attacks
Percentage of drop attacks
Causes (39/108 cases)
Combined cardiac and cerebrovascular disease
Unknown causes (69/108 cases)
Based on 166 patients seen at the Mayo Clinic from 1976 to 1983. Fifty-eight patients were excluded, most because of cardiogenic causes with changes in consciousness. One hundred and eight patients (76 women and 32 men) met the definition of ‘a falling spell occurring without warning or post-ictal symptoms, with immediate righting, and without loss of awareness or consciousness’. Mean age was 70 years (most patients over the age of 60); follow-up was 6–7 years. Ninety-two of the 108 were alive at follow-up. Eight-four percent of 58 untreated patients were asymptomatic. Stroke rate was 0.5 per year, similar to the controls rate.
Reproduced with permission from Lee MS, Marsden CD. Drop attacks. In: Negative Motor Phenomena (Advances in Neurology,Vol. 67). Eds Fahn S, Hallett M, Luders HO, Marsden CD. Lippincott Williams & Wilkins, 1995; 67:41–52. © Lippincott Williams & Wilkins.
In 35 consecutive elderly referrals with drop attacks reported by Dey et al. (1997) the diagnosis was felt to be uncertain in only 29%. The cause was considered to be due to carotid sinus syncope in 51%, orthostatic hypertension in 14%, and imbalance of gait in 3%. In 21% more than one of these diagnoses were present. This marked predominance of cardiovascular causes may have resulted from referral bias as the study was carried out in a cardiovascular investigation unit. The authors provided only sketchy detail of the testing and none of the criteria used to establish the diagnosis. Nonetheless, it is in keeping with the hypothesis that cardiovascular abnormalities are the commonest cause of drop attacks in elderly people.
The natural history and prognosis of drop attacks clearly depends on their underlying cause. In the series of Meissner et al. (1986) 54% of patients received no treatment. Similar percentages of treated (82%) and untreated (84%) cases were symptom free at follow-up. They also found that the stroke rate in the overall group was approximately 0.5% per annum. This was not significantly different from that in a normal age – and sex – matched population. There are many specific types of drop attacks for which the outcome is much less favourable. These are mentioned below but include epileptic drop attacks.
A systemic fall in blood pressure caused by a change in cardiac rhythm or orthostatic hypotension can result in falling. While symptoms of faintness, dizziness, or loss of consciousness probably occur during the majority of such bouts this is not invariably the case (Dey et al. 1997). A definite diagnosis of cardiac dysrhythmia really requires Holter monitoring during the event, but presumptive evidence can be derived from associated disturbances in interictal cardiac rhythm or precipitatory manoeuvres. One manoeuvre is carotid sinus massage which may reveal a hypersensitive carotid sinus. This is probably more frequent in the elderly and has been said to occur in up to 25% of such patients who have unexplained falls, dizziness, or syncope (Kenny and Traynor 1991, Richardson et al. 1997). While the associated symptoms of faintness, giddiness, and presyncope would exclude many such patients from consideration here a small number may present with drop attacks. In these cases precipitation by head movement or vagal stimuli may give a clue to the aetiology (Kenny and Traynor 1991). These episodes and drop attacks resulting from other causes of cardiac dysrhythmia may be able to be controlled by cardiac pacing.
While drop attacks due to cardiovascular disorders are more common in the elderly they can occur at any age, including in the paediatric age group. Long-QT syndrome (Romano-Ward syndrome) seems a particularly likely cause of cardiac drop attacks in the paediatric age group (Pfammatter et al. 1995). In most children these episodes are accompanied by recognizable loss of consciousness. Therapy consists of beta blockers. An implantable cardioverter defibrillator or left cervicothoracic sympathetic denervation are therapeutic options in patients who remain symptomatic despite beta-blocker therapy [for review of the long QT syndrome see Goldenberg and Moss (2008) and Roden (2008)].
Focal cerebral transient attacks
Episodes of transient brainstem ischaemia may cause falls associated with other features of vertebrobasilar territory dysfunction, including visual disturbance, tinnitus, deafness, vertigo, vomiting, dysarthria, dysphagia, incoordination, unsteadiness, and long tract symptoms or signs. It is probably uncommon, however, for transient ischaemia to produce drop attacks unaccompanied by some of these or by recognizable loss of consciousness. Some authors consider that drop attacks do not occur due to focal episodes of transient cerebral ischaemia unless there are other localizing symptoms (Fisher 1958, Baker et al. 1966, 1968, Friedman et al. 1969). Others, however, disagree (Millikan and Siekert et al. 1955, Klee and Mordhorst 1961, Williams and Wilson 1962, Lund 1963, Gortvai 1964, Kameyama 1965, Russo 1979). Brust et al. (1979) published the case of a 65-year-old man who had several attacks of transient limb weakness with falling, some of which were unaccompanied by loss of consciousness and rapid recovery occurred. Neurological examination within 5 minutes of one such attack was said to be normal. Within days the patient developed more sustained evidence of a brainstem lesion and at autopsy was shown to have infarction in the pons and medulla, which particularly involved the corticospinal tracts. There was also damage to the reticular formation nuclei and their rostral projections. The authors felt that at least some of the drop attacks resulted from transient ischaemia of the corticospinal tracts. In the absence of demonstrable brainstem lesions or symptoms the aetiological association between focal ischaemia and drop attacks is often based on the demonstration of cerebrovascular disease in those suffering falls. By and large, this is an unsatisfactory way of establishing causality. Demonstration of vascular disease within the vertebrobasilar territory is more convincing and relief of symptoms by therapy provides the most compelling evidence. A number of studies have reported abolition of drop attacks in subclavian steal syndrome by bypass surgery (Edwards and Mulherin 1983, Vitti et al. 1994, Ciocca et al. 1995) or by angioplasty (Imparato et al. 1981). Although such patients have been reported to have such drop attacks, the precise details of the bouts have usually been sketchy.
In addition to the possibility that brainstem ischaemia can cause drop attacks it has also been reported that episodic lapses of postural control which typify asterixis can result from ischaemic damage to the mesencephalic reticular formation. It has been proposed that these might represent a segmental form of drop attack (Bril et al. 1979). Whether bouts of transient ischaemia within the carotid territory can cause drop attacks is a moot point. Hemiparesis or paralysis of a leg resulting in falling would not normally be considered a drop attack. It has been postulated that if both anterior cerebral arteries are supplied by one carotid, which becomes transiently blocked, leg weakness and drop attack might follow (Meissner et al. 1986). This remains speculative.
Although focal brainstem ischaemia can undoubtedly result in falling, associated loss of consciousness, other brainstem symptoms and signs, and the more prolonged nature of the event usually serve to differentiate this from the typical drop attack as we have defined above. We thus consider it as a rare cause of ‘pure’ drop attack.
As mentioned above, Hunt (1922) was the first to describe epileptic drop attacks. He regarded them as being due to ‘sudden losses of postural control’ with ‘falling to the ground’ and ‘rising almost immediately’. He felt there should be ‘very slight’ or no loss of consciousness. They have subsequently been known by a variety of other names, including ‘astatic’, ‘akinetic’, and ‘inhibitory seizures’. Brief falling due to epilepsy can result from several different abnormalities of postural control and from a variety of types of epilepsy. Thus, the falls may be triggered by tonic seizures, a clonic jerk, or atonia. Sometimes a myoclonic jerk may proceed atonia. The exact mechanism depends on the seizure type.
Perhaps the best known form of epileptic drop attacks is that which is found in Lennox-Gastaut syndrome (Lennox 1960, Gastaut and Regis 1961, Gastaut et al. 1966, Gastaut et al. 1974) in which falls are usually associated with absence seizures and myoclonus. Onset is typically in childhood, frequently between 3 and 6 years of age. Attacks can occur spontaneously or be provoked by photic stimulation. The drop attacks usually only last seconds. Lennox-Gastaut syndrome can be cryptogenic or symptomatic of other disorders, with about 70% falling into the latter group in many series. About half of the symptomatic group may have West's syndrome (Oguni et al. 1996). In addition to the common childhood form of Lennox-Gastaut syndrome, a so-called late variant has been described in which onset is usually in the teens (Oller Daurella 1970, Lipinski 1977, Bauer et al. 1983).
Gastaut and Broughton (1972) demonstrated that drop attacks were accompanied by generalized bilaterally synchronous spike and wave discharges lasting 1–3 seconds, which were rapidly replaced by generalized slow wave activity. They considered the brief attacks to be due to intense inhibition of the motor centres maintaining posture. Thus, drop attacks in Lennox-Gastaut syndrome come to be thought of as resulting from a sudden loss of muscle tone, but in about half they may actually result from generalized tonic seizures or spasms, which seem more likely to occur in those who have had West's syndrome (Oguni et al. 1996). Simultaneous video-EEG monitoring has shown that these tonic seizures are a type of brief axial flexor tonic spasm in which the head and trunk are suddenly bent forwards. In somewhat less than a quarter of drop attacks there is a myoclonic jerk followed by a period of atonia (myoclonic-atonic), while in a similar or smaller number there is a true atonic seizure (Egli et al. 1985, Ikeno et al. 1985). Long-term follow-up of Lennox-Gastaut syndrome has shown a poor outcome with intellectual deterioration, worsening gait, and persisting seizures in the majority even with treatment. Drop attacks may become very disabling in almost half, especially over 10 years of age and, along with the gait disturbance, result in many patients being chair bound (Oguni et al. 1996).
In 1985 Doose described a variety of childhood epilepsy which has become known as myoclonic-astatic epilepsy of early childhood. Epilepsy starts between the ages of 1 and 6 years and is characterized by myoclonic, myoclonic-astatic, and astatic seizures which often cause the patient to fall. Development prior to onset of epilepsy is normal and there is a genetic predisposition. The EEG usually shows a 4–7Hz rhythm which is accentuated in the parietal region. Drop attacks in this condition can be due to sudden myoclonus causing flexion of the head and trunk, an initial myoclonic jerk, followed by an atonic period or by sudden atonia (Oguni et al. 1992). Some of the episodes that appear to be purely atonic may be preceded by subtle myoclonic twitching, which is really only visible with combined video/EEG monitoring (Oguni et al. 1997). In these atonic attacks children collapse straight on to their buttocks and they are usually able to get up again almost immediately (Fig. 52.1). There is sudden interruption of electromyography (EMG) in the postural or antigravity muscles lasting up to 400 msec. This coincides with the slow wave phase of generalized spike and wave complexes on EEG and the intensity of the seizures seems to parallel the slow wave amplitude (Oguni et al. 1992).
Drop attacks can also occur in juvenile myoclonic epilepsy. In these a large generalized myoclonic jerk is usually followed by a degree of atonia. Sometimes this cessation of muscle contraction is brief and can only be detected by use of concomitant EMG, but on other occasions it results in loss of posture (Oguni et al. 1994).
Migrational disorders are a potent cause of epilepsy and seem particularly likely to produce drop attacks (Palmini et al. 1991). In this context, there is polymicrogyria which is characterized by an excessive number of small and prominent brain gyri, separated by shallow sulci. In congenital bilateral perisylvian polymicrogyria, seizures usually commence between 4 and 12 years of age and include atypical absence, atonic/tonic, and generalized tonic-clonic seizures. The disorder has been linked to the X chromosome (Villard et al. 2002). Kuzniecky et al. (1994) found 73% in a series of 31 patients had experienced atonic or tonic drop attacks. Multilobar polymicrogyria may also be associated with frequent atonic drop attacks, many of which seem to cease spontaneously in later childhood (Guerrini et al. 1998[b]).
In 1950 Ethelberg described five patients with drop attacks, which he called ‘chalastic fits’ or ‘symptomatic cataplexy’, which resulted from structural lesions of the frontal cortex. Falls have subsequently been reported to be the main ictal manifestation of frontal lobe lesions, occurring in about 80% of patients (Geier et al. 1977). About 70% of cases with drop attacks due to partial epilepsy have the focus in the frontal region (Tinuper et al. 1998) (Fig. 52.2). Temporal lobe lesions are perhaps the next most common site, making up about 16% (Jacome 1989, Gambardella et al. 1994, Tinuper et al. 1998). They can, however, arise due to a focus in other areas, including the parietal lobes (Smith 1983). The pathologies underlying these drop attacks have been quite varied.
While some authors have postulated a focal discharge via the cortico-reticular pathways into the pontine reticular formation (Smith 1983, Gambardella et al. 1994), it seems likely that most drop attacks are caused by secondary bilateral synchrony resulting from rapid spread of the focal ictal discharge via the corpus callosum and/or hippocampal commisure to the contralateral hemisphere. In one series 74% of such drop attacks showed the EEG pattern of secondary bilateral synchrony during their revolution and it has been suggested this discharge either activates (tonic) or inhibits (atonic) centres controlling postural tone (Tinuper et al. 1998).
Drop attacks occurring in partial epilepsy are usually a late manifestation, arising some years after the onset of seizures. There is usually unconsciousness for a minute or two followed by a brief period of confusion. The prognosis for seizure control with anticonvulsants is poor (Pazzaglia et al. 1985, Gambardella et al. 1994, Tinuper et al. 1998). About three quarters of patients have a bad outlook, with mental retardation in almost a half and continuing drop attacks in a similar proportion.
Gelastic or laughing seizures are the best known manifestation of hypothalamic hamartomas, but a variety of other seizures including drop attacks may occur (Cascino et al. 1993). Other lesions around the third ventricle may also cause drop attacks (see later) and, while the mechanism related to these is uncertain, it seems likely that those due to hamartomas are epileptic, not only because of their association with other seizure types but also because of their response to callosotomy.
Another type of epileptic drop attack that has been described is that which arises from stimulus sensitive seizures in which a sudden unexpected somatosensory stimulus can cause tonic posturing with falling. This can be associated with infantile hemiplegia (Oguni et al. 1998).
The response of epileptic drop attacks to medication depends on the underlying disorder. Juvenile myoclonic epilepsy is usually well controlled with valproate, but most other forms of drop attack are relatively resistant to anticonvulsant medication. Thus, the falling episodes seen in Lennox-Gastaut syndrome, myoclonic-astatic epilepsy, hypothalamic hamartomas, and focal cortical lesions tend to respond poorly to phenytoin, carbamazepine, and valproate. Felbamate (The Felbamate Study Group 1993, Burdette and Sackellares 1994), lamotrigine (Motte et al. 1977), and to a lesser extent benzodiazepines such as clobazam, clonazepam, and nitrazepam (Peterson 1967, Geller and Christoff 1971, Hansen and Menkes 1972, Canadian Clobazam Cooperative Group 1991, Dichter and Brodie 1996) may be helpful in generalized seizures causing drop attacks, particularly in Lennox-Gastaut syndrome. Topiramate also holds promise (Langtry et al. 1997). The tricyclic imipramine has occasionally been reported to be helpful in children (Hurst 1986).
The response to surgery has been reasonable. On occasions removal of an epileptogenic focus has been helpful (Gambardella et al. 1994, Lipinsky 1997). Extripation of a hypothalamic hamartoma has infrequently been reported to help drop attacks (Nishio et al. 1994) but is normally ineffective (Cascino et al. 1993). On the other hand, sectioning of the corpus callosum may be worthwhile, although other types of seizures associated with these hamartomas are unlikely to respond (Cascino et al. 1993). Callostomy, even in its anterior half to two thirds (Mamelak et al. 1993), has been found to be helpful in a range of drop attacks due to both cryptogenic epilepsy and focal cortical lesions. Significant improvement in attacks has been noted in between 50 and 85% of cases. In Lennox-Gastaut syndrome atonic seizures respond best and axial spasms the worst (Carmant and Holmes 1994, Phillips and Sakas 1996, Papo et al. 1997, Rougier et al. 1997). Good results in drop attacks associated with partial epilepsy have been published by a number of different groups (Wilson et al. 1982, Gates et al. 1984, 1987, Spencer et al. 1985, 1988, Oguni et al. 1991).
Although division of the corpus callosum has been reported to help drop attacks related to bilateral polymicrogyria (Kuzniecky et al. 1994), caution is needed because, as mentioned above, attacks tend to cease spontaneously in late childhood (Guerrini et al. 1998[b]).
Third ventricular lesions
In 1951 Kelly described drop attacks in patients with third ventricular colloid cysts. They had brief attacks of paraplegia and dilated lateral ventricles were present in all. Pecker et al. (1974) considered such attacks occurred in over a third of patients with colloid cysts. Following the fall the patient was able to get up without difficulty, but the weakness might persist for 5–15 minutes. He noted that such attacks may occur several times daily.
Similar drop attacks have been reported in a variety of other third ventricular mass lesions including meningioma (Crisculo and Symon 1986) and colloid plexus papilloma (Pollack et al. 1995). The mechanism of the attacks remains obscure and it is uncertain whether they result from direct mechanical effects on the adjacent third ventricular structures or are secondary to the associated hydrocephalus (see later).
Posterior fossa lesions
Space taking lesions in the posterior fossa have infrequently been associated with drop attacks. Kremer (1958) described these in three young adults. He noted a ‘profound diminution of tone’ when the neck was extended in one who had a compressive lesion extending through the foramen magnum. He speculated that brainstem ischaemia may have been the mechanism, particularly by interfering with blood supply ‘to the connections of the cerebellum which deprives the postural-tone mechanism of the control of the gamma-fibre servoloops which go out of action’. There have been many other descriptions of sudden and unexpected falls caused by similar lesions. One of Kremer's (1958) patients had a fourth ventricular ependymoma, but large arachnoid cyst (Shinoda et al. 1998), giant vertebral artery aneurysm (Gautier et al. 1982), Chiari type I malformation (Bardella et al. 1984), and basilar impression (Bewermeyer et al. 1984) have all been recorded. Congenital separation of the bony margin of the foramen magnum, a so-called proatlas (Gil-Nagal et al. 1992), is another abnormality in this area which has been associated with drop attacks.
Drop attacks have also been reported as a manifestation of occult hydrocephalus. Botez et al. (1977) reported five cases in which such falls were attributed to ventricular dilatation. In at least three there was associated cerebral atrophy. They considered the mechanism of the drop attacks to be similar to that occurring in patients with colloid cysts and infratentorial masses, possibly as the result of tentorial herniation following a rise in intracranial pressure. Brain ischaemia caused by hydrocephalus was also considered as a possible cause of the falls. It remains uncertain whether the hydrocephalus associated with mass lesions of the third ventrical or posterior fossa is responsible for the drop attacks or whether they are caused by the mechanical effects of the lesions themselves.
Drop attacks may occur on head movement (Sheehan et al. 1960, Gortvai 1964, Kubala and Millikan 1964, Wilkinson 1971). Most commonly this has been attributed to compression of the vertebral artery with resultant brainstem ischaemia. Many such reports are in the older literature and it is uncertain whether some of these patients also had other brainstem symptoms suggestive of vertebrobasilar transient ischaemic episodes, which would take them out of the realm of pure drop attacks. Compression of the spinal cord has also been associated with drop attacks (Maurice-Williams 1974) and such bouts may occur in cases with extreme cervical instability or fracture (Kremer 1958, van Norel and Verhagen 1996). Even in these cases, however, the mechanism may be ischaemic, as suggested by dizziness, confusion, and dysarthria, which have been reported to occur in association with transient tetraparesis (van Norel and Verhagen 1996).
In 1936 Tumarkin described sudden attacks of falling, unassociated with episodic vertigo, tinnitus, hearing loss, and a sensation of pressure in the ear which occurred in patients with Meniere's disease. He speculated that the problem resulted from a ‘hydrolithic catastrophie’ caused by mechanical deformation of the otolithic organs. There have been many subsequent descriptions of this phenomenon. It probably occurs in about 5–7% of patients with Meniere's disease (Black et al. 1982, Baloh et al. 1990) and may sometimes afflict patients with other peripheral vestibular disorders (Kuhl 1980). Although drop attacks may start many years after the onset of Meniere's syndrome it can rarely be the initial manifestation. These patient's symptoms differ from those occurring in other forms of drop attacks in that they experience a sensation of being pushed, thrown, or knocked to the ground or a sudden illusion of movement of the environment, which leads to the fall (Table 52.4) (Baloh et al. 1990). Patients may ‘fall like a tree’ and this is often in the same direction with repeated attacks (Kuhl 1980). They are usually able to get up immediately after the episode.
Table 52.4 Description of typical drop attacks in 12 patients with Meniere's syndrome
Sudden fall to ground as though pushed
While sitting at dining table, fell forward into food, as if pushed from behind
Sensation of being slapped on the side of the head, fell to the ground
‘Knocking episodes,’ first occurred while sitting in taxi, thought someone pushed her to the floor
Suddenly ‘thrown’ to the ground from sitting or standing position
While sitting had illusion that the chair was falling backward, fell forward onto the floor
Sudden fall to ground as though pushed
Sudden falls as though pushed, hit head on concrete, dazed but no loss of consciousness
Sitting at lab bench, thought bench suddenly moved away from him, fell backward from stool to floor
Sensation of sudden push to the ground, along with an electric shock-like sensation in centre of head
Sudden fall from a bar stool (before first drink) with illusion of tilting of the environment
Room suddenly tilts, must grab onto something or fall to ground ‘like an earthquake’
Reproduced with permission from Baloh RW, Jacobson BA, Winder T. Drop attacks with Meniere's syndrome. Annals of Neurology 1990; 28:384–387. © John Wiley & Sons.
Drop attacks tend to occur in bouts which eventually resolve spontaneously. Baloh et al. (1990) found that only two out of 12 patients had more than six attacks and in only two cases did they continue for more than 1 year. A similar self-limiting course has been noted by others (Janzen and Russell 1988). Patients show sensorineural hearing loss and in most cases there is an abnormality of caloric responses on the affected side. The pathophysiological mechanism of the bouts is uncertain but it has been postulated that there is a sudden stimulation of the otolithic membrane of the utricle, saccule, or both. Mechanical deformation due to pressure differentials within the inner ear or sudden change in electrolyte content of endolymph due to rupture of the membranous labyrinthine might cause the stimulation. It has been suggested that a burst of neural impulses might pass directly into the vestibulo-spinal reflex pathways or to cortical centres involved in spatial orientation, resulting in a sudden fall.
In patients in whom the bouts do not resolve spontaneously, intratympanic injections of gentamycin (Odkvist and Bergenius 1988, Chung et al. 2007) or vestibular nerve section (Baloh et al. 1990) may be helpful. If there is severe hearing loss, cochleosacculotomy (Kinney et al. 1995) or labyrinthectomy (Black et al. 1982) might be required.
Cataplexy is characterized by episodes of weakness and loss of muscle tone precipitated by emotion. It is usually part of the narcoleptic syndrome. Although Gelineau (1880) noted attacks of emotionally induced muscular weakness in narcolepsy, it was not until Loewenfeld's (1902) fuller description that the relationship became firmly established. Subsequent reports expanded the syndrome into the narcoleptic tetrad. Thus, narcolepsy or inappropriate daytime sleep was associated not only with cataplexy but also with episodes of paralysis (‘sleep paralysis’) and vivid hallucinations when going off to sleep or waking (‘hypnogogic hallucinations’). Cataplexy is not only the second commonest symptom of narcolepsy but also the most specific one (Billard et al. 2006). However, there is also a form of narcolepsy without cataplexy. The criteria for narcolepsy are listed in Table 52.5.
Table 52.5 The essential diagnostic criteria of narcolepsy with and without cataplexy
Essential diagnostic criteria of narcolepsy with cataplexy
A. Complaints of excessive daytime sleepiness occurring almost every day for at least 3 months
B. A definite history of cataplexy, defined as sudden and transient episodes of loss of muscle tone triggered by emotions, is present
C. Whenever possible confirmation by nocturnal polysomnography followed by a multiple sleep latency test. On the latter, the mean sleep latency is at least 8 min and two or more sleep onset rapid eye movement periods (SOREMPs) are observed following sufficient nocturnal sleep (minimum 6 h) during the night prior to the test. Alternatively, hypocretin-1 levels in the CSF are 110 pg/ml or more, or one-third of mean normal control values
D. The hypersomnia is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder
Essential diagnostic criteria of narcolepsy without cataplexy
Criteria A and D have to be fulfilled. For criteria B and C:
B. Typical cataplexy is not present, although doubtful or atypical cataplexy-like episodes may be reported
C. Confirmed by nocturnal polysomnography followed by a multiple sleep latency test. The mean sleep latency on MSLT is at least 8 min and two or more SOREMPs are observed following sufficient nocturnal sleep (minimum 6 h) during the night prior to the test
Reproduced with permission from Billiard M, Bassetti C, Dauvilliers Y, Dolenc-Groselj L, Lammers GJ, Mayer G, Pollmächer T, Reading P, Sonka K; EFNS Task Force. EFNS guidelines on management of narcolepsy. Eur J Neurol 2006; 13:1035–48. © John Wiley & Sons. MSLT = multiple sleep latency test
Although pathophysiological mechanisms underlying cataplexy and narcolepsy are uncertain, they may involve a disturbance of brainstem cholinergic, serotinergic, and/or catecholamine systems, which are thought to control regulation of muscle tone and rapid eye movement and non-rapid eye movement sleep. In narcoleptic and cataplectic dogs the number of cholinergic receptors in the pontine reticular formation is increased and cholinergic drugs induced cataplexy, while atropine reverses this effect (Reid et al. 1994). PET studies in humans have not confirmed an increase in muscarinic cholinergic receptors (Sudo et al. 1998). Another important neurotransmitter for sleep regulation is orexin/hypocretin, a hypothalamic neuropetide involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions (Sakurai et al. 1998) [see Nishino (2007) for review]. Alterations in orexin levels can clinically be detected as reduced levels in the cerebrospinal fluid (CSF) (Nishino et al. 2001), and this is one of the diagnostic criteria by the International Classification of Sleep Disorders (Table 52.5).
Although most cases of human narcolepsy are sporadic, there is emerging evidence that human narcolepsy is human leukocyte antigen (HLA)-associated, multigenic, and environmentally influenced (see Mignot 2004), and genetic mutations have been identified in animals with narcolepsy. In humans an increased incidence of HLA DRI5 (DR2) and DQB10602 has been found. The latter is particularly associated with cataplexy and is found in 85% of cases compared with 38% of controls (Rogers et al. 1997, Mignot 1998). Mutations in hypocretin/orexin-related genes are, however, rare in humans.
A variety of pathologies involving the ponto-medullary region can cause symptomatic narcolepsy and cataplexy, including encephalitis (Wilson 1928), tumour (Onofrj et al. 1992, D’Cruz et al. 1994), head injury (Lankford et al. 1994, Maeda et al. 1995, Francisco and Ivanhoe 1996), multiple sclerosis (D’Cruz et al. 1994, Sandyk 1996), and inherited metabolic disorders such as type C Niemann-Pick (Boor and Reitter 1997) and Norrie's disease (Vossler et al. 1996).
Hypersomnolence is the most common member of the tetrad, followed by cataplexy, which is present in two thirds of narcoleptics (Yoss and Daly 1960). Approximately a third to a half of cases with narcolepsy are familial (Kamphuisen 1981). Most inherited cases, however, usually have a lower incidence of cataplexy. In a large family described by Daly and Yoss (1959) only 25% of patients had cataplexy which was occasional and mild. Cataplexy may occur in patients unaffected by the rest of the syndrome and this has been striking in occasional families. Gelardi and Brown (1967) reported 11 patients in three generations with isolated hereditary cataplexy. The disorder seemed to be inherited as an autosomal dominant trait with high penetrance, but transmission from father to child did not occur and there was a strong female preponderance.
The prevalence of cataplexy is uncertain, but narcolepsy affects 0.03–0.16% of the general population (Kamphuisen 1981, Shimizu 1998, Nishino 2007). Onset ranges from childhood to adult life. In cases with both features narcolepsy usually predates cataplexy, often by many years. In approximately 10%, however, cataplexy develops before narcolepsy (Daly and Yoss 1977). The severity of cataplexy usually mirrors that of the hypersomnolence (Mitler et al. 1998).
Cataplectic attacks are triggered by emotional events and, generally speaking, the stronger the emotion the more severe the attack. Surprise, anger, anxiety, pleasure, and amusement are all precipitants. Laughter is among the most potent. Even normal subjects can develop a degree of weakness with intense emotions, such as fear or laughter, but loss of positional tone in narcolepsy has been estimated to be almost 10 times greater than in controls (Parkes et al. 1998). Cataplexy may be more likely to occur if the patient is drowsy. Both weakness and loss of muscle tone occur. Attacks can vary from a focal feeling of mild weakness to complete generalized paralysis. There may be diplopia, ptosis, facial weakness, or paralysis of jaw muscles. The mouth can sag open or the head slump forwards. Weakness of limbs and trunk may result in the arms falling to the sides, the knees buckling, or toppling from the sitting position. Generalized paralysis with falling may endanger the patient. Cataplectic attacks usually last less than half a minute and seldom exceed a few minutes. Rarely they persist for a more prolonged period, sometimes for hours, a state that has been called ‘status cataplecticus’. Approximately a quarter of children with narcolepsy, however, are reported to have experienced this (Challamel et al. 1994).
Cataplexy is unaccompanied by loss of consciousness or tongue biting. Incontinence has only rarely been recorded (Vgontzas et al. 1996). Blood pressure may rise and be accompanied by a fall in pulse (Guilleminault 1998). Examination during an attack is reported to show flaccid weakness with areflexia (Roth 1957, 1962). H-reflexes are lost (Daly Yoss 1977, Guilleminault et al. 1998). In spite of this the response of axial and limb muscles to magnetic stimulation of the motor cortex during cataplexy is normal, possibly due to enhanced cortical excitability (Rosler et al. 1994). The EEG, however, shows no significant change (Daly and Yoss 1977).
Diagnosis is based on clinical features, although EEG may show that sleep commences with a period of rapid eye movement instead of the normal initial slow wave sleep. The maintenance of wakefulness test, which involves multiple measurements of the latency to EEG sleep onset in a darkened room, is abnormal with 85% of narcoleptics showing an average latency of 12 minutes or less (Mitler et al. 1998). A number of other EEG sleep abnormalities have been reported (Hishikawa et al. 1976). Assessment of HLA status may assist diagnosis. Initial reports of subtle MRI changes in the pontine tegmentum have not been substantiated (Bassetti et al. 1997). For the diagnostic criteria of narcolepsy see Table 52.5.
In 2006, the European Neurological Society published guidelines on the management of narcolepsy with or without cataplexy. The authors concluded that several classes of drugs are recommended for the treatment, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy, and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioural measures can be of notable value (Billard et al. 2006).
However, although methylphenidate and dexamphetamine improve narcolepsy, they are ineffective in the treatment of cataplexy, sleep paralysis, and hypnogogic hallucinations (Daly and Yoss 1977). However, as mentioned above, the tricyclic antidepressants clomipramine and imipramine improve these other features (Hishikawa et al. 1966). The selective serotonin re-uptake inhibitors (Billiard 1998), the non-selective monoamine oxidase inhibitor tranylcypromine (Gernaat et al. 1995), and the monoamine oxidase-B inhibitor selegiline (deprenyl) have all been reported to lessen cataplexy (Hublin et al. 1994, Mayer et al. 1995). Interestingly, Norrie's disease, mentioned above, is accompanied by virtual absence of monoaminine oxidase-A and -B (Vossler et al. 1996). Carbamazepine may be worth trying in resistant cataplexy (Vaughan and D’Cruz 1996). Gammahydroxybuterate (under the name sodium oxybate) has been said to ameliorate all aspects of the narcoleptic tetrad (Scharf et al. 1998), but the effect on cataplexy has been uncertain in some early studies (Lammers et al. 1993). However, since sodium oxybate has now become the first-line treatment of cataplexy, second-line treatments are antidepressants, either tricyclics or newer antidepressants (Billard et al. 2006).
Modafinil, a non-amphetamine awakening drug, reduces somnolence (US Modafinil in Narcolepsy Multicentre Study Group 1998). However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Particularly in view of the overuse of amphetamines and such like agents, this should be considered (Billard et al. 2006).
Idiopathic drop attacks
Drop attacks, during which the subject suddenly collapses to the ground without warning, or apparent loss of consciousness may occur without recognized cause. Stevens and Matthews (1973) estimated these affected at least 3.5% of adult females but were unable to find any cases among males. Although the cause was uncertain, they effectively excluded the narcoleptic syndrome, epilepsy, vestibular disturbance, transient ischaemic attacks, syncope, and cervical spondylosis. They speculated that attacks were due to the female ‘mechanism of walking’ and that central factors were not involved. It has been proposed that a delay in long-loop transcortical reflexes may be responsible so that the subject falls before sufficient tension can be generated in the quadriceps to prevent this (Greenwood and Hopkins 1982).
Almost 30% of patients have a positive family history with other close female relatives having been affected (Stevens and Matthews 1973). The average age of onset is approximately 45 years and in two thirds it commences during the 5th decade. The frequency of attacks can range from a single fall to over one a month. Episodes sometimes occur in bouts with prolonged intervals of freedom (Stevens and Matthews 1973).
The falls virtually always occur when walking and do not seem to relate to the type of footwear being worn. Episodes are more frequent out of doors. In the majority the fall is forwards. Most patients are able to break their fall, but it is common to injure the face or upper limbs. Approximately a third recall starting to fall and half are aware of striking the ground (Stevens and Matthews 1973). The attack is so brief that some patients are uncertain about preservation of consciousness, but in none is it definitely suspended. Unless injured, patients are able to rise immediately and have no sequellae.
It is uncertain to what extent idiopathic falls in the elderly overlap with or are an extension of these drop attacks of middle age. Many such bouts in older people, however, may be due to unrecognized cardiac, cerebrovascular, blood pressure, neuromuscular, balance, or gait disturbances, or carotid sinus hypersensitivity (Sheldon 1960, Overstall et al. 1977, Brocklehurst et al. 1978, Gordon et al. 1982).
Psychogenic drop attacks
Drop attacks, like pseudo seizures, occasionally have a psychological basis (Meissner et al. 1986). They resemble brief pseudo seizures, without associated motor activity.
Hemifacial spasm is a movement disorder of the face consisting of involuntary irregular twitching of muscles innervated by the seventh cranial nerve. While the movements are generally clonic, fusion of these into a more sustained tonic spasm can occur.
Schultze first described this condition in 1875 and by 1888 Gowers had differentiated it from other forms of facial spasm. As it may result in simultaneous contraction at separate sites, it has long been considered to result from abnormal generation of nerve impulses rather than being an innate muscle spasm. It was not until 1947, however, that Campbell and Keedy recognized that irritation caused by a blood vessel in contact with the facial nerve close to the brainstem might be the aetiology. This was largely ignored until Gardner and Sava (1962) reported that surgical microvascular decompression, performed by separating the blood vessel from the nerve, could result in remission of the movements. It is now accepted that this is by far the commonest cause of hemifacial spasm. The exact proportion of cases that have such a vascular aetiology varies from one series to another, depending on referral bias. In a review of 1,688 cases of hemifacial spasm previously reported in the literature Digre and Corbett (1988) found that in only 30% a vascular mechanism had been defined. In 57%, however, an aetiology was not specified. Reported surgical series tend to skew the picture by emphasizing those with either a vascular loop or some other type of mass lesion. Conversely, in groups referred for medical treatment, some mass lesions may have been selected out. In about 90% of cases no other aetiology can be found and it is probably likely most of these harbour such a vascular abnormality (Wang and Jankovic 1998). There is a suggestion that vascular abnormality may be related to the presence of arterial hypertension (Oliveira et al. 1999). Arterial hypertension was found in 66% of their cases with hemifacial spasm as compared to 38% with blepharospasm. In a case-control study, Defazio et al. (2000) also found that arterial hypertension occurred more frequently among 115 patients with primary hemifacial spasm than among age and sex matched controls. The association was not confounded by education level, smoking history, diabetes, or other diseases. However, hypertension in this sample either preceded or followed the onset of hemifacial spasm (Defazio et al. 2000).
When the cause is irritation from an adjacent blood vessel, this is virtually always arterial, with only a few per cent being venous (Loeser and Chen 1983, Caces et al. 1996, Girard et al. 1997). A vascular loop of the posterior inferior cerebellar artery seems to be the most common offending vessel (Caces et al. 1996 Girard et al. 1997), although the anterior inferior cerebellar artery has been responsible in many cases and, according to some authors (Digre and Corbett 1988), may be the most frequent. The vertebral artery has variously been reported to account for about 20–40% of cases. Yuan et al. (2005) reviewed 1200 cases of hemifacial spasm who had undergone microvascular decompression. The authors had found the offending vessel to be the anteroinferior cerebellar artery (AICA) in 511 patients (42.6%) and the posteroinferior cerebellar artery (PICA) in 255 (21.3%). A combination of both AICA and PICA were found in 154 patients (12.8%), AICA and the vertebral artery in 10%, PICA and the vertebral artery in 7%. Finally, all three vessels had offended the nerve in 6%. Sometimes the basilar artery is in contact with the facial nerve. When the vertebral or basilar are involved they may be dolichoectatic and hence elongated and distended. While it is usually the root entry zone of the facial nerve that is affected, the vascular compression can be closer to the internal auditory canal (Fukuda et al. 1997, Ryu et al. 1998[a]). Vascular lesions causing hemifacial spasm have rarely been described, even more distally, including at the geniculate ganglion (Asaoka et al. 1997) and in the parotid space (Rakover et al. 1996).
A variety of other pathologies can trigger this disorder. While these are usually situated intracranially and commonly near the root entry zone of the facial nerve, they may also occur more distally. Bell's palsy is a well-recognized antecedent and Wang and Jankovic (1998) found this in 5.7% of cases. Direct injury to facial nerve may be the cause (Martinelli et al. 1983, 1992) and 3.2% of Wang and Jankovic's patients had significant trauma to that side of the skull or face in the 6 months to 4 years prior to onset of involuntary movements. Injuries included skull fracture and facial laceration. The literature is also awash with cases of hemifacial spasm secondary to other lesions involving the cerebello-pontine angle, brainstem or other sites in the posterior fossa. Usually these have been ipsilateral but occasionally they have been contralateral and thought to result from irritation caused by displacement of the brainstem and seventh cranial nerve (Nishi et al. 1987, Matsuura and Kondo 1996). The frequency of mass lesions causing facial spasm has varied between 0.3 and 1.3% of cases (Auger et al. 1986, Sprik and Wirtschafter 1988, Nagata et al. 1992, Wang and Jankovic 1998). These have included meningioma (Nagata et al. 1992, Rhee et al. 1995, Bhayani and Goel 1996), epidermoid tumour/cholesteoma (Auger and Piepgras 1989, Nagata et al. 1992, Brodkey et al. 1996, Hotta et al. 1996, Magnan et al. 1997), lipoma (Sprik and Wirtschafter 1988, Inoue et al. 1995), schwannoma/acoustic neurinoma (Sprik and Wirtschafter 1988, Samii and Matthies 1995, Kudo et al. 1996), neurinoma (Nagata et al. 1992), ganglioglioma (Bills 1991, Harvey et al. 1996), arachnoid cyst (Takano et al. 1998), glomus juglare tumour (Hausmann et al. 1997, Kinney et al. 1999), subarachnoid cysticerci (Del Brutto 1997), cavernous haemangioma (Asaoka et al. 1997), and arteriovenous malformation (Kim et al. 1991). Other vascular abnormalities that have been recorded in association with this disorder include venous angioma (Chen et al. 1996[a]) and dissection of the basilar artery (Mizutani 1996). Brainstem infarction (Ambrosetto and Forlani 1988, Wang and Jankovic 1998), haemorrhage (Ellis and Speed 1998), and multiple sclerosis plaques (Telishi et al. 1991, van de Bienzenbos et al. 1992) are other examples of intrinsic brainstem pathologies that may lead to hemifacial spasm.
Non-traumatic bony abnormalities of the skull base, including cranio-occipital malformation (Arnould et al. 1962), basilar impression (Klaus and Bohunek 1958), and Paget's disease (Gardner and Dohn 1966), have occasionally been associated, as have benign intracranial hypertension (Selky and Purvin 1994), superficial haemosiderosis of the central nervous system (River et al. 1994), and tuberculous meningitis (Sandyk 1995).
Although it is clear from the literature that lesions affecting the brainstem or seventh cranial nerve along its course can trigger hemifacial spasm, in the vast majority of patients the abnormality seems to lie in the nerve root exit zone, adjacent to the pons. This is sometimes called the Obersteiner-Redlich zone after the pathologists who first described it in 1894. It is the boundary region where the myelin sheath changes from the thicker central nervous system type to the thinner variety found in the peripheral nervous system. There is often loose connective tissue in this area and it is ensheathed only by arachnoid membrane. Biopsies of this zone in patients suffering from hemifacial spasm show both nerve fibres with hypertrophied myelin sheaths and axons that are devoid of myelin and in contact with connective tissue. Normal fibres may be intermixed. These abnormalities are not dissimilar to those reported in trigeminal neuralgia (Jannetta et al. 1970, Kumagani 1974, Ruby and Jannetta 1975). It has been suggested that this region of the nerve is particularly vulnerable to damage by compression.
There are a variety of abnormal neurophysiological findings in hemifacial spasm, some of which appear contradictory and are difficult to explain on the basis of a single unified hypothesis. None the less, they shed considerable light on the possible pathophysiological mechanisms underlying this disorder. EMG of facial muscles shows the brief visible twitches are accompanied by isolated bursts of repetitive motor unit discharge, usually at very high frequencies. Bursts consist of 2–40 discharges of the same motor unit at frequencies between 100 and 400 Hz. Prolonged spasms may result in superimposed irregular discharges of many motor units, some of which fire at lower frequencies, in the order of 20–40Hz (Hjorth and Willison 1973). Infiltration of dilute procaine around the nerve in the region of the parotid gland can abolish such motor activity without causing weakness, perhaps suggesting gamma motor fibre hyperactivity and involvement of peripheral reflexes (Rushworth 1961).
Although facial synkinesis, which occurs when muscles in one part of the face contract automatically as those in another area are activated, may not be apparent on clinical examination, EMG recordings can usually demonstrate this. Stimulating one peripheral branch of the facial nerve results in ‘lateral spread’ of the nerve impulse so that it may cause muscles elsewhere on the ipsilateral side of the face to respond (Auger 1979, Auger et al. 1981, Nielsen 1985). The electrically elicited blink reflex, in which stimulation of the fifth cranial nerve causes a response in the seventh cranial nerve, results in early R1 and late R2 components. The former is a unilateral response which is thought to pass through a simple pontine reflex arc, while the latter is a bilateral response that is felt to descend in the ipsilateral spinal tract of the trigeminal nerve before ascending to activate both the ipsilateral and contralateral facial nerve nuclei (Kimura and Lyon 1972). In hemifacial spasm the size of R1 is increased, suggesting lateral spread with involvement of more fibres (Kimura et al. 1969, Auger 1979). In addition, there is activation of muscles in the lower face during both the R1 and R2 components (Fig. 52.3), although this is variable from one trial to the next, unlike that seen in the synkinesis which accompanies Bell's palsy (Auger et al. 1979). The facial synkinesis in Bell's palsy is thought to result from regrowth of nerves following axonal degeneration with some fibres being erroneously redirected to muscles at a site distant from those from which they originally innervated. Such aberrant regeneration, however, seems unlikely to be the cause of these synkinetic responses in hemifacial spasm as most patients have had no evidence of axonal loss and, as just mentioned, this response can be variable in a way not seen with aberrant reinnervation. It has thus been proposed that the abnormality in the nerve root entry zone might lead to ‘cross talk’ or ‘ephaptic transmission’ (Auger 1979, Auger et al. 1981). This envisages nerve impulses passing from one nerve fibre to another in the nerve root entry zone due to defects in myelination.
Moller and Jannetta (1984, 1985) found, however, that when one branch of the facial nerve was stimulated and recording made from muscles activated by other branches, the latency of response in some cases was a few milliseconds longer than could be accounted for by ephaptic transmission through the nerve root entry zone. This led to the postulation that such lateral spread might be due to nerve impulses passing through the facial nucleus. The motor nucleus of the fifth cranial nerve has thus been envisaged as being ‘kindled’ by the abnormality in the nerve root entry zone so that not only do neurons respond in a hypersensitive way to antidromic nerve pulses from their peripheral nerve fibres but also their hyperactivity causes the spontaneous facial twitching. Using a paradigm of paired stimuli separated by a small interval, one stimulus being delivered to a branch of the facial nerve and the other by way of exciting the blink reflex on the same side, it has been found that the abnormal muscle response resulting from lateral spread and the R1 component of the blink reflex can each suppress whichever response comes second. It has been argued that this supports an interaction within the facial nucleus and that lateral spread may actually be an exaggerated F-response (Moller 1991). A re-evaluation of this lateral response has led others to support its interpretation as an F-wave (Ishikawa et al. 1996[a] and [c], Ishikawa et al. 1997). It is facilitated by repetitive stimulation, which has also been taken to favour its origin in the motor neurons and their hyperexcitability (Ishikawa 1996[b]). In addition, the R2 component of the electrically elicited blink response can be inhibited by a second such stimulus if the inter-stimulus interval is short. In hemifacial spasm the recovery of R2 on the affected side of the face is enhanced, which has also been interpreted as suggesting hyperexcitability of the facial nucleus. In support of this is the report by Eekhoff et al. (2000) comparing patients with Bell's palsy synkinesis to those with hemifacial spasm. The former had a prolonged R1 latency on the affected side in orbicularis oculi and smaller mental compound muscle action potential amplitude as an indication of facial nerve damage and nerve fibre loss. This was not found in patients with hemifacial spasm, who showed an increased amplitude of the R1 and R2 responses in orbicularis oris. Patients with Bell's palsy showed only an increased R1 amplitude in orbicularis oris. Both groups of patients had signs of synkinesis. Lateral spreading was present in all patients with hemifacial spasm but only in half of those with Bell's palsy. The authors suggested that in addition to alterations in facial nucleus excitability in both conditions, ectopic re-excitation of facial nerve axons in hemifacial spasm was possible (Eekhof et al. 2000). Many of these neurophysiological abnormalities are reversed by successful microvascular decompression of the nerve root entry zone of the facial nerve, including the spontaneous EMG discharge, lateral spread on stimulating a branch of facial nerve, and abnormalities of blink response. In some cases these findings revert to normal when the dura or arachnoid are opened at operation, prior to the actual decompression itself, but in the majority the improvement seems to be simultaneous with the actual separation of the artery from the nerve. The lateral spread phenomenon has been noted to disappear intra-operatively in about 66% of cases (Moller and Jannetta 1987). In other patients surgery decreases such EMG abnormality and in many it will revert to normal over the ensuing months. This correlates with the clinical relief of the spasms. Similar changes have been reported by a number of authors and also involve the blink reflex (Moller and Jannetta 1986, Haines and Torres 1991, Ishikawa et al. 1994, 1996[c]). The fact that such changes can occur intra-operatively supports the notion that in spite of the histological findings, the pathophysiological mechanism underlying the spasms involves direct contact between the artery and the nerve root entry zone. Ephaptic transmission through a demyelinated area would not be expected to show such immediate reversal.
Hemifacial spasm usually commences in adult life and the mean age of onset is usually given between 45 and 50 years (Ehni and Voltman 1945, Wang and Jankovic 1998) with a range between about 15 and 90 years. In occasional patients it may develop during childhood. Most such cases, however, are likely to be due to pathology other than compression by a vascular loop in the nerve root entry zone. Hemifacial spasm in infancy seems particularly likely to occur with ganglioglioma. It is usually associated with other physical signs and may be due to epileptic seizures arising in the cerebellum (Harvey et al. 1996). Congenital hemifacial spasm, without obvious cause and with spontaneous remission, has been reported (Zafeiriou et al. 1997). Wang and Jankovic noted that the mean age of onset in a series of 158 patients was similar to that of patients with cranial dystonia but 7 years younger than the mean age of their series of patients with isolated blepharospasm.
There tends to be a slight preponderance of women in the ratio of about 3:2 (Ehni and Voltman 1945, Wang and Jankovic 1998). No racial predilection has been noted. Although most cases are sporadic, familial hemifacial spasm has occasionally been described (Friedman et al. 1989, Carter et al. 1990, Coad et al. 1991, Micheli et al. 1994).
The disorder usually commences with occasional minor twitching of facial muscles, which gradually becomes more frequent and persistent over the ensuing months and years. This most frequently starts in the periocular muscles, particularly those of the lower eyelid (Ehni and Voltman 1945). In only 10% of cases is the initial involvement noted in other parts of the face. Even if the orbicularis oculi is not affected first, it is eventually involved in spasms in virtually every case (Table 52.6).
Table 52.6 Symptom location and anatomic distribution in 158 patients with hemifacial spasm
Site of onset by history [n (%)]
Affected site by examination [n (%)]
Reproduced with permission from Wang A, Jankovic J. Hemifacial spasm: clinical findings and treatment. Muscle Nerve 1998; 21:1740–7. © John Wiley & Sons.
Orbicularis oris is involved in about two thirds and the zygomatic muscles in about half of patients. In about 20–30% of cases frontalis, the paranasal muscles, mentalis, and/or platysma are affected. There may be isolated momentary muscle twitches which can be felt by the patient, seen, or palpated. While annoying, these are not usually functionally disabling. Commonly patients also experience bouts in which a rapid succession of such twitches fuse into a tonic contraction that can be sustained for many seconds (Fig. 52.4). This is usually more troublesome and may temporarily interfere with vision. Rarely, bilateral hemifacial spasm can occur, usually after a typical unilateral onset (Tan and Jankovic 1999). In five such patients, the opposite side was involved on average 8.4 years later (Tan and Jankovic 1999).
A number of factors may trigger the involuntary movements, most prominently emotional stress, anxiety, fatigue, and facial activity (Table 52.7). Maximal voluntary facial movements are especially likely to trigger them, even if they are not otherwise obvious. Thus, screwing up the eyes, frowning, corrugating the forehead, grimacing, parting the lips, tensing platysma, or flaring the nostrils may make twitches or spasms appear or turn the former into the latter. Occasional patients have fluctuation in severity of hemifacial spasm with change in head position, which seems likely to be due to postural alteration in the amount of pressure being applied to the nerve (Moore 1984). Relaxation, alcohol, and touching the affected area will help relieve the symptoms in some patients. Movements commonly persist during sleep and about 80% of patients will be aware of this (Wang and Jankovic 1998). The movements tend to progressively decrease during the deeper stages of sleep and are at a minimum during rapid eye movement sleep (Montagna et al. 1986).
Table 52.7 Factors modifying symptoms in 158 patients with hemifacial spasm (number of patients affected)
Unknown or no effect
Touching the area
Reproduced with permission from Wang A, Jankovic J. Hemifacial spasm: clinical findings and treatment. Muscle Nerve 1998; 21:1740–7. © John Wiley & Sons.
Patients with hemifacial spasm experience a variety of symptoms in addition to the sensation of facial twitching or spasm (Table 52.8). The most common of these is embarrassment when meeting and socializing with other people. The movements around the eye cause a number of ocular symptoms, most commonly intermittent impairment of vision. Watering and irritation of the eye can also be bothersome and occasional patients feel that light worsens their symptoms.
Table 52.8 Symptoms in 158 patients with hemifacial spasm
Percentage of patient group
Interference with vision
Discomfort or pain
Reproduced with permission from Wang A, Jankovic J. Hemifacial spasm: clinical findings and treatment. Muscle Nerve 1998; 21:1740–7. © John Wiley & Sons.
Pain is not normally a feature, unless there is associated trigeminal neuralgia (see later). A number of patients, however, complain of diffuse discomfort including aching and tightness. Facial parasthesiae are occasionally reported. In a small number the spasms may interfere with articulation and result in intermittent dysarthria. Dribbling from the affected corner of the mouth, bruxism, and occasionally trismus are reported. Intermittent contractions of the tensor tympani or stapedius muscles (Auger 1986, Illingworth et al. 1996, Wang and Jankovic 1998) infrequently produce clicking or ticking noises in the ear ipsilateral to the facial movements and sometimes the patient notes that these occur synchronously with the facial movements. Rarely patients complain of transient hearing loss on the affected side during bouts of muscle spasm (Wang and Jankovic 1998).
Apart from the involuntary facial movements, neurological examination is usually unremarkable. A small number of patients have mild facial weakness and this was noted in 15% of cases reported by Ehni and Voltman (1945). They had excluded cases in which there was an identifiable cause. The repetitive movements may result in muscle hypertrophy and this has been noted in about 5% (Wang and Jankovic 1998). A degree of deafness has been reported in about 13% (Ehni and Voltman 1945, Wang and Jankovic 1998) but the side does not necessarily correlate with that of the hemifacial spasm. Nonetheless, some patients do experience related hearing loss and audiograms may be abnormal in up to a quarter of patients, with an unusual ‘notch’ in the pure tone audiogram or a low-frequency up-slooping pure tone threshold (Moller and Moller 1985). In addition, a small number of patients suffer from pulsatile or continuous tinnitus ipsilateral to their hemifacial spasm and it has been reported that neurovascular compression of the eighth cranial nerve is common in this group and that decompression relieves the tinnitus. Such a vascular loop contacting the eighth cranial nerve has been noted in only 6% of patients at the time of surgery when tinnitus has not been present (Ryu et al. 1998[b]).
Very occasionally neurovascular compression of the facial nerve extends to other adjacent nerves causing symptoms, the best known being so-called tic convulsif, a term coined by Cushing in 1920 to describe the concurrence of hemifacial spasm and trigeminal neuralgia. This association is found in about 5% of cases of hemifacial spasm (Harsh et al. 1991, Wang and Jankovic 1998). Either hemifacial spasm or trigeminal neuralgia can develop first and the disorder occurs more frequently in women (Digre and Corbett 1988). A patient with familial trigeminal neuralgia and contralateral hemifacial spasm has been reported. The mother of the patient, five siblings, and one nephew also had trigeminal neuralgia (but not hemifacial spasm) inherited in an autosomal dominant fashion. It is possible that the occurrence of hemifacial spasm in this one family member could be by chance. However, sporadic examples occurring in combination with hemifacial spasm has also been reported. Glossopharyngeal neuralgia (Platania et al. 1997). Kobata et al. (1998) used the term hyperactive dysfunction syndrome to describe patients with a combination of trigeminal neuralgia, hemifacial spasm, and/or glossopharyngeal neuralgia. Reviewing 1472 patients presenting with one of these conditions they found 41 (2.8%) with this syndrome who had a combination of such conditions. In this study, all but three of the cases, which were due to tumours or arteriovenous malformations, were idiopathic (Kobata et al. 1998). Overall, aetiologies other than irritation by a simple loop of the anterior inferior or posterior inferior cerebral arteries seem more common in tic convulsif, and dolichoectasia of the vertebrobasilar system, aneurysm, arteriovenous malformation, tumours, and cysts appear to predominate (Digre and Corbett 1988). So-called geniculate or Hunt's neuralgia (Kempe and Smith 1969, Yeh and Tew 1984) has also been reported in association with hemifacial spasm.
Hemifacial spasm is usually a very characteristic disorder and is not difficult to diagnose. They include most disorders causing involuntary facial movement, including facial synkinesis with or without hemifacial contracture following facial nerve palsy, hemifacial contracture associated with brainstem lesions, facial myokymia, facial fasciculations, cranial dystonia, facial tics, focal seizures, facial myoclonus, and hemimasticatory spasm (Digre and Corbett 1988, Auger et al. 1992, Wang and Jankovic 1998).
The neurophysiological and audiological investigations mentioned above are usually only performed in selected cases. Radiology, however, should ideally be performed in all patients, unless the aetiology of the hemifacial spasm is already known. The most useful investigation is CT or MR scan of the posterior fossa. This is important to exclude structural lesions other than a vascular loop, which might require treatment in their own right. If surgery is being considered, MRI can be especially useful in screening for abnormal vessels causing compression. While some studies have suggested vascular compression can be seen in about 65% of cases compared with 6% of controls (Adler et al. 1992), the rate of identification of aetiological vessels can be increased by adopting a variety of specialized techniques. This, however, may increase the rate of false positive identifications. In not all reports has surgery been performed to confirm that the vessel seen on the MRI is responsible for the complaint. Positive identification rates of between 85 and 100% of cases and false positive rates of between 7 (Jespersen et al. 1996) and 13.8% (Hosoya et al. 1995) respectively have been quoted. False negative rates as low as 1% have been reported (Girard et al. 1997). In many patients it is possible to make a reasonably accurate anatomical prediction as to the offending vessel. A thick and/or long high-intensity line along the root entry zone has been reported to be caused by the vertebral artery in 80% of cases, whereas a thin and/or short high-intensity line in the same area was related to compression by the posterior inferior cerebellar artery or anterior inferior cerebellar artery in 100% of patients using pre-operative oblique sagittal gradient-echo MR imaging followed by neurosurgical confirmation (Nagaseki et al. 1998).
A variety of treatments has been used to treat hemifacial spasm. Earlier unsuccessful treatments included ‘nerve tonics’, electric shocks, counter irritation resulting from a blister behind the ear (Gowers 1888), and bathing the face with hot water (Russell 1910). Membrane stabilizing anticonvulsants, such as carbamazepine and phenytoin, which have proved so successful in treatment of trigeminal neuralgia, are disappointing. In a few reports, however, they have been helpful (Shaywitz 1974, Alexander and Moses 1982). Other anticonvulsants which have also been said to help individual patients include clonazepam (Herzberg 1985) and felbamate (Mellick 1995, Patel and Naritoku 1996). Baclofen has also been reported to be useful in a small number of cases (Sandyk and Gillman 1987) as has orphenadrine (Hughes et al. 1980) and levodopa (Milan-Guerrero et al. 2000). While there has been a lack of controlled studies, the overall impression is one of an occasional idiosyncratic improvement rather than any reliable long-lasting benefit. Wang and Jankovic (1998) reported 83% of their patients were tried on a variety of medications but that only 3.8% remained on these. This testifies to their disappointing efficacy.
The medical treatment of hemifacial spasm has been revolutionized by botulinum toxin injections. Significant relief of spasms has been reported in between about 85 and 97% of patients (van den Bergh et al. 1995, Chen et al. 1996[b], Mauriello et al. 1996, Jitpimolmard et al. 1998, Wang and Jankovic 1998, Kenney and Jankovic 2008). Injections are usually made into the obicularis oculi muscle near the inner and outer canthi. While injections can be made into the zygomatic or perioral muscles, these are usually avoided because weakness may result in significant disability. In addition, a ‘trickle down’ effect from injections into the obicularis oculi often results in some reduction in involuntary movements in these lower facial muscles. As mentioned below, however, this may not be due to direct diffusion of toxin.
The mean latency from injection to onset of benefit was found to be 9.4 days and the average duration of benefit was 18.4 weeks in 84 patients treated by Wang and Jankovic (1998). They reported side effects in 37.3% but these were mild and not disabling. They included lower facial weakness, lid weakness, ptosis, a disturbance of lacrimation, diplopia, and haematoma.
The exact mechanism of the action of botulinum toxin in hemifacial spasm is uncertain. While it reduces compound muscle action potential in the obicularis oculi, the lateral spread response or F-wave in this muscle when stimulating branches of the seventh nerve elsewhere in the face is abolished (Glocker et al. 1995). This suggests that the effect is not restricted to the peripheral parts of the nerve. In addition, neurophysiological studies confirm this effect can be noted in muscles too distant to be affected by direct diffusion of toxin (Eleopra et al. 1996). In an interesting experiment to investigate interactions between face and hand representations in the human motor cortex, Liepert et al. (1999) studied patients with hemifacial spasm before and after treatment with botulinum toxin. Focal transcranial magnetic stimulation was used to assess the cortical motor output map of the abductor pollicis brevis muscle (APB) on both sides. Prior to botulinum toxin treatment the representation of the APB ipsilateral to the facial muscle contractions (iAPB) was significantly smaller than on the contralateral side. Two weeks after successful therapy, the iAPB output area was significantly enlarged and expanded into the direction of the face representation. The results showed brain plasticity changes so that the facial cortical area diminished once the spasms were improved, indicating activity-dependent interactions between hand and face representations in the motor cortex.
A variety of other procedures involving needling of the face have been used, most directed against branches of the facial nerve. Usually these have been carried out using EMG guidance. They include injections of alcohol or phenol, which usually result in relief of spasm, but recurrence within 1 year is common (Wakasugi 1972, Toremalm et al. 1977[a], Seidman and Vacharat 1980, Elmquist et al. 1982, Takahashi and Dohi et al. 1983). While the terminal branches of the nerve have usually been favoured for injections, as this allows greater control over the degree of weakness, some have targeted the main branch (Russell 1910, Toremalm 1977[b]). Thermolysis, which involves heating the tip of the needle in contact with the nerve to between 55 and 65°C, may also be helpful (Battista 1977, Hori et al. 1981). Even the small amount of physical damage caused by putting a needle into the nerve may be enough to improve the spasms (Wakasugi 1972, Ludman 1976). While this has generally been done in its distal segments, needling through the tympanic membrane has been reported to be effective (Ogale et al. 1995). Another approach has been to inject the muscles with doxorubicin and it has been proposed that the use of a priming injection of local anaesthetic 2 days before the doxorubicin may make the procedure more effective (Nguyen et al. 1998, Wirtschafter and McLoon 1998).
Direct surgical attack on the muscles and peripheral nerve branches has also been employed. While orbital myectomy has been more commonly employed for treatment of blepharospasm, it has also been helpful in hemifacial spasm (Garland et al. 1987, Friedman et al. 1989). Selective or complete facial neurotomy, involving avulsion of sections of nerve, has also been advocated (Scoville 1969, Miehlke 1981, Iwakuma et al. 1982). In some cases neurectomy has been associated with anastomosis of the distal stump to the spinal accessory or hypoglossal nerve (Harris 1932, Harrison 1976). By and large, such direct surgical attacks on facial muscles and nerves may result in unacceptable facial weakness, a variety of complications including epiphora, ectropion, and punctate keratitis, and a high recurrence rate due to regrowth of nerves (Samii et al. 1981).
In addition to the above destructive procedures, complete decompression of the facial nerve in the petrous block has been attempted, with about half of patients experiencing relief. Facial paralysis is, however, frequent (Pulec 1972, Wizmann and Dieckmann 1982).
Microvascular compression of the facial nerve root exit zone was introduced by Gardner and Sava in 1962 and subsequently popularized by Jannetta (Jannetta et al. 1977). It involves separating the facial nerve from the compressing vessel using a piece of suitable material. Excellent or satisfactory relief of facial spasms has been reported in about 70% (Rushworth and Smith 1982) to 90% (Illingworth et al. 1996) of cases and results tend to be better in large more recently reported series (Barker et al. 1995, Caces et al. 1996, Acevedo et al. 1997, Kondo 1997). Although, as mentioned above, neurophysiological improvement may occur intra-operatively and spasms cease from the time of surgery, there are a number of patients in whom improvement occurs more gradually and some authors have advised that re-operation for unsuccessful surgery is delayed, possibly for 1–2 years (Sindou et al. 1996, Ishikawa et al. 1997, Shin et al. 1997). On the other hand, however, others have reported that re-operation is more successful if performed within 1 month (Barker et al. 1995) In the series by Yuan et al. (2005) of 1200 hemifacial spasm patients who had undergone microvascular decompression symptoms had disappeared immediately after operation in 66%.
There is an incidence of recurrence of hemifacial spasm, even after apparently successful microvascular decompression, and the rate of such failures has varied widely from 1 or 2% to 55.5% (Rushworth and Smith 1982, Illingworth 1996, Kondo 1997, Yuan et al. (2005)). Jankovic and Wang (1998) reported recurrence in 21% of patients. In addition, significant long-term complications have been reported in most series and vary from about 3% to almost 30% (Barker et al. 1995, Caces et al. 1996, Acevedo et al. 1997, Kondo 1997, Wang and Jankovic 1998). Ipsilateral hearing loss is the commonest, followed by facial weakness. Tinnitus, ataxia, meningitis, leakage of cerebrospinal fluid, diplopia, hydrocephalus, intracranial haematoma, stroke, and death have all been reported.
Because of the ease of administration, excellent results, and lack of serious side effects, botulinum A injections into the obicularis oculi muscle are the preferred initial mode of treatment for this disorder. Surgery should be considered only for patients in whom the results are unsatisfactory and microvascular decompression of the facial nerve root entry zone is the procedure of choice. Other forms of therapy seem best reserved for the occasional case in whom these other forms of therapy are unsatisfactory (Wirtschafter and McLoon 1998).
Involuntary movements in amputation stumps
In 1852 Hancock described a case of a 29-year-old woman who had an above elbow amputation because of septic arthritis. Three months later she developed pain in the stump followed by ‘spasmodic twitchings’ of the shoulder and neck. This may have been the first description of involuntary movements in amputation stumps, although the question of simple partial seizures has been raised because the platysma and leg subsequently became involved. In 1872 Mitchell published a monograph on the ‘Injuries of nerves and their consequences’, relating experiences from the American Civil War. He described severe phantom pain in amputated limbs along with tremor, jerks, and spasms in the stump. A number of further reports were produced in the early part of the 20th century (Tinel 1927, Vinard 1927, Thomas and Amyot 1928). In 1929 Amyot wrote a thesis on stump spasms entitled ‘Les Convulsions des Moignons’. There has subsequently been a smattering of other reports but most have included only a small number of patients (Ritchie 1970, Russell 1970, Steiner et al. 1974, Baruah 1984, Iacono et al. 1987[a], Marion et al. 1989, Kulisevsky et al. 1992). A case of psychogenic ‘jumpy stump’ has also been described (Zadikoff et al. 2007).
Jerking or jactitation of an amputation stump, often coinciding with momentary severe local pain, may occur in the post-operative period and then settle over the ensuing weeks or months (Henderson et al. 1948, Russell 1970). In most of the published papers, however, the movements have been chronic. They have generally commenced within days to months of surgery (Marion et al. 1989, Kulisevsky et al. 1992). Pain has been a feature of many cases and this can be a persistent aching, gnawing, burning sensation or lancinating neuralgic discomfort. The pain tends to be at its worst when the stump is moving. This has led to the suggestion that the movements may be similar to those seen with causalgia and reflex sympathetic dystrophy (Kulisevsky et al. 1992) (see Chapter 43). In some patients, however, pain has been absent or inconspicuous (Marion et al. 1989, Kulisevsky et al. 1992). Both upper and lower limb amputation stumps have been affected.
Most studies have described the movements as being ‘jerks’ or ‘jumps’ and sometimes they have been considered to be myoclonic (Baruah 1984). While they are generally present at rest, they may be precipitated or accentuated by involuntary movement. Touching the stump has in some cases triggered the jerking, but in most cases this feature has been absent. Not infrequently stump movements have prevented rehabilitation with a prosthesis.
The cause of these movements is uncertain. It has been suggested that it may relate to hypersensitivity of the neuroma, which is formed by axonal sprouting at the end of the nerve (Steiner et al. 1974, Marion et al. 1989). The onset within days of surgery, however, would make this unlikely. Functional changes in spinal or cortical circuitry have also been proposed (Marion et al. 1989), but the exact pathophysiological mechanisms underlying the movements remain uncertain. Parallels have been drawn with the movements associated with causalgia and reflex sympathetic dystrophy, dystonia occurring after peripheral nerve trauma (see Chapter 43), and the syndrome of ‘painful legs and moving toes’ (see Chapter 48).
Marion et al. (1989) suggested that ‘traumatic amputation, infection of the limb and/or amputation stump and central nervous system trauma’ have been common to many of the reported cases and point out that such involuntary movements seemed to be more frequent in the latter part of the 19th and early part of the 20th century than they are today. They suggest improvements in surgical technique with less extensive soft tissue injury may be responsible for the apparent decrease in the incidence.
EMG of the stump muscles merely shows bursts of motor unit firing occurring coincident with the movements. Brain scan, EEG, and backaveraged EEG have been unremarkable (Marion et al. 1989, Kulisevsky et al. 1992).
While these involuntary movements usually persist and have been reported to continue for up to 40 years (Marion et al. 1989), spontaneous remission may occur. As mentioned above, resolution is particularly likely in the first few months following surgery (Kulisevsky et al. 1992).
By and large, attempts at suppressing the movements using a variety of medications have been ineffective. These include phenytoin, carbamazepine, chlorpromazine, propranolol, and benzodiazepines (Jankovic and Glass 1985). Clonazepam (Marion et al. 1989), doxepin (Iacono et al. 1987[a]), and baclofen (Iacono et al. 1987[b]) have been reported to give some relief in individual cases.
Dorsal rhizotomy and sympathectomy do not prevent the movements (Jankovic and Glass 1985, Kulisevsky et al. 1992). Mazars and Merienne (1980) claimed that these involuntary movements can be suppressed by deep brain stimulation using chronically implanted electrodes in the parvocellular portion of the ventral posterolateral nucleus of the thalamus. They reported this also suppresses associated stump pain but that the dyskinesias are controlled whether or not pain is a feature. They considered that sensory deafferentation was the important feature and could not obtain the same results with stimulation in this region in patients with other dyskinetic disorders unassociated with sensory impairment (Merienne and Mazars 1982).
The relationship of these movements to deafferentation and the sensory illusion of phantom limb remains uncertain. The phantom sensation can be reproduced by stimulating the post-central gyrus following amputation of the contralateral limb and abolished by lesions of the parietal cortex (Hecaen et al. 1956). While it is known that widespread peripheral and central changes occur to the nervous system following amputation of a limb, including atrophy of the contralateral sensory motor cerebral cortex (Campbell 1905, Sunderland 1978), it is uncertain what alterations occur in the thalamus, neostriatum, or globus pallidus. They may, however, be affected and it has been reported that dopamine receptor blocking drugs may trigger the development of a dyskinetic phantom sensation in an amputated limb and this can be persistent, even when dyskinetic movements elsewhere in the body have settled (Jankovic and Glass 1985).
Involuntary movements of the abdominal wall
Involuntary movements of the abdominal wall can take a number of different forms. Brief jerks can result from myoclonus. As part of a generalized myoclonic jerk, the abdominal contraction is unlikely to be seen as a distinctive entity. The brief contraction, however, may be localized to the abdominal and adjacent truncal muscles in spinal myoclonus (Jankovic and Pardo 1986). Propriospinal myoclonus (Brown et al. 1991) and spinal reflex myoclonus (Kono et al. 1994) are variants that can also produce localized abdominal jerks. Palatal myoclonus may also cause rhythmic twitches of the abdominal muscles.
Occasionally isolated jerking of the abdominal muscles may have a cerebral origin. Partial epileptic seizures are an example (Matsuo 1984). Tardive dyskinesia can also produce focal involvement of abdominal muscles (Furukawa 1979) and l-dopa or dopamine agonists can result in abdominal dyskinesia in Parkinson's disease or other parkinsonian syndromes (Shan et al. 1996). These movements have been covered in the chapters dealing with these various disorders.
In addition to these there are other involuntary movements of the abdomen which are of less certain aetiology. Diaphragmatic flutter results in repetitive jerks of the upper abdominal and lower intercostal muscles and diaphragm, which are unrelated to respiration. They may be irregular in both rhythm and amplitude. Sometimes they occur in clusters followed by pauses. There can be associated slower movements of the muscles of the abdominal wall causing umbilical movement. It has been suggested that this disorder can represent a restricted form or variant of palatal myoclonus and thus be due to a lesion of the dentatorubro-olivary connections (Iliceto et al. 1990).
Another type of involuntary abdominal movement has been described which is more gradual, sinuous, sustained, and flowing. Frequency of these movements tends to have been between 15 and 30 per minute, but EMG bursts are relatively prolonged lasting 200–1000 msec and may follow a complex pattern of organization. Thus, contraction in muscles of the central abdominal wall (rectus abdominis) may alternate with that in the muscles of the lateral abdominal wall (external oblique) (Fig. 52.5). This can produce a writhing contorting movement of the umbilicus, which has led to the term ‘belly dancer's dyskinesia’ (Iliceto et al. 1990). Four such cases were reported by Iliceto et al. (1990). In three patients abdominal surgery preceded the onset, and in the other the abdominal movements followed childbirth. Pain was a predominant symptom in two cases and occurred in the region affected by the abdominal movements. Four similar cases were reported by Caviness et al. (1994), all of whom experienced pain. Three of them had previous abdominal surgery. Onset of belly dancer's dyskinesia following central pontine and extrapontine myelinolysis associated with severe hyponatriemia (Roggendrof et al. 2007) and a case related to an intramedullary spinal tumor (Shamim and Hallett 2007) have also been described.
These movements have been present when lying, sitting, standing, and walking. In some cases they have been able to be suppressed involuntarily for short periods and have been reduced by deep breathing and breath holding. Stress appears to have exacerbated them and they have been reported to both continue (Iliceto et al. 1990) and disappear (Caviness et al. 1994) during sleep. Pregnancy, menstruation, and hyperthyroidism may exacerbate them (Iliceto et al. 1990).
Brain scan, EEG, visual evoked responses, somatosensory evoked potentials, myelography, and CSF examination have been reported to be normal or may show a space occupying lesion as in the case of the intramedullary spinal tumor. Alcohol, halloperidol, chlorpromazine, tetrabenazine, l-dopa, benzhexol, carbamazepine, balcofen, cyproheptadine, and benzodiazepines do not seem to provide significant relief.
The nature of these movements is uncertain. Their flowing appearance has been somewhat suggestive of chorea, but against this is their stereotyped nature and restriction to a body segment. It has been suggested that these might be examples of focal dystonia, possibly triggered by local trauma, and thus be similar to that which occurs after injury to the limbs (see Chapter 43).
The characteristics of stereotypy have been defined in Chapter 3 on ‘Clinical Assessment’. This type of movement disorder, however, is not easily defined. We regard it as a repetitive, coordinated movement, posture, or noise which has no purpose, although superficially it may seem to have a function. Thus, phenomenologically there is overlap between tics and stereotypies in that in both the motor act is repeated in a similar form time after time. Stereotypies are often ritualistic. Stereotypies are the type of involuntary movement most commonly seen in mentally disturbed patients and they are particularly common in the borderland between neurology and psychiatry. Stereotypies are sometimes accompanied by somatic discomfort or an unpleasant psychological feeling, such as tension or compulsion, and the movement may temporarily relieve this. They can normally be suppressed by an act of will.
These activities may be simple, such as rocking the body, tapping with the hand, or touching the face. Other stereotypic movements are complex and these can involve quite complicated rituals, such as crouching and standing up, sitting and getting out of a chair, wringing the hands together, and crossing or uncrossing the legs. Stereotypies thus overlap with and may be difficult to distinguish from tics and obsessive compulsive behaviour. Other movement disorders including orofacial dyskinetic movements are sometimes regarded as stereotypies. Stereotypies can also closely resemble mannerisms which are little fragments of behaviour peculiar to an individual. These latter movements help give a person his or her manner. While most are part of normal behaviour, some border on the pathological and overlap with stereotyped movements.
The pathophysiological mechanisms underlying stereotypy are uncertain. Similar activities have been observed in animals and it has been suggested they are more common with caging or restraint. This has been considered to perhaps result from reduced stimulation, and the stereotypy has been seen as a self-stimulating device, possibly associated with reduction in stress (Dantzer 1986). It has been noted that such movements are accompanied by a reduction in the range of behaviour that would normally be seen in unrestricted animals.
Stimulation of dopamine receptors by agonists or by drugs which release dopamine stores produces a range of repetitive activities in rodents, which have been regarded as stereotypies. These include licking, washing, sniffing, rearing, and head shaking (Costall et al. 1977, Koller and Herbster 1988). Dopamine receptor blocking drugs will abolish these movements (Tschanz and Rebeck 1988). It has also been suggested that activation of D2 dopamine receptors and not D1 receptors causes stereotypy, although D1 receptor stimulation seems to potentiate the D2-mediated effect (Chipkin et al. 1987, Koller and Herbster 1988). Both striatal (Kuczenski and Segal 1989, Jicka and Salamone 1991, Maraganore et al. 1991) and the nucleus accumbens–amygdala neural curcuit have been felt to be involved (Costall et al. 1977, Hiroi and White 1989). Other neurotransmitters such as serotonin (Kuczenski and Segal 1989), cholecystokinin, and neurotensin (Blumstein et al. 1987) might also be involved.
Stereotypies can involve any area of the body. As mentioned above, they overlap with tics and these can be seen in many otherwise normal individuals, particularly in children. Thus, what has been regarded as simple childhood tic and discussed in Chapter 26 could equally well be regarded as physiological stereotypy. Most such movements spontaneously subside in later childhood or early adult life. In addition, stereotypies can be associated with a variety of pathological disorders and these are listed in Table 52.9.
Table 52.9 Causes of stereotypy
Same as simple childhood tic. See Chapter 26
See Chapter 52
See Chapter 52
See Chapter 52
See Chapter 52
See Chapter 52
See Chapter 21
Mental retardation and autism
A wide range of disorders causing mental retardation are associated with stereotypic movements. Dura et al. (1987) found 34% of mentally retarded institutionalized adult patients had stereotypy, including rhythmic movement (26%), bizarre posturing (13%), and manipulation of objects (7%).
As many as six per every 1000 children may have a form of autistic spectrum disorder. Autism commences in infancy or early childhood and is characterized by impoverished interaction with others and reduced verbal and non-verbal expression. There is marked loss of interest and reduction in general activities. Repetitive noises, facial movements, waving the hand or objects in front of the face, body rocking, handling or touching objects, toe walking, and adoption of strange postures are some of the stereotypies seen. Others may include inflicting self injury by biting, head banging, and scratching.
Infantile autism has some common features and overlaps with Asperger's syndrome (Gillberg and Gillberg 1989, Szatmari et al. 1989). Asperger's syndrome is usually later in onset and does not become fully evident until 2–3 years of age. Speech is usually better developed than in infantile autism. Other disorders causing autism include the fragile X syndrome and the eponymously named Kanner's and Heller's diseases (Wing and Attwood 1987, Burd et al. 1989).
Self-injurious stereotypic movements are not infrequent in autistic patients and have been said to be improved after opiate blockers, such as naloxone and naltrexone. Along with a possible increase in plasma and CSF beta-endorphin levels, it has been suggested to be evidence of abnormality of the endogenous opiate system (Sandman 1988).
In 1966 Rett described a disorder in 22 girls who developed mental retardation, autism, and a movement disturbance, which included stereotypy. He also noticed increased blood ammonium levels. Hagberg et al. in 1983 reported 35 more girls who had similar findings, apart from the hyperammonaemia, and labelled it ‘Rett's syndrome’. This is an X-linked recessive disorder which occurs almost exclusively in females and it has been proposed that this is caused by an X-linked dominant mutation with lethality in hemizygous males. Exclusion mapping studies using Rett's syndrome families mapped the locus to Xq28. Using a systematic gene screening approach, Amir et al. (1999) showed that Rett's syndrome is caused by mutations in the X-linked gene called MECP2, encoding methyl-CpG-binding protein 2. This has been confirmed by other groups (Bienvenu et al. 1999, Wan et al. 1999, Huppke et al. 2000), and many different mutations (mostly truncating or missense) seem to cause the disorder. With the discovery of the gene a much broader phenotypic variability seems to be emerging including the fact that rarely males with MECP2 mutations may survive (Wan et al. 1999, Clayton-Smith et al. 2000) and female heterozygotes with favourably skewed X-inactivation patterns may have little or no clinical signs (Wan et al. 1999).
Normal psychomotor development proceeds until 6–18 months of age when there is failure to progress, followed by gradual loss of motor skills, speech, and social responsiveness. As learned manual abilities disappear they are replaced by stereotypic movements. These also involve other body parts. The disorder is gradually progressive and associated with mental retardation and withdrawal.
In an analysis of the motor and behavioural findings in 32 patients aged 21 months to 30 years, FitzGerald et al. (1990[a], [b]) found that they all had stereotypic movements and gait abnormalities. The most frequent stereotypic movements were clapping, wringing, and clenching, followed by washing, patting, and rubbing (Figs 52.6 and 52.7). These are often asymmetrical and in about 20% may be virtually unilateral. Even in the absence of involuntary movements, upper limbs are seldom engaged in purposeful activity and are generally useless (Elian and Rudolf 1996). Body rocking and shifting weight from one leg to another is also common. FitzGerald et al. (1990[a],[b]) also reported dystonic movements, including bruxism in 97%, ocular deviations, usually upwards, in 63%, and focal or generalized dystonia in 59%. Myoclonus particularly of the head and trunk was present in 34% and choreoathetosis usually affecting the hands was seen in 13%. They noted that these hyperkinetic movement disorders were especially prominent in the younger patients and that with age an akinetic–rigid syndrome became more prominent with dribbling (75%), reduced facial expression (63%), rigidity (44%), and bradykinesia (41%).
For a genotype–phenotype analysis Temudo et al. (2008) studied 88 patients who fulfilled the current revised clinical criteria for Rett's syndrome (Hagberg et al. 2002). Of these, 60 patients were found positive for MECP2 mutations. All but one patient exhibited hand stereotypies. Other stereotypies were also frequent (95%), particularly bruxism (80%). Generalized dystonia was more common in those with truncating mutations (present in 46.2%) compared to those with missense mutations (17%). The latter group more commonly had focal dystonia (42% compared to 20% among those with truncating mutations). Both tremor and rigidity were present each in half of the patients. Myoclonus was rare and only present in one patient (Temudo et al. 2008).
Gait disturbance is common. A jerky gait ataxia was seen in 31% and 28% were unable to walk (FitzGerald et al. 1990). A broad base, toe-walking, and mixed gait disturbances were present in the remainder. The disturbance in walking is gradually progressive and in a report of 30 patients aged 22–44 years (Witt-Engerstrom and Hagberg 1990) only 20% were still ambulant, although 60% had previously been able to walk. Dystonia was particularly common in those who had lost walking skills, while the group who had never walked had lower motor neuron findings, including peroneal weakness and pes cavus. In addition, spasticity, hyperreflexia, and extensor plantar responses are common (Rett 1977). Scoliosis is seen in about half of the cases and may result from truncal dystonia (FitzGerald et al. 1990[a]). In the study by Temudo et al. a similar number acquired independent gait (63%). In some 40% of those, gait was both ataxic and rigid. Dystonia was present in more than 60% and scoliosis (probably a consequence of truncal dystonia) was seen in 72%.
Growth failure is frequent and it has been attributed to the additional energy requirements caused by the involuntary movements (Motil et al. 1994).
Epileptic seizures are common and a peculiar respiratory abnormality is seen in the majority of patients with bouts of breath holding followed by hyperventilation. Stereotypic movements may increase during the bouts of over-breathing (Kerr et al. 1990, Elian and Rudolf 1996). The involuntary movements and abnormal respiratory pattern disappear during sleep (Marcus et al. 1994). There is, however, disturbance of sleep phases on polysomnography (Segawa and Nomura 1992). In the study by Temudo et al. (2008) epilepsy was present in 57% of the patients and all were under treatment with one or more of the subsequent antiepileptics: valproate, carbamazepine, and lamotrigine.
MRI scans have shown generalized brain and bilateral caudate atrophy (Casanova et al. 1991, Reiss et al. 1993). Neuropathological findings include microcephally, diffuse cortical atrophy, mild gliosis, increased neuronal lipofuscin, underpigmentation of the zona compacta of the substantia nigra with reduced immunoreactivity for tyrosine hydroxylase, decreased numbers of basal forebrain cholinergic neurons, and cerebellar atrophy. Abnormal neurites and reactive or degenerative axonal swellings have been noted in the frontal cortex and caudate nucleus, and it has been suggested that abnormality of the dopaminergic nigrostriatal pathways may be responsible for this. There are also minor changes in the hypothalamus and pituitary (Jellinger 1988, Armstrong 1992, Wenk 1997).
Much work has concentrated on the state of the catecholaminergic systems, but even with the histological changes mentioned above, showing decreased numbers of neurons and evidence of cell death in the substantia nigra (Kitt and Wilcox 1995), no clear picture has emerged. In spite of earlier reports of decreased striatal levels of dopamine, these have subsequently been found to be within the normal range (Lekman et al. 1989, Wenk 1996), as have the concentrations of homovanillic acid, dopamine re-uptake sites, and D1 and D2 receptors (Wenk 1995, 1996). However, this may have to do with what sort of MECP2 mutation the patient is carrying (Amir et al. 2000). Comparing, CSF neurochemistry in patients with missense mutations and those carrying truncating mutations, Amir et al. (2000) reported that patients with truncating mutations had a higher incidence of awake respiratory dysfunction and lower levels of CSF homovanillic acid. One persistent finding, however, has been an increase in beta-endorphin levels in the CSF (Myer et al. 1988, Zoghbi et al. 1989, Nagamitsu et al. 1997).
Although the mechanisms underlying the stereotypies in Rett's syndrome remain uncertain, enlarged somatosensory evoked potentials, a hyperexcitable and markedly prolonged C-reflex, and normal motor evoked potentials following cortical stimulation have led to the speculation that the jerks may be a form of cortical reflex myoclonus with prolonged intracortical delay of the long-loop reflex (Guerrini et al. 1998[a]).
Catatonia and schizophrenia
Catatonia is discussed in more detail below. It should be noted here, however, that in the original description of catatonia by Kahlbaum in 1873, half of the patients had involuntary movements, including jaw clenching, grimacing, and lip protrusion, which were similar to orofacial dyskinesia and could be regarded as stereotypies. Catatonia can be associated with a variety of stereotypic movements, particularly when it has a psychiatric cause or is due to neuroleptic medication. Characteristic stereotypies include saying the same phrases (verbigeration) or repeating someone else's speech (echolalia), bucco-lingual movements, touching, maintenance of abnormal posture, repetitively moving, and ritualistic behaviour. There are also many descriptions of such stereotypies in non-catatonic schizophrenic patients prior to the introduction of neuroleptic medication into the medical armamentarium.
Obsessive-compulsive disorders and Gilles de la Tourette's syndrome
As mentioned above, obsessive compulsive disorders and the complex tics of Gilles de la Tourette's syndrome may produce repetitive behaviour similar to, or identical with, stereotypy. The distinction is frequently impossible and may be artificial. Patients may repetitively perform the same activity, such as touching, hitting, putting objects in order, washing, and performing rituals. These have been dealt with in Chapter 27.
Akathisia and tardive stereotypies
The tardive dyskinesias caused by neuroleptics may resemble stereotypies. In a study of patients with drug-induced movement disorders Miller and Jankovic (1990, Jankovic 1994) felt 63% had tardive stereotypy. The problem was four times more common in women and the majority of patients were in their 6th or 7th decades. Bucco-lingual dyskinesia and truncal movements were the commonest. Stacey et al. (1993) reported stereotypy to be present in 78% of patients with tardive dyskinesia. Many of the restless actions seen in drug-induced akathisia might also be regarded as complex stereotypies (Burke et al. 1989, Miller and Jankovic 1990). To a large extent it is a matter of nomenclature, definition, and interpretation. Tardive movement disorders are covered in Chapter 23 and akathisia in Chapter 46.
Anti-N-methyl-D-aspartate (NMDA)-receptor encephalitis
Limbic encephalitis is a group of disorders characterized by subacute onset of seizures, cognitive decline and personality changes. In a subset specific autoantibodies directed against surface-expressed neuronal proteins can be detected. Distinct movement disorders may be assoicated, like faciobrachial dystonic seizures in LGI1-associated limbic encephalitis or complex hyperkinetic movements in the anti-NMDA-receptor variant (Irani et al. 2011).
Of these, anti-N-methyl-D-aspartate (NMDA)- receptor encephalitis is a recently described paraneoplastic syndrome often associated with ovarian teratoma. Among others patients develop a hyperkinetic movement disorder with stereotypic and choreic movements with orofacial grimacing. However, the movement disorder may be complex and difficult to classify and the disorder is thus discussed here in this section.
The disorder most commonly affects young females accouting for 91% in a series of 100 cases reported by Dalmau et al. (2008). In another series, among 44 patients, 31 were females (70%) and ages ranged from 2 to 49 years (median 22 years) (Irani et al. 2010).
The most common presenting features include behavioral abnormalities, confusion, amnesia, psychosis and seizures which are thought to due to cortical temporal lobe dysfunction, as frequently seen in classical limbic encephalitis. (Irani et al. 2010). Rare symptoms at onset may include hyperacusis, deafness, ataxia and dystonia. Preceding infections may occur which may reflect an inflammatory event. (Irani et al. 2010) The most distinctive clinical features, however, occur later and include stereotypies and choreoathetoid movements with prominent orofacial involvement with grimacing. There may be complex movements of the extremities, abdomen or pelvis with abnormal postures, as well as muscle rigidity, or increased tone. (Dalmau et al. 2008) Oculogyric deviation may be present. Overall, movement disorders of any kind were observed in 86% of patients in one large series. (Dalmau et al. 2008). Furthermore, episodic dysautonomia is characteristic with hypoventilation and tachy- or bradycardia and a spontaneous fall in conscious level so patients are often stuporous and mute. (Irani et al. 2010) Overall, the typical clinical evolution of anti-NMDA-receptor encephalitis can be divided into five phases:
♦ phase I (prodromal phase) – a ‘viral-like’ illness;
♦ phase II – characterized by acute psychosis and behavioral symptoms;
♦ phase III – intractable seizures, central hypoventilation and dysautonomia;
♦ phase IV – a hyperkinetic phase with prominent orofacial grimacing;
♦ phase V – the gradual recovery from the illness.
Notably, most patients progress to a severe clinical syndrome and require admission to intensive care, but mild forms may occur. An average hospital stay of 160 days has been reported with long periods of ventilation and multiple infectious complications.
Investigations reveal lymphocytosis in the CSF analysis in early disease stages, followed by absence of CSF lymphocytosis in later stages. In contrast there is early absence of CSF-specific oligoclonal bands compared to their later presence. Brain imaging is often normal (in 89% at initial MRI) and remains normal (in 77%). (Irani et al. 2010) Some patients may show mild alterations in the hippocampi or within white matter regions on T2/fluid attenuated inversion recovery scans. Electroencephalography demonstrated epileptiform discharges in half of the patients in the Irani series, which were present usually early during the course of the disease. Later during the disorder there was generalized slowing in the slow theta or delta range, present in 80% of patients. Thus, switches in the CSF, MRI and EEG findings have been found, suggesting that the neurological disease occurs in two distinct clinical and neuropathological stages.
Anti-NMDA receptor antibody encephalitis has been associated with tumours, especially teratomas. Other malignancies such as Hodgkin's lymphoma or testicular teratomas have also rarely been associated. In the 100 cases described by Dalmau et al. (2008) 59% had ovarian tumours. However, the data vary and in the study of 44 patients by Irani et al. 2010 only eight female patients were detected to have ovarian teratomas (26%), with no other tumours in females. Among the 13 males there was only one tumour, namely the recurrence of a previously-treated Hodgkin's lymphoma at the age of 49 years. In the remaining 23 females and 12 males there was no detectable tumours, despite intensive whole body/pelvic imaging in all. Thus, besides, as a paraneoplastic syndrome, this disorder may be idiopathic in 30% to 40% of patients.
NMDA-receptor encephalitis is related to antibodies against NR2B or NR2A subunits of NMDA receptors in serum and cerebrospinal fluid. NR2B binds glutamate and are thought to inhibit NMDA receptors in presynaptic GABAergic interneurons, resulting in reduced GABA release and disinhibition of postsynaptic glutamatergic transmission with excessive release of glutamate in the prefrontal/subcortical structures. (see Irani et al. 2010) The pathogenic role of these antibodies is further supported by their disappearance in parallel to the clinical improvement. In view of the relatively high proportion of non-Caucasians patients it has been suggested that there may be human leucocyte antigen or other genetic factors involved in disease susceptibility. (Irani et al. 2010).
The treatment is removal of the underlying neoplasm, combined with immunotherapy, plasma exchange, intravenous immunoglobulin, and corticosteroids. Paraneoplastic patients may remain severely affected until tumour removal. Patients who received early tumour treatment (usually with immunotherapy) had better outcome and fewer neurological relapses and a trend has been noted towards better outcomes when corticosteroids were combined with at least one other immunotherapy rather than given alone. While in patients with teratoma its removal plus immunotherapy have resulted in substantial recovery, in the minority of patients without a tumour, recovery appeared to be less impressive (Dalmau et al. 2007, 2008).
Overall, in the series by Dalmau et al. (2008) 75% of patients recovered or had mild deficits and 25% had severe deficits or died. Relapses occurred in about 15–25% patients with a median time between initial presentation and last relapse of about 18 months (1 month – 6 years) (Dalmau et al. 2008, Irani et al. 2010). As stated above outcomes have been better when corticosteroids had been combined with at least one other immunotherapy and analysis revealed that among the relapsers a proportion had received no immunotherapy or were administered only 3–5 days of intravenous glucocorticosteroids. Relapses immediately after glucocorticosteroid withdrawal have also been observed.
Thus, anti-N-methyl-D-aspartate (NMDA)- receptor encephalitis should be considered predominantly in young women who develop a subacute-onset encephalopathy and commonly a prominent movement disorder. Frequently an underlying ovarian teratoma is associated.
In 1873 Ludwig Kahlbaum described 25 psychotic patients with depression or mania who had a motor disturbance which he entitled ‘catatonia’. They showed a variety of features, including generalized immobility or akinesia, withdrawal, staring, refusal to eat, mutism, verbigeration, echolalia, negativism, rigidity, and waxy flexibility, so that they would tend to maintain the position following displacement of a limb. They also exhibited a variety of repetitive movements, particularly of the face and mouth, which have been mentioned above under ‘Stereotypy’. In some patients the immobility was broken by periods of hyperactivity. Since that time the term ‘catatonia’ has been used to describe a number of other conditions and states, including the similar features that may be caused by a variety of general medical and intracranial disease states. Its use has thus become somewhat loose and it has often been applied to withdrawn patients with impaired responsiveness who do not demonstrate features such as negativism or waxy flexibility. Some authors have even regarded stupor occurring in isolation as evidence of catatonia (Benegal et al. 1992). We think this interpretation is too liberal. Increased motor activity has often been absent from cases with general medical disorders that have been labelled as ‘catatonic’ in the literature. This can, however, occur. Patients with psychogenically determined catatonia may be more likely to exhibit excitement, hyperactivity, and restlessness, particularly as the catatonic phase commences.
Thus, while the concept of catatonia has broadened since Kahlbaum's description, diagnosis should be based on the basic features he outlined. There have been a number of attempts to establish diagnostic criteria (Rosebush et al. 1990, Lund et al. 1991, Bush et al. 1996[b], Northoff et al. 1999). Bush et al. (1990) proposed that the diagnosis of retarded catatonia should be based on the coexistence of three cardinal features (immobility, mutism, and withdrawal/refusal to eat or drink) or two cardinal signs plus at least two secondary features (staring, rigidity, posturing, grimacing, negativism, waxy flexibility, echolalia/echopraxia, stereotypy). Northoff et al. (1999) used a rating scale with three different categories, i.e. motor, behavioural, and affective, containing 40 items, each of which was scored on a three-point scale. They claimed that psychogenic catatonia can be diagnosed by having a score of > 7 and with at least one item being positive in each of the three categories. While such instruments are useful for reporting studies of catatonic patients, they are of limited use in day to day practice.
We regard catatonia as a non-specific syndrome, which can result from organic or psychogenic conditions or follow withdrawal of neuroleptics. Organic catatonia in turn can result from specific brain disease or be secondary to a variety of systemic disorders, such as metabolic disturbance, toxic substances, or an acute febrile illness. Focal intracranial lesions causing such a state are particularly likely to involve structures in the cortico-striato-thalamo-cortical circuit and hence affect the frontal lobe (Gelenberg 1976, Wolanczyk et al. 1997), or basal ganglia (Mettler 1955, Kleist 1960, Neuman et al. 1996). Other specific intracranial disorders that can produce a catatonic state include acute viral encephalitis (Primavera et al. 1994) and encephalopathies due to HIV, progressive multifocal leukoencephalopathy, and the like (Carroll 1994).
Catatonia can be caused by a variety of acute or chronic metabolic disturbances. For example, it can occur due to decreased levels of thiamine and nicotinic acid (Teare et al. 1993) or be associated with such conditions as Wilson's disease (Akil et al. 1991, Davis and Bordet 1993) and late-onset Tay-Sach's disease (Rosebush et al. 1995). It has also been reported in renal failure (Carroll et al. 1994). Pharmacological agents with effects on brain neurotransmitter systems can induce catatonia. Thus, dopamine receptor blockers, including those used as antiemetics or vestibulo-sedatives (Rodgers 1992), and drugs resulting in dopamine receptor stimulation, such as amphetamine (Ebadi et al. 1990, Chern and Tsai 1993), can have this effect, as can those acting on glutamatergic (phencyclidine), serotonergic (mescaline), and GABAergic (ethanol) systems (Klimke and Klieser 1994[a]). As mentioned below, catatonia can also follow rapid tapering or abrupt withdrawal of dopamine receptor blocking neuroleptic medication and has occasionally been reported on abrupt cessation of benzodiazepines. In fact, it has been proposed that many reported cases of catatonia attributed to general medical conditions might actually have resulted from benzodiazepine withdrawal (Rosebush and Mazurek 1996). It is also a rare idiosynchratic reacion to a number of other medications, including valproate (Lauterbach 1998), fluoroquinolone antibiotics, such as ciprofloxacin (Akhtar and Ahmad 1993), maprotiline, and adrenocorticotrophic hormone (Klimke and Klieser 1994[a]). An overwhelming systemic infection, usually in association with high fever, can produce a catatonic-like state and non-convulsive status epilepticus may result in a similar appearance (Louis and Pflaster 1995).
Although psychogenically determined catatonia has been traditionally classified as a subtype of schizophrenia, it is more commonly seen in affective disorders. The exact proportion of psychogenic catatonia which is due to schizophrenia depends on the diagnostic criteria used. Diagnostic systems, such as the DSM-III-R, tended to have enlarged the spectrum of affective disorders at the expense of schizophrenia. Thus, patients diagnosed as having schizophrenia on the DSM-I and -II systems would now be regarded as having an affective disorder (Ries 1985). While about 10% of psychiatric inpatients have catatonia (Rosebush et al. 1990, Blumer 1997), in more than two thirds of psychogenic catatonia the diagnosis is that of an affective disorder, especially mania or a bipolar illness, and only between 5 and 20% have schizophrenia (Morrison 1973, Abrams and Taylor 1976, Fein and McGrath 1990, Peralta et al. 1997). Catatonia, however, may be especially likely to occur in elderly patients who develop severe depression (Starkstein et al. 1996). In those fulfilling the criteria of DSM-III-R catatonic schizophrenia, two patterns of catatonia have been distinguished, ‘systematic’ and ‘periodic’. The latter is a largely familial condition which is probably genetically based and shows anticipation from one generation to the next (Stober et al. 1995, Beckmann et al. 1996). Other psychiatric disorders displaying features of catatonia include dissociative states, hysteria, and post-traumatic stress disorder (Gelenberg 1976, Shiloh et al. 1995). When catatonia is present in patients with chronic psychiatric disorders it may be associated with involuntary movements, particularly involving the orofacial musculature, and these may be regarded as stereotypies or tardive dyskinesia, depending on whether neuroleptic medication has been administered (Kahlbaum 1873, Bush et al. 1997). If antipsychotic medication has been exhibited there may be coexisting parkinsonism (Bush et al. 1997). The question of antipsychotic related catatonia, however, is discussed below.
A febrile life-threatening catatonic state was first described by Calmeil in 1832 and in 1934 Stauder termed it ‘lethal catatonia’. It is also referred to as ‘malignant catatonia’ and defined as a life-threatening febrile neuropsychiatric disorder characterized by psychosis with autonomic instability, hyperactivity, mutism, and stuperous exhaustion (Baker et al. 2008). Typically there is a prodromal period lasting about 2 weeks in which there is difficulty with sleeping, variability of mood, and possibly anorexia. Marked motor excitability and the appearance of catatonia follow this. Delusions, hallucinations, and confusion may be present. Fever, tachycardia, hypertension, sweating, and dehydration are frequent during this hyperactive stage, which can go on for hours or weeks but usually lasts approximately a week. Eventually the patient becomes exhausted, stuperose, and lapses into a coma. Marked hyperthermia, cardiovascular collapse, and death may supervene (Fricchione 1985, Mann et al. 1986, Bridler and Hell 1997). Although historically nearly always fatal, in younger years mortality declined, secondary to earlier diagnoses and appropriate treatment implementation, such as administration of standing benzodiazepines and electroconvulsive therapy (ECT) (Baker et al. 2008) (also see later).
Dopamine D2 receptor blocking neuroleptic drugs can produce catatonia with withdrawal, mutism, akinesia, posturing, and waxy flexibility. In some patients there may be additional parkinsonian features and/or tardive dyskinesia (May 1959, Behrman 1972, Rifkin et al. 1975, Gelenberg and Mandel 1977). It can be difficult to differentiate this from aggravation of the underlying psychiatric state. In addition, such drugs may trigger the neuroleptic malignant syndrome, which was first reported by Delay et al. in 1960 (see Chapter 13). A similar disorder can result from sudden withdrawal of l-dopa or other antiparkinsonian medication (Toru et al. 1981, Friedman et al. 1985) and has occasionally been noted following cessation of atypical neuroleptics (Lee and Robertson 1997). It has also been suggested that the toxic serotonin syndrome, in addition to the neuroleptic malignant syndrome, is a variety of catatonic disorder (Fink 1996). Withdrawal, mutism, akinesia, rigidity, fever, tachycardia, and fluctuating blood pressure are present. Many authors have regarded neuroleptic malignant syndrome and malignant catatonia as being the same or closely related disorders (Hynes and Vickar 1996, Topka and Buchkrener 1996). While the prodromal phase of motor excitement is usually absent in neuroleptic malignant syndrome, it has occasionally been reported (Lee and Robertson 1997).
As mentioned above, non-convulsive epileptic status may present with a clinical picture resembling catatonia. In addition, however, patients with acute catatonia may develop epileptic seizures secondary to intracranial pathology (Primavera et al. 1994). Another complication of catatonia is pulmonary embolus and it has been suggested that this may partly explain excess early mortality in this disorder (McCall et al. 1995). Dehydration, infection, and malnutrition also add to the morbidity. Because of the risk of serious complications and death, it is important a diagnosis of the underlying cause of the catatonia is made at an early stage and this requires a full range of ancillary investigations including plasma biochemistry, screening for toxins and infections, as well as EEG, brain scan, and CSF examination in selected cases.
Treatment may be non-specific and supportive, designed to correct and maintain fluid balance, electrolyte status, and temperature, or it may be specifically aimed at abolition of the catatonia. The latter involves measures to decrease associated akinesia and rigidity, as well as treating the underlying cause of the syndrome. Institution of early therapy is important because of the potentially life-threatening nature of the problem. A flow diagram outlining possible courses of management is shown in Fig. 52.8. Benzodiazepines seem to be beneficial in most cases, although clearly should be avoided in the rare instances in which the cause is benzodiazepine overdose (Ebadi et al. 1990). Care must be taken to avoid respiratory or cardiovascular depression (Sassin and Grohmann 1988, Klimke and Kliesler 1994[b]). The most commonly used agent has been lorazepam (with the initial dose being in the order of 1–2 mg) (Menza and Harris 1989, Hawkins et al. 1995, Bush et al. 1996[a], Fink 1996). In a prospective series of over 100 episodes, approximately 85% of patients with retarded catatonia showed complete resolution of catatonic features within 3 hours of administration of 1–3 mg sublingual or intramuscular lorazepam. Patients with schizophrenia are less likely to improve and response rates may be in the order of 40–50% (Rosebush and Mazurek 1999). Other benzodiazepines may be effective, including diazepam (10–20 mg) (McEvoy and Lohr 1984), clonazepam (1–2 mg) (Martenyi et al. 1989), and midazolam (5 mg) (Delisle 1991). While benzodiazepines are the drugs of choice in treatment of acute catatonia, they are not satisfactory for its long-term control, so that it is important to start other therapy aimed at the underlying cause.
In patients with psychogenic catatonia, ECT has often been recommended if benzodiazepines fail. It should be considered if there is no response to 1–3 doses of benzodiazepine (Rosebush and Mazurek 1999). In some series up to 80% of drug-resistant, non-febrile (Klimke and Klieser 1994[a]), and young patients (Rey and Walter 1997) have been said to be improved by ECT. It may be particularly indicated in malignant catatonia and some have suggested it is the therapy of first choice (Mann 1986, Heils and Lesch 1997). Some authors have claimed that ECT may be better if combined with a benzodiazepine (Petrides et al. 1997).
Other aspects of treatment of psychogenic catatonia will depend on the underlying psychiatric diagnosis and in an affective disorder may include antidepressants, lithium carbonate, and carbamazepine, while in schizophrenia antipsychotics may be appropriate (Klimke and Kiesler 1994[a]). In antipsychotic-induced catatonia, reduction or discontinuation of neuroleptic or change to an atypical neuroleptic, such as clozapine, will probably be appropriate. In occasional non-febrile patients anticholinergics may be considered, but scientific evidence of efficacy is lacking (Klimke and Kiesler 1994[a]).
In neuroleptic malignant syndrome, withdrawal of antipsychotics and administration of benzodiazepines is appropriate. In addition, the administration of dopamine agonists such as bromocriptine has been advocated (Levenson 1985, Adityanjee and Chawla 1989), although some studies have not found these to be useful (Rosebush and Stewart 1989). Similarly dantrolene (no 4) has been used (Ward et al. 1986), although it was no better than supportive care in one trial (Rosebush and Stewart 1989). The N-methyl-D-aspartate (NMDA) receptor antagonists amantadine and memantine have also been advocated, not only in neuroleptic malignant syndrome (Weller and Kornhuber 1992) but also in non-neuroleptic-related catatonia (Northof et al. 1997).
Abrams R, Taylor MA (1976) Catatonia. A prospective clinical study. Arch Gen Psychiatry 33:579–581.Find this resource:
Acevedo JC, Sindou M, Fischer C, et al. (1997) Microvascular decompression for the treatment of hemifacial spasm. Retrospective study of a consecutive series of 75 operated patients – electrophysiologic and anatomical surgical analysis. Stereotactic and Functional Neurosurgery 68:260–265.Find this resource:
Adityanjee DP, Chawla HM (1989) Neuroleptic malignant syndrome and psychotic illness. Br J Psychiatry 155:852–854.Find this resource:
Adler CH, Zimmerman RA, Savino PJ (1992) Hemifacial spasm: evaluation by magnetic resonance imaging and magnetic resonance tomographic angiography. Annals of Neurology 32:502–506.Find this resource:
Akhtar S, Ahmad H (1993) Ciprofloxacin-induced catatonia. J Clin Psychiatry 54:115–116.Find this resource:
Akil M, Schwartz JA, Dutchak D, et al. (1991) The psychiatric presentations of Wilson's disease. Journal of Neuropsychiatry and Clinical Neurosciences 3:377–382.Find this resource:
Ambrosetto P, Forlani S (1988) Lacune pontine infarction presenting as isolated hemifacial spasm. Stroke 19:784–785.Find this resource:
Amir RE, Van den Veyver IB, Wan M, et al. (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23: 185–188.Find this resource:
Amir RE, Van den Veyver IB, Schultz R, et al. (2000) Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes. Ann Neurol 47: 670–679.Find this resource:
Armstrong DD (1992) The neuropathology of the Rett syndrome. Brain and Development 14:S89–98.Find this resource:
Arnould G, Tridon P, Laxenaire M, et al. (1962) Hemispasme facial et malformation de la charniere occipito-vertebrale. Rev Oto-Neuro-Ophthalmol 43:80–84.Find this resource:
Asaoka K, Sawamura Y, Tada M, et al. (1997) Hemifacial spasm caused by a haemangioma at the geniculate ganglion. Neurosurgery 41:1195–1197.Find this resource:
Auger RG (1979) Hemifacial spasm: clinical and electrophysiologic observations. Neurology 29:1202–1272.Find this resource:
Auger RG, Piepgras DG (1989) Hemifacial spasm associated with epidermoid tumour of the cerebellopontine angle. Neurology 39:577–580.Find this resource:
Auger RG, Piepgras DG, Laws ER, et al. (1981) Microvascular decompression of the facial nerve for hemifacial spasm: clinical and electrophysiologic observations. Neurology 31:346–350.Find this resource:
Auger RG, Piepgras DG, Laws ER (1986) Hemifacial spasm: results of microvascular decompression of the facial nerve in 54 patients. Mayo Clin Proc 61:640–644.Find this resource:
Auger RG, Litchy WJ, Cascino TL, et al. (1992) Hemimasticatory spasm: clinical and electrophysiologic observations. Neurology 42:2263–2266.Find this resource:
Baker RN, Ramseyer JC, Schwartz WS (1968) Prognosis in patients with transient cerebral ischemic attacks. Neurology (Minneap) 18:1157–1165.Find this resource:
Baker RN, Schwartz WS, Rose AS (1966) Transient ischaemic strokes: a report of a study of anticoagulant therapy. Neurology (Minneap) 16:841–847.Find this resource:
Baker AS, Suh E, Prudic J (2008) Malignant catatonia: role of right unilateral electroconvulsive therapy. J ECT 24:168–170.Find this resource:
Baloh RW, Jacobson BA, Winder T (1990) Drop attacks with Meniere's syndrome. Ann Neurol 28:384–387.Find this resource:
Bardella L, Maleci A, Di Lorenzo N (1984) Drop attack as the only symptoms of type I Chiari malformation. Rivista di Patologia Nervosa e Mentale 105:217–222.Find this resource:
Barker FG, Jannetta PJ, Bissonette DJ, et al. (1995) Microvascular decompression for hemifacial spasm. J Neurosurg 82:201–210.Find this resource:
Baruah JK (1984) Spinal myoclonus. J Bone Jt Surg 66-A:88–112.Find this resource:
Bassetti C, Aldrich MS, Quint DJ (1997) MRI findings in narcolepsy. Sleep 20:630–631.Find this resource:
Battista AF (1977) Hemifacial spasm and blepharospasm. NY State J Med 77:2234–2237.Find this resource:
Bauer G, Aichner F, Saltuari L (1983) Epilepsies with diffuse slow spikes and waves of late onset. Eur Neurol 22:344–350.Find this resource:
Beckmann H, Franzek E, Stober G (1996) Genetic heterogeneity in catatonic schizophrenia: a family study. American Journal of Medical Genetics 67:289–300.Find this resource:
Behrman S (1972) Mutism induced by phenothiazines. Br J Psychiatry 121:599–604.Find this resource:
Benegal V, Hingorani S, Khanna S, et al. (1992) Is stupor by itself a catatonic symptom? Psychopathology 25:229–231.Find this resource:
Bewermeyer H, Dreesbach HA, Hunermann B, et al. (1984) MR imaging of familial basilar impression. Journal of Computer Assisted Tomography 8:953–956.Find this resource:
Bienvenu T, Carrie A, de Roux N, et al. (2000) MECP2 mutations account for most cases of typical forms of Rett syndrome. Hum Mol Genet 9:1377–1384.Find this resource:
Billiard M, Bassetti C, Dauvilliers Y, et al. (2006) EFNS Task Force. EFNS guidelines on management of narcolepsy. Eur J Neurol 13:1035–1048.Find this resource:
Billiard M, Carlander B (1998) Wake disorders. 1. Primary wake disorders. Revue Neurologique 154:111–129.Find this resource:
Bills DC, Hanieh A (1991) Hemifacial spasm in an infant due to 4th ventricular ganglioma. J Neurosurg 75:134–137.Find this resource:
Black FL, Effron MZ, Burns DS (1982) Diagnosis and management of drop attacks of vestibular origin: Tumarkin's otolithic crises. J Otolaryngol Head Neck Surg 90:256–262.Find this resource:
Blumer D (1997) Catatonia and the neuroleptics: psychobiologic significance of remote and recent findings. Comprehensive Psychiatry 38:193–201.Find this resource:
Blumstein LK, Crawley JN, Davis LG, et al. (1987) Neuropeptide modulation of apomorphine-induced stereotyped behavior. Brain Res 404:293–300.Find this resource:
Boor R, Reitter B (1997) Cataplexy in type C Niemann-Pick disease. Klinische Padiatrie 209:88–90.Find this resource:
Botez MI, Ethier R, Leveille J, et al. (1977) A syndrome of early recognition of occult hydrocephalus and cerebral atrophy. Quarterly Journal of Medicine 46:365–380.Find this resource:
Bridler R, Hell D (1997) Akute lebensbedrohliche Katatonie (ALK)-klinische Bedetung und therapeutische Moglichkeiten. Journal Suisse de Medecine 127:1531–1538.Find this resource:
Bril V, Sharpe JA, Ashby P (1979) Midbrain asterixis. Annals of Neurology 6:362–364.Find this resource:
Brodkey JA, Robertson JH, Shea JJ, et al. (1996) Cholesterol granulomas of the petrous apex: combined neurosurgical and otological management. J Neurosurgery 85:625–633.Find this resource:
Brocklehurst JC, Exton-Smith AN, Barber L, et al. (1978) Fracture of the femur in old age: a two centre study of associated clinical factors and the cause of the fall. Age Ageing 7:7–15.Find this resource:
Brown P, Thompson PD, Rothwell JC, et al. (1991) Axial myoclonus of propriospinal origin. Brain 14:197–214.Find this resource:
Brust JCM, Plank CR, Healton EB, et al. (1979) The pathology of drop attacks: a case report. Neurology 29:786–790.Find this resource:
Burd I, Fisher W, Kerbeshian J (1989) Pervasive disintegrative disorder: are Rett syndrome and Heller dementia infantilis subtypes? Dev Med Child Neurol 31:609–616.Find this resource:
Burdette DE, Sackellares JC (1994) Felbamate pharmacology and use in epilepsy. Clinical Neuropharmacology 17:389–402.Find this resource:
Burke RE, Kang UJ, Jankovic J, et al. (1989) Tardive akathisia: an analysis of clinical features and response to open therapeutic trials. Movement Disorders 4:157–175.Find this resource:
Bush G, Fink M, Petrides G, et al. (1996[a]) Catatonia. II. Treatment with lorazepam and electroconvulsive therapy. Acta Psychiatrica Scandinavica 93:137–143.Find this resource:
Bush G, Fink M, Petrides G, et al. (1996[b]) Catatonia. Rating scale and standardised examination. Acta Psychiatr Scand 93:129–143.Find this resource:
Bush G, Petrides G, Francis A (1997) Catatonia and other motor syndromes in a chronically hospitalized psychiatric population. Schizophrenia Research 27:83–92.Find this resource:
Caces F, Chays A, Locatelli P, et al. (1996) Neurovascular decompression in hemifacial spasm: anatomical, electrophysiological and therapeutic results apropos of 100 cases. Rev Laryngol Otolog Rhinol 117:347–351.Find this resource:
Campbell AW (1905) Histological Studies on the Localisation of Cerebral Function, London: Cambridge University Press.Find this resource:
Campbell E, Keedy C (1947) Hemifacial spasm: a note on the etiology in two cases. J Neurosurg 4:342–347.Find this resource:
Canadian Clobazam Cooperative Group (1991) Clobazam in treatment of refractory epilepsy: the Canadian experience: a retrospective study. Epilepsia 32:407–416.Find this resource:
Carmant L, Holmes GL (1994) Commissurotomies in children. Journal of Child Neurology 9:50–60.Find this resource:
Carroll BTY, Anfinson TJ, Kennedy JC, et al. (1994) Catatonic disorder due to general medical conditions. Journal of Neuropsychiatry and Clinical Neurosciences 6:122–133.Find this resource:
Casanova MF, Naidu S, Goldberg TE, et al. (1991) Quantitative magnetic resonance imaging in Rett syndrome. Clinical and Research Reports 4:66–72.Find this resource:
Cascino GD, Andermann F, Berkovic SF, et al. (1993) Gelastic seizures and hypothalamic hamartomas: evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment. Neurology 43:747–750.Find this resource:
Caviness JN, Gabellini A, Kneebone CS, et al. (1994) Unusual focal dyskinesias: the ears, the shoulders, the back and the abdomen. Movement Disorders 9:531–538.Find this resource:
Challamel MJ, Mazzola ME, Nevismalova S, et al. (1994) Narcolepsy in children. Sleep 17:S17–S20.Find this resource:
Chen HJ, Lee TC, Liu CC (1996[a]) Hemifacial spasm caused by a venous angioma. Journal of Neurosurgery 85:716–717.Find this resource:
Chen RS, Lu CS, Tsai CH (1996[b]) Botulinum toxin A injection in the treatment of hemifacial spasm. Acta Neurol Scand 94:207–211.Find this resource:
Chern CH, Tsai WJ (1993) Acute amphetamine intoxication with catatonia: a case report. Chinese Medical Journal 51:322–327.Find this resource:
Chipkin RE, McQuade RD, Iorio LC (1987) D1 and D2 dopamine binding site up-regulation and apomorphine-induced stereotypy. Pharmacol Biochem Behav 28:477–482.Find this resource:
Chung WH, Chung KW, Kim JH, et al. (2007) Effects of a single intratympanic gentamicin injection on Meniere's disease. Acta Otolaryngol Suppl 558:61–66.Find this resource:
Ciocca RG, Wilkerson DK, Madson DL, et al. (1995) Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria. Annals of Vascular Surgery 9:204–208.Find this resource:
Clayton-Smith J, Watson P, Ramsden S, et al. (2000) Somatic mutation in MECP2 as a non-fatal neurodevelopmental disorder in males. Lancet 356:830–832.Find this resource:
Coad JE, Wirtschafter JD, Haines SJ, et al. (1991) Familial hemifacial spasm associated with arterial compression of the facial nerve. J Neurosurg 74:290–296.Find this resource:
Costall B, Marsden CD, Naylor RJ, et al. (1977) Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei. Brain Res 123:89–111.Find this resource:
Criscuolo GR, Symon L (1986) Intraventricular meningioma. Acta Neurochirurgica 83:83–91.Find this resource:
Cushing H (1920) The major trigeminal neuralgias and their surgical treatment based on experience with 332 gasserian operations. The varieties of facial neuralgia. Am J Med Sci 160:157–185.Find this resource:
Daly DD, Yoss RE (1977) Narcolepsy. In: Handbook of Clinical Neurology, Eds Vinken PJ, Bruyn GW. Amsterdam: North Holland, Vol. 15, pp. 836–852.Find this resource:
Daly DD, Yoss RE (1959) A family with narcolepsy. Proc Mayo Clin 34:313–319.Find this resource:
Dalmau J, Gleichman AJ, Hughes EG, et al. (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098.Find this resource:
Dalmau J, Tuzun E, Wu HY, et al. (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36.Find this resource:
Dantzer R (1986) Behavioral, physiological and functional aspects of stereotyped behavior: a review and re-interpretation. J Animal Sci 62:1776–1786.Find this resource:
Davis EJ, Borde M (1993) Wilson's disease and catatonia. British Journal of Psychiatry 162:256–259.Find this resource:
D’Cruz OF, Vaughan BV, Gold SH, et al. (1994) Symptomatic cataplexy in pontomedullary lesions. Neurology 44:2189–2191.Find this resource:
Defazio G, Berardelli A, Abbruzzese G, et al. (2000) Primary hemifacial spasm and arterial hypertension: a multicenter case-control study. Neurology 54:1198–1200.Find this resource:
Delay J, Pichot P, Lemperière T (1960) Un neuroleptique majeur non phenothiazine et non reserpinique, l'haloperidol, dans le traitement des psychoses. Ann Med Psychol 118:145–152.Find this resource:
Del Brutto OH (1997) Albendazole therapy for subarachnoid cysticerci: clinical and neuroimaging analysis of 17 patients. Journal of Neurology, Neurosurgery and Psychiatry 62:659–661.Find this resource:
Delisle JD (1991) Catatonia unexpectedly reversed by midazolam. Am J Psychiatry 148:809.Find this resource:
Dey AB, Stout N R, Kenny RA (1997) Cardiovascular syncope is the most common cause of drop attacks in the elderly. Pacing and Clinical Electrophysiology 20:818–819.Find this resource:
Dichter MA, Brodie MJ (1996) New antiepileptic drugs. New Engl J Med 334:1583–1590.Find this resource:
Digre K, Corbett JJ (1988) Hemifacial spasm: differential diagnosis, mechanism and treatment. In: Advances in Neurology, Eds Jankovic J, Tolosa E, New York: Raven Press, pp. 151–176.Find this resource:
Duff JM, Spinner RJ, Lindor NM, et al. (1999) Familial trigeminal neuralgia and contralateral hemifacial spasm. Neurology 53:216–218.Find this resource:
Dura JR, Mullick JA, Rasnake LK (1987) Prevalence of stereotypy among institutionalized nonambulatory profoundly mentally retarded people. Am M Ment Defic 91:548–549.Find this resource:
Ebadi M, Pfeiffer RF, Murrin LC (1990) Pathogenesis and treatment of neuroleptic malignant syndrome. Clin Pharmacol 21:367–386.Find this resource:
Edwards MJ, Dale RC, Church AJ, et al. (2004) Adult-onset tic disorder, motor stereotypies, and behavioural disturbance associated with antibasal ganglia antibodies. Mov Disord 19:1190–1196.Find this resource:
Edwards WG, Mulherin JL (1983) The management of brachiocephalic occlusive disease. American Surgeon 49:465–471.Find this resource:
Eekhof JL, Aramideh M, Speelman JD, et al. (2000) Blink reflexes and lateral spreading in patients with synkinesia after Bell's palsy and in hemifacial spasm. Eur Neurol 43:141–146.Find this resource:
Egli M, Mothersill I, O’Kane M, et al. (1985) The axial spasm – the predominant type of drop seizure in patients with secondary generalised epilepsy. Epilepsia 26:401–415.Find this resource:
Eleopra R, Tugnoli V, Caniatti L, et al. (1996) Botulinum toxin treatment in the facial muscles of humans: evidence of an action in untreated near muscles by peripheral local diffusion. Neurology 46:1158–1160.Find this resource:
Elian M, Rudolf N de M (1996) Observations on hand movements in Rett syndrome: a pilot study. Acta Neurol Scand 94:212–214.Find this resource:
Ellis KL, Speed J (1998) Pharmacological management of movement disorder after midbrain haemorrhage. Brain Injury 12:623–628.Find this resource:
Elmquist D, Toremalm NG, Elner A, et al. (1982) Hemifacial spasm: electrophysiological findings and the therapeutic effect of facial nerve block. Muscle Nerve 5:S89–S94.Find this resource:
Ethelberg S (1950) Symptomatic “cataplexy” or chalastic fits in cortical lesion of the frontal lobe. Brain 53:499–511.Find this resource:
Fisher CM (1958) The use of anticoagulants in cerebral thrombosis. Neurology (Minneap) 8:311–332.Find this resource:
Fein S, McGrath MG (1990) Problems in diagnosing bipolar disorder in catatonic patients. J Clin Psychiatry 51:203–205.Find this resource:
Fink M (1996) Toxic serotonin syndrome or neuroleptic malignant syndrome?. Pharmacopsychiatry 29:159–161.Find this resource:
FitzGerald PM, Jankovic J, Glaze DG, et al. (1990[a]) Extrapyramidal involvement in Rett's syndrome. Neurology 40:293–295.Find this resource:
FitzGerald PM, Jankovic J, Percy AK (1990[b]) Rett syndrome and associated movement disorders. Movement Disorders 5:195–203.Find this resource:
Francisco GE, Ivanhoe CB (1996) Successful treatment of post-traumatic narcolepsy with methylphenidate. Am J Phys Med Rehab 75:63–65.Find this resource:
Fricchione GL (1985) Neuroleptic catatonia and its relationship to psychogenic catatonia. Biol Psychiatry 20:304–313.Find this resource:
Friedman A, Jamrozik Z, Bojakowski J (1989) Familial hemifacial spasm. Mov Disord 4:213–218.Find this resource:
Friedman JH, Feinberg SS, Felman RG (1985) A neuroleptic malignant syndrome due to levodopa therapy withdrawal. JAMA 254:2792–2795.Find this resource:
Fukuda M, Kameyama S, Honda Y, et al. (1997) Hemifacial spasm resulting from facial nerve compression near the internal acoustic meatus. Neurol Med Chir 37:771–774.Find this resource:
Furukawa T (1979) Rocking belly movement. Neurol Med 2:492.Find this resource:
Gambardella A, Reutens DC, Andermann F et al. (1994) Late onset drop attacks in temporal lobe epilepsy: a reevaluation of the concept of temporal lobe syncope. Neurology 44:1074–1078.Find this resource:
Gardner WJ, Dohn DF (1966) Trigeminal neuralgia – hemifacial spasm – Paget's disease. Brain 89:555–562.Find this resource:
Gardner WJ, Sava G (1962) Hemifacial spasm – a reversible pathophysiologic state. J Neurosurg 19:240–247.Find this resource:
Garland PE, Patrinely JR, Anderson RL (1987) Hemifacial spasm. Results of unilateral myectomy. Ophthalmology 94:288–294.Find this resource:
Gastaut H, Broughton R (1972) Atonic seizures. In: Epileptic Seizures, Clinical and Electroencephalographic Features, Diagnosis and Treatment, Eds Gastaut H, Broughton R, Springfield: Charles C Thomas, pp. 85–88.Find this resource:
Gastaut H, Broughton R, Roger J, et al. (1974) Generalised convulsive seizures without local onset. In: Handbook of Clinical Neurology, Eds Vinken PJ, Bruyn GW, Amsterdam: North Holland–Elsevier, Vol. 15, pp. 107–144.Find this resource:
Gastaut H, Regis H (1961) On the subject of Lennonx's akinetic petit mal. Epilepsia 2:298–305.Find this resource:
Gastaut H, Roger J, Soulayrol R, et al. (1966) Childhood epileptic encephalopathy with diffuse slow spike waves (otherwise known as “petit mal variant”) or Lennox's syndrome. Epilepsia 7:139–179.Find this resource:
Gates JR, Leppik IL, Yap J, et al. (1984) Corpus callostomy: clinical and encephalographic effects. Epilepsia 25:308–316.Find this resource:
Gates JR, Rosenfeld WE, Maxwell RE, et al. (1987) Response of multiple seizure types to corpus callosum section. Epilepsia 28:28–34.Find this resource:
Gautier JC, Morelot D, Gray F, et al. (1982) Giant aneurysm of both vertebral arteries. Drop-attacks. Revue Neurologique 138:63–67.Find this resource:
Geier S, Bancaud J, Talairach J, et al. (1977) The seizures of frontal lobe epilepsy. A study of clinical manifestations. Neurology 27:951–958.Find this resource:
Gelardi JM, Brown JW (1967) Hereditary cataplexy. J Neurol Neurosurg Psych 30:455–457.Find this resource:
Gelenberg AJ (1976) The catatonic syndrome. Lancet 1:1339–1341.Find this resource:
Gelenberg AJ, Mandel MR (1977) Catatonic reactions to high-potency neuroleptic drugs. Arch Gen Psychiatry 34:947–950.Find this resource:
Gelineau JBE (1880) De La narcolepsie. Gaz Hop (Paris) 53:626–628.Find this resource:
Geller M, Christoff N (1971) Diazepam in the treatment of childhood epilepsy. JAMA 215:2087.Find this resource:
Gernaat HB, Haffmans PM, Knegtering H, et al. (1995) Tranylcypromine in narcolepsy. Pharmacopsychiatry 28:98–100.Find this resource:
Gillberg and Gillberg (1989) Asperger syndrome in 23 Swedish children. Dev Med Child Neurol 31:520–531.Find this resource:
Gil-Nagel A, Morlan L, Balseiro J, et al. (1992) Drop attacks as a manifestation of occipital vertebra. Neurologia 7:113–115.Find this resource:
Girard N, Poncet M, Caces F, et al. (1997) Three-dimensional MRI of hemifacial spasm with surgical correlation. Neuroradiology 39:46–51.Find this resource:
Glocker FX, Guschlbauer B, Lucking CH, et al. (1995) Effects of local injections of botulinum toxin on electrophysiological parameters in patients with hemifacial spasm: role of synaptic activity and size of motor units. Neurosci Lett 187:161–164.Find this resource:
Goldenberg I, Moss AJ (2008) Long QT syndrome. J Am Coll Cardiol 51:2291–2300.Find this resource:
Gordon M, Huang M, Gryfe CI (1982) An evaluation of falls, syncope and dizziness by prolonged ambulatory cardiographic monitoring in a geriatric institutional setting. Gerontology 30:6–12.Find this resource:
Gortvai P (1964) Insufficiency of vertebral artery treated by decompression of its cervical part. Br Med J 2:233–234.Find this resource:
Gowers WR (1888) A Manual of Diseases of the Nervous System, Philadelphia: P Blakiston.Find this resource:
Guerrini R, Bonanni P, Parmeggiani L, et al. (1998[a]) Cortical reflex myoclonus in Rett syndrome. Annals of Neurology 43: 472–479.Find this resource:
Guerrini R, Genton P, Bureau M, et al. (1998[b]) Multilobar polymicrogyria, intractable drop attack seizures, and sleep related electrical status epilepticus. Neurology 51:504–512.Find this resource:
Guilleminault C, Heinzer R, Mignot E, et al. (1998) Investigations into the neurologic basis of narcolepsy. Neurology 50:S8–15.Find this resource:
Hagberg B, Aicardi J, Dias K, et al. (1983) A progressive syndrome of autism, dementia, ataxia and loss of purposeful hand use in girls; Rett's syndrome: report of 35 cases. Annals of Neurology 14: 471–479.Find this resource:
Hagberg B, Hanefeld F, Percy A, et al. (2002) An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett Syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001. Eur J Paediatr Neurol 6:293–297.Find this resource:
Haines SJ, Torres F (1991) Intraoperative monitoring of the facial nerve during decompressive surgery for hemifacial spasm. Journal of Neurosurgery 74:254–257.Find this resource:
Hancock H (1852) Convulsive movements of the stump. Lancet I:281–283.Find this resource:
Hansen RA, Menkes JH (1972) A new anticonvulsant in the management of minor motor seizures. Dev Med Child Neurol 14:3.Find this resource:
Harsh GR, Wilson CB, Hieshima GB, et al. (1991) Magnetic resonance imaging of vertebrobasilar ectasia in tic convulsif. Journal of Neurosurgery 74:999–1003.Find this resource:
Harris W, Wright AD (1932) Treatment of clonic facial spasm. Lancet 1:657–662.Find this resource:
Harrison MS (1976) The facial tics. J Laryngol Otol 90:561–570.Find this resource:
Harvey AS, Jayakar P, Duchowny M, et al. (1996) Hemifacial seizures and cerebellar ganglioglioma: an epilepsy syndrome in infancy with seizures of cerebellar origin. Ann Neurol 40:91–98.Find this resource:
Hausmann ON, Kirsch E, Lyrer A, et al. (1997) Bilateral glomus tumours with a blood pressure regulation disorder due to baroreceptor dysfunction. Dtsch Med Wochen 122:253–258.Find this resource:
Hawkins JM, Archer KJ, Strakowski SM, et al. (1995) Somatic treatment of catatonia. International Journal of Psychiatry in Medicine 25:345–369.Find this resource:
Hecaen H, Penfield W, Bertrand C, et al. (1956) The syndrome of apractognosia due to lesions of the minor cerebral hemisphere. Arch Neurol Psychiat 75:400–434.Find this resource:
Heils Al, Lesch KP (1997) Das maligne neuroleptische Syndrome und die akute lebensbedrochliche Katatonie-zwei gegensatzliche Krankheitsentitaten? Fortschritte der Neurologie-Psychiatrie 65:8–15.Find this resource:
Henderson WR, Smyth GE (1948) Phantom limbs. Journal of Neurology, Neurosurgery and Psychiatry 11:88–112.Find this resource:
Herzberg L (1985) Management of hemifacial spasm with clonazepam. Neurology 35:1676–1677.Find this resource:
Hiroi N, White NM (1989) Conditioned stereotype: behavioural specification of the UCS and pharmacologic investigation of the neural change. Pharmacol Biochem Behav 32:249–258.Find this resource:
Hishikawa Y, Ida H, Nakai K, et al. (1966) Treatment of narcolepsy with imipramine (Tofranil) and desmethylimipramine (Pertofran). J Neurol Sci 3:453–461.Find this resource:
Hishikawa Y, Wakamatsu H, Furuya E, et al. (1976) Sleep satiation in narcoleptic patients. Encephal Clin Neurophysiol 41:1–18.Find this resource:
Hjorth RJ, Willison RG (1973) The electromyogram in facial myokymia and hemifacial spasm. Journal of Neurological Sciences 20:117–126.Find this resource:
Hori T, Fukushima T, Terao H, et al. (1981) Percutaneous radiofrequency facial nerve coagulation in the management of facial spasm. J Neurosurgery 54:655–658.Find this resource:
Hosoya T, Watanabe N, Yamaguchi K, et al. (1995) Three-dimensional MRI of neurovascular compression in patients with hemifacial spasm. Neuroradiology 37:350–352.Find this resource:
Hotta J, Kubokura T, Ozawa H, et al. (1996) Cerebellopontine angle epithelial cyst presenting as hemifacial spasm. No To Shinkei-Brain and Nerve 48:281–285.Find this resource:
Hughes EC, Brackmann DE, Weinstein RC (1980) Seventh nerve spasm: effect of modification of cholinergic balance. Otolaryngol Head Neck Surg 88:491–499.Find this resource:
Hunt JR (1922) On the occurrence of static seizures in epilepsy. J Nerv Ment Dis 56:351.Find this resource:
Huppke P, Laccone F, Kramer N, et al. (2000) Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients. Hum Mol Genet 22: 1369–1375.Find this resource:
Hurst DL (1986) The use of imipramine in minor motor seizures. Paediatric Neurology 2:13–17.Find this resource:
Hynes AF, Vickar EL (1996) Case study: neuroleptic malignant syndrome without pyrexia. Journal of the American Academy of Child and Adolescent Psychiatry 35:959–962.Find this resource:
Iacono RP, Linford J, Tourian A, et al. (1987b) Baclofen in the treatment of post-amputation autonomous stump movements. European Neurol 26:141–144.Find this resource:
Iacono RP, Sandyk R, Bamford R, et al. (1987a) Post-amputation phantom pain and autonomous stump movements responsive to doxepin. Functional Neurol 2:343–349.Find this resource:
Ikeno T, Shigematsu H, Miyakoshi M, et al. (1985) An analytic study of epileptic falls. Epilepsia 26:612–621.Find this resource:
Iliceto G, Thompson PD, Day BL, et al. (1990) Diaphragmatic flutter, the moving umbilicus syndrome, and “belly dancer's” dyskinesia. Movement Disorders 5:15–22.Find this resource:
Illingworth RD, Porter DG, Jakubowski J (1996) Hemifacial spasm: a prospective long-term follow-up of 83 cases treated by microvascular decompression at two neurosurgical centres in the United Kingdom. Journal of Neurology, Neurosurgery and Psychiatry 60:72–77.Find this resource:
Imparato AM, Riles TS, Kim GE (1981) Cervical vertebral angioplasty for brain stem ischaemia. Surgery 90:842–852.Find this resource:
Inoue T, Maeyama R, Ogawa H (1995) Hemifacial spasm resulting from cerebellopontine angle lipoma. Neurosurgery 36:846–850.Find this resource:
Irani SR, Bera K, Waters P, et al. (2010) N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 133:1655–67.Find this resource:
Irani SR, Michell AW, Lang B, et al. (2011) Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892–900.Find this resource:
Ishikawa M, Ohira T, Namiki J, et al. (1996[a]) Abnormal muscle response (lateral spread) and F-wave in patients with hemifacial spasm. Journal of Neurological Sciences 137:109–116.Find this resource:
Ishikawa M, Namiki J, Takase M, et al. (1996[b]) Effect of repetitive stimulation on lateral spreads and F-waves in hemifacial spasm. Journal of Neurological Sciences 142:99–106.Find this resource:
Ishikawa M, Ohira T, Namiki J, et al. (1996[c]) F-wave in patients with hemifacial spasm: observations during microvascular decompression operations. Neurol Res 18:2–8.Find this resource:
Ishikawa M, Ohira T, Namiki J, et al. (1997) Electrophysiological investigation of hemifacial spasm after microvascular decompression: F waves of the facial muscles, blink reflexes and abnormal muscle responses. J Neurosurg 86:654–661.Find this resource:
Ishikawa M, Ohira T, Namiki J, et al. (1994) Neurophysiological study of hemifacial spasm-F wave of the facial muscles. No To Shinkei-Brain and Nerve 46:360–365.Find this resource:
Iwakuma T, Matsumoto A, Nakamura N (1982) Surgical results of hemifacial spasm: comparison of partial sectioning of the facial nerve, selective neurectomy and microvascular decompression. In: Disorders of the Facial Nerve, Eds Graham MD, House WF, New York: Raven Press, pp. 323–329.Find this resource:
Jacome DE (1989) Temporal lobe syncope: clinical variants. Clin Electroencephalogr 20:58–65.Find this resource:
Jankovic J (1994) Stereotypies. In: Movement Disorders, Eds Marsden CD, Fahn S, Oxford: Butterworth-Heinmann, Vol. 3, pp. 503–517.Find this resource:
Jankovic J, Glass JP (1985) Metoclopramid-induced phantom dyskinesia. Neurology 35:432–435.Find this resource:
Jankovic J, Pardo R (1986) Segmental myoclonus: clinical and pharmacologic study. Arch Neurol 43:1025–1031.Find this resource:
Jannetta PJ, Abbasy M, Maroon JC, et al. (1977) Aetiology and definitive microsurgical treatment of hemifacial spasm. Journal of Neurosurgery 47:321–328.Find this resource:
Jannetta PJ, Hackett E, Ruby JR (1970) Electromyography and electron microscopic correlates in hemifacial spasm treated by microsurgical relief of neurovascular compression. Surg Forum 21:449–451.Find this resource:
Janzen VD, Russell RD (1988) Conservative management of Tumarkin's otolithic crises. J Otolaryngol 17:359–361.Find this resource:
Jellinger K, Armstrong D, Zoghbi HY, et al. (1988) Neuropathology of Rett syndrome. Acta Neuropathologica 76:142–158.Find this resource:
Jespersen JH, Dupont E, Gelineck J, et al. (1996) Hemifacial spasm: magnetic resonance angiography. Acta Neurologica Scandinavica 93:35–38.Find this resource:
Jicha GA, Salamone JD (1991) Vacuous jaw movements and feeding deficits in rats with ventrolateral striatal dopamine depletion: possible relation to parkinsonian symptoms. Journal of Neurological Sciences 11:3822–3829.Find this resource:
Jitpimolmard S, Tiamkao S, Laopaiboon M (1998) Long term results of botulinum toxin type A (Dysport) in the treatment of hemifacial spasm: a report of 175 cases. Journal of Neurology, Neurosurgery and Psychiatry 64:751–757.Find this resource:
Kameyama M (1965) Vertigo and drop attack: with special reference to cerebrovascular disorders and atherosclerosis of the vertebral-basilar system. Geriatrics 20:892–900.Find this resource:
Kamphuisen HAC (1981) The narcoleptic syndrome. In: Handbook of Clinical Neurology, Eds Vinken PJ, Bruyn GW, Amsterdam: North Holland, Vol. 42, pp. 710–714.Find this resource:
Kahlbaum KL (1873) Catatonia, Eds Levi Y, Pridon T, Baltimore: John Hopkins University Press.Find this resource:
Kelly R (1951) Colloid cysts of the third ventricle: analysis of twenty-nine cases. Brain 74:23–65.Find this resource:
Kempe LG, Smith DR (1969) Trigeminal neuralgia, facial spasm, intermedius and glossopharyngeal neuralgia with persistent carotid basilar anastomosis. Journal of Neurosurgery 31:445–451.Find this resource:
Kenney C, Jankovic J (2008) Botulinum toxin in the treatment of blepharospasm and hemifacial spasm. J Neural Transm 115:585–591.Find this resource:
Kenny RA, Traynor G (1991) Carotid sinus syndrome – clinical characteristics in elderly patients. Age and Aging 20:449–454.Find this resource:
Kerr A, Southall D, Amos P, et al. (1990) Correlation of electroencephalogram, respiration and movement in the Rett syndrome. Brain and Development 12:61–68.Find this resource:
Kiley MA, Voyvodic F, Burns RJ (1999) An unusual case of hemifacial spasm. J Clin Neurosci 6:349–351.Find this resource:
Kim Y, Tanaka A, Kimura M, et al. (1991) Arteriovenous malformation in the cerebellopontine angle presenting as hemifacial spasm. Neurologia Medico-Chirurgica 31:109–112.Find this resource:
Kimura J, Ishida T, Yamada T (1985) Electrically and mechanically elicited blink reflex. Adv Ophthalmol Plast Reconstruct Surg 4:103–124.Find this resource:
Kimura J, Lyon LW (1972) Orbicularis oculi reflex in Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve. Journal of Neurology, Neurosurgery and Psychiatry 35:228–233.Find this resource:
Kimura J, Powers JM, Van Allen MW (1969) Reflex response of orbicularis oculi muscle to supraorbital stimulation. Study in normal subjects and in peripheral facial paresis. Arch Neurol 21:193–199.Find this resource:
Kinney WC, Nalepa N, Hughes GB, et al. (1995) Cochleosacculotomy for the treatment of Meniere's disease in the elderly patient. Laryngoscope 105:934–937.Find this resource:
Kitt CA, Wilcox BJ (1995) Preliminary evidence for neurodegenerative changes in the substantia nigra of Rett syndrome. Neuropediatrics 26:114–118.Find this resource:
Klee A, Mordhorst CH (1961) Intermittent insufficiency and thrombosis of the basilar artery. Psychiatr Neurol 142: 1–12.Find this resource:
Kleist K (1960) Schizophrenia symptoms in cerebral pathology. J Ment Sci 106:246–255.Find this resource:
Klimke A, Klieser E (1994[a]) Catatonia. Current therapeutic recommendations. Practical Ther 2:280–291.Find this resource:
Klimke A, Klieser E (1994[b]) Sudden death after intravenous application of lorazepam in a patient treated with clozapine. Am J Psychiatry 151:780.Find this resource:
Kobata H, Kono A, Iwasaki K, et al. (1998) Combined hyperactive dysfunction syndrome of the cranial nerves: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia: 11 year experience and review. Neurosurgery 43:1351–1356.Find this resource:
Koller WC, Herbster G (1988) D1 and D2 dopamine receptor mechanisms in dopaminergic behaviors. Clin Neuropharmacol 11:221–231.Find this resource:
Kondo A (1997) Follow-up results of microvascular decompression in trigeminal neuralgia and hemifacial spasm. Neurosurgery 40:46–51.Find this resource:
Kono I, Ueda Y, Araki K, et al. (1994) Spinal myoclonus resembling belly dance. Movement Disorders 9:325–329.Find this resource:
Kramer U, Achiron A (1993) Drop attacks induced by hypothyroidism. Acta Neurologica Scandinavica 88:410–411.Find this resource:
Kremer M (1958) Sitting, standing and walking. Br Med J 2:63–68.Find this resource:
Kubala MJ, Millikan CH (1964) Diagnosis, pathogenesis and treatment of “drop attack”. Arch Neurol 11:107–113.Find this resource:
Kuczenski R, Segal D (1989) Concomitant characterisation of behavioural and neurotransmitter response to amphetamine using in vivo microdialysis. J Neurosci 9:2051–2065.Find this resource:
Kudo A, Susuki M, Kudo N, et al. (1996) Schwannoma arising from the intermediate nerve and manifesting as hemifacial spasm. Journal of Neurosurgery 84:277–279.Find this resource:
Kuhl W (1980) Vestibular-cerebral syncopes. Dtsch Med Wochenschr 105:41–42.Find this resource:
Kulisevsky J, Marti-Fabregas J, Grau JM (1992) Spasms of amputation stumps. Journal of Neurology, Neurosurgery and Psychiatry 55:626–627.Find this resource:
Kumagami H (1974) Neuropathological findings of hemifacial spasm and trigeminal neuralgia. Arch Otolaryngol 99:160–164.Find this resource:
Kuzniecky R, Andermann F, Guerrini R (1994) The epileptic spectrum in the congenital bilateral perisylvian syndrome. Neurology 44:379–385.Find this resource:
Lammers GJ, Arends J, Declerck AC, et al. (1993) Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. Sleep 16:216–220.Find this resource:
Langtry HD, Gillis JC, Davis R (1997) Topiramate. A review of its pharmacodynamic and pharmacokinetic properties and the clinical efficacy in the management of epilepsy. Drugs 54:752–773.Find this resource:
Lankford DA, Wellman JJ, O’Hara C (1994) Post-traumatic narcolepsy in mild to moderate closed head injury. Sleep 17:S25–28.Find this resource:
Lauterbach EC (1998) Catatonia-like events after valproic acid with risperidone and sertraline. Neuropsychiatry, Neuropsychology and Behavioural Neurology 11:157–163.Find this resource:
Lee MS, Marsden CD (1995) Drop attacks. In: Negative Motor Phenomena, Eds Fahn S, Hallett M, Luders HO, Marsden CD, Advances in Neurology? Philadelphia: Lippincott-Ravan, Vol. 67, pp. 41–52.Find this resource:
Lee JW, Robertson S (1997) Clozapine withdrawal catatonia and neuroleptic malignant syndrome: a case report. Annals of Clinical Psychiatry 9:165–169.Find this resource:
Lekman A, Witt-Engerstrom I, Gottfries J, et al. (1989) Rett syndrome: biogenic amines and metabolites in postmorten brain. Pediatr Neurol 5:357–362.Find this resource:
Lennox WG (1960) Epilepsy and Related Disorders, Boston: Little Brown and Co., Vols 1 and 2, p. 1168.Find this resource:
Liepert J, Oreja-Guevara C, Cohen LG, et al. (1999) Plasticity of cortical hand muscle representation in patients with hemifacial spasm. Neurosci Lett 272: 33–36.Find this resource:
Lipinski CG (1977) Epilepsies with astatic seizures of late onset. Epilepsia 18:13–20.Find this resource:
Loeser JD, Chen J (1983) Hemifacial spasm: treatment by microsurgical facial nerve decompression. Neurosurgery 13:141–146.Find this resource:
Loewenfeld L (1902) Uber Narkolepsie. Munch Med Wschr 49:1041–1045.Find this resource:
Levenson JL (1985) Neuroleptic malignant syndrome. Am J Psychiatry 142:1137–1145.Find this resource:
Louis ED, Pflaster NL (1995) Catatonia mimicking nonconvulsive status epilepticus. Epilepsia 36:943–945.Find this resource:
Ludman H (1976) Facial spasm. Clin Otolaryngol 1:147–152.Find this resource:
Lund C, Mortimer A, Rogers D, et al. (1991) Motor, volitional and behavioural disorders in schizophrenia. Br J Psychiatry 158:323–327.Find this resource:
Lund M (1963) Drop-attacks in association with parkinsonism and basilar artery sclerosis. Acta Neurol Scand 39:226–229.Find this resource:
McCall WV, Mann SC, Shelp FE, et al. (1995) Fatal pulmonary embolism in the catatonic syndrome: two case reports and a literature review. Journal of Clinical Psychiatry 56:21–25.Find this resource:
McEvoy JP, Lohr JB (1984) Diazepam for catatonia. Am J Psychiatry 141:284–285.Find this resource:
Maeda M, Tamaoka A, Hayashi A, et al. (1995) A case of HLA-DR2, DQw1 negative post-traumatic narcolepsy. Clinical Neurology 35:811–813.Find this resource:
Magnan J, Cases F, Locatelli P, et al. (1997) Hemifacial spasm: endoscopic vascular decompression. Otolaryngology-Head and Neck Surgery 117:308–314.Find this resource:
Mamelak AN, Barbaro NM, Walker JA, et al. (1993) Corpus callosotomy: a quantitative study of the extent of resection, seizure control, and neuropsychological outcome. Journal of Neurosurgery 79:688–695.Find this resource:
Mann SC, Caroff SN, Bleier HR, et al. (1986) Lethal catatonia. Am J Psych 143:1374–1381.Find this resource:
Maraganore DM, Lees AJ, Marsden CD (1991) Complex stereotypies after right putaminal infarction: a case report. Movement Disorders 6:358–361.Find this resource:
Marcus CL, Carroll JL, McColley SA, et al. (1994) Polysomnogrpahic characteristics of patients with Rett syndrome. Journal of Pediatrics 125:218–224.Find this resource:
Marion MH, Gledhill RF, Thompson PD (1989) Spasms of amputation stumps: a report of 2 cases. Movement Disorders 4:1354–1358.Find this resource:
Martényi F, Harangozó J, Mód L (1984) Clonazepam for the treatment of stupor in catatonic schizophrenia. Am J Psychiatry 146:1230.Find this resource:
Martinelli P, Guiliani S, Ippoliti M (1992) Hemifacial spasm due to peripheral injury of facial nerve. A nuclear syndrome. Mov Disord 7:181–184.Find this resource:
Martinelli P, Gabellini AS, Lugaresi E (1983) Facial nucleus involvement in post-paralytic hemifacial spasm. Journal of Neurology, Neurosurgery and Psychiatry 46:586–587.Find this resource:
Matsuo F (1984) Partial epileptic seizures beginning in the truncal muscles. Acta Neurol Scand 69:264–270.Find this resource:
Matsuura N, Kondo A (1996) Trigeminal neuralgia and hemifacial spasm as false localising signs in patients with a contralateral mass of the posterior cranial fossa. Journal of Neurosurgery 84:1067–1071.Find this resource:
Mauriello JA, Leone T, Dhillon S, et al. (1996) Treatment choices of 119 patients with hemifacial spasm over 11 years. Clin Neurol Neurosurg 98:213–216.Find this resource:
Maurice-Williams RS (1974) Drop attacks from cervical cord compression. Br J Clin Prac 28:215–216.Find this resource:
May RH (1959) Catatonic-like states following phenothiazine therapy. Am J Psychiatry 115:1119–1120.Find this resource:
Mayer G, Ewert MK, Hephata K (1995) Selegeline hydrochloride treatment in narcolepsy. A double-blind placebo-controlled study. Clinical Neuropharmacology 18:306–319.Find this resource:
Mazars G, Merienne L (1980) Control of dyskinesias due to sensory deafferentation by means of thalamic stimulation. Acta Neurochirurgica – Supplementum 30:239–243.Find this resource:
Meissner I, Wiebers DO, Swanson JW, et al. (1986) The natural history of drop attacks. Neurology 36:1029–1034.Find this resource:
Menza MA, Harris D (1989) Benzodiazpines and catatonia; an overview. Biol Psychiatry 26:842–846.Find this resource:
Merienne L, Mazars G (1982) Traitement de certaines dyskinesies par stimulation thalamique intermittente. Neuro-Chirurgie 28:201–206.Find this resource:
Mettler FA (1955) Perceptual capacity functions of the corpus striatum and schizophrenia. Psych Q 29:89–111.Find this resource:
Micheli F, Scorticati MC, Gatto E, et al. (1994) Familial hemifacial spasm. Mov Disord 9:330–332.Find this resource:
Miehlke A (1981) Management of hemifacial spasm. In: The Cranial Nerves, Eds Samii M, Jannetta PJ, Berlin: Springer, pp. 478–483.Find this resource:
Mignot E (1998) Genetic and familial aspects of narcolepsy. Neurology 50:S16–22.Find this resource:
Mignot E (2004) Sleep, sleep disorders and hypocretin (orexin). Sleep Med 5:S2–8.Find this resource:
Millan-Guerrero RO, Tene-Perez E, Trujillo-Hernandez B (2000) Levodopa in hemifacial spasm. A therapeutic alternative. Gac Med Mex 136:565–571.Find this resource:
Miller LG, Jankovic J (1990) Neurological approach to drug-induced movement disorders: a study of 125 patients. South Med J 83:525–535.Find this resource:
Millikan CH, Siekert RG (1955) Studies in cerebrovascular disease. I. The syndrome of intermittent insufficiency of the basiler arterial system. Mayo Clin Proc 30:61–68.Find this resource:
Mitchell SW (1872) Injuries of Nerves and their Consequences, New York: JB Lippincott.Find this resource:
Mitler MM, Walsleben J, Sangal RB, et al. (1998) Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs. Electroencephalography and Clinical Neurophysiology 107:33–38.Find this resource:
Mizutani T (1996) A fatal, chronically growing basilar artery: a new type of dissecting aneurysm. J Neurosurgery 84:962–971.Find this resource:
Moller AR (1991) Interaction between the blink reflex and the abnormal muscle response in patients with hemifacial spasm: results of intraoperative recordings. Journal of Neurological Sciences 101:114–123.Find this resource:
Moller AR, Jannetta PJ (1987) Monitoring facial EMG responses during microvascular decompression operations of hemifacial spasm. Journal of Neurosurgery 66:681–685.Find this resource:
Moller AR, Jannetta PJ (1986) Physiological abnormalities in hemifacial spasm studied during microvascular decompression operations. Exper Neurol 93:584–600.Find this resource:
Moller AR, Jannetta PJ (1985) Hemifacial spasm: results of electrophysiologic recording during microvascular decompression operations. Neurology 35:969–974.Find this resource:
Moller AR, Jannetta PJ (1984) On the origin of synkinesis in hemifacial spasm: results of intracranial recordings. J Neurosurgery 61:569–576.Find this resource:
Moller MB, Moller AR (1985) Audiometric abnormalities in hemifacial spasm. Audiology 24:396–405.Find this resource:
Montagna P, Imbriaco A, Zucconi M, et al. (1986) Hemifacial spasm in sleep. Neurology 36:270–273.Find this resource:
Moore AP (1984) Postural fluctuation of hemifacial spasm. Journal of Neurosurgery 60:190–191.Find this resource:
Morrison JR (1973) Catatonia: retarded and excited types. Arch Gen Psych 28:39–41.Find this resource:
Motil KJ, Schultz R, Brown B, et al. (1994) Altered energy balance may account for growth failure in Rett syndrome. Journal of Child Neurology 9:315–319.Find this resource:
Motte J, Trevathan E, Arvidsson JFV, et al. (1997) Lamotrigine for generalised seizures associated with the Lennox-Gastaut syndrome. New Engl J Med 337:1807–1812.Find this resource:
Myer EC, Morris DL, Brase DA, et al. (1988) Hyperendorphonism in Rett syndrome: cause or result? Ann Neurol 24:340–341.Find this resource:
Nagata S, Matsushima T, Fujii K, et al. (1992) Hemifacial spasm due to tumour, aneurysm or arteriovenous malformation. Surg Neurol 38:204–209.Find this resource:
Nagamitsu S, Matsuishi T, Kisa T, et al. (1997) CSF beta-endorphin levels in patients with infantile autism. J Autism Develop Dis 27:155–163.Find this resource:
Neuman E, Rancurel G, Lecrubier Y, et al. (1996) Schizophreniform catatonic on 6 cases secondary to hydrocephalus with subthalamic mesencephalic tumor associated with hypodopaminergia. Neuropsychobiology 34:76–81.Find this resource:
Nguyen LT, McLoon LK, Wirschafter JD (1998) Doxorubicin chemomyectomy is enhanced when performed two days following bupivacaine injections; the effect coincides with the peak of muscle satellite cell division. Invest Ophthalmol Visual Sci 39:203–206.Find this resource:
Nielsen VK (1985) Electrophysiology of the facial nerve in hemifacial spasm: ectopic/ephaptic excitation. Muscle Nerve 8:545–555.Find this resource:
Nishi T, Matsukado Y, Nagahiro S, et al. (1987) Hemifacial spasm due to contralateral acoustic neuroma. Neurology 37:339–342.Find this resource:
Nishino S (2007) Clinical and neurobiological aspects of narcolepsy. Sleep Med 8:373–399.Find this resource:
Nishino S, Ripley B, Overeem S, et al. (2001) Low CSF hypocretin (orexin) and altered energy homeostasis in human narcolepsy. Ann Neurol 50:381–388.Find this resource:
Nishio S, Morioka T, Fukui M, et al. (1994) Surgical treatment of intractable seizures due to hypothalamic hamartoma. Epilepsia 35:514–519.Find this resource:
Northoff G, Eckert J, Frtitze J (1997) Glutamatergic dysfunction in catatonia? Successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine. Journal of Neurology, Neurosurgery and Psychiatry 62:404–406.Find this resource:
Northoff G, Koch A, Wenke J, et al. (1999) Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms. Movement Disorders 14:404–416.Find this resource:
Obersteiner H,Redlich E. Uber Wesen und Pathogenese der tabischen Hinterstrangsdegeneration. Arb Neurol Inst Univ Wien 1894;1-3:158–172.Find this resource:
Odkvist LM, Bergenius J (1988) Drop attacks in Meniere's disease. Acta Oto-Laryngologica 455:82–85.Find this resource:
Ogale SB, Chopra S, Thakur S (1995) Transtympanic facial nerve needling: a curative surgical option for hemifacial spasms. Acta Otolaryngol 115:405–407.Find this resource:
Oguni H, Fukuyama Y, Imaizumi Y, et al. (1992) Video-EEG analysis of drop seizures in myoclonic astatic epilepsy of early childhood (Doose syndrome). Epilepsia 33:805–813.Find this resource:
Oguni H, Hayashi K, Osawa M (1996) Long-term prognosis of Lennox-Gastaut syndrome. Epilepsia 37:44–47.Find this resource:
Oguni H, Hayashi K, Usui N, et al. (1998) Startle epilepsy with infantile hemiplegia: report of two cases improved with surgery. Epilepsia 29:93–98.Find this resource:
Oguni H, Mukahira K, Oguni M, et al. (1994) Video-polygraphic analysis of myoclonic seizures in juvenile myoclonic epilepsy. Epilepsia 35:307–316.Find this resource:
Oguni H, Olivier A, Andermann F, et al. (1991) Anterior callostomy in the treatment of medically intractable epilepsies: a study of 43 patients with a mean follow-up of 39 months. Ann Neurol 30:357–364.Find this resource:
Oguni H, Uehara T, Imai K, et al. (1997) Atonic epileptic drop attacks associated with generalised spike-and-slow wave complexes: video-polygraphic study in two patients. Epilepsia 38:813–818.Find this resource:
Oliveira LD, Cardosa F, Vargas AP (1998) Hemifacial spasm and arterial hypertension. Mov Disord 14:832–835.Find this resource:
Oller Daurella L (1970) Un type special de crises observées dans le syndrome de Lennox-Gastaut d'apparition tardive. Rev Neurol (Paris) 122:459–462.Find this resource:
Onofrj M, Curatola L, Ferracci F, et al. (1992) Narcolepsy associated with primary temporal lobe B-cells lymphoma in a HLA DR2 negative subject. Journal of Neurology, Neurosurgery and Psychiatry 55:852–853.Find this resource:
Overstall PW, Exton-Smith AN, Imms FJ, et al. (1977) Falls in the elderly related to postural imbalance. Br Med J 1:261–264.Find this resource:
Palmini A, Andermann F, Olivier A, et al. (1991) Focal neuronal migration disorders and intractable partial epilepsy: a study of 30 patients. Ann Neurol 30:741–749.Find this resource:
Papo I, Quattrini A, Ortenzi A, et al. (1997) Predictive factors of callosotomy in drug-resistant epileptic patients with a long follow-up. Journal of Neurosurgical Sciences 41:31–36.Find this resource:
Parkes JD, Chen SY, Clift SJ, et al. (1998) The clinical diagnosis of the narcoleptic syndrome. Journal of Sleep Research 7:41–52.Find this resource:
Patel J, Naritoku DK (1996) Gabapentin for the treatment of hemifacial spasm. Clin Neuropharmacol 19:185–188.Find this resource:
Pazzaglia PD Alessandro R, Ambrosetto G, et al. (1985) Drop attacks: an ominous change in the evolution of partial epilepsy. Neurology 35:1725–1730.Find this resource:
Pecker J, Guy G, Scarabin J-M (1974) Third ventricle tumours including tumours of the septum pellucidum, colloid cysts and subependymal glomerate astrocytoma. In: Handbook of Clinical Neurology, Eds Vinken PJ, Bruyn GW, Amsterdam: Elsevier–North Holland, Vol. 17, pp. 440–489.Find this resource:
Peralta V, Cuesta MJ, Serrano JF, et al. (1997) The Kahlbaum syndrome: a study of its clinical validity, nosological status, and relationship with schizophrenia and mood disorder. Comprehensive Psychiatry 38:61–67.Find this resource:
Peterson WG (1967) Clinical study of Mogodon. Neurology 17:878–881.Find this resource:
Petrides G, Divadeenam KM, Bush G, et al. (1997) Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia. Biological Psychiatry 42:375–381.Find this resource:
Pfammatter JP, Donati F, Durig P, et al. (1995) Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation. Acta Paediatrica 84:569–572.Find this resource:
Phillips J, Sakas DE (1996) Anterior callosotomy for intractable epilepsy: outcome in a series of twenty patients. British Journal of Neurosurgery 10:351–356.Find this resource:
Platania N, Nicoletti GF, Barbagallo G, et al. (1997) Concurrent trigeminal and glossopharyngeal neuralgia, hemifacial spasm and hypertension of neurovascular compression. Journal of Neurosurgical Sciences 41:303–307.Find this resource:
Pollack IF, Schor NF, Martinez AJ, et al. (1995) Bobble-head doll syndrome and drop attacks in a child with a cystic choroid plexus papilloma of the third ventricle. Case report. Journal of Neurosurgery 83:729–732.Find this resource:
Primavera A, Fonti A, Novello P, et al. (1994) Epileptic seizures in patients with acute catatonic syndrome. Journal of Neurology, Neurosurgery and Psychiatry 57:1419–1422.Find this resource:
Pulec JL (1972) Idiopathic hemifacial spasm. Ann Otol 81:664–676.Find this resource:
Rakover Y, Dharan M, Rosen G (1996) Hemifacial spasm associated with external carotid artery compression of the facial nerve. Journal of Laryngology and Otology 110:1081–1083.Find this resource:
Reiss AL, Faruque F, Naidu S, et al. (1993) Neuroanatomy of Rett syndrome: a volumetric imaging study. Ann Neurol 34:227–237.Find this resource:
Rett A (1966) Uber ein eigenartiges hirnatrophisches syndrom bei hyperammonamie im kindersalter. Wien Med Wochenscher 116:723–738.Find this resource:
Rett A (1977) Cerebral atrophy associated with hyperammonemia. In: Handbook of Clinical Neurology, Eds Vinken PJ, Bruyn GW, Amsterdam: Elsevier, Vol. 29, pp. 305–329.Find this resource:
Rey JM, Walter G (1997) Half a century of ECT use in young people. American Journal of Psychiatry 154:595–602.Find this resource:
Rhee BA, Kim TS, Kim GK, et al. (1995) Hemifacial spasm caused by cerebellopontine angle meningioma. Neurosurgery 36:393–395.Find this resource:
Richardson DA, Bexton RS, Shaw FE, et al. (1997) Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the Accident and Emergency Dept with “unexplained”or “recurrent falls”. Pains and Clinical Electrophysiol 20:820–823.Find this resource:
Ries RK (1985) DSM-III implications of the diagnoses of catatonia and bipolar disorder. Am J Psychiatry 142:1471–1474.Find this resource:
Rifkin A, Quitkin F, Klein DF (1975) Akinesia: a poorly recognised drug-induced extrapyramidal behavioural disorder. Arch Gen Psychiatry 32:672–674.Find this resource:
Ritchie RW (1970) Neurological sequela of amputation. Br J Hosp Med 6:607–609.Find this resource:
River Y, Honigman S, Gomori JM, et al. (1994) Superficial hemosiderosis of the central nervous system. Movement Disorders 9:559–562.Find this resource:
Roden DM (2008) Clinical practice. Long-QT syndrome. N Engl J Med 358:169–176.Find this resource:
Rodgers C (1992) Extrapyramidal side effects of antiemetics presenting as psychiatric illness. General Hospital Psychiatry 14:192–195.Find this resource:
Rogers AE, Meehan J, Guilleminault C, et al. (1997) HLA DR15 (DR2) and DQB1 0602 typing studies in 188 narcoleptic patients with cataplexy. Neurology 48:1550–1556.Find this resource:
Roggendorf J, Burghaus L, Liu WC, et al. (2007) Belly dancer's syndrome following central pontine and extrapontine myelinolysis. Mov Disord 22:892–894.Find this resource:
Rosebush PI, Hildebrand AM, Furlong B, et al. (1990) Catatonic syndrome in a general psychiatric inpatient population: frequency, clinical presentation and response to lorazepam. J Clin Psychiatry 51:357–362.Find this resource:
Rosebush PI, MacQueen GM, Clarke JT, et al. (1995) Late-onset Tay-Sachs disease presenting as catatonic schizophrenia: diagnostic and treatment issues. J Clin Psychiatry 56: 347–353.Find this resource:
Rosebush PI, Mazurek MF (1996) Catatonia after benzodiazepine withdrawal. Journal of Clinical Psychopharmacology 16:315–319.Find this resource:
Rosebush PI, Mazurek MF (1999) Catatonia: re-awakening to a forgotten disorder. Mov Disorders 14:395–397.Find this resource:
Rosebush PI, Stewart T (1989) A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry 146:717–725.Find this resource:
Rosler KM, Nirkko AC, Rihs F, et al. (1994) Motor-evoked responses to transcranial brain stimulation persist during cataplexy: a case report. Sleep 17:168–171.Find this resource:
Roth B (1957) Narcolepsy and hypersomnia from the aspect of physiology of sleep. Statni Zdravotnicke Nakladatelstvi (Prague). p. 331.Find this resource:
Roth B (1962) Narkolepsie und Hypersomnie vom Standpunkt der Physiologie des Schlafes. Berlin: VEB Verlag Volk und Gesundheit.Find this resource:
Rougier A, Claverie B, Pedespan JM, et al. (1997) Callosotomy for intractable epilepsy: overall outcome. Journal of Neurosurgical Sciences 41:51–57.Find this resource:
Ruby JR, Jannetta PJ (1975) Hemifacial spasm: ultrastructural changes in the facial nerve induced by neurovascular compression. Surg Neurol 4:369–370.Find this resource:
Rushworth RG (1961) Spasm of skeletal muscle. In: Proceedings of a Symposium on Skeletal Muscle Spasm, Riker Laboratories, pp. 9–29.Find this resource:
Rushworth RG, Smith SF (1982) Trigeminal neuralgia and hemifacial spasm. Med J Aust 1:424–426.Find this resource:
Russell JSR (1910) Facial spasm. In: A System of Medicine, Eds Allbutt C, Rolleston HD, London: Macmillan, Vol. 8, pp. 638–649.Find this resource:
Russell WR (1970) Neurological sequelae of amputation. Br J Hosp Med 6:607–609.Find this resource:
Russo LS (1979) The pathology of drop attacks? Neurology (NY) 29:1440.Find this resource:
Ryu H, Yamamoto S, Sugiyama K, et al. (1998[a]) Hemifacial spasm caused by vascular compression of the distal portion of the facial nerve. Journal of Neurosurgery 3:605–609.Find this resource:
Ryu H, Yamamoto S, Sugiyama K, et al. (1998[b]) Neurovascular decompression of the 8th cranial nerve in patients with hemifacial spasm and incidental tinnitus: an alternative way to study tinnitus. J Neurosurg 88:232–236.Find this resource:
Sakurai T, Amemiya A, Ishii M, et al. (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585.Find this resource:
Samii M (1981) Surgical treatment for hemifacial spasm. In: The Cranial Nerves, Eds Samii M, Jannetta PJ, Berlin: Springer, pp. 502–504.Find this resource:
Samii M, Matthies C (1995) Acoustic neurinomas associated with vascular compression syndromes. Acta Neurochir 134:148–154.Find this resource:
Sandman CA (1988) ß-endorphin disregulation in autistic and self-injurious behavior: a neurodevelopmental hypothesis. Synapse 2:193–199.Find this resource:
Sandyk R, Gillman MA (1987) Baclofen in hemifacial spasm. Int J Neurosci 33:261–264.Find this resource:
Sassim N, Grohmann R (1988) Adverse drug reactions with clozapine and simultaneous application of benzodiazepines. Pharmacopsychiatry 21:306–307.Find this resource:
Scharf MB, Lai AA, Branigan B, et al. (1998) Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients. Sleep 21:507–514.Find this resource:
Schultze F (1875) Linksseitiger facialiskrampf in folge eines aneurysma der arteria vertebralis sinistra. Archiv Pathol Anat 65:385–391.Find this resource:
Scoville WB (1969) Partial extracranial section of seventh cranial nerve for hemifacial spasm. Journal of Neurosurgery 31:106–108.Find this resource:
Segawa M, Nomura Y (1992) Polysomnography in the Rett syndrome. Brain and Development 14:S46–54.Find this resource:
Seidman MS, Vacharat N (1980) Idiopathic hemifacial spasm treated with alcohol injection. Ophthalmic Surg 11:109–111.Find this resource:
Selky AK, Purvin VA (1994) Hemifacial spasm. An unusual manifestation of idiopathic intracranial hypertension. J Neuro-Ophthalmology 14:196–198.Find this resource:
Shamim EA, Hallett M (2007) Intramedullary spinal tumor causing “belly dancer syndrome”. Mov Disord 22:1673–1674.Find this resource:
Shan DE, Kwan SY, Ho HH, et al. (1996) Belly dystonia induced by levodopa and biperiden in a case of suspected multiple-system atrophy. Movement Disorders 11:455–456.Find this resource:
Shaywitz BA (1974) Hemifacial spasm in childhood treated with carbamazepine. Arch Neurol 31:63.Find this resource:
Sheehan S, Bauer RB, Meyer JS (1960) Vertebral artery compression in cervical spondylosis. Neurology (Minneap) 10:968–986.Find this resource:
Sheldon JH (1948) The Social Incidence of Old Age: Report of an Inquiry in Wolverhampton, London: Oxford University Press.Find this resource:
Sheldon JH (1960) On the natural history of falls in old age. Br Med J 2:1685–1690.Find this resource:
Shiloh R, Schwartz B, Weizman A, et al. (1995) Catatonia as an unusual presentation of posttraumatic stress disorder. Psychopathology 28:285–290.Find this resource:
Shimizu T (1998) Narcolepsy. A review. Japanese Journal of Clinical Medicine 56:376–381.Find this resource:
Shin JC, Chung UH, Kim YC, et al. (1997) Prospective study of microvascular decompression in hemifacial spasm. Neurosurgery 40:730–734.Find this resource:
Shinoda S, Tanaka K, Kawaguchi K (1998) A huge retrocerebellar arachnoid cyst with syringomyelia: case report. No To Shinkei Geka Neurological Surgery 26:363–367.Find this resource:
Sindou M, Rischer C, Derraz S, et al. (1996) Microsurgical vascular decompression in the treatment of FHS. A retrospective study of a series of 65 cases and review of the literature. Neuro-Chir 42:17–28.Find this resource:
Smith T (1983) Cataplexy in association with meningiomas. Acta Neurol Scand 94:45–47.Find this resource:
Spencer SS (1988) Corpus callosum section and other disconnection procedures for medically intractable epilepsy. Epilepsia 29:S85–89.Find this resource:
Spencer SS, Spencer DD, Williamson PD et al. (1985) Effects of corpus callosum section on secondary bilaterally synchronous interictal EEG discharges. Neurology 35:1689–1694.Find this resource:
Sprik C, Wirtschafter JD (1988) Hemifacial spasm due to intracranial tumour. An international survey of botulinum toxin investigators. Ophthalmology 95:1042–1045.Find this resource:
Stacey M, Cardoso F, Jankovic J (1993) Tardive stereotypy and other movement disorders in tardive dyskinesia. Neurology 43:937–941.Find this resource:
Starkstein SE, Petracca G, Teson A, et al. (1996) Catatonia in depression: prevalence, clinical correlates and validation of a scale. Journal of Neurology, Neurosurgery and Psychiatry 60:326–332.Find this resource:
Stauder KH (1934) Die tödliche katatonie. Arch Psych Nervenkr 102:614–634.Find this resource:
Steiner JL, DeJesus PV, Mancall EL (1974) Painful jumping amputation stumps: pathophysiology of a ‘sore circuits’. Trans Am Neurol Assoc 99:253–255.Find this resource:
Stevens DL, Matthews WB (1973) Cryptogenic drop attacks: an affliction of women. Brit Med J 1:439-442.Find this resource:
Stober G, Franzek E, Lesch KP, et al. (1995) Periodic catatonia: a schizophrenic subtype with major gene effect and anticipation. European Archives of Psychiatry and Clinical Neuroscience 245:135–141.Find this resource:
Sudo Y, Suhara T, Honda Y, et al. (1998) Muscarinic cholinergic receptors in human narcolepsy: a PET study. Neurology 51:1297–1302.Find this resource:
Sunderland S (1978) Nerve and Nerve Injuries, Edinburgh: Churchill Livingstone, pp. 421–447.Find this resource:
Szatmari P, Bremner R, Nagy J (1989) Asperger syndrome: a review of clinical features. Can J Psychiatry 34:554–560.Find this resource:
Takahashi T, Dohi S (1983) Hemifacial spasm: a new technique of facial nerve blockade. Br J Anaesth 55:333–337.Find this resource:
Takano S, Maruno T, Shirai S, et al. (1998) Facial spasm and paroxysmal tinnitus associated with arachnoid cyst of the cerebellopontine angle. Neurol Med Chir 38:100–103.Find this resource:
Tan EK, Jankovic J (1999) Bilateral hemifacial spasm: a report of five cases and a literature review. Mov Disord 14:345–349.Find this resource:
Teare JP, Hyams G, Pollock S (1993) Acute encephalopathy due to coexistent nicotinic acid and thiamine deficiency. British Journal of Clinical Practice 47:343–344.Find this resource:
Telischi FF, Grobman LR, Sheremata WA, et al. (1991) Hemifacial spasm. Occurrence in multiple sclerosis. Arch Otolaryngol-Head and Neck Surgery 117:554–556.Find this resource:
Temudo T, Ramos E, Dias K, et al. (2008) Movement disorders in Rett syndrome: an analysis of 60 patients with detected MECP2 mutation and correlation with mutation type. Mov Disord 23:1384–1390.Find this resource:
The Felbamate Study Group in Lennox-Gastaut Syndrome (1993) Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med 328:29–33.Find this resource:
Thomas A, Amyot R (1928) Un cas de trepidation du moignon. Rev Neurol 35:391–397.Find this resource:
Tinel J (1927) Un cas d'epilepsie du moignon. Rev Neurol 34:370–378.Find this resource:
Tinuper P, Cerullo A, Marini C, et al. (1998) Epileptic drop attacks in partial epilepsy: clinical features, evolution, and prognosis. Journal of Neurology, Neurosurgery and Psychiatry 64:231–237.Find this resource:
Topka H, Buchkremer G (1996) Katatonie, malignes neuroleptisches Syndrom und Myositis ossificans. Nervenarzt 67:413–417.Find this resource:
Toremalm NG, Elmqvist D, Elner A, et al. (1977[a]) Hemifacial spasm. Nerve block with phenol under electromyographic control. Acta Oto-Laryngol 83:341–348.Find this resource:
Toremalm NG, Elmqvist D, Elner A, et al. (1977[b]) Hemifacial spasm. Acta Oto-Laryngol 83:341–348.Find this resource:
Toru M, Matsuda O, Makiguchi K et al. (1981) Neuroleptic malignant syndrome-like state following withdrawal of antiparkinsonian drugs. J Nerv Ment Dis 169:324–327.Find this resource:
Tschanz JT, Rebec GV (1988) Atypical antipsychotic drugs unlock selective components of amphetamine-induced stereotypy. Pharmacol Biochem Behav 31:519–522.Find this resource:
US Modafinil in Narcolepsy Multicentre Study Group (1998) Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Annals of Neurology 43:88–97.Find this resource:
Van den Bergh P, Francart J, Mourin S et al. (1995) Five-year experience in the treatment of focal movement disorders with low-dose Dysport botulinum toxin. Muscle Nerve 18:720–729.Find this resource:
Van den Bienzenbos JB, Horstink MW, van de Vlasakker CJ, et al. (1992) A case of bilateral alternating hemifacial spasms. Mov Disord 7:68–70.Find this resource:
Van Norel GJ, Verhagen WIM (1996) Drop attacks and instability of the degenerate cervical spine. J Bone Joint Surg (British Volume) 78:495–496.Find this resource:
Vgontzas AN, Sollenberger SE, Kales A, et al. (1996) Narcolepsy-cataplexy and loss of sphincter control. Postgraduate Medical Journal 72:493–494.Find this resource:
Villard L, Nguyen K, Cardoso C, et al. (2002) Locus for bilateral perisylvian polymicrogyria maps to Xq28. Am J Hum Genet 70:1003–1008.Find this resource:
Vinard M (1927) Epilepsie du moignon d'origine tetanique. Rev Neurol 34:639–646.Find this resource:
Vitti MJ, Thompson BW, Read RC, et al. (1994) A carotid-subclavian bypass: a twenty-two year experience. Journal of Vascular Surgery 20:411–417.Find this resource:
Vossler DG, Wyler AR, Wilkus RJ, et al. (1996) Cataplexy and monoamine oxidase deficiency in Norrie disease. Neurology 46:1258–1261.Find this resource:
Wakasugi B (1972) Facial nerve block in the treatment of facial spasm. Arch Otolaryngol 95:356–358.Find this resource:
Wan M, Lee SS, Zhang X, et al. (1999) Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 65:1520–1529.Find this resource:
Wang A, Jankovic J (1998) Hemifacial spasm: clinical findings and treatment. Muscle and Nerve 21:1740–1747.Find this resource:
Ward A, Chaffman MO, Sorkin EM (1986) Dantrolene: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. Drugs 32:130–168.Find this resource:
Weller M, Kornhuber J (1992) Pathophysiologie und Therapie des malignen neuroleptischen Syndroms. Nervenarzt 63:645–655.Find this resource:
Wenk GL (1997) Rett syndrome: neurobiological changes underlying specific symptoms. Progress in Neurobiology 51:383–391.Find this resource:
Wenk GL (1996) Rett syndrome: evidence for normal dopaminergic function. Neuropediatrics 27:256–259.Find this resource:
Wenk GL (1995) Alterations in dopaminergic function in Rett syndrome. Neuropediatrics 26:123–125.Find this resource:
Williams D, Wilson TG (1962) The diagnosis of major and minor syndromes of basilar insufficiency. Brain 85:741–774.Find this resource:
Wilkinson M (1971) Cervical Spondylosis: Its Early Diagnosis and Treatment, Philadelphia: WB Saunders, Vol. 48, p. 67.Find this resource:
Wilson DH, Reeves AG, Gazzaniga MS (1982) Central commisurotomy for intractable generalised epilepsy: series two. Neurology 32:687–697.Find this resource:
Wilson SAK (1928) The narcolepsies. Brain 51:63–109.Find this resource:
Wing L, Attwood A (1987) Syndromes of autism and atypical development. In: Handbook of Autism and Pervasive Developmental Disorders, Eds Cohen DJ, Donnelan AM, Paul R, New York: John Wiley, pp. 3–19.Find this resource:
Wirtschafter JD, McLoon LK (1998) Long-term efficacy of local doxorubicin chemomyectomy in patients with blepharospasm and hemifacial spasm. Ophthalmology 105:342.Find this resource:
Witt-Engerstrom I, Hagberg B (1990) The Rett syndrome: gross motor disability and neural impairment in adults. Brain and Development 12:23–26.Find this resource:
Wizmann A, Dieckmann G (1982) Intracranial facial nerve decompression in the management of hemifacial spasm. Appl Neurophysiol 45:291–294.Find this resource:
Wolanczyk T, Komender J, Brzozowska A (1997) Catatonic syndrome preceded by symptoms of anorexia nervosa in a 14-year-old boy with arachnoid cyst. European Child and Adolescent Psychiatry 6:166–169.Find this resource:
Yeh H, Tew JM (1984) Tic convulsif, combination of geniculate neuralgia and hemifacial spasm. Neurology 682–684.Find this resource:
Yoss RE, Daly DD (1960) Narcolepsy. Med Clin N Amer 44:953–968.Find this resource:
Yuan Y, Wang Y, Zhang SX, Zhang L, Li R, Guo J. Microvascular decompression in patients with hemifacial spasm: report of 1200 cases. Chin Med J (Engl). 2005 May 20;118(10):833–6.Find this resource:
Zadikoff C, Mailis-Gagnon A, Lang AE (2006) A case of a psychogenic “jumpy stump”. J Neurol Neurosurg Psychiatry 77:1101.Find this resource:
Zafeiriou DI, Mauromatis IV, Hatjisevastou HK, et al. (1997) Benign congenital hemifacial spasm. Ped Neurol 17:174–176.Find this resource:
Zoghbi HY, Milstien S, Butler IJ, et al. (1989) Cerebrospinal fluid biogenic amines and biopterin in Rett's syndrome. Ann Neurol 25:56–60.Find this resource: