Brainstem syndromes typically cause ipsilateral cranial nerve lesions and contralateral long tract signs. They are commonly due to brainstem ischaemia, but can also be caused by neoplasia, demyelination, infective and hamartomatous lesions. Imaging, ideally with MRI rather than CT, is obligatory and only then—and possibly following other investigations to identify systemic abnormality or cerebrospinal fluid changes—can appropriate therapy be introduced.
Particular brainstem syndromes
These include: (1) Thalamic syndrome—typically presents with unpleasant dysaesthetic burning pain, often following a hemiplegic and hemianaesthetic stroke. First-line treatment is with centrally acting analgesic agents, e.g. amitriptyline. (2) Midbrain syndromes—characterized by contralateral long tract signs and ipsilateral defects of the third and fourth cranial nerves. (3) Pontine syndromes—present with ipsilateral cerebellar signs, abnormalities of ocular movements, and contralateral paralysis and impairment of sensation, with details of the deficits depending on the location of the lesion within the pons. (4) Medullary syndromes—(a) medial—causes paralysis of the tongue on the side of the lesion, with contralateral paralysis of the arm and leg, and impaired proprioception over the contralateral half of the body; (b) lateral—causes ipsilateral Horner’s syndrome, vocal cord paralysis, limb ataxia and sensory loss, oscillopsia and nystagmus, and contralateral impairment of pain and thermal sensation.
The classic presentation of brainstem syndromes, including the long tracts and deficits of cranial nerve nuclei, commonly causes crossed cranial nerve and motor or sensory long tract deficits; the cranial nerve lesions are ipsilateral to the lesion and the long tract signs are contralateral. It is important to assess the extracranial vascular supply to the posterior circulation, especially to listen for bruits over the subclavian vessels and to record the pulse and blood pressure in both upper limbs, remembering that the vertebral arteries arise from the subclavian vessels. Apart from the cranial nerve and long tract deficits, there may be ataxia, vertigo, the presence of an internuclear ophthalmoplegia and unreactive pupils, the symptoms of diplopia and oscillopsia, and the finding of nystagmus or ocular paresis.
The circulation to the brainstem is supplied by the vertebral arteries, which are the main arteries to the medulla, and then the basilar artery, which supplies the pons and midbrain. The vertebral arteries are frequently asymmetrical and commonly give rise to the large posteroinferior cerebellar arteries shortly before they join to form the basilar artery. The vertebral arteries are susceptible to trauma within the cervical spine, but the most common lesion affecting the vertebral arteries is dissection, which is probably under-recognized, and thrombosis.
The basilar artery branches are paramedian, supplying the area of the pons close to the midline, the short circumferential branches that supply the lateral two-thirds of the pons, the long circumferential branches that are the supero- and anteroinferior cerebellar arteries, and several interpeduncular branches that arise at the bifurcation of the basilar artery and supply the subthalamic and high midbrain regions.
Strokes in the posterior circulation account for 20% of all ischaemic cerebro-vascular disease. Although most brainstem syndromes are due to vascular or inflammatory demyelinating lesions, an increasing proportion are shown on MRI to be due to cavernomas, which may or may not calcify and which were impossible to diagnose before modern imaging. The management of such cavernomas is difficult and may involve surgery or stereotactic radiotherapy. A small proportion of lesions in the brainstem are infective and inflammatory; occasionally a causative organism, commonly an adenovirus, can be identified, and may be seen as a complication of AIDS; when no identifiable infective agent is identified, the condition is termed ‘Bickerstaff’s encephalitis’.
The brainstem syndromes
Commonly seen in children under the age of 3 years, Russell’s syndrome consists of emaciation with increased appetite, euphoria, vomiting, and excessive sweating. There may also be motor hyperactivity. The differential diagnosis includes hyperthyroidism, diabetes mellitus, a tumour in the region of the fourth ventricle, such as a malformation of the great vein of Galen, and a hypothalamic tumour.
There may often be optic atrophy and rarely nystagmus. Investigation may show an elevated serum growth hormone and an MRI will show a hypothalamic mass lesion. Although contraindicated if there is a significant structural pathology, the cerebrospinal fluid may contain malignant cells or an excess of human chorionic gonadotropin in the case of germinoma.
Originally described by Dejerine and Roussy in 1906, thalamic pain has a particularly distressing quality. Sometimes spontaneously, but commonly after a recognized hemiplegic and hemianaesthetic stroke, the patient develops altered sensation in a hemisensory distribution together with unpleasant dysaesthetic burning pain (thalamic pain). The pain may be worsened by stimulation and is associated with hemianaesthesia, sometimes proprioceptive loss, and some evidence of hemiparesis. Anatomically the lesion is usually in the ventroposterolateral nucleus of the thalamus and is commonly caused by either a vascular event or a tumour. The investigation required is imaging and therapy is with centrally acting analgesic agents, such as amitriptyline, carbamazepine, gabapentin, and pregabalin. When pain is intractable, deep brain stimulation to the ventroposteromedial nuclei may be considered.
There is a rare syndrome associated with damage at the level of the inferior colliculi, due to either neoplasia or vascular lesions, which results in bilateral deafness with associated difficulty in coordination, weakness, and vertigo. The condition must be differentiated from bilateral conductive hearing loss, cochlear disorders, bilateral cranial nerve VIII lesions, and pure word deafness. Brain imaging will identify the lesion.
Thalamic stroke syndrome
Lesions affecting the thalamus are commonly vascular and arise from infarction within the distribution of the posterior communicating artery, the basilar, and the anterior and posterior choroidal arteries. There is usually hemiparesis with hemianopia, hemianaesthesia, and sometimes hemiataxia. There is often confusion and disorientation, and there may be language disturbance. On occasion there may be vertical gaze ophthalmoplegia, loss of pupillary reflexes, and an inability to converge the eyes. There may also be memory impairment and on occasions visual perceptual disturbances are recorded.
Damage to areas of the midbrain is characterized by long tract signs contralateral to the lesion with defects of cranial nerves III and IV ipsilaterally. They may occur with lesions in the brainstem or as the evolution of symptoms of rostrocaudal deterioration associated with supratentorial brain swelling (Figs. 24.9.1 and 24.9.2). They are characterized by ipsilateral cranial nerve III and IV palsies together with contralateral hemiparesis, loss of vibration, proprioception, and stereognosis, contralateral loss of pain and temperature, and an ipsilateral Horner’s syndrome. Ataxia may occur and there can be eyelid ptosis, diplopia, supranuclear horizontal-gaze paresis, and an internuclear ophthalmoplegia. The association of an ipsilateral oculomotor palsy with a crossed hemiplegia due to a lesion at the base of the midbrain is called Weber’s syndrome. Claude’s syndrome causes an ipsilateral oculomotor palsy with contralateral cerebellar ataxia and tremor, and is due to a lesion in the tegmentum of the midbrain involving the red nucleus and nerve III nucleus. Benedikt’s syndrome also involves the tegmentum of the midbrain, resulting in an oculomotor palsy with contralateral cerebellar ataxia, tremor, and corticospinal signs; it can be regarded as a combination of Claude’s and Weber’s syndromes. Nothnagel’s syndrome occurs with unilateral or bilateral involvement of nerve III nucleus together with the superior cerebellar peduncle and causes bilateral ptosis, paralysis of gaze, and cerebellar ataxia.
Damage in the region of the dorsal midbrain results in Parinaud’s syndrome in which there is paralysis of upward gaze due to damage to the supranuclear mechanisms for upward gaze, loss of accommodation, and fixed pupils. Although this may be seen with ischaemic lesions, it is more common with pineal tumours.
Lesions in the pons and medulla are commonly identified as involving either the medial or the lateral aspect of the brainstem, depending upon whether the paramedian or short circumferential vessels from the basilar have been involved. In the pons the following three levels of damage can be identified and the basal syndrome can occur at any level.
Superior pontine syndrome
The medial superior pontine syndrome results in ipsilateral cerebellar ataxia, internuclear ophthalmoplegia, and palatal and pharyngeal myoclonus with contralateral paralysis of face, arm, and leg, and sometimes loss of sensation contralaterally. The lateral superior syndrome causes ataxia of the limbs and gait with dizziness, nausea, and vomiting; there is horizontal nystagmus, paresis of conjugate gaze towards the side of the lesion, loss of optokinetic nystagmus, and sometimes skew deviation of the eyes. There may also be an ipsilateral Horner’s syndrome, and there is contralateral loss of pain and thermal sensation on the face and limbs with impaired touch, vibration, and position sense (Fig. 24.9.3).
The medial, midpontine syndrome causes ipsilateral ataxia of the limbs and gait with contralateral paralysis of the face, arm, and leg, deviation of the eyes away from the lesion, and variably impaired sensation contralaterally. The lateral syndrome at this level causes ataxia of the limbs on the side of the lesion together with paralysis of the muscles of mastication and impaired sensation over the face on the same side due to damage to cranial nerve V (Figs. 24.9.4 and 24.9.5).
Inferior pontine syndrome
The medial syndrome causes paralysis of conjugate gaze to the side of the lesion, nystagmus, ataxia of limbs on the same side, and double vision on gaze to that side. Contralaterally there is paralysis of the face, arm, and leg, with impaired touch and proprioception over the opposite side of the body. The lateral syndrome involves ipsilateral, horizontal, and vertical nystagmus with vertigo and nausea, ipsilateral facial paralysis, paralysis of conjugate gaze to the side of the lesion, deafness, tinnitus, and ataxia on the side of the lesion, with impaired sensation of the face on that side. On the opposite side there is impaired sensation over half the body (Fig. 24.9.6).
Basal pontine syndrome (locked-in syndrome)
Bilateral lesions of the paramedian vessels from the basilar, commonly seen in patients with hypertension, result in infarction of the basal pontine and cause quadriplegia with loss of the ability to speak. The ascending reticular activating system is intact and consciousness is therefore preserved. Vertical eye movements and eye closure are all that are possible and under voluntary control in the ‘locked-in syndrome’.
Bilateral lesions of the long descending tracts in the brainstem can result in pseudobulbar palsy, although this condition is more commonly seen with lesions higher in the cerebrum. The symptoms are those of spastic dysarthria, dysphagia, bilateral facial weakness with quadriparesis, and emotional lability.
The medial medullary syndrome may occur with occlusion of the vertebral artery or a branch of the lower basilar artery; it causes paralysis and atrophy of the tongue on the side of the lesion with contralateral paralysis of the arm and leg but sparing the face and impaired tactile proprioceptive sensation over the contralateral half of the body.
The lateral medullary syndrome, eponymously called Wallenberg’s syndrome, occurs most commonly with dissection or occlusion of the vertebral artery, resulting in ischaemia into the posteroinferior cerebellar artery; this causes pain, numbness, and impaired sensation of the ipsilateral half of the face with ataxia of limbs on that side, the symptoms of vertigo and nausea, double vision, and oscillopsia, and the signs of nystagmus. There is an ipsilateral Horner’s syndrome, often dysphagia with paralysis of the vocal fold ipsilaterally, and loss of sensation on the arm, trunk, and leg. There is contralateral impaired pain and thermal sensation over half the body and possibly the face (Fig. 24.9.7).
A syndrome involving ipsilateral cranial nerve VII and VI palsies with a contralateral hemiplegia is called the Millard–Gubler syndrome; the involvement of cranial nerve X, causing paralysis of the soft palate and vocal fold with contralateral hemianaesthesia, is termed Avellis’s syndrome and is due to a lesion in the tegmentum of the medulla.
Investigations and treatment
Brainstem syndromes occurring on a vascular basis are increasingly easy to diagnose because of MRI and MR angiography. Once a brainstem lesion is suspected, its detection and identification will require neuroimaging, preferably by MR techniques including diffusion weighted imaging (DWI) and perfusion studies. The use of newer techniques in CT imaging with dual energy and iterative reconstruction makes CT perfusion more usable and both MRI and CT complement interventional radiology. Interventional angiography may be used to direct the delivery of fibrinolytic agents, attempt the rescue of an embolus, or stent a narrowed portion of the vertebral or basilar artery but such techniques remain the subject of controlled trials and benefit is not yet established.
Other investigations, e.g. to search for systemic disease including vasculitis, immunodeficiency, or sources of emboli, may also be required. Vascular lesions within the brainstem often carry a remarkably good prognosis, but, if the syndrome appears to be evolving, the possibility of anticoagulation must be considered. In those lesions in which damage affects the medulla, it may be important to protect the airway and avoid aspiration during the early phases of the illness.
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