A. Introduction. Altered mental status has a wide variety of causes, ranging from metabolic derangements (e.g., alcohol withdrawal) to acute focal brain lesions (e.g., stroke) to chronic neurodegenerative diseases (e.g., Alzheimer’s dementia).
Two keys to diagnosing neurologic conditions are: (1) distinguish between a focal deficit, delirium, and dementia; and (2) determine the onset and time course of the presenting complaints.
a. Delirium is an alteration in mental status that is characterized by acute onset, fluctuating course, impaired attention, and either a disturbance in the level of consciousness or disorganized thinking.
i. History regarding the relatively acute onset and fluctuating course is usually obtained from family members or care providers. Sudden onset is uncommon; gradual impairment is often the rule, and symptoms will typically develop over hours or days.
ii. Patients with impaired attention have difficulty keeping track of a conversation and are easily distractible.
iii. A disturbance in the level of consciousness may span the spectrum from may span the spectrum from hypervigilant to severe somnolence.
iv. Disorganized thinking is manifested by rambling or irrelevant speech or an illogical flow of ideas, often resulting in the inability to obtain a coherent history from the patient. Other cognitive deficits in delirium may involve orientation, memory, judgment, abstract thinking, recognition, language skills, or personality.
b. A focal lesion that results in aphasia or other higher cognitive deficits (e.g., apraxia, neglect) can mimic delirium. However, it is uncommon for a focal lesion to result in isolated cognitive symptoms without other focal neurologic signs such as motor, sensory, or visual deficits. A careful neurologic examination will help identify subtle focal signs in patients with altered mental status to differentiate an acute focal lesion from other causes of altered mental status such as delirium or dementia. The most common type of focal lesion—acute stroke—typically has a sudden onset and is associated with additional neurologic findings.
c. Dementia. If the change in mental status presents as a slow deterioration in cognition and appears chronic, it is much more likely to be dementia. However, patients with dementia can also have superimposed delirium, and thus the two diagnoses are not mutually exclusive.
Patients with dementia are at high risk for developing a concomitant delirium.
B. Causes of Acutely Altered Mental Status. The mnemonic “MIST-P” is a useful way to help remember a long list of differential diagnoses and roughly divides the causes into three broad classes:
a. Metabolic, Infectious, Inflammatory, and Inherited disorders—this broad group is responsible for most cases of altered mental status, most commonly resulting in delirium.
b. Seizures and Structural problems (stroke/vascular disorders, Tumor, Trauma)—these are focal lesions.
c. Psychiatric disorders.
Medicines: medications that are either directly psychoactive (e.g., benzodiazepines) or have significant cognitive side effects (e.g., anticholinergics)
Electrolyte derangements (e.g., disorders of sodium, magnesium, or calcium)
Endocrine disorders (increased or decreased levels of glucose, cortisol, thyroid hormone)
Temperature derangements (i.e., hypothermia or hyperthermia)
Alcohol and other drugs, either in toxicity or causing a withdrawal syndrome
B12 and other vitamin deficiencies, (e.g., niacin deficiency [pellagra] or thiamine deficiency [Wernicke-Korsakoff syndrome])
Oxygen deficiency or hypercarbia (oxygen deficiency may result from insufficient oxygen in the blood [i.e., hypoxemia], an inadequate number of red blood cells (RBCs) to carry the oxygen [i.e., anemia], or insufficient forward flow [i.e., decreased cardiac output])
Liver or kidney disease causing encephalopathy
Infectious disorders either affecting the central nervous system (CNS) directly (e.g., encephalitis, brain abscess, prion disease) or a distant/systemic site (e.g., sepsis, urinary tract infection)
Inflammatory (e.g., collagen vascular diseases, sarcoidosis, autoimmune encephalitis [such as anti-NMDA receptor encephalitis])
Inherited or degenerative diseases (e.g., Huntington’s disease, Alzheimer’s disease)
Seizures (actively seizing or due to a postictal state)
Strokes and other vascular disorders
Bleeds (epidural, subdural, subarachnoid, or intracerebral)
Thrombotic thrombocytopenic purpura (TTP) or disseminated intravascular coagulation (DIC)
Hyperviscosity syndrome (seen with plasma cell dyscrasias or significantly elevated RBC counts)
Tumors: malignant processes may lead to altered mental status either because of an intracranial lesion or because of a paraneoplastic process
Trauma (e.g., concussion)
Although a single cause of altered mental status is sought, a combination of factors is often responsible (e.g., a urinary tract infection in an older adult who has Alzheimer’s disease and is receiving multiple medications).
C. Approach to the Patient. Given the wide variety of potential causes as well as the potential consequences of an incorrect or delayed diagnosis, all patients with altered mental status should be evaluated in a thorough and systematic manner. In addition to MIST-P, consider the following potential causes of altered mental status:
Consider Creutzfeldt-Jacob disease (CJD) in older adults who present with rapidly progressive dementia and myoclonus.
Consider anti-NMDA receptor encephalitis in a woman with delirium and an ovarian mass.
a. Perform the ABCs.
i. Airway. Consider intubation if the airway appears compromised, especially if the Glasgow Coma Scale score is less than 8.
ii. Breathing. Consider intubation.
iii. Circulation. Check vital signs.
b. Assess the need for intravenous access and fluids, oxygen, and electrocardiographic monitoring.
c. Rule out easily reversible conditions.
i. Thiamine (100 mg IV) is usually given to rule out Wernicke’s psychosis.
ii. 50% dextrose (D50) can be given empirically when a fingerstick test for glucose is not readily available or if severe hypoglycemia (e.g., an insulin-dependent diabetic patient found down) is possible.
Hypoglycemia can look just like an acute stroke.
iii. Naloxone hydrochloride should be administered if an opiate overdose is suspected. Rapid improvement in mental status with administration of naloxone is both diagnostic and therapeutic for opioid overdose.
Remember to always carefully consider all the medications a patient has been receiving as a potential cause of altered mental status.
d. Rule out common, immediately life-threatening conditions. Check the pupils, corneal reflexes, oculocephalic reflex, gag, motor response, meningeal signs, and vital signs, looking for evidence of any of the following disorders:
i. Mass effect. If mass effect (e.g., tumor, infarct, bleed, abscess) is suspected, make arrangements for emergent neuroimaging and neurosurgical evaluation. Mannitol, steroids, or intubation with hyperventilation may be indicated if increased intracranial pressure is contributing to the presentation.
ii. Meningitis. Initial measures include lumbar puncture, blood cultures, and early empiric antibacterial therapy (see Chapter 87).
iii. Status epilepticus. Benzodiazepines are first-line treatment, and speed of administration is essential. Intravenous (IV) lorazepam or diazepam (intramuscular [IM] midazolam is an option if IV access is not immediately available) are first-line options. If seizure activity does not immediately cease, fosphenytoin, valproic acid, or levetiracetam are administered (see Chapter 85) in addition to repeated doses of benzodiazepines.
iv. Hypertensive encephalopathy. Nitroprusside is often administered to reduce systemic pressure.
v. Hyperthermia. Cooling measures should be initiated.
e. Continue the workup if the cause of altered mental status is still not apparent.
i. Patient history and physical examination. Perform a thorough examination, with particular focus on the neurologic examination and a search for occult infection.
ii. Laboratory studies. The following studies are often useful:
1. Complete blood count (CBC)
2. Electrolyte panel (including glucose and calcium)
3. Blood urea nitrogen (BUN) and creatinine levels
4. Liver tests
5. Prothrombin time (PT) and partial thromboplastin time (PTT)
6. Arterial blood gases (possibly including carboxyhemoglobin)
7. Toxicology screen
iii. Other studies. An electrocardiogram (EKG), chest radiograph, and lumbar puncture (with an opening pressure) should be urgently obtained if meningitis/encephalitis is clinically suspected. These tests can be obtained less urgently if they are part of the evaluation of altered mental status without a clearly defined etiology. Additional tests—such as head computed tomography (CT), magnetic resonance imaging (MRI) scan, and electroencephalogram (EEG)—may be appropriate.
iv. Neurology consult. Consultation with a neurologist may be necessary if the diagnosis still cannot be made.
f. Treatment of delirium involves a three-tiered approach:
i. Treat the underlying cause whenever possible.
ii. Nonpharmacologic measures. Frequently reorient patients, use sitters and family members, provide eyeglasses and hearing aids, avoid restraints and Foley catheters, and maintain normal sleep-wake cycles.
iii. Pharmacologic measures. Use only if delirium is disrupting necessary medical care or compromising patient safety. Low doses of antipsychotics (e.g., haloperidol) are preferred. Benzodiazepines should be reserved for cases of alcohol withdrawal, as their use in other conditions may perpetuate or worsen delirium.
Suggested Further Readings
Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults. Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr 2016;16:48–61.Find this resource:
Mathai SK, Josephson SA, Badlam J, Saint S, Janssen WJ. Scratching below the surface. N Engl J Med 2016;375:2188–93.Find this resource:
Mitchell SL. Advanced dementia. N Engl J Med 2015;372:2533–40.Find this resource:
Zenilman ME. Delirium: an important postoperative complication. JAMA 2017;317:77–8.Find this resource: