Delirium and Acute Personality Changes (Continued)

Substance abuse very frequently leads to various confusional presentations. The use of illicit substances and overuse of alcohol are usually denied in medical settings; however, ingestion of toxins and drug overdose, either recreational or suicidal, should be considered in all cases of delirium. Alcohol, barbiturates, and benzodiazepines all have life-threatening withdrawal syndromes, as well as syndromes of intoxication. Antipsychotics are not a treatment for withdrawal syndromes. Replacement therapy and controlled taper for alcohol, benzodiazepine, and barbiturate-dependent patients are lifesaving.

Very rarely, anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis, a novel and significantly underdiagnosed diffuse encephalopathy, manifests primarily (80%) in women with a combination of psychosis, including catatonia, as well as dyskinesias, memory deficits, and convulsions. The abnormal movements are varied, often including oral-lingual-facial akathisia but also choreoathetosis, dystonia, oculogyric crisis, dystonia, rigidity, and opisthotonos. Often, there is a less than 2-week history of a prodromal febrile illness, including headache and respiratory or gastrointestinal symptoms. This anti-NMDAR encephalitis is either a paraneoplastic disorder, secondary to an underlying ovarian teratoma, or a primary autoimmune disorder occurring in young adults or children. This is potentially reversible if recognized early and treated with surgery and/or immunosuppression. Prognosis largely depends on adequate immunotherapy and, in paraneoplastic cases, complete tumor removal.

Regardless of the individual case, a comprehensive history, examination, and review of the medical record must be completed to determine the underlying cause(s). Seizures and focal signs on examination require brain imaging (magnetic resonance imaging [MRI]/computed tomography [CT]) and/or electroencephalography (EEG) to assess for acute structural lesions, infection, or inflammation. The nature of the patient’s underlying medical condition requires standard laboratory tests, including blood cultures as well as cerebrospinal fluid examination to demonstrate evidence of possible systemic infections, electrolyte disturbance, volume depletion, liver failure, uremia, thyrotoxicosis, and other systemic disorders.

The examiner must consider potential permanently damaging conditions, such as thiamine deficiency (Wernicke encephalopathy), herpes encephalitis, or NMDAR encephalitis, all requiring emergent therapy. A careful review of medications and toxicology screens is essential. Drug toxicity accounts for 30% of delirium cases; over-the-counter drugs, such as diphenhydramine, require attention, and other specific drug syndromes exist as well. When no mechanism is identified for the acute personality change, particularly in young women, abdominal/pelvic imaging studies as well as anti-NMDAR autoantibodies must be evaluated in serum or cerebrospinal fluid to exclude anti-NMDAR encephalitis.

Antipsychotic medications can precipitate the neuroleptic malignant syndrome, a triad of acute confusion, rigidity, and hyperthermia. Antipsychotic medications, often useful for behavioral control of an agitated patient, may also cause their own behavioral syndrome of severe motor restlessness, or akathisia, which is usually accompanied by markedly increased muscular tone and cramping. Combinations of antidepressants, migraine medications, and some antibiotics can trigger the serotonin syndrome, causing a triad of confusion, autonomic instability, and clonus. Lithium, along with other narrow-window therapeutic drugs, such as digitalis, can cause delirium even with levels in the recommended therapeutic range. Lithium toxicity usually manifests with vomiting or diarrhea, severe tremors, and ataxia, whereas digitalis toxicity often causes paranoia and hallucinations. Serum levels of any drug the patient is taking should be checked when available, and all nonessential medications should be held.

Treatment of delirium requires identification of the underlying medical problem, judicious use of psychoactive medication to keep the patient and others safe from aberrant behavior, and maintaining a peaceful environment. The presence of delirium is a well-established source of increased morbidity and mortality—and a syndrome in urgent need of a diagnosis.

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