CASE: Confusion after discharge
Mr. G, age 37, is transferred to our medical center from a local hospital for treatment of altered mental status. His wife reports that 1 month ago he had been admitted to a different hospital for a heroin overdose. His urine toxicology screen then was positive for benzodiazepines, cocaine, and opioids. Mr. G’s 2-week stay was complicated by respiratory arrest, intubation, and mechanical ventilation. He also developed hypotension, acute renal failure, and aspiration pneumonia, but recovered.
His wife says 2 weeks after Mr. G was discharged home, she noticed he was becoming increasingly confused and forgetful. Initially she observed dificulty with short-term memory. He was involved in a motor vehicle accident far from home while reporting to a job he no longer held. She found him confused and watering the lawn in the rain. After she discovered him talking on the phone with no one on the line, she brought him to the emergency room (ER).
His urine toxicology screen was negative. Routine examination of cerebrospinal fluid and tests for glucose, protein, lactate, lactate dehydrogenase, red blood cell count, white blood cell count with differential, syphilis serology, Gram’s stain, and bacterial culture were negative.
Brain MRI showed diffuse new white matter signal abnormality superior to the tentorium of the cerebellum, suggestive of low-grade white matter ischemia or inflammation. Mr. G’s mental status did not improve in the ER, and he was transferred to our facility.
The authors’ observations
Based on abnormal brain imaging findings, we initially suspect a type of white matter disorder ( Table 1 ).1 We attempt to conduct a thorough history.
Table 1
Differential diagnoses: Types of white matter disorders
| Category | Example |
|---|---|
| Genetic | Metachromatic leukodystrophy |
| Demyelinative | Multiple sclerosis |
| Infectious | AIDS dementia complex |
| Inflammatory | Systemic lupus erythematosus |
| Toxic | Toluene leukoencephalopathy |
| Metabolic | Vitamin B12 deficiency |
| Vascular | Binswanger’s disease* |
| Traumatic | Traumatic brain injury |
| Neoplastic | Gliomatosis cerebri |
| Hydrocephalic | Normal pressure hydrocephalus |
| *Degenerative dementia caused by thinning of subcortical white matter of the brain | |
| AIDS: acquired immune deficiency syndrome | |
| Source: Reference 1 | |
HISTORY: Missing information
Attempts to obtain collateral information are largely unsuccessful. Mr. G denies having a history of medical or psychiatric illness. He is vague about substance use but may have a history of opioid and cocaine dependence and alcohol abuse. He says he takes no prescribed or over-the-counter medications and has no known drug allergies.
Mr. G’s wife provides limited additional information. She married Mr. G 6 months ago; before that, he was in jail for 3.5 years for unclear reasons. He is unemployed, and the couple has no children.
Mr. G’s wife reports that Mr. G’s father had a history of diabetes mellitus and dialysis and died in his 40s from “Staph infection of the brain.” Mr. G is estranged from his mother. He has no family history of neurologic or psychiatric illness.
Mr. G’s wife denies that her husband has had recent fever, chills, weight loss, nausea, vomiting, diarrhea, or skin rash. He has no history of alcohol withdrawal symptoms, seizures, headache, diplopia, vertigo, hearing loss, swallowing difficulty, focal weakness, or sensory or speech changes. She did not notice personality or behavior changes in her husband before his recent confusion.
The authors’ observations
During our interview, Mr. G maintains minimal eye contact. His speech is minimal with impaired fluency; he responds to questions with 1- or 2-word answers. He describes his mood as “fine” but exhibits an incongruent and constricted affect, alternately laughing and crying. We are unable to assess his thought process and content because Mr. G is emotionally labile and unable to respond rationally to many of our questions. Mr. G’s insight and judgment are poor. His hygiene, grooming, and teeth also are poor, and he is wearing diapers for bowel/bladder incontinence.
Mr. G scores 9/30 on the Mini-Mental State Exam (MMSE), indicating severe cognitive impairment. He is not oriented to place or time, and cannot:
- spell “world” backwards
- subtract serial 7s from 100
- repeat the phrase “no ifs, ands, or buts”
- name 5 U.S. cities
- write any words
- copy a figure of intersecting pentagons.
Neurologic exam reveals apathy, inattention, impaired executive function, and generalized hyperreflexia with bilateral unsustained ankle clonus and Babinski’s sign. In addition, Mr. G has a snout reflex, bilateral hand and foot grasping, and bilateral palmomental reflexes but no mydriasis or nasal septum perforation. Repeat MRI shows the same white matter changes.
Based on Mr. G’s history and brain imaging findings, we suspect that he is suffering from toxic leukoencephalopathy. He meets these diagnostic criteria:
- documented exposure to a toxin
- neurobehavioral deficits
- neuroradiologic abnormalities.2
Toxic leukoencephalopathy can be caused by environmental exposure, radiation, chemotherapy, or substance abuse.3 Because Mr. G has a history of substance abuse, we believe his symptoms developed as a result of heroin vapor inhalation.