A 41-year-old woman presented to the emergency room of another hospital with recent confusion and impaired balance. She had been using cocaine daily for seven months. MRI FLAIR images showed multiple white matter signal changes in both cerebral hemispheres in a predominantly periventricular distribution (Fig. –) sparing the corpus callosum, cerebellum and brainstem. Restricted diffusion was present in many lesions (not shown). Subtle gadolinium enhancement was present in a few lesions (not shown). She was treated with supportive care for one week and then discharged with partial recovery. She resumed cocaine use and was then admitted to our centre six weeks after the previous hospital discharge because of worsening neurological symptoms. She was completely bedridden with inability to walk, incontinence, severely impaired communication skills, behavioural problems, cognitive impairment, and multifocal neurological deficits. MRI FLAIR images showed marked progression compared to the previous study. Confluent white matter abnormalities involved both cerebral hemispheres (Fig. –). There was subtle scattered restricted diffusion and no gadolinium enhancement. Urine testing was positive for cocaine, oxycodone, opiates, benzodiazepines, tramadol and citalopram, and negative for cannabinoids, amphetamine and methadone. Other investigations included the following normal or negative results: complete blood count, electrolytes, glucose, liver enzymes, thyroid stimulating hormone, T3, T4, creatinine kinase, angiotensin converting enzyme, HIV, Hepatitis A, B, and C screens, Lyme serology, syphilis screen, blood screen for salicylates, acetaminophen and ethanol. The serum creatinine was elevated (137 micromoles/l) as was the urea (7.6 millimoles/l). Serum albumin was low (29 g/l). The erythrocyte sedimentation rate ranged from 22 to 64 on multiple samplings, C-reactive protein was elevated at 11 mg/l while antinuclear antibodies, pANCA, cANCA, C3, C4, NMDA receptor and anti-thyroid peroxidase antibodies were normal. The vitamin B12 level was low at 166 picomole/l (normal >180). Copper, zinc and ceruloplasmin levels were normal. CSF protein was slightly elevated at 0.48 g/l. The glucose, chloride and cell count (4 × 106/l) were normal. No CSF acid fast bacilli were seen and cultures for bacteria and fungi were negative. CSF PCR for CMV and HSV1–2 were negative. She was treated with intravenous methylprednisolone, 1000 mg/day for five days, and plasma exchange. She showed substantial, albeit partial, recovery soon thereafter which continued over the course of several months. At four months follow-up multiple domains of cognitive function were improved but she had some residual deficits in attention, calculation, and visuospatial function. She was independent with respect to walking and most activities of daily living. Follow-up MRI at that time showed improvement of the subcortical and periventricular signal abnormalities and no new lesions. Similarly, no new lesions were seen on MRI 13 months after presentation (not shown).
A 57-year-old man with substance abuse disorder was brought by his family to the emergency room because of strange behavior. Five days prior to admission, he fell off his bicycle and came home with a scalp laceration on the left side of the head. Since then, his family noticed him acting oddly. He was seen walking back and forth in the house between the front door and the back door. He emptied the ice tray and he poured sugar into a shopping bag for no reason. He could no longer perform habitual tasks, such as cooking. His family described his gait as slow “like a zombie.” It was also unusual for him not to leave the house 5 days in a row. He does not see a primary care physician. According to his family, he smoked tobacco regularly (2 packs/day for 40 years), consumed alcohol rarely, and abused marijuana and cocaine.\nThe patient did not complain of headache, nausea, dizziness, and so on; he thinks nothing is wrong with him. Blood pressure was 187/104 mm Hg, heart rate 77 beats/min, respiratory rate 16 breaths/min, temperature 36.6°C, and blood oxygen saturation 100%. Criteria for hypertensive emergency or urgency were not met. He was awake and alert with normal thought content and intact ability to answer questions, but his affect was flat, he was indifferent to his condition, and he exhibited psychomotor retardation. On neurological examination, he was oriented to self, place, and immediate situation, but was oblivious of the month, day, and year. His ability to concentrate was mildly impaired and he pauses frequently when speaking; nevertheless, speech and language function were intact. Cranial nerve functions and motor strength were all normal. Deep tendon reflexes were brisk (3+) in all extremities. Ankle clonus and Babinski sign were absent. Cerebellar signs were also absent. Head computed tomography showed mild diffuse brain atrophy. Blood counts and chemistry were all normal except for mild hyperammonemia (39 µmol/L).\nHe was admitted to the neurology service. Urine was positive for cocaine and benzodiazepine, but only cocaine was found significant on quantitative analysis (levamisole was not tested). Additional studies, including thyroid stimulating hormone; folate; B12; HgbA1C; HIV; hepatitis panel; heavy metal screen for lead, arsenic, and mercury; and blood toxicology for ethanol, methanol, salicylates, acetaminophen, and so on, were all negative. Brain MRI revealed diffuse confluent subcortical white matter hyperintensities on T2-FLAIR and diffusion-weighted imaging (DWI) with low-apparent diffusion coefficient (ADC) in some areas (restricted diffusion) and high ADC in other areas (T2 shine-through effect). The cerebral cortex, cerebellum, basal ganglia, thalamus, and brainstem were all normal (). EEG showed mild diffuse slowing with inordinate amounts of theta waves intermixed with low-voltage beta and alpha activity (). Lumbar puncture was considered but not pursued because we were convinced that he has cocaine-induced TL and we could not justify exposing him to the risk of brain herniation. Albeit infrequent, brain herniation may occur with diffuse brain edema (eg, liver failure).\nImmunosuppressive therapy in cocaine-induced TL has been associated with a favorable or unfavorable outcome (see “Introduction”). Notwithstanding this uncertainty, we chose to treat the patient with a 5-day course of prednisone because of the extent of his disease. Prednisone 60-mg qd was administered on hospital day 4, tapered to 20 mg qd over 5 days, and stopped on hospital day 9. Nutritional therapy and assistance with activities of daily living resulted in gradual normalization of mental status and behavior. After 3 weeks in acute care, the patient was discharged to a rehabilitation facility. He missed his appointments and was seen again in clinic after 5 months. His family pointed out that his cognitive function returned to normal 2 weeks after he was discharged from acute care and at that point he started engaging again in the activities of daily living. During clinic visit, he reported (and his family agreed) that he no longer takes cocaine and other drugs of abuse. Neurological examination and cognitive evaluation did not detect any abnormalities. Follow-up brain MRI showed complete absence of diffusion restriction and near-100% resolution of white matter hyperintensity (). Follow-up EEG showed normal alpha rhythm posteriorly and normal beta activity anteriorly during wakefulness ().