A 29-year-old man was referred to the emergency department (ED) due to severe headache and behavioral changes.\nThe symptoms had started 12 days before admission with the headache considered as migraine and treated by oral pain killers. The patient came back to the ED 2 days later with persisting headache and right-sided paresthesia. Brain computed tomography (CT) failed to reveal any abnormality, and the patient was sent home again with nonsteroidal anti-inflammatory drugs and tramadol.\nTwo days later, he developed severe behavioral and cognitive changes with incomprehensible vocalizations, anterograde amnesia, aggressiveness towards his family members, and agitation. Sleeping rhythm was inverted with alternating periods of apathy/somnolence and agitation.\nPatient's medical history was unremarkable, and he did not take any medication. Occasional use of tobacco and alcohol was reported. We learned from his father that he had started regular cocaine consumption 3 months ago but should have stopped about one week before admission.\nOn admission, the patient was awake, but disorientated in time and place, and did not properly answer to questions. There was no sign of lateralization and cerebellar tests were normal. Neck stiffness and photophobia were noted.\nRoutine laboratory investigations were unremarkable, as well as blood and urine toxicological screening. Repeated brain CT was also normal. Lumbar puncture showed a normal opening pressure, and cerebrospinal fluid (CSF) analysis revealed 7 mononuclear cells/mm3 and a high protein level at 224 mg/dL. The albumin quotient was highly increased (37.9, normal value <6.5 under 40 years of age), confirming, together with the further brain magnetic resonance imaging (MRI) findings, significant alteration of the blood-CSF barrier permeability. Microbiological and viral CSF tests were negative. No CSF-specific IgG oligoclonal bands were found. As infectious encephalitis was ruled out, antimicrobial and antiviral therapy was interrupted.\nWhile staying in the ICU, the patient had been less agitated but remained disoriented in time and space and had suffered from transcortical sensitive aphasia. Brain MRI was performed 14 days after symptom onset which showed ubiquitous small lesions within white matter displaying high signal intensity on diffusion-weighted images and water diffusivity restriction on apparent diffusion coefficient (ADC) maps. The radiologist initially considered the hypothesis of disseminated ischemic foci due to cocaine-related vasoconstriction (not illustrated). Brain MRI examination was repeated after 3 days and showed numerous additional punctate lesions involving the corpus callosum, together with abnormal meningeal enhancement and contrast agent leakage in the CSF (Fig. ).\nRetinal fluoroangiography revealed multiple segmental occlusions of the central retinal artery (Fig. ), and an audiogram showed bilateral but asymmetric sensorineural hearing loss, with a left predominance.\nAfter the diagnosis of SS, bolus corticosteroid therapy was initiated using methylprednisolone 1 g daily for 5 days, followed by tapering oral doses. Toxicological investigations were completed by hair analysis using ultra-performance liquid chromatography tandem mass spectrometry operating in positive electrospray mode (Quattro Premier, Waters, Milford, MA, USA). Hair samples were cut into six segments of 1 cm, and the presence of cocaine, levamisole, opioids, and several amphetamines was investigated. Only cocaine together with metabolites, levamisole, and tramadol were detected. Quantification was possible using deuterated analogues: cocaine-D3 for cocaine and norcocaine, benzoylecgonine-D8 for benzoylecgonine, methylecgonine-D3 for methylecgonine, 6-acetylmorphine-D6 for levamisole, and tramadol-D3 for tramadol. The following concentration ranges were found in the hair: cocaine (>5,000 pg/mg), benzoylecgonine (>5,000 pg/mg), methylecgonine (68–113 pg/mg), norcocaine (581 to >1,000 pg/mg), levamisole (73–139 pg/mg), and tramadol (1,378–2,155 pg/mg). The patient was transferred from our institution to a rehabilitation center 13 days after admission. Cognitive status progressively improved, but the patient remained dysexecutive and had features of frontal lobe syndrome. Five weeks after discharge, the patient presented with a subacute left-eye central scotoma and altitudinal visual field deficit while still on a daily oral dose of 16 mg methylprednisolone. New retinal branch artery occlusions were documented on fluoroangiography (Fig. ). However, brain MRI did not show additional microvascular ischemic lesions when compared to previous examination, and lepto-meningeal enhancement had significantly decreased (not shown). This relapse (or progression of the initial lesions) was again treated by repeated methylprednisolone pulse therapy followed by oral tapering. Immunosuppressive treatment with mycophenolate mofetil was started. At 10-month follow-up, the patient was asymptomatic. He resumed work and did not report any residual cognitive deficit, as confirmed by neuropsychological testing performed 3 months after the initial episode.
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 ().