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 25-year-old man with history of cocaine use presented to the emergency room with left-sided upper and lower limb weakness as well as sensory impairment involving the face. Symptoms evolved such that he was bed-ridden after 48 h. He had no history of previous neurological or systemic symptoms. Computed tomography (CT) of the brain showed bilateral periventricular hypodensities. CT angiography of cervical and intracranial vessels was unremarkable. An MRI study of the brain demonstrated increased FLAIR signal deep in the right and left hemispheres (Fig. ), which also displayed patchy gadolinium enhancement (Fig. ) and restricted diffusion (Fig. –). Five days after admission he developed swallowing difficulty, dysarthria, and confusion. In addition to the previously noted MRI abnormalities, repeat imaging showed new lesions in the left internal and external capsules, putamen and corona radiata, right medial pons and left cerebellar peduncle, with heterogenous gadolinium enhancement (Fig. –). The neuroradiological impression was that the lesions were most compatible with demyelinating disease. A urine screen was positive for cocaine, cannabinoids, and oxycodone, and negative for amphetamine, methadone, benzodiazepines, and barbiturates. Other investigations included the following normal or negative results: complete blood count, serum electrolytes, urea, creatinine, glucose, erythrocyte sedimentation rate, antinuclear antibodies, rheumatoid factor, perinuclear and cytoplasmic anti-neutrophil cytoplasmic antibodies (pANCA and cANCA respectively), extractable nuclear antigens, lupus inhibitor, C3, C4, CH50, urinalysis, vitamin B12, angiotensin converting enzyme level, thyroid stimulating hormone level, free T3 and T4, cortisol level, lipid profile, very long chain fatty acids, viral serology for HIV, CMV, Hepatitis A, B, and C, Lyme serology, syphilis screen, blood screen for salicylate, acetaminophen, and ethanol. Liver enzymes (AST, ALT and GGT) were mild to moderately elevated and subsequently normalized over a period of six months. Cerebrospinal fluid (CSF) results included: slightly elevated protein at 0.50 g/l (normal 0.20–0.40 g/l), normal glucose and chloride, normal total cell count (3 × 106/l), negative oligoclonal bands, normal IgG index, elevated albumin index at 9.0 (2.7–4.7), negative cryptoccocal antigen, negative cultures for bacteria and fungi, negative polymerase chain reaction (PCR) studies for CMV and HSV 1–2, and normal cytology.\nHe was treated with intravenous methylprednisolone, 1000 mg daily for five consecutive days, and subsequently underwent plasma exchange. During plasma exchange his neurological condition stabilized and he subsequently achieved good, albeit partial, recovery. At three months follow-up he had mild residual left-sided hemiplegia but was otherwise independent in activities of daily living and starting to return to work. Follow up MRI five months after presentation showed reduction in the size of lesions, no enhancement, and no new lesions (Fig. –). MRI 21 months after the initial presentation also showed no new lesions (not shown).