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 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).