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 53-year-old man was admitted to the Neurology Department of Farabi Hospital (Kermanshah, Iran) with walking inability and recognition disorder. Patient history showed that he had referred to hospital with vomiting, vertigo and headache 8 months before after consumption of two sachet of levamisole (for veterinary use) which each sachet contained 1.5 gram of levamisole hydrochloride. One month later, he had been stricken by progressive walking inability and recognition disorder up to administration to our hospital. The patient had not any previous illness.\nOn neurologic examination, he was confused and did not establish a good relationship with the bystander. On mental and cognitive power examinations, using the Mini Mental State Examination (MMSE), he earned 17 points (out of a total score of 30) with no signs of meningeal irritation (such as stiffness of neck). In addition, cranial nerves were normal. The power of limbs was within normal range but deep tendon reflexes in all of four limbs had increased in conjunction with extensor plantar response and reduced abdominal skin reflex. The patient had primitive reflexes including grasp, snout and palmomental. On cerebellar examination, finger to nose test and heel to shin was impaired and the gait was ataxic.\nOn the initial laboratory tests, complete blood count (CBC), blood sugar, urea, creatinine, and liver enzymes were normal. In cerebrospinal fluid analysis, color, pressure, cells, and sugar were normal but protein was increased (69 mg/dl). Oligoclonal band (OGB) was negative.\nOn electroencephalography (EEG), bilateral paroxysmal slow waves were seen. In visual evoked potential (VEP), there was a bilaterally prolonged P100 latency. Brain magnetic resonance imaging (MRI) showed mild cerebral atrophy and multiple focal lesions distributed in periventricular and cerebellar white matter and also in pons and midbrain (). These lesions had low-signal intensity on T1-weighted images and high-signal intensity in fluid-attenuated inversion recovery (FLAIR) view and T2-weighted images.\nFollowing clinical examinations and ruling out of other causes, including infectious and vascular causes, trauma and metabolic, central nervus system (CNS) vasculitis and paraneoplastic syndromes; and according to the patient's history, the patient was diagnosed as multifocal inflammatory leukoencephalopathy following levamisole consumption. The patient did not give consent for brain biopsy.\nThe patient was treated with intravenous methylprednisolone (500 mg) every 12 hours for 7 days followed by two weeks oral consumption of the prednisolone (50 mg/day) during hospitalization. No change was noticed in cerebellar signs and gait disorder but a brief improvement was seen in mentality and cognition after 1 and 3 months. After a month of treatment, MRI did not show a reduction or remission of the lesions. ()