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ObjectiveTo provide a detailed analysis of the clinical features and course of ischemic stroke secondary to sarcoidosis of the CNS and to observe the effects of immunosuppression in the prevention of recurrent cerebrovascular disease.BackgroundCerebrovascular disease is rarely reported in neurosarcoidosis and constitutes one of its least well-described forms, though recognition for it has grown in the last decade with recent studies estimating a higher frequency of occurrence than previously known.Design/MethodsPatients with ischemic stroke were included if the mechanism was directly attributable to sarcoidosis of the CNS. Patients were excluded if an alternative stroke etiology was of equal or higher likelihood than CNS sarcoidosis.ResultsNeurologic disease was the initial presenting manifestation of sarcoidosis in 8/11 (72.7%), and ischemic stroke was an inaugural manifestation of sarcoidosis in 4/11 (36.4%). Small vessel disease was the predominant ischemia subtype (10/11, 90.9%) with pontine perforating vessels (6/11, 54.5%) and lenticulostriate arteries (3/11, 27.3%) being the vessels most often affected. Vessels with a more rostral supratentorial distribution were uncommonly affected. Common neuroinflammatory accompaniments included leptomeningitis (10/11, 90.9%) and cranial nerve disease (4/11, 36.4%). Recurrent strokes occurred in 8/11 (72.7%), and recurrent neuroinflammation occurred in 7/11 (63.6%). Antiplatelet drugs were used in 6/11 (54.5%). Most patients (10/11, 90.9%) required at least two lines of immunosuppression to achieve inflammatory disease remission in this context; infliximab was the most successfully employed immunosuppressant (7/8 treatment courses, 87.5%). The presenting median modified Rankin Scale score of 4.0 improved to 2.0 over a median period of follow-up of 52.0 months.ConclusionsIschemic strokes in neurosarcoidosis occur in a caudal-to-rostral distribution, tend to affect small caliber blood vessels that lack collateral blood flow, and typically associate with inflammatory leptomeningeal disease.

A 23-year-old woman with a history of uncomplicated migraine headaches presented with 2 days of headache. Her typical migraines were preceded by visual aura and usually resolved after taking a triptan. This headache was different in that there was no preceding aura, it did not respond to Imitrex, and it was accompanied by nausea/vomiting, dizziness, subjective fevers, and binocular vertical diplopia. She had had a mild upper respiratory tract infection 1 week prior to presentation. She had no sick contacts or recent travel history. Initial bedside examination showed hypertropia OD (figure 1) that did not change with direction of gaze. The degree of hypertropia improved with supine positioning. Her extraocular movements were otherwise not restricted, and her pupillary responses were normal. She had no other abnormalities on her neurologic examination.

Neuro-Sweet disease (NSD) should be considered in any patient with a history of Sweet syndrome who presents with neurologic symptoms.

A 40-year-old man presented with altered mentation, preceded a few days earlier by a 38°C fever and shortness of breath. He was diagnosed “....influenza A pneumonia, of the H3N2 subtype, with parainfectious...” hemorrhagic encephalitis and required intubation for hypoxia and depressed consciousness. Brain MRI showed numerous hemorrhages (figure 1). He received oseltamivir, switched to peramivir for better gut absorption. He was discharged to rehabilitation 1 month later. At 6-month follow-up (figure 2), he had residual deficits in memory and concentration. Montreal Cognitive Assessment score was 28/30. He returned to full-time work as a financial manager at 9 months, and felt subjective normal cognition at 1.5 years after onset.

Objective:To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor–α.Methods:Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.Results:Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24–71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4–8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location.Conclusions:Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments.Classification of evidence:This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

Background: Cognitive impairment continues to be a significant neurologic complication of HIV infection and has been associated with oxidative stress-induced neuronal injury. Selegiline is an MAO-B inhibitor with antioxidant and neurotrophic properties. This rationale has led to the design and implementation of this Selegiline Transdermal System (STS) study with the primary aims of assessing safety and tolerability of STS as well as improvement in cognitive performance. Methods: HIV-1 infected individuals with impaired cognitive functioning were enrolled in this placebo-controlled, three-arm study of STS across 17 sites. Cognitive impairment was determined using a standard battery of neuropsychological tests. Subjects were randomized to receive STS 3 mg/24 hours, STS 6 mg/24 hours, or matching placebo patches daily. The primary efficacy endpoint was defined as the change in neuropsychological composite Z-score (NPZ-6) from baseline to week 24. Measures of safety included frequencies of adverse experiences and abnormal results on laboratory tests. Results: A total of 128 subjects (88% men, 51% white) were enrolled, median age 45 years. Most subjects (62%) had mild to moderate AIDS dementia complex. The 24-week NPZ-6 median (interquartile range) changes were 0.22 (−0.28, 0.55) for the selegiline 3 mg/24 hours arm, 0.21 (−0.18, 0.62) for the selegiline 6 mg/24 hours arm, and 0.28 (−0.16, 0.64) for the placebo arm (a positive score indicates improvement from baseline) ( p = 0.914). Severe laboratory abnormalities were few and occurred in similar proportion among the three treatment arms. Conclusion: Selegiline was safe and well tolerated by HIV-infected individuals with cognitive impairment and mild to moderate immune suppression; however, no cognitive or functional improvement was observed in this phase II study.

A 44-year-old man presented with 2 weeks of progressive right body numbness, weakness, and circumferential burning sensation around his trunk. MRI spine demonstrated longitudinally extensive myelitis (figure 1). MRI brain and laboratory investigations were normal except for CSF lymphocytic pleocytosis (9 leukocytes/mm3). CT revealed hilar and mediastinal lymphadenopathy, which on biopsy showed noncaseating granulomas suggestive of sarcoidosis. As the patient had multiple clinical relapses on steroids, he was treated with infliximab infusions (5 mg/kg every 4 weeks) and had complete clinical and radiologic resolution after 1 year (figure 2). Myelitis as the presenting feature of sarcoidosis is exceptionally rare and responds to infliximab.1,2

A 34-year-old woman presented initially with meningococcal meningitis and with Streptococcus mitis meningitis 6 months later. A right cribriform plate area meningoencephalocele was discovered on MRI at the second episode. In retrospect, this abnormality was present on initial MRI (figure). The patient recalled intermittent watery rhinorrhea for 1 year preceding the first meningitis episode, but without head trauma. The anterior cranial fossa defect was repaired, without recurrence of rhinorrhea or meningitis in 2-year follow-up.

Objective: To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations. Methods: Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent 1H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification. Results: Both N-acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4+ T lymphocytes and a higher number of CD8+ T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8+ T cells, especially effector CD8+ T cells. Conclusions: These results verify metabolism changes occurring in the brain early during HIV infection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8+ T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus–host interactions involved in CNS functional deficits.

A 44-year-old right-handed homosexual man was referred for gradual deterioration of skills as a chef, impairment of memory, and decreased fluency and comprehension of speech. He had prominent personality change from an easygoing nature to irritability and anxiety. Over a year, his mental abilities deteriorated such that he was unable to drive a car, maintain a job, or live independently. He had no prior neurologic, psychiatric, or systemic illness. Episodes of agitation, confusion, and body tremors appeared 1.5 years after onset. Evaluation by a neurologist at that time at another hospital revealed disorientation, disinhibition, poor attention and recall, tremors during handwriting, and motor impersistence. Mini-Mental State Examination score was 23 out of 30. There was diffuse cerebral atrophy on MRI (figure, A), and the EEG was normal. CSF had protein of 97 mg/dL, 1 WBC/mm3, and many oligoclonal bands. CSF Venereal Disease Research Laboratory test (VDRL), CSF 14-3-3 level, serum HIV and Lyme antibody, toxicology screen, thyroid and liver functions, …

A 41-year-old man required right hemicraniectomy for cerebral edema from intracranial abscesses. Four months later, he had worsening left-sided weakness attributed to communicating hydrocephalus (figure, A). A large volume lumbar puncture led to clinical improvement, but 5 days …