Intravenous Thrombolysis for Stroke and Presumed Stroke in Human Immunodeficiency Virus-Infected Adults: A Retrospective, Multicenter US Study.

BACKGROUND AND PURPOSE: Human immunodeficiency virus (HIV) infection has been shown to increase both ischemic and hemorrhagic stroke risks, but there are limited data on the safety and outcomes of intravenous thrombolysis with tPA (tissue-type plasminogen activator) for acute ischemic stroke in HIV-infected patients. METHODS: A retrospective chart review of intravenous tPA-treated HIV patients who presented with acute stroke symptoms was performed in 7 large inner-city US academic centers (various search years between 2000 and 2017). We collected data on HIV, National Institutes of Health Stroke Scale score, ischemic stroke risk factors, opportunistic infections, intravenous drug abuse, neuroimaging findings, and modified Rankin Scale score at last follow-up. RESULTS: We identified 33 HIV-infected patients treated with intravenous tPA (mean age, 51 years; 24 men), 10 of whom were stroke mimics. Sixteen of 33 (48%) patients had an HIV viral load less than the limit of detection while 10 of 33 (30%) had a CD4 count <200/mm3. The median National Institutes of Health Stroke Scale score at presentation was 9, and mean time from symptom onset to tPA was 144 minutes (median, 159). The median modified Rankin Scale score for the 33-patient cohort was 1 and for the 23-patient actual stroke cohort was 2, measured at a median of 90 days poststroke symptom onset. Two patients had nonfatal hemorrhagic transformation (6%; 95% confidence interval, 1%-20%), both in the actual stroke group. Two patients had varicella zoster virus vasculitis of the central nervous system, 1 had meningovascular syphilis, and 7 other patients were actively using intravenous drugs (3 cocaine, 1 heroin, and 3 unspecified), none of whom had hemorrhagic transformation. CONCLUSIONS: Most HIV-infected patients treated with intravenous tPA for presumed and actual acute ischemic stroke had no complications, and we observed no fatalities. Stroke mimics were common, and thrombolysis seems safe in this group. We found no data to suggest an increased risk of intravenous tPA-related complications because of concomitant opportunistic infections or intravenous drug abuse.

Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

BACKGROUND: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized ß = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized ß = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

Exploring the effect of glatiramer acetate on cerebral gray matter atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS). DESIGN/METHODS: We studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups. RESULTS: During the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5). CONCLUSIONS: In this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course.

Traumatic Rupture of a Skull Base Dermoid Cyst Mimicking Chronic Meningitis.

Cranial dermoid cysts are rare, embryologic tumors containing fat, hair, and other ectodermal elements. They occur most frequently in the posterior fossa and are typically diagnosed as incidental findings on brain imaging done for an unrelated reason. Traumatic rupture of a previously unidentified intracranial dermoid cyst can mimic symptoms of post-concussion syndrome and should be ruled out with magnetic resonance imaging (MRI). Surgical intervention after traumatic rupture may not result in complete symptom control due to the persistence of dermoid cyst debris in the subarachnoid space. Here, we present the clinical scenario and radiological features of a ruptured dermoid cyst due to trauma, highlighting a rare complication of a classically benign lesion.

Extended B-cell depletion beyond 6-months in patients receiving ocrelizumab or rituximab for CNS demyelinating disease.

OBJECTIVES: To investigate the duration of B-cell depletion in a cohort of patients receiving ocrelizumab or rituximab for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD). METHODS: We retrospectively searched our database for patients diagnosed with MS or NMOSD, who were receiving ocrelizumab or rituximab and had available CD19 measurements. We collected demographic data, infusion doses, infusion dates, CD19 absolute counts and percentages, and their collection dates. We paired each infusion with the subsequent CD19 measurements recorded before the next infusion, discarding measurements done during a washout period of 30 days after each infusion. We applied three definitions for B-cell depletion, the most stringent of which was an absolute B-cell count ≤20 cells/uL. RESULTS: From 695 patients with demyelinating diseases in our database, over the period of January 1st 2010 to March 1st 2020, we identified 188 patients (178 with MS and 10 with NMOSD), who had received ocrelizumab or rituximab and had available CD19 measurements. 1054 CD19 measurements were captured. B-cell depletion, as defined above, was recorded as far out as 22.8 months after an ocrelizumab infusion, and 22.3 months after a rituximab infusion. Out of 90 B-cell measurements done ≥8 months (>210 days) after ocrelizumab infusion, 45(50%) measurements showed B-cell depletion. Similarly for rituximab, out of 113 measurements, 49(43%) showed B-cell depletion. CONCLUSIONS: This study demonstrates that B-cell depletion after ocrelizumab and rituximab continues beyond the traditional 6-month re-infusion interval in many patients. Our report provides data that can support clinical trials testing increasing the interval of re-infusion with ocrelizumab and rituximab beyond 6-months guided by B-cell measurements.

A Multifaceted Approach to Improving Postischemic Stroke Dysphagia Screening at a Community Hospital.

BACKGROUND: Dysphagia is a common complication seen in acute ischemic stroke patients, and can lead to morbidity and mortality. As such, quality measures have been instituted to track adherence to dysphagia screening in all stroke patients. In our 217-bed community hospital, we were faced with a low rate in successfully screening for dysphagia. METHODS: Quality control interventions were implemented after an analysis of the reasons for dysphagia screening failures was performed. Interventions included online educational sessions for nurses, face-to-face sessions with medical residents, distribution of educational laminated cards, changing the method of documenting the dysphagia screen in our electronic record and others. RESULTS: There was an increase of rates of screening for dysphagia from 67% to 91%. CONCLUSION: We conclude that failure analysis, implementation of quality control measures to address the cause of failures and re-evaluating success rates periodically was effective to address this problem.

Unilateral Relapsing Primary Angiitis of the CNS: An Entity Suggesting Differences in the Immune Response Between the Cerebral Hemispheres.

OBJECTIVE: To determine whether studying patients with strictly unilateral relapsing primary angiitis of the CNS (UR-PACNS) can support hemispheric differences in immune response mechanisms, we reviewed characteristics of a group of such patients. METHODS: We surveiled our institution for patients with UR-PACNS, after characterizing one such case. We defined UR-PACNS as PACNS with clinical and radiographic relapses strictly recurring in 1 brain hemisphere, with or without hemiatrophy. PACNS must have been biopsy proven. Three total cases were identified at our institution. A literature search for similar reports yielded 4 additional cases. The combined 7 cases were reviewed for demographic, clinical, imaging, and pathologic trends. RESULTS: The median age at time of clinical onset among the 7 cases was 26 years (range 10-49 years); 5 were male (71%). All 7 patients presented with seizures. The mean follow-up duration was 7.5 years (4-14.1 years). The annualized relapse rate ranged between 0.2 and 1. UR-PACNS involved the left cerebral hemisphere in 5 of the 7 patients. There was no consistent relationship between the patient's dominant hand and the diseased side. When performed (5 cases), conventional angiogram was nondiagnostic. CSF examination showed nucleated cells and protein levels in normal range in 3 cases and ranged from 6 to 11 cells/µL and 49 to 110 mg/dL in 4 cases, respectively. All cases were diagnosed with lesional biopsy, showing lymphocytic type of vasculitis of the small- and medium-sized vessels. Patients treated with steroids alone showed progression. Induction therapy with cyclophosphamide or rituximab followed by a steroid sparing agent resulted in the most consistent disease remission. CONCLUSIONS: Combining our 3 cases with others reported in the literature allows better clinical understanding about this rare and extremely puzzling disease entity. We hypothesize that a functional difference in immune responses, caused by such discrepancies as basal levels of cytokines, asymmetric distribution of microglia, and differences in modulation of the systemic immune functions, rather than a structural antigenic difference, between the right and left brain may explain this phenomenon, but this is speculative.

IgG4-related disease of the central and peripheral nervous systems.

IgG4-related disease can involve nearly any organ system, including the central and peripheral nervous systems. The pathology findings are consistent from organ to organ, but careful clinicopathological correlation is necessary to establish the diagnosis. Many non-neurological and neurological inflammatory conditions, previously regarded as idiopathic in nature, are now recognised to fall within the spectrum of IgG4-related disease. The condition is highly treatable, but probably remains substantially under-recognised. In this Review, we offer an important and timely update on the current and emerging aspects of this neurological disease. Following a short overview of IgG4-related disease, we describe the current understanding of neurological findings, pathophysiology, approaches to diagnosis, and treatment of IgG4-related disease affecting the central and peripheral nervous systems.

Fibrocartilaginous embolism: a comprehensive review of an under-studied cause of spinal cord infarction and proposed diagnostic criteria.

BACKGROUND: Most spinal cord infarctions are due to aortic pathologies and aortic surgeries. Fibrocartilaginous Embolism (FCE) has been reported to represent 5.5% of spinal cord infarctions. Some believe that FCE is more common than presumed and is rather under-diagnosed due to vagueness surrounding its clinical presentation. METHOD: A literature search was conducted for case reports of FCE published before August 2014. PubMed, the Cochrane Central Register and Google Scholar were searched for different combinations of the key words "fibrocartilaginous, "nucleus pulposus", "embolism", "spinal cord", "inter-vertebral disc", "infarction", "stroke", "paraplegia", "quadriplegia", "myelopathy". RESULT: Fifty-five case articles were reviewed, ten of which were translated from foreign languages. A total of 67 cases of FCE were found, 41 tissue-confirmed and 26 clinically suspected. A comprehensive summary of the clinical anatomy, patho-physiologic mechanisms, epidemiology, diagnosis and treatment of FCE is described, along with the conflicting opinions on its incidence and relevance after reviewing all of the related literature. The 41 tissue proven cases are summarized and a schematic approach to the clinical diagnosis of FCE, deducted from their clinical findings, is presented. CONCLUSION: FCE of the spinal cord, often mis-diagnosed as transverse myelitis, may be more common than presumed. Future research into FCE, including the development of a chondrolytic therapy that can be given empirically upon its clinical suspicion to acutely reverse its symptoms, may be of value.