The core mission of National Institute of Neurological Disorders and Stroke (NINDS) is twofold. First, NINDS seeks fundamental knowledge about the brain and nervous system. Second, NINDS aims to use that knowledge to reduce the burden of neurological diseases. In support of its mission, NINDS performs and funds basic, translational, and clinical neuroscience research on more than 600 neurological diseases, including genetic diseases (e.g. Huntington’s disease; muscular dystrophy), developmental disorders (e.g. cerebral palsy), neurodegenerative diseases (e.g. Parkinson’s disease; Alzheimer’s disease; multiple sclerosis), metabolic diseases (e.g. Gaucher’s disease), cerebrovascular diseases (e.g. stroke; vascular dementia), trauma (e.g. spinal cord and head injury), convulsive disorders (e.g. epilepsy), infectious diseases (e.g. AIDS dementia) and brain tumors. Common marmosets (Callithrix jacchus) offer unique, powerful advantages to both components of the NINDS mission. In support of the first component, marmosets are particularly well suited for neuroanatomical and functional brain studies, as their brains retain the typical anatomical and functional organization of the primate brain. A major advantage is that the marmoset is a lissencephalic primate, which greatly facilitates the mapping of functional brain areas by neuroimaging techniques, such as fMRI and optical imaging, as well as by electrophysiology, with high spatial resolution. In support of the second component, marmosets are excellent models of neurological disorders. Unlike rodents, marmosets are outbred and every individual is genetically different. Further, the marmoset brain has a gray-to-white matter ratio comparable to humans, which strongly facilitates modeling diseases such as multiple sclerosis and small vessel disease. The species also exhibits the breadth of cognitive sophistication that distinguishes primates from other taxonomic groups. Finally, geneedited marmosets can be generated with an intergeneration time and establishment of transgenic lines 2-3 times faster than other primate species, which makes marmosets be the ideal primate species for the development of genetically engineered lines. For all of the above reasons, marmosets are poised to be a central player to advance the core mission of the NINDS.

National Institute of Neurological Disorders and Stroke

B cells play a central role in the pathogenesis in multiple sclerosis (MS), being involved in the activation of proinflammatory T cells, secretion of proinflammatory cytokines, and production of autoantibodies directed against myelin. Hence, the usage of B-cell-depleting monoclonal antibodies as therapy for autoimmune diseases including MS lay near at hand. Rituximab was the first therapeutic B-cell-depleting chimeric monoclonal antibody to be used successfully in MS. Ocrelizumab, a second-generation humanized anti-CD20 antibody, was explored in a large phase II, randomized, placebo-controlled multicentre trial in patients with relapsing-remitting disease. Compared with placebo, two doses of ocrelizumab (600 and 2000 mg on days 1 and 15) showed a pronounced effect on disease activity seen in magnetic resonance imaging (MRI) as gadolinium-enhanced lesions (89% and 96% relative reduction, both p < 0.001) and also had a significant effect on relapses. In exploratory analyses, both doses of ocrelizumab had better effect on gadolinium-enhanced lesions than interferon beta-1a intramuscularly that was used as a reference arm. Adverse effects were mainly infusion-related reactions, in particular during the first infusion. Serious infections occurred at similar rates in ocrelizumab and placebo-treated patients, and no opportunistic infections were reported. However, progressive multifocal leukoencephalopathy (PML) has been reported in patients treated with anti-CD20 monoclonal antibodies for other indications. Other anti-CD20 monoclonal antibodies have been tested as treatments for MS, including ofatumumab that has shown beneficial results in placebo-controlled phase II trials in patients with relapsing-remitting MS. Ocrelizumab is now in phase III development for the treatment of relapsing-remitting MS, as well as primary progressive MS, and the results of ongoing clinical trials are eagerly awaited and will determine the place of ocrelizumab in the armamentarium of MS therapies.

https://journals.sagepub.com/doi/pdf/10.1177/1756285615601933

The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects

Cladophialophora bantiana is a phaeoid fungus that only rarely has been isolated from sources other than the human brain. It has a particular tropism for the central nervous system (CNS). We have integrated and updated large-scale data related to several aspects of C. Bantiana and reviewed all the available reports on its cerebral infections, focusing on their geographical distribution, infection routes, immune status of infected individuals, type and location of infections, clinical manifestations and treatment and outcome, briefly looking over the spectrum of other disease entities associated with C. bantiana, that is, extra-cerebral and animal infections and on the environmental sources of this fungus. Among the agents of phaeohyphomycosis, a term used to describe an infection caused by a dark pigmented fungus, C. bantiana has some significant specific features. A total of 120 case reports were identified with a significantly higher percentage of healthy subjects than immune-debilitated patients (58.3% vs. 41.7%). Infections due to C. bantiana occur worldwide. The main clinical manifestations are brain abscess (97.5%), coinfection of brain tissue and meninges (14.2%) and meningitis alone (2.5%). Among immunocompetent patients, cerebral infection occurred in the absence of pulmonary lesions. The mortality rate is 65.0% regardless of the patient's immune status. The therapeutic options used include surgery or antifungals alone, and the combination of both, in most cases the fatal outcome being rapid after admission. Since the fungus is a true pathogen, laboratory workers should be made aware that BioSafety Level-3 precautions might be necessary.

/pdf/an-updated-comprehensive-systematic-review-of-251ox70f4b.pdf

An updated comprehensive systematic review of Cladophialophora bantiana and analysis of epidemiology, clinical characteristics, and outcome of cerebral cases.

Study objectives
The goal of this study was to identify publications in the medical literature that support the efficacy or value of Emergency Medicine (EM) as a medical specialty and of clinical care delivered by trained emergency physicians. In this study we use the term "value" to refer both to the "efficacy of clinical care" in terms of achieving desired patient outcomes, as well as "efficiency" in terms of effective and/or cost-effective utilization of healthcare resources in delivering emergency care. A comprehensive listing of publications describing the efficacy or value of EM has not been previously published. It is anticipated that the accumulated reference list generated by this study will serve to help promote awareness of the value of EM as a medical specialty, and acceptance and development of the specialty of EM in countries where EM is new or not yet fully established.

/pdf/the-efficacy-and-value-of-emergency-medicine-a-supportive-35e2nack8k.pdf

The efficacy and value of emergency medicine: A supportive literature review

Background Leptomeningeal inflammation is associated with increased cortical damage and worse clinical outcomes in MS. It may be detected on contrast-enhanced T2-FLAIR imaging as focal leptomeningeal contrast-enhancement (LME). Objective To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers. Methods PMS patients had a screening MRI to detect LME. Participants satisfying eligibility criteria underwent two IT administrations of 25 mg rituximab 2 weeks apart. Follow-up lumbar puncture and MRI were performed at 8 and 24 weeks after the first treatment. Results Of 36 patients screened 15 had LME, 11 consented, and 8 received study treatment. Mean age was 56.7 years and number of LME lesions ranged from 1 to 3. No serious adverse effects occurred. We noted profound reductions in peripheral B cells from baseline to week 2 and 8 with some return at week 24. We also observed transient reductions in CSF B cells and CXCL-13 levels with an increase in BAFF levels. However, the number of LME did not change following treatment. Conclusions IT rituximab was well tolerated in PMS patients and had transient effects on CSF biomarkers but did not change LME.

Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.

Rituximab has demonstrated a major effect in B-cell lymphoma and in a wide range of autoimmune disorders.Unfortunately, the blood-brain-barrier excludes the disorders restricted to the central nervous system (CNS) from the actionof rituximab. The progressive phase of multiple sclerosis (MS) is a prototypical CNS autoimmune disorder characterizedby an intrathecal compartmentalization of inflammation resisting all the available immunosuppressive treatments. Asa consequence, intrathecal therapeutics are promising new approach in progressive MS. We first review data gatheredfrom animal models and human off-label intrathecal rituximab use in CNS lymphomas, then summarize the recent evidencesupporting the need for trials based on the intrathecal use of rituximab in multiple sclerosis. The experience obtainedin these settings offers valuable preliminary data for future studies in CNS autoimmunity.

Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials.

OBJECTIVE A significant advancement in the management of acute ischemic stroke has been the use of the recombinant tissue plasminogen activator (rtPA). French guidelines recommend that stroke patients should be treated in stroke units (SU); however, community hospitals experience practical difficulties in treating their patients because SUs are not sufficient in number. Only one SU is available in the Aquitaine area (southwest of France) and it is located in Bordeaux. To improve quality of care and to provide modern stroke therapy, we decided to assess whether thrombolysis was feasible in our community hospital located in Pau, 200 km from Bordeaux. METHODS Selected patients were treated with rtPA and observed for 24 h in the emergency department. According to French legislation, rtPA therapy was defined as 'off-label use'. National Institutes of Health stroke scale (NIHSS) was obtained on admission, immediately after treatment and 24 h after treatment. RESULTS Results from the first 40 patients are reported in this study. They were treated between September 2004 and June 2006. In total, 1169 patients were admitted for stroke during this period. Outcomes and mortality rates were consistent with experience elsewhere. CONCLUSIONS According to the local infrastructural criteria and prerequisites described in this study, thrombolysis is a viable and feasible treatment option for stroke patients in emergency departments of French community hospitals. In the absence of an SU, this type of emergency treatment can be used as an alternative until SUs become more numerous throughout the country.

Stroke thrombolysis in the emergency department as an alternative service for community hospitals lacking a stroke unit.

Infarctus cérébraux révélant une tumeur bénigne primitive cardiaque

Introduction. – MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare genetic mitochondrial disease which can cause cerebral

Mutisme et troubles du comportement aigus revelant un

Mutisme et troubles du comportement aigus révélant un syndrome MELAS

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