Autoantibodies Against the Node of Ranvier in Seropositive Chronic inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients;and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications

Gait Analysis in Idiopathic Normal Pressure Hydrocephalus: A Single Centre Experience

Introduction:Gait impairment is the earliest symptom of idiopathic normal pressure hydrocephalus (iNPH). This study objectively investigates gait changes using Ambulatory Parkinson’s Disease Monitoring inertial sensors after cerebrospinal fluid withdrawal in patients with iNPH.Methods:Two-minute walkway tests were performed in eleven patients with iNPH before and after the spinal tap test (TT) or ventriculoperitoneal shunt surgery. Gait parameters were analyzed and compared for each patient individually before and after the intervention.Results:Eleven patients with iNPH (six female, five male) with a median age of 76 (68-76) were included in the study. After the spinal TT or ventriculoperitoneal shunt surgery, patients exhibited increased cadence (steps per minute) and decreased step and stride time (p=0.008, for all).Conclusion:APDM inertial sensors may provide a quantitative gait assessment in patients with iNPH

Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS. MethodsSamples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression. ResultsThere were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 x 10(-12)), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0x10(-7)). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded C9orf72 repeats was shorter than in those without expanded C9orf72 repeats (p = 5.0x10(-4)). DiscussionAlthough telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications

Akut İskemik İnmede Manyetik Duyarlılık Ağırlıklı Görüntüleme (Susceptibility Weighted İmaging, Swı) Bulgularının, Diğer Klinik ve Görüntüleme Bulgularıyla İlişkisinin İncelenmesi

Certain neuroimaging signs detected in SWI and FLAIR sequences are considered to provide information about tissue perfusion and therefore can be useful in making projections regarding clinical/radiological prognosis in acute ischemic stroke. This information is especially critical for many centers in which perfusion imaging cannot be performed routinely. In this study, we aimed to investigate the prevalence of these neuroimaging signs observed on FLAIR and SWI, such as prominent cortical veins (PCV), brush sign and distal FLAIR hyperintense vessel (FHV) sign, assess their correlation with each other and determine the relationship of these signs with clinical and radiological prognosis. We therefore retrospectively analyzed a consecutive series of ischemic stroke patients with proximal MCA occlusion who underwent MR imaging within 24 hours after symptom onset. Among 50 patients who fulfilled the inclusion criteria, PCV, brush sign and FHV sign was positive in 74%, 40% and 92% of patients, respectively. PCV and FHV number were moderately, significantly correlated (r=0.421, p<0.01). In multivariate analysis PCV sign remained significantly associated with high discharge NIHSS (p=0.03) and mRS (p=0.02) scores and also with infarct growth (p=0.02). In bivariate analysis prominent deep medullary veins and associated brush sign was also associated significantly with prognostic scales and follow-up infarct volume, but this association did not persist in multivariate analysis. Prominent distal FHV was not associated with clinical or radiological prognosis. Our findings highlight the prognostic importance of SWI in ischemic stroke.Akut iskemik inmeli hastalarda SWI ve FLAIR gibi kolayca elde edilebilen MR görüntüleme sekanslarında saptanan bazı işaretlerin beynin perfüzyon durumu ve dolayısıyla klinik ve radyolojik prognoz hakkında bilgi verebileceği düşünülmektedir. Bu bilgiler özellikle perfüzyon görüntüleme yapılamayan pek çok merkez için önem taşıma potansiyeline sahiptir. Biz bu çalışmamızda SWI belirgin kortikal ven (BKV) işareti, fırça işareti ve distal FLAIR hiperintens damar (FHD) işareti gibi bazı bulguların sıklığını, birbirleriyle olan korelasyonunu ve ayrıca bu bulguların klinik ve radyolojik prognozla ilişkisini araştırmayı hedefledik. Bu amaçla kliniğimize 3 yıl boyunca proksimal orta serebral arter oklüzyonu ile başvuran ve 24 saat içinde MR görüntüleme yapılmış tüm hastaları retrospektif olarak inceledik. Çalışmaya dâhil edilme kriterlerini karşılayan 50 hastada BKV görünümü %74, fırça işareti %40, FHD işareti %92 oranında mevcuttur. BKV sayısıyla FHD sayısı orta derecede ancak istatistiksel olarak anlamlı bir korelasyon göstermekteydi (r=0,421, p<0,01). Bu işaretlerden BKV bulgusu çok değişkenli analiz sonucunda yüksek taburculuk NIHSS (p=0,03) ve mRS (p=0,02) skorlarıyla ve enfarkt büyümesiyle (p=0,02) ilişkili bulundu. Belirginleşmiş derin medüller venler ve ilişkili fırça işareti de iki değişkenli analizlerde prognostik skalalarla ve takip enfarkt hacmiyle ilişkili bulundu, ancak çok değişkenli analizlerde istatistiksel anlamlılığa ulaşmadı. Distal FHD bulgusunun belirginliği ise klinik ve radyolojik prognozla ilişkili bulunmadı. Çalışmamız SWI görüntüleme bulgularının iskemik inme hastalarındaki prognostik önemini ortaya koymaktadır

Acute Stroke Through the Perspective of a County Hospital: Problems and Opportunities

Objective: Stroke is one of the most important public health issues worldwide, and ranks as the second highest cause of mortality in our country. Regular follow-up of stroke statistics and taking necessary precautions upon determining deficits by countries themselves constitute the most important way of improving prognosis and survival after stroke incidents. To achieve this goal, statistical studies should be performed at various levels of healthcare services. Tertiary care hospitals are the most suitable centers to perform these studies. However, the majority of the population receives service at secondary care centers where the actual statistics remain unknown. The objective of this study was to examine all patients with acute stroke who presented to a county hospital over a one-year period and obtain related data, discuss deficits, and provide solutionbased recommendations. Materials and Methods: All patients diagnosed as having acute stroke between July 2013-July 2014 were included in the study. Demographic, clinical, and radiologic data, in addition to the timing of presentation and baseline National Institutes of Health Stroke Scale (NIHSS) scores were recorded retrospectively, and patients were classified by the type of stroke. All patients were followed up for at least one year after the stroke incident and cumulative survival scores were calculated using Kaplan-Meier analysis. Results: Hemorrhagic stroke was determined in four out of 49 patients with acute stroke; the 45 patients diagnosed as having ischemic stroke were included in the study. Among these, 44.4% (n=20) of the patients presented within the first three hours of onset of clinical symptoms, 4.4% (n=2) presented at 3.-4.5 hours. Baseline NIHSS was 1-4 (mild stroke) in 50% (n=10) of patients who presented in the first three hours, and >5 (moderate or severe stroke) in 50% (n=10) of the remaining patients. The etiologic cause was embolic in 37.1% (n=13), large artery atherosclerosis in 20% (n=7), small vessel disease in 8.6% (n=3), arterial dissection 2.9% (n=1), and undetermined in 31.4% (n=11) of the patients. Twenty-one patients died during follow-up. The survival rates at one, three, and twelve months were 82.2%, 57.8%, and 53.3%, respectively. Conclusion: Treatment of patients with acute stroke is more difficult at secondary care centers compared with tertiary care centers. Precautions taken in developed countries should be adapted to our country to improve stroke prognosis nationwide

Central Neurogenic Hyperventilation In Anti-Nmda Receptor Encephalitis

Central neurogenic hyperventilation (CNH) is a rare condition that is generally associated with infiltrative tumors of the brainstem. Respiratory dysfunction, particularly central hypoventilation, is common in anti-N-methyl D-aspartate (NMDA) receptor encephalitis. CNH, to the best of our knowledge, has not been described previously in this disease. A 24-year-old woman was diagnosed with anti-NMDA receptor encephalitis secondary to ovarian teratoma. In addition to the typical symptoms of the disease, recurrent CNH episodes were observed during the course of the illness, which subsided with midazolam and propofol infusion. Supportive and disease-specific treatments, including oopherectomy, plasmapheresis and intravenous immunoglobulin, provided excellent recovery. These observations suggest that NMDA receptors may play a role in the pathophysiology of CNH.WoSScopu