关键词： HLA   Glutamic acid decarboxylase   Limbic encephalitis   Cerebellar ataxia   Stiff person syndrome  

摘要： The primary cause of neurological syndromes with antibodies against glutamic acid decarboxylase 65 (GAD65-Ab) is unknown, but genetic predisposition may exist as it is suggested by the co-occurrence in patients and their relatives of other organ-specific autoimmune diseases, notably type 1 diabetes mellitus (T1DM), and by the reports of a few familial cases. We analyzed the human leukocyte antigen (HLA) in 32 unrelated patients and compared them to an ethnically matched sample of 137 healthy controls. Four-digit resolution HLA alleles were imputed from available Genome Wide Association data, and full HLA next-generation sequencing-based typing was also performed. HLA DQA1*05:01-DQB1*02:01-DRB1*03:01 was the most frequent class II haplotype in patients (13/32, 41%). DQB1*02:01 was the only allele found to be significantly more common in patients than in controls (20/137, 15%, correctedp = 0.03, OR 3.96, 95% CI [1.54-10.09]). There was also a trend towards more frequent DQA1*05:01 among patients compared to controls (22/137, 16%;correctedp = 0.05, OR 3.54, 95% CI [1.40-8.91]) and towards a protective effect of DQB1*03:01 (2/32, 6% in patients vs. 42/137, 31% in control group;correctedp = 0.05, OR 0.15, 95% CI [0.02-0.65]). There was no significant demographic or clinical difference between DQ2 and non-DQ2 carriers (p > 0.05). Taken together, these findings suggest a primary DQ effect on GAD65-Ab neurological diseases, partially shared with other systemic organ-specific autoimmune diseases such as T1DM. However, it is likely that other non-HLA loci are involved in the genetic predisposition of GAD65-Ab neurological syndromes.

关键词： Eye tracking   Cognition   Neurology   Amyotrophic lateral sclerosis   Alzheimer's disease   Parkinson's disease   Multiple sclerosis   Epilepsy  

摘要： Purpose of review Eye tracking is a powerful method to investigate the relationship between behavior and neural mechanisms. In recent years, eye movement analysis has been used in patients with neurological disorders to assess cognitive function. In this review, we explore the latest eye tracking researches in neurological disorders that are commonly associated with cognitive deficits, specifically, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and epilepsy. We focus on the application of ocular measures in these disorders, with the goal of understanding how eye tracking technology can be used in the clinical setting. Findings Eye tracking tasks (especially saccadic tasks) are often used as an adjunct to traditional scales for cognitive assessment. Eye tracking data confirmed that executive dysfunction is common in PD and ALS, whereas AD and MS are characterized by attention deficits. Research in evaluating cognitive function in epilepsy using eye tracking is still in its early stages, but this approach has shown advantages as a sensitive quantitative method with high temporal and spatial resolution. Eye tracking technology can facilitate the assessment of cognitive impairment with higher temporal resolution and finer granularity than traditional cognitive assessment. Oculomotor data collected during cognitive tasks can provide insight into biological processes. Eye tracking provides a nonverbal and less cognitively demanding method of measuring disease progression in cognitively impaired patients.

关键词： antiviral   cat   corona virus   ophthalmology  

摘要： Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS-441524 (5-10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]-PCR) and serial ocular imaging using Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS-441524 shows clinical efficacy and may result in clearance and long-term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

关键词： depressed fracture over superior sagittal sinus   surgical elevation   manifestations of increased intracranial pressure   benign intracranial hypertension  

摘要： Objective To present our experience in the diagnosis and management protocol of 13 patients with a depressed skull fracture over the superior sagittal sinus (SSS) who developed delayed neurologic deterioration. Patients and Methods This retrospective study was conducted in the Neurosurgical Department, Assiut University Hospitals, between May 2012 and May 2017. All patients with a depressed skull fracture over the SSS were reviewed. Only those patients who were neurologically intact after trauma but suffered delayed neurologic deterioration were included in this study. Preoperative characteristics of age, sex, cause of trauma, type and site of the depressed skull fracture, and clinical presentation were reviewed and evaluated. Neuroimaging including brain computed tomography and computed tomography venography were evaluated. Results Of 612 patients with depressed skull fractures admitted to our department, 63 had the fracture segment on the SSS. Thirteen patients, nine males and four females, met the inclusion criteria (age range: 5-42 years). The most common cause of trauma was assault from others (seven patients). Eight patients had a compound depressed fracture;the other five fractures were simple. Interval between trauma and neurologic deterioration ranged between 4 days and 3 weeks. Clinical deterioration included decrease of consciousness, headache, blurred vision, and repeated vomiting. Deterioration of consciousness was seen in four patients. Eight patients had sixth cranial nerve palsy. Visual deterioration was seen in four patients. All the included patients were operated on for elevation of the depressed segment. Eleven patients improved;two patients who presented initially with visual deterioration did not improve. Their visual deterioration persisted after surgery. For both these patients, lumbar puncture revealed high cerebrospinal fluid (CSF) pressure. Clinical improvement followed the insertion of a thecoperitoneal shunt. Conclusion Increased intracr

关键词： Extracorporeal membrane oxygenation   Seizures   Stroke   Intracranial hemorrhage   Electroencephalography  

摘要： Extracorporeal membrane oxygenation is extracorporeal life support for life-threatening cardiopulmonary failure. Since its introduction, the use of extracorporeal membrane oxygenation has expanded to patients with more complex comorbidities without change in patient mortality rates. Although many patients survive, significant neurological complications like seizures, ischemic strokes, and intracranial hemorrhage can occur during extracorporeal membrane oxygenation care. The risks of these complications often add to the complexity of decision-making surrounding extracorporeal membrane oxygenation support. In this review, we discuss the pathophysiology and incidence of neurological complications in children supported on extracorporeal membrane oxygenation, factors influencing the incidence of these complications, commonly used neurological monitoring modalities, and outcomes for this complex patient population. We discuss the current literature on the use of electroencephalography for both seizure detection and monitoring of background electroencephalographic changes, in addition to the use of less commonly used imaging modalities like transcranial Doppler. We summarize the knowledge gaps and the lack of clinical consensus guidelines for managing these potentially life-changing neurological complications. Finally, we discuss future work to further understand the pathophysiology of extracorporeal membrane oxygenation-related neurological complications. (C) 2020 Elsevier Inc. All rights reserved.

关键词： artemin   cancers   glial cell line-derived neurotrophic factor   neurological disorders  

摘要： Artemin (ARTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs), which encompasses family members, GDNF, neurturin (NRTN) and persephin (PSPN). ARTN is also referred to as Enovin or Neublastin, and bears structural characteristics of the TGF-beta superfamily. ARTN contains a dibasic cleavage site (RXXR) that is predicted to be cleaved by furin to yield a carboxy-terminal 113 amino acid mature form. ARTN binds preferentially to receptor GFR alpha 3, coupled to a receptor tyrosine kinase RET, forming a signalling complex for the regulation of intracellular pathways that affect diverse outcomes of nervous system development and homoeostasis. Standard signalling cascades activated by GFLs via RET include the phosphorylation of mitogen-activated protein kinase or MAPK (p-ERK, p-p38 and p-JNK), PI3K-AKT and Src. Neural cell adhesion molecule (NCAM) is an alternative signalling receptor for ARTN in the presence of GFR alpha 1, leading to activation of Fyn and FAK. Further, ARTN also interacts with heparan sulphate proteoglycan syndecan-3 and mediates non-RET signalling via activation of Src kinases. This review discusses the role of ARTN in spinal cord injury, neuropathic pain and other neurological disorders. Additionally, ARTN plays a role in non-neuron tissues, such as the formation of Peyer's patch-like structures in the lymphoid tissue of the gut. The emerging role of ARTN in cancers and therapeutic resistance to cancers is also explored. Further research is necessary to determine the function of ARTN in a tissue-specific manner, including its signalling mechanisms, in order to improve the therapeutic potential of ARTN in human diseases.

关键词： Transient neurological symptoms   Diffusion-weighted imaging   Acute ischemic lesions   Dawson score   The Diagnosis of TIA score  

摘要： Background The clinical characteristics of diffusion-weighted imaging (DWI) abnormalities after transient neurological symptoms are of great significance for the early diagnosis and urgent intervention of transient ischemic attack (TIA). This study was aimed to investigate the clinical characteristics associated with acute DWI lesions in transient neurological symptoms. Methods We retrospectively recruited 302 patients with transient neurological symptoms. According to DWI findings, they were divided into DWI positive and DWI negative group. The clinical characteristics and the TIA-related scores such as ABCD2, ABCD3, ABCD3I, Dawson score, and the Diagnosis of TIA (DOT) score were compared between the two groups. Logistic regression analysis and receiver operating characteristic curves were used to identify the independent factors and compare the predictive value of different TIA scores for acute DWI lesions. Results A total of 302 patients were enrolled in this study. The mean age was 61.8 years, and 67.2% were male. We found 89 (29.5%) patients with DWI positivity. Logistic regression analysis showed the characteristic associated with DWI lesions was dysphasia (OR 2.226, 95% CI 1.220-4.062). The area under the curve for Dawson score and the DOT score was 0.610 (95% CI 0.543-0.678) and 0.625 (95% CI 0.559-0.691), respectively. Conclusion We found that DWI lesions were detected in 29.5% of patients with transient neurological symptoms and were associated with dysphasia. Dawson score and DOT score could have a higher predictability of DWI lesions in patients with transient neurological symptoms.

关键词： Coronavirus   SARS-CoV-2   COVID-19   Neurological manifestations   Encephalitis  

摘要： Background: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement. Objective: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease. Methods: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barre, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease. Results: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS-CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients. Conclusion: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.

关键词： COVID-19   SARS-CoV-2 RNA   RT-PCR   Neurological manifestations   Cerebrospinal fluid  

摘要： We report that patients with COVID-19 displaying distinct neurological disorders have undetectable or extremely low levels of SARS-CoV-2 RNA in the cerebrospinal fluid, indicating that viral clearance precede the neurological involvement. This finding points to the need for the development of more sensitive molecular tests and the investigation of other neurotropic pathogens to exclude concurrent neuroinfection. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.