关键词： autism   channelopathy   epilepsy   GluN   glutamate receptor   intellectual disability   missense variants   movement disorder   neurological diseases   translation study   transmembrane domain  

摘要： N-methyl-D-aspartate receptors (NMDARs) mediate slow excitatory postsynaptic transmission in the central nervous system, thereby exerting a critical role in neuronal development and brain function. Rare genetic variants in the GRIN genes encoding NMDAR subunits segregated with neurological disorders. Here, we summarize the clinical presentations for 18 patients harboring 12 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M2 re-entrant loop, a region that lines the pore and is intolerant to missense variation. These de novo variants were identified in children with a set of neurological and neuropsychiatric conditions. Evaluation of the receptor cell surface expression, pharmacological properties, and biophysical characteristics show that these variants can have modest changes in agonist potency, proton inhibition, and surface expression. However, voltage-dependent magnesium inhibition is significantly reduced in all variants. The NMDARs hosting a single copy of a mutant subunit showed a dominant reduction in magnesium inhibition for some variants. These variant NMDARs also show reduced calcium permeability and single-channel conductance, as well as altered open probability. The data suggest that M2 missense variants increase NMDAR charge transfer in addition to varied and complex influences on NMDAR functional properties, which may underlie the patients' phenotypes.

关键词： Neurological Manifestations   Review   Motor Activity   Vibration  

摘要： Objective This systematic review was conducted to examine the effects of whole-body vibration training on motor impairments among patients with neurological disorders and to investigate which the whole-body vibration training parameters induced improvement in motor impairments. Design PubMed, SCOPUS, PEDro, REHABDATA, and Web of Science were searched for randomized controlled trials and pseudo-randomized controlled trials investigated the effect of whole-body vibration on motor impairments in patients with neurological disorders. The methodological quality was rated using the Cochrane Collaboration's tool. Results Twenty studies were included in this systematic review. Four studies included patients with multiple sclerosis, cerebral palsy (n = 2), stroke (n = 9), Parkinson disease (n = 3), spinal cord injuries (n = 1), and spinocerebellar ataxia (n = 1). The results showed different evidence of benefits and nonbenefits for whole-body vibration training in motor impairments outcomes. Conclusions There is weak evidence for a positive effect of short-term whole-body vibration training on spasticity of lower limbs, mobility, balance, and postural control. Besides, positive effect of the long-term effect of whole-body vibration training on mobility in patients with neurological disorders. The optimal whole-body vibration training parameters in treating patients with neurological disorders remain unclear.

关键词： muscarinic acetylcholine receptor   allosteric modulator   signal bias   neurological disorder   PAM   NAM  

摘要： Muscarinic acetylcholine receptors (mAChR) play important roles in regulating complex behaviors such as cognition, movement, and reward, making them ideally situated as potential drug targets for the treatment of several brain disorders. Recent advances in the discovery of subtype-selective allosteric modulators for mAChRs has provided an unprecedented opportunity for highly specific modulation of signaling by individual mAChR subtypes in the brain Recently, mAChR allosteric modulators have entered clinical development for Alzheimer's disease (AD) and schizophrenia, and have potential utility for other brain disorders. However, mAChR allosteric modulators can display a diverse array of pharmacological properties, and a more nuanced understanding of the mAChR will be necessary to best translate predinical findings into successful clinical treatments.

关键词： Organ donation   Right ventricular dysfunction   Heart donor  

摘要： Purpose: Right ventricular RV dysfunction among transplant recipients correlates with transplant outcome, but its frequency in donors is unknown. The purpose of this study was to describe the epidemiology of RV dysfunction in potential heart donors." Methods: In a seven-year retrospective study of potential heart donors, we explored the incidence of RV dysfunction as observed on echocardiography and explored the association of four distinct factors with RV dysfunction: brain injury diagnosis, thoracic trauma, vasopressin infusion and left ventricular (LV) dysfunction. Results: All 123 potential heart donors underwent echocardiography: 55 had RV dysfunction (44.7%). Fourty-one (33.3%) had LV dysfunction. Isolated RV dysfunction was present in 27 subjects (22%). LV dysfunction was the only factor significantly associated with RV dysfunction (OR = 4.6 (95% CI 1.9-11.4)). We observed no difference in heart acceptance between subjects with or without RV dysfunction. Conclusion: We observed a high frequency of RV dysfunction in a sample of potential heart donors. However, the temporal evolution of RV dysfunction, the hemodynamic predictors of RV dysfunction, as well the link between donor RV dysfunction and recipient outcomes need to be assessed with further prospective studies. (C) 2019 Published by Elsevier Inc.

关键词： CK   motor neuron disease   myopathy   neuromuscular disorders   polyneuropathy  

摘要： Introduction Elevated creatine kinase (CK) level was redefined by the European Federation of Neurological Societies)EFNS(as 1.5 times the upper limit of normal. In the current study we sought to determine the sensitivity and specificity of CK testing for the diagnosis of neuromuscular disorders. Methods Demographics and CK levels were retrospectively extracted from an electronic database for 234 patients with neuromuscular disorders. Sensitivity, specificity, and likelihood ratios and the area under curve were determined for each diagnosis and different cutoff CK values. Results Using the EFNS cutoff values significantly reduced CK test sensitivity. Creatine kinase values >1000 IU/L showed a high likelihood (11.04) for myopathies and a low likelihood for polyneuropathies (0). Discussion European Federation of Neurological Societies cutoff values significantly reduce CK sensitivity for diagnosing neuromuscular disorders. While low CK values cannot exclude a neuromuscular disease, values >1000 IU/L are associated with a high likelihood of myopathy.

关键词： Cervical spine   Degenerative cervical myelopathy   Patient-perceived outcomes   Surgery  

摘要： BACKGROUND: In patients with neurological disorders, a divergence can exist between patients' perceptions regarding the outcomes and the objective neurological findings. Degenerative cervical myelopathy (DCM), a prevalent condition characterized by progressive compression of the cervical spinal cord, can produce debilitating symptoms and profound neurological findings. The purpose of the present study was to determine whether the physician-derived neurological examination findings, as recorded by American Spine Injury Association (ASIA) summary score, correlated with the patient-derived outcome measures for DCM. METHODS: A total of 78 patients underwent surgical management of DCM with completion of preoperative and 6-month follow-up assessments. Surgical management consisted of either anterior or posterior cervical decompression. All patients underwent a neurological evaluation, including an ASIA assessment before surgery and 6 months after surgery, and completed the modified Japanese Orthopaedic Association (mJOA), neck disability index (NDI), and Short-Form 36-item (SF-36) scales pre- and postoperatively to measure both disease-specific and general perceived outcomes. RESULTS: The objective physician-derived neurological testing (ASIA) did not correlate with the patient-derived scales (mJOA, NDI, and SF-36) pre- or postoperatively. Patients reported significant improvements (P < 0.001) at 6 months postoperatively in extremity functioning (mJOA), neck pain (NDI), overall physical health (SF-36), and objective strength and sensory functioning (ASIA). All patient-perceived outcome measures correlated with each other pre- and postoperatively (P < 0.01). - CONCLUSIONS: Objective scoring of postoperative neurological function did not correlate with patientperceived outcomes before and after surgery for DCM. Traditional testing of motor and sensory function as part of the neurological assessment may not be sensitive enough to assess the scope of neurological changes expe

关键词： Systemic lupus erythematosus   Acute ischemic stroke   Intracerebral hemorrhage   Cerebral venous sinus thrombosis   Demyelination   Multiple sclerosis   Peripheral neuropathy  

摘要： Purpose of Review Systemic lupus erythematosus (SLE) is commonly associated with neurological manifestations. Rapid recognition and treatment of these complications may improve outcomes. In this article, we review the neurological conditions associated with SLE, their diagnosis and management strategies. Recent Findings Recent meta-analysis showed that patients with neuropsychiatric manifestations of SLE were more likely to have positive antiphospholipid, antiribosomal P, and antineuronal antibodies. Another meta-analysis showed an association between SLE and antiphospholipid antibodies with cognitive impairment. Two large retrospective studies have shown that the peripheral nervous system is commonly involved in SLE frequently alongside the central nervous system. Summary Neurological manifestations occur in most of SLE patients. Antiphospholipid antibodies are common in patients with SLE and increase the odds of neurological complications. Management typically involved a combination of treatments directed toward the neurological complication and therapies directed toward SLE itself. The efficacy of these treatment protocols, however, has not been rigorously studied and deserves further investigation.

关键词： White matter   Healthy volunteers   Diffusion tensor imaging   Functional magnetic resonance imaging  

摘要： Objectives Although white matter hyperintensities (WMHs) are quite commonly found incidentally, their aetiology, structural characteristics, and functional consequences are not entirely known. The purpose of this study was to quantify WMHs in a sample of young, neurologically asymptomatic adults and evaluate the structural and functional correlations of lesion load with changes in brain volume, diffusivity, and functional connectivity. Methods MRI brain scan using multimodal protocol was performed in 60 neurologically asymptomatic volunteers (21 men, 39 women, mean age 34.5 years). WMHs were manually segmented in 3D FLAIR images and counted automatically. The number and volume of WMHs were correlated with brain volume, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) data. Diffusion parameters measured within WMHs and normally appearing white matter (NAWM) were compared. Results At least 1 lesion was found in 40 (67%) subjects, median incidence was 1 lesion (interquartile range [IQR]=4.5), and median volume was 86.82 (IQR=227.23) mm(3). Neither number nor volume of WMHs correlated significantly with total brain volume or volumes of white and grey matter. Mean diffusivity values within WMHs were significantly higher compared with those for NAWM, but none of the diffusion parameters of NAWM were significantly correlated with WMH load. Both the number and volume of WMHs were correlated with the changes of functional connectivity between several regions of the brain, mostly decreased connectivity of the cerebellum. Conclusions WMHs are commonly found even in young, neurologically asymptomatic adults. Their presence is not associated with brain atrophy or global changes of diffusivity, but the increasing number and volume of these lesions correlate with changes of brain connectivity, and especially that of the cerebellum.

关键词： Ischemic stroke   Neurological deterioration   cEEG   Penumbra   Metabolic crisis   Periodic abnormalities  

摘要： Objective: Despite improvement in acute stroke care, almost 40% of patients with ischemic stroke present neurological deterioration. Neurological deterioration is associated with higher death and dependency rates. Neurological deterioration mechanisms are unknown, and half of neurological deterioration remains unexplained. We postulate that a substantial proportion of neurological deterioration in ischemic stroke is associated with periodic discharges/non-convulsive seizures that negatively impact the recovery of ischemic stroke and worsen symptoms. Methods: Retrospective review of 24 h continuous EEG monitoring (cEEG) performed for neurological deterioration in the stroke unit of a tertiary academic centre. Results: Eighty-one patients were included. cEEG detected epileptic activities in 44% of cases (Nonconvulsive seizures/non-convulsive status epilepticus: 10/81 (12%), periodic discharges: 17/81 (21%) and sporadic epileptiform discharges in 14/81 (17%)). The proportion of patients who did not receive recanalization therapy was significantly higher in the NCSE/NCSz/PDs group than in the group devoid of NCSE/NCSz/PDs: 17/22 (77%) vs 13/59 (22%);p < 0,001. Treatment of Non-convulsive seizures/nonconvulsive status epilepticus and periodic discharges was followed by EEG improvement in respectively 7/8 and 10/16 of treated patients. Conclusions: Non-convulsive seizures/non-convulsive status epilepticus/periodic discharges are associated to neurological deterioration after ischemic stroke. Significance: Treatment of Non-convulsive seizures/non-convulsive status epilepticus and periodic discharges, if such patterns are detected, could help prevent adverse metabolic consequences of epileptic activities on ischemic brain tissue. (C) 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

关键词： Incretin-based therapies   type 2 diabetes   network meta-analysis   dizziness   headache  

摘要： As a new class of antidiabetic drug, incretin-based therapies, which include dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have raised concerns about symptoms of withdrawal in patients with type 2 diabetes mellitus (T2DM), such as dizziness and headache. To systematically evaluate whether incretin-based therapies may lead to dizziness and headache in patients with T2DM compared to other traditional antidiabetic drugs or placebo. We searched Medline, Embase, the Cochrane library, and *** from inception through June 23, 2017, to identify randomized controlled trials of the safety of DPP-4Is or GLP-1 RAs versus placebo or other antidiabetic drugs in T2DM patients. We used the network meta-analysis under the frequentist framework to compare the association between multiple antidiabetic drugs and dizziness and headache. A total of 233 clinical trials with nine treatments and 147,710 patients were included: two incretin-based therapies, one placebo, and six traditional antidiabetic drugs (metformin, insulin, sulfonylurea, thiazolidinediones, alpha-glucosidase inhibitor, and sodium-glucose co-transporter 2). Compared to insulin, thiazolidinediones, or placebo, GLP-1 RAs statistically significantly increased the risk of dizziness (odds ratios [ORs]: 1.92, 1.57, and 1.40, respectively) and headache (ORs: 1.34, 1.41, and 1.18, respectively). DPP-4Is increased the risk of headache (OR: 1.22, 95% confidence interval [CI]: 1.02 to 1.46;moderate quality) and dizziness (OR: 1.46, 95% CI: 1.05 to 2.03;moderate quality) compared to insulin. Of the incretin-based therapies, DPP-4Is had a lower risk of dizziness than GLP-1 RAs (OR: 0.76, 95% CI: 0.67 to 0.87;high quality). Ranking probability analysis indicated that GLP-1 RAs may have the greatest risk of both dizziness and headache among the nine treatments (22.5% and 23.4%, respectively), whereas DPP-4Is were in the middle (46.2% and 45.0%, respectively). Incret