关键词： hyponatremia   neurological manifestations   portal hypertension   terlipressin  

摘要： What is known and objective Terlipressin has been shown to be effective in controlling variceal bleeding and decreasing associated mortality. Terlipressin is a synthetic analogue of vasopressin and is safer than arginine vasopressin;it induces selective vasoconstriction by stimulating the vasopressin V1 receptors that are predominantly located in the splanchnic tissues. However, severe hyponatraemia may occur during terlipressin treatment, resulting in neurological manifestations. Case summary We describe two patients who presented a marked decrease in serum sodium levels and developed obvious neurological manifestations after receiving terlipressin therapy. Although the two patients were given sodium supplementation, their serum sodium levels continually declined. After the discontinuation of terlipressin, their serum sodium levels rapidly recovered to normal limits, and the neurological manifestations subsequently disappeared in both patients. What is new and conclusion Some studies have reported hyponatraemia as a side effect of terlipressin;however, severe hyponatraemia with neurological manifestations has rarely been reported. We presented the cases of 2 patients with obvious neurological manifestations after receiving terlipressin therapy. Severe hyponatraemia may develop in patients treated with terlipressin, resulting in associated neurological symptoms. Therefore, the close monitoring of serum sodium is necessary.

摘要： The 'non-linear' genome, or the spatial proximity of non-contiguous sequences, emerges as an important regulatory layer for genome organization and function, including transcriptional regulation. Here, we review recent genome-scale chromosome conformation mappings ('Hi-C') in developing and adult human and mouse brain. Neural differentiation is associated with widespread remodeling of the chromosomal contact map, reflecting dynamic changes in cell-type-specific gene expression programs, with a massive (estimated 20-50%) net loss of chromosomal contacts that is specific for the neuronal lineage. Hi-C datasets provided an unexpected link between locus-specific abnormal expansion of repeat sequences positioned at the boundaries of self-associating topological chromatin domains, and monogenic neurodevelopmental and neurodegenerative disease. Furthermore, integrative cell-type-specific Hi-C and transcriptomic analysis uncovered an expanded genomic risk space for sequences conferring liability for schizophrenia and other cognitive disease. We predict that spatial genome exploration will deliver radically new insights into the brain nucleome in health and disease.

摘要： Colour vision impairments have been identified in early stages of neurological disorders such as Parkinson′s disease, and the relative contribution of retinal versus cortical mechanisms remains a matter of intense debate. Similar considerations can be raised concerning other neurological disorders such as Multiple Sclerosis (with or without optic neuritis) and Alzheimer's Disease. This may be due to the fact the retina may mirror the brain in terms of pathology, or suffer from retrograde degeneration in the case of multiple sclerosis. Moreover cortical changes secondary to retinal disease, such as glaucoma and diabetic retinopathy may also bias colour perception. Here we review current evidence concerning the relative role of the retina in colour vision deficits in a broad range of neurological and ophthalmological disorders. In particular, we discuss the potential role of colour vision measures as disease related biomarkers that can be used for diagnostic, prognostic and treatment effects assessment. [ABSTRACT FROM AUTHOR]

关键词： POEMS syndrome   vascular endothelial growth factor (VEGF)   peripapillary retinal thickness (pRT)   autologous peripheral blood stem cell transplantation   predictive marker  

摘要： Purpose: We present our findings in two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, one with and one without optic disc edema (ODE), after autologous peripheral blood stem cell transplantation. Method: Both patients underwent an autologous peripheral blood stem cell transplantation. The peripapillary retinal thickness (pRT) was determined by spectral‐domain optical coherence tomography (SD‐OCT) to assess the degree of optic disc edema. The SD‐OCT examinations consisted of a 3.45 mm diameter circular scan centered on the optic disc. The pRT thickness was measured at the baseline and at 12 months after beginning the treatment. The serum level of VEGF was determined by enzyme‐linked immunosorbent assays (ELISAs) at the baseline and at 12 months after beginning the treatment. Neurological examinations, e.g., grip strength and compound muscle action potentials (cMAPs) of the upper limb, were also measured at the baseline and 12 months after the transplantation. Result: The pRT in the case without ODE was 310 μm at the baseline. At 12 months after the transplantation, the serum levels of VEGF decreased from 7050 to 511 pg/ml, the grip strength increased from 13 kg to 19 kg, and the cMAP amplitudes increased from 4.31 mV to 7.02 mV. On the other hand, the pRT in the case with severe ODE was 1167 μm at the baseline, and it did not change after the transplantation. The serum levels of VEGF decreased from 9060 pg/ml to 99 pg/ml after the transplantation, the grip strength decreased from 32 kg to 29 kg, and the amplitudes of the cMAP decreased from 2.16 mV to 0.32 mV at 12 months after the transplantation. Conclusion: These results suggest that the baseline degree of ODE before an autologous peripheral blood stem cell transplantation might be a predictive marker on the effectiveness of the transplantation on patients with the POEMS syndrome. However, further studies with a larger sample size are needed. Keywo

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