关键词： Spinal cord injury   Biomarkers   Syringomyelia   Cerebrospinal fluid   Tethering of the spinal cord (TSC)   Glial fibrillary acidic protein (GFAP)   Ubiquitin C-terminal hydrolase L1 (UCH-L1)   Neurofilament   Post-traumatic myelopathy  

摘要： Background Years after a traumatic spinal cord injury (SCI), a subset of patients may develop progressive clinical deterioration due to intradural scar formation and spinal cord tethering, with or without an associated syringomyelia. Meningitis, intradural hemorrhages, or intradural tumor surgery may also trigger glial scar formation and spinal cord tethering, leading to neurological worsening. Surgery is the treatment of choice in these chronic SCI patients. Objective We hypothesized that cerebrospinal fluid (CSF) and plasma biomarkers could track ongoing neuronal loss and scar formation in patients with spinal cord tethering and are associated with clinical symptoms. Methods We prospectively enrolled 12 patients with spinal cord tethering and measured glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and phosphorylated Neurofilament-heavy (pNF-H) in CSF and blood. Seven patients with benign lumbar intradural tumors and 7 patients with cervical radiculopathy without spinal cord involvement served as controls. Results All evaluated biomarker levels were markedly higher in CSF than in plasma, without any correlation between the two compartments. When compared with radiculopathy controls, CSF GFAP and pNF-H levels were higher in patients with spinal cord tethering (p <= 0.05). In contrast, CSF UCH-L1 levels were not altered in chronic SCI patients when compared with either control groups. Conclusions The present findings suggest that in patients with spinal cord tethering, CSF GFAP and pNF-H levels might reflect ongoing scar formation and neuronal injury potentially responsible for progressive neurological deterioration.

摘要： This letter comments on the letter by

关键词： clinical trials   Miro1   mitochondria   mitophagy   Parkinson's disease   precision  

摘要： Parkinson's disease (PD) is a debilitating movement disorder, significantly afflicting the aging population. Efforts to develop an effective treatment have been challenged by the lack of understanding of the pathological mechanisms underlying neurodegeneration. We have shown that Miro1, an outer mitochondrial membrane protein, situates at the intersection of the complex genetic and functional network of PD. Removing Miro1 from the surface of damaged mitochondria is a prerequisite for mitochondrial clearance via mitophagy. Parkinson's proteins PINK1, Parkin, and LRRK2 are the molecular helpers to remove Miro1 from dysfunctional mitochondria destined for mitophagy. We have found a delay in clearing Miro1 and initiating mitophagy in postmortem brains and induced pluripotent stem cell-derived neurons from PD patients harboring mutations inLRRK2,PINK1, orParkin, or from sporadic PD patients with no known mutations. In addition, we have shown that reducing Miro1 by both genetic and pharmacological approaches can correct this Miro1 phenotype and rescue Parkinson's-relevant phenotypes in human neurons and fly PD models. These results suggest that the Miro1 defect may be a common denominator for PD, and compounds that reduce Miro1 promise a new class of drugs to battle PD. We propose to couple this Miro1 phenotype with Miro1-based drug discovery in future therapeutic studies, which could significantly improve the success of clinical trials. (c) 2020 International Parkinson and Movement Disorder Society

关键词： COVID-19   Stroke   Rehabilitation  

摘要： The article reports on the neurological signs and symptoms associated with COVID-19 infection in a hospitalized population in Wuhan, China, the initial epicenter of the disease. It mentions that persistence of symptoms that affect the nervous system, such as headache and dizziness, can have a profound impact on function. It also mentions that neurological disease is recognized as a grave concern in a subset of patients with COVID-19.

关键词： COVID-19   Functional neurological disorders   Functional movement disorders   Psychogenic non-epileptic seizures   Conversion disorders  

关键词： Anoxic-ischemic encephalopathy   Cardiac arrest   Computed tomography   Neuroimaging   Cerebral networks   Prognostication  

摘要： Purpose: To quantitatively assess the severity of anoxic-ischemic brain injury early after cardiac arrest (CA) using a novel automated method applied to head computed tomography (HCT). Methods: Adult patients who were comatose and underwent HCT < 24 h after arrest were included in a retrospective analysis. Principal endpoint was unfavorable outcome (UO) defined as Cerebral Performance Category (CPC) of 3-5 at hospital discharge. We developed an automated processing algorithm for HCT images to be registered, atlas-segmented in 181 regions, and region-specific radiologic densities determined in Hounsfield Units. This approach was compared with an established manual method evaluating grey-white matter ratios (GWR). We tested univariable and multivariable prognostic models which integrated clinical and HCT features including densities in lobes and in nodes of cerebral networks linked to CA recovery. Results: Ninety-one patients were enrolled among whom 66 (73%) had an UO. HCTs were interpreted as normal or without acute abnormality by a neuroradiologist in 77 cases (85%). Compared to the favorable outcome group, UO patients had significantly lower densities in all lobes and in nodes of cerebral networks. A model combining clinical variables with the automated method applied to cerebral network nodes had the highest prognostic performance although not significantly different than the combined clinical-GWR method (AUC [95% CI] 0.94 [0.86-1.00] and 0.92 [0.83-1.00] respectively). Conclusion: In comatose survivors of CA, automated quantitative analysis of HCT revealed very early multifocal changes in brain tissue density which are mostly overlooked on conventional neuroradiologic interpretation and are associated with neurological outcome.

关键词： Auditory brainstem response   Cardiac arrest   Coma   Infrared pupillometry  

摘要： Aim: Assessment of brainstem function plays a key role in predicting the neurological outcome after cardiac arrest. However, the relationship of the two quantitative brainstem assessment methods-automated infrared pupillometry (AIP) and auditory brainstem response (ABR)-with neurological prognoses remains unclear. This study compares the prognostic value of AlP and ABR after cardiopulmonary arrest. Methods: This retrospective observational study included 124 comatose patients after cardiopulmonary arrest. ABR and AIP measurements were performed simultaneously within 72 h after return of spontaneous circulation. Neurological outcome was assessed at discharge by estimating the cerebral performance category (CPC) score;favourable neurological outcome (CPC score, 1 2) or poor neurological outcome (CPC score, 3 5). The correlation of each AIP parameter and ABR I-V wave latency was tested using Pearson's product moment correlation coefficient, and the prognostic value was compared using the area under the receiver operating characteristics curve (AUC). Results: Pupillary light reflex (PLR) was not detected in 69 patients, and ABR wave V was not detected in 47 patients. All these patients had poor neurological outcome. Among those whose PLR and ABR could be measured, each AlP parameter had a tendency to be correlated with ABR I-V wave latency. Pupil constriction velocity provided the greatest AUC (0.819), with 81% sensitivity and 77% specificity. ABR I-V wave latency provided extremely low AUC (0.560). Conclusions: Although AIP and ABR were correlated, the AlP measures were superior in predicting the neurological outcome after cardiac arrest as compared with the ABR measures.

关键词： Out-of-hospital cardiac arrest   Neurological outcome prognostication   Serum biomarkers of neurological injury  

摘要： Objective: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. Methods: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AU ROC of NSE. Results: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88 0.89;UCH-L1 0.85 0.87) or in combination (AU ROC 0.90 0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75 0.85) at all time-points. At specificities >= 95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. Conclusion: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.

关键词： acute kidney injury   ataxia   central nervous system   hemodialysis  

摘要： Background The ingestion of grapes or raisins has been reported to cause acute kidney injury (AKI) in dogs, with a clinical picture dominated by early gastrointestinal signs and rapidly developing uremia. Ataxia is mentioned in a few reports, but not further characterized. Objectives To evaluate the clinical, laboratory, and pathological features of dogs diagnosed with grape or raisin toxicosis (GRT) with emphasis on renal and neurological manifestations, compared to a control group of dogs with AKI from other causes. Animals Fifteen client-owned dogs with GRT and 74 control dogs. Methods Retrospective study over 17 months. Results All dogs with GRT were presented with severe AKI (grade 4, n = 5;grade 5, n = 10). Eleven dogs (73%) had marked forebrain, cerebellar, or vestibular signs. These manifestations dominated the clinical picture in some dogs, but were not associated with the severity of azotemia or the presence of systemic hypertension. Eight dogs (53%) survived, and 5 dogs experienced a complete neurological recovery. Causes of death were unrelated to the neurological manifestations. Neuropathological examination of 4 dogs did not identify any structural central nervous system abnormality. Only 2 control dogs (3%) displayed neurological signs with seizures unrelated to the AKI;42 control dogs (57%) survived. Conclusions and Clinical Importance Severe forebrain, cerebellar, or vestibular signs may be an important feature of GRT and dominate the early clinical picture. The described features suggest a reversible functional brain injury specific to GRT and unrelated to uremia.

关键词： angiogenesis   ischaemic stroke   microRNA-130a   middle cerebral artery occlusion   neurological deficit   X-linked inhibitor of apoptosis protein  

摘要： MicroRNAs (miRNAs) have already been proposed to be implicated in the development of ischaemic stroke. We aim to investigate the role of miR-130a in the neurological deficit and angiogenesis in rats with ischaemic stroke by regulating X-linked inhibitor of apoptosis protein (XIAP). Middle cerebral artery occlusion (MCAO) models were established by suture-occluded method, and MCAO rats were then treated with miR-130a mimics/inhibitors or/and altered XIAP for detection of changes of rats' neurological function, nerve damage and angiogenesis in MCAO rats. The oxygen-glucose deprivation (OGD) cellular models were established and respectively treated to determine the roles of miR-130a and XIAP in neuronal viability and apoptosis. The expression levels of miR-130a and XIAP in brain tissues of MCAO rats and OGD-treated neurons were detected. The binding site between miR-130a and XIAP was verified by luciferase activity assay. MiR-130a was overexpressed while XIAP was down-regulated in MCAO rats and OGD-treated neurons. In animal models, suppressed miR-130a improved neurological function, alleviated nerve damage and increased new vessels in brain tissues of rats with MCAO. In cellular models, miR-130a inhibition promoted neuronal viability and suppressed apoptosis. Inhibited XIAP reversed the effect of inhibited miR-130a in both MCAO rats and OGD-treated neurons. XIAP was identified as a target of miR-130a. Our study reveals that miR-130a regulates neurological deficit and angiogenesis in rats with MCAO by targeting XIAP.