The pandemic due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has rapidly engulfed the entire world, and continues to evolve at an aggressive pace. Although the characteristic ...concern in patients with COVID-19 is acute respiratory distress, there is meteoric accrual of data on neurological involvement. Neurological manifestations in COVID-19 have staggering diversity, ranging from mild olfactory and gustatory perception abnormalities to necrotising encephalopathy and stroke. Understanding of pathophysiological mechanisms underlying neurological invasion and disease is still nascent, and dictated largely by evidence from previous coronavirus infections which are known to have neuroinvasive potential. It has also been postulated that SARS CoV2 may affect the medullary respiratory centres in the brain stem thereby playing a possible role in causing neurogenic acute respiratory failure. Preliminary data suggest a role of immune hyperinflammation and hyperthrombosis mediating neurological features. Apart from acute neurological manifestations, immune dysregulation may contribute to para and post-infectious complications and potentially, neurodegenerative conditions. These concepts are paramount in developing therapeutic paradigms to mitigate the impact of the pandemic. In this review, we summarise putative pathophysiological underpinnings of neurological manifestations of COVID-19 and guidance for their management.
Friedreich's ataxia (FRDA) is a multisystem disease affecting the predominately nervous system, followed by muscle, heart, and pancreas. Current research focused on therapeutic interventions aimed at ...molecular amelioration, but there are no reliable noninvasive signatures available to understand disease pathogenesis. The present study investigates the alterations of plasma cell-free microRNAs (miRNAs) in FRDA patients and attempts to find the significance in relevance with the pathogenesis. Total RNA from the plasma of patients and healthy controls were subjected to miRNA microarray analysis using Agilent Technologies microarray platform. Differentially regulated miRNAs were validated by SYBR-green real-time polymerase chain reaction (Thermo Fisher Scientific). The study identified 20 deregulated miRNAs (false discovery rate < 0.01, fold change ≥ 2.0 ≤) in comparison with healthy controls; out of which 17 miRNAs were upregulated, and 3 miRNAs were downregulated. Target and pathway analysis of these miRNAs have shown association with neurodegenerative and other clinical features in FRDA. Further validation (
= 21) identified a set of significant (
< 0.05) deregulated miRNAs; hsa-miR-15a-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-223-3p, hsa-24-3p, and hsa-miR-21-5p in comparison with healthy controls. These miRNAs were reported to influence various pathological features associated with FRDA. The present study is expected to aid in the understanding of disease pathogenesis.
The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases ...compared to controls using SWATH-MS proteomics approach.
CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2.
We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis.
Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.
•Composite Autonomic Severity Score (CASS) was assessed for the first time in SCA1 and SCA2 patients.•SCA patients were found to have majorly a moderate autonomic failure.•There was a significant ...impairment in the baroreflex dependent autonomic loop with a predominantly normal functioning non – baroreflex dependent autonomic loop in SCA1 and SCA2 patients.•Sudomotor abnormalities was found to be more in SCA1 than SCA2 patients.
The aim of the present study was to evaluate the integrity of autonomic nervous system in spinocerebellar ataxia (SCA) type 1 and 2 patients using battery of autonomic function tests and their comprehensive scoring using composite autonomic severity score (CASS).
Battery of autonomic function test comprising of cardiovascular (baroreflex dependent and non-baroreflex dependent) and sudomotor functions were assessed in age and gender-matched SCA1 (n = 31), SCA2 (n = 40) patients along with healthy controls (n = 40). To assess the grade of autonomic abnormalities, the composite autonomic severity score (CASS) was computed using the results of the standard autonomic function tests.
We found reduction in baroreflex dependent autonomic reactivity parameters predominantly a significant fall of systolic blood pressure (<0.001) and lower 30:15 ratio (<0.001) during head up tilt in both the SCA1 and SCA2 as compared to controls. On sudomotor assessment, distal leg latency of sweat response was prolonged in SCA1 than SCA2 patients. Moderate generalized autonomic failure was commonly found amongst SCA1 (80.65%) and SCA2 (85%) patients. Severe autonomic failure was found to be more in SCA1 (6.45%) than SCA2 (2.50%) patients.
Cardiovascular autonomic function assessment in SCA1 and SCA2 patients revealed a significant impairment in the baroreflex loop integrity. Severity scoring using CASS suggests the existence of moderate autonomic failure in majority of both SCA1 and SCA2 patients.
Outcomes of pallidal stimulation in KMT2B dystonia have been infrequently reported prospectively. We report the six-month outcomes of bilateral GPi DBS in an Asian Indian patient with early-onset ...generalized dystonia associated with a novel heterozygous variant in the KMT2B gene.
Background: The recovery of the upper-limb (UL) motor function after ischemic stroke (IS) remains a major scientific, clinical, and patient concern and it is hard to predict alone from the clinical ...symptoms. Objective: To determine the accuracy of the prediction of the recovery of UL motor function in patients with acute ischemic middle cerebral artery (MCA) stroke using individual clinical, transcranial magnetic stimulation (TMS) or diffusion tensor imaging (DTI) parameters or their combination. Methods and Material: The first-ever acute ischemic MCA stroke patients within 7 days of the stroke onset who had an obvious UL motor deficit underwent TMS for the presence of motor-evoked potential (MEP) and DTI to evaluate the integrity of corticospinal tracts. Multivariate logistic regression analysis was done to test for the accuracy of the prediction of the recovery of UL motor function. Results: Twenty-nine acute ischemic MCA stroke patients (21 males and 8 females) with a mean age of 51.45 ± 14.26 years were recruited. Model-I included clinical scales (Fugl-Meyer Assessment FMA + Motricity Index MI) + TMS (MEP) + DTI (fractional anisotropy FA) were found to be the most accurate predictive model, with the overall predictive ability (93.3%; 95% confidence interval CI: 0.87-0.99) and sensitivity: 94.9% (95% CI: 0.87-1.0) and specificity: 95.8% (95% CI: 0.89-1.0); respectively. Conclusion: The accuracy of UL motor recovery can be predicted through the clinical battery and their elements as well as TMS (MEP) and DTI (FA) parameters. Further, well-designed prospective studies are needed to confirm our findings.
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