The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic.

/pdf/emerging-covid-19-neurological-manifestations-present-2t16e4wf00.pdf

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic.

Cognitive impairment is a common and debilitating symptom in multiple sclerosis (MS). There is limited evidence that disease-modifying therapies are effective in treating cognitive dysfunction. Cognitive rehabilitation is a promising approach to treat cognitive dysfunction in MS, gaining empirical support over the last 10 years. The current review will provide a brief overview of cognitive rehabilitation in MS. Overall, there is evidence that cognitive rehabilitation programs (either restorative or compensatory) are efficacious in treating MS-related cognitive dysfunction. Clinicians should consider this low-cost, low-risk, yet effective treatment approach for their patients.

Neurological update: cognitive rehabilitation in multiple sclerosis.

Cerebrovascular dysregulation during hypotension occurs after fluid percussion brain injury (FPI) in the newborn pig owing to impaired K channel function. This study was designed to (1) determine the role of gender and K channel activation in adrenomedullin (ADM) cerebrovasodilation, (2) characterize the role of gender in the loss of hypotensive cerebrovasodilation after FPI, and (3) determine the role of gender in the ability of exogenous ADM to modulate hypotensive dysregulation after FPI. Lateral FPI (2 atm) was induced in newborn male and female newborn pigs (1 to 5 days old) equipped with a closed cranial window, n = 6 for each protocol. Adrenomedullin-induced pial artery dilation was significantly greater in female than male piglets and blocked by the KATP channel antagonist glibenclamide, but not by the Kca channel antagonist iberiotoxin. Cerebrospinal fluid ADM was increased from 3.8 ± 0.7 to 14.6 ± 3.0 fmol/mL after FPI in female but was unchanged in male piglets. Hypotensive pial artery dilation...

Adrenomedullin reduces gender dependent loss of hypotensive cerebrovasodilation after newborn brain injury through activation of ATP dependent K channels

Traumatic Brain Injury-Related Pediatric Mortality and Morbidity in Low- and Middle-Income Countries: A Systematic Review.

Neuropsychiatric diseases are manifested by maladaptive behavioral plasticity. Despite the greater understanding of the neuroplasticity underlying behavioral adaptations, pinpointing precise cellular mediators has remained elusive. This has stymied the development of pharmacological interventions to combat these disorders both at the level of progression and relapse. With increased knowledge on the putative role of the transforming growth factor (TGF- β) family of proteins in mediating diverse neuroadaptations, the influence of TGF-β signaling in regulating maladaptive cellular and behavioral plasticity underlying neuropsychiatric disorders is being increasingly elucidated. The current review is focused on what is currently known about the TGF-β signaling in the central nervous system in mediating cellular and behavioral plasticity related to neuropsychiatric manifestations.

Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders.

Traumatic brain injury (TBI) is exceptionally prevalent in society and often imposes a massive burden on patients’ families and poor prognosis. The evidence reviewed here suggests that gender can influence clinical outcomes of TBI in many aspects, ranges from patients’ mortality and short-term outcome to their long-term outcome, as well as the incidence of cognitive impairment. We mainly focused on the causes and mechanisms underlying the differences between male and female after TBI, from both biological and sociological views. As it turns out that multiple factors contribute to the gender differences after TBI, not merely the perspective of gender and sex hormones. Centered on this, we discussed how female steroid hormones exert neuroprotective effects through the anti-inflammatory and antioxidant mechanism, along with the cognitive impairment and the social integration problems it caused. As to the treatment, both instant and long-term treatment of TBI requires adjustments according to gender. A further study with more focus on this topic is therefore suggested to provide better treatment options for these patients.

/pdf/sex-differences-in-traumatic-brain-injury-a-multi-30hu4g1b0o.pdf

Sex differences in traumatic brain injury: a multi-dimensional exploration in genes, hormones, cells, individuals, and society

Therapeutic Effect of Aerobic Exercise for Adolescents After Mild Traumatic Brain Injury and Sport-Related Concussion: A Meta-Analysis from Randomized Controlled Trials.

Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with phenytoin. Therefore, a meta-analysis was carried out to assess the value of levetiracetam versus phenytoin in the pharmacotherapy of benzodiazepine-refractory SE. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of levetiracetam and phenytoin in the treatment of benzodiazepine-refractory SE. The MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that had been conducted to evaluate levetiracetam versus phenytoin for benzodiazepine-refractory SE, to April 2020. The data were assessed using Review Manager 5.3 software. The risk ratio (RR) was analyzed using dichotomous outcomes, and calculated using a random-effect model. We pooled 1850 patients from 12 RCTs. Patients in the levetiracetam group had a significantly higher rate of clinical seizure cessation than in the phenytoin group (75.2% vs. 67.8%; RR 1.14, 95% confidence interval [CI] 1.05–1.25, p = 0.003). Moreover, less adverse events were observed in the levetiracetam group than in the phenytoin group (17.8% vs. 21.4%; RR 0.82, 95% CI 0.70–0.97, p = 0.02). In subgroup analysis, clinical seizure cessation was achieved more frequently with a higher dose of levetiracetam (> 30 mg/kg) [RR 1.15, 95% CI 1.00–1.32, p = 0.05]. Furthermore, in the subgroup of children, levetiracetam showed a higher rate of clinical seizure cessation than phenytoin (RR 1.13, 95% CI 1.02–1.25, p = 0.02). Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.

Levetiracetam versus Phenytoin for the Pharmacotherapy of Benzodiazepine-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Sex differences in traumatic brain injury: a multi-dimensional exploration in genes, hormones, cells, individuals, and society

Therapeutic Effect of Aerobic Exercise for Adolescents After Mild Traumatic Brain Injury and Sport-Related Concussion: A Meta-Analysis from Randomized Controlled Trials.

Levetiracetam versus Phenytoin for the Pharmacotherapy of Benzodiazepine-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials