Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review.

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1-2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.

Neurological Manifestations of COVID-19 Associated Multi-system Inflammatory Syndrome in Children: A Systematic Review and Meta-analysis.

BACKGROUND: Children comprise only 1-5% of COVID-19 cases. Recent studies have shown that COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) can present with neurological signs and symptoms. In this systematic review and meta-analysis, we have reviewed neurological involvement in these patients. METHODS: A comprehensive electronic literature search was done on PubMed, Google Scholar, Embase, Cochrane database, and SCOPUS for the published English language articles from December 1, 2019, to February 28, 2021. A meta-analysis of the proportion was expressed as a pooled proportion with a 95% confidence interval (CI). Representative forest plots showing individual studies and the combined effect size were generated to provide an overview of the results. RESULTS: This systematic review and meta-analysis analyzed 15 published MIS-C studies with a total of 785 patients. Neurological manifestations in patients with MIS-C was found in 27.1%. We found that 27% developed headaches, 17.1% developed meningism/meningitis and 7.6 % developed encephalopathy. Other uncommon neurological manifestations of MIS-C includes anosmia, seizures, cerebellar ataxia, global proximal muscle weakness and bulbar palsy. In MIS-C patients with neurological feature, neuroimaging showed signal changes in the splenium of the corpus callosum. Electroencephalography showed slow wave pattern and nerve conduction studies and electromyography showed mild myopathic and neuropathic changes. CONCLUSIONS: Our study revealed that neurological manifestations are not uncommon in patients with MIS-C. Further large prospective studies are needed to better explore the disease spectrum and to unravel the underlying pathophysiology.

Neurological manifestations of COVID-19: a systematic review.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding of the impact this virus has on the nervous system is limited. Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients. METHODS: Any study, released prior to May 20, 2020, that reported neurological manifestations in patients infected by SARS-CoV-2 was systematically reviewed using the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement. RESULTS: Our systematic review included data from 37 articles: twelve retrospective studies, two prospective studies, and the rest case reports/series. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia. Uncommonly, COVID-19 can also present with central nervous system manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, peripheral nervous manifestations such as Guillain-Barré syndrome and Bell's palsy, and skeletal muscle manifestations such as rhabdomyolysis. CONCLUSION: While COVID-19 typically presents as a self-limiting respiratory disease, it has been reported in up to 20% of patients to progress to severe illness with multi-organ involvement. The neurological manifestations of COVID-19 are not uncommon, but our study found most resolve with treatment of the underlying infection. Although the timeliness of this review engages current challenges posed by the COVID-19 pandemic, readers must not ignore the limitations and biases intrinsic to an early investigation.

Efficacy and safety of inhaled budesonide on prevention of acute mountain sickness during emergent ascent: a meta-analysis of randomized controlled trials.

BACKGROUND: Acute Mountain Sickness (AMS) is a pathophysiologic process that occurs in non-acclimated susceptible individuals rapidly ascending to high-altitude. Barometric pressure falls at high altitude and it translates to a decreased partial pressure of alveolar oxygen (PAO2) and arterial oxygen (PaO2). A gradual staged ascent with sufficient acclimatization can prevent AMS but emergent circumstances requiring exposure to rapid atmospheric pressure changes - such as for climbers, disaster or rescue team procedures, and military operations - establishes a need for effective prophylactic medications. This systematic review and meta-analysis aim to analyze the incidence of AMS during emergent ascent of non-acclimatized individuals receiving inhaled budesonide compared to placebo. METHODS: This current meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Google Scholar and Embase for relevant studies. The efficacy of budesonide in reducing incidence of AMS was evaluated by calculating the pooled ORs and 95% CIs. The efficacy of budesonide in maintaining hemoglobin-oxygen saturation was evaluated by calculating standard mean difference (SMD) and 95% confidence intervals. RESULTS: We found that at high altitude, inhaled budesonide was effective in reducing the incidence of mild AMS [OR: 0.37; 95% CI, 0.14 to 0.9, p = 0.042] but was ineffective in reducing the incidence of severe AMS [OR: 0.46; 95% CI, 0.14 to 1.41, p = 0.17]. Inhaled budesonide was also effective in maintaining SpO2 (SMD: 0.47; 95% CI, 0.09 to 0.84, p = 0.014) at high altitude. However, it was not effective in maintaining or improving pulmonary function at high altitude. Systematic-review found no adverse effects of budesoide in the dose used for prophylaxis of AMS. CONCLUSIONS: Our systematic review showed that prophylactic inhaled budesonide is effective in preventing mild AMS during emergency ascent but not effective in preventing severe AMS. Though statistically significant, authors recommend caution in interpretation of data and questions for further well designed randomized studies to evaluate the role of budesonide in prophylaxis of AMS during an emergent ascent.

Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene polymorphism (rs4998386) and Parkinson's disease susceptibility: A meta-analysis.

OBJECTIVE: Dopaminergic neuronal degeneration seen in Parkinson's disease (PD) might result from a single nucleotide polymorphism (SNP) in the glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene. We thus performed a meta-analysis exploring the relationship between the rs4998386 SNP of the GRIN2A gene and PD susceptibility. METHODS: We searched PubMed, EMBASE, Web of Science, Google Scholar, and China National Knowledge Infrastructure for studies published between January 2005 and January 2019. The association between the rs4998386 polymorphism and PD susceptibility was evaluated by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Meta-analysis results did not show a significant association between the rs4998386 polymorphism of the GRIN2A gene and PD susceptibility when assuming an allelic model (OR, 0.90; 95% CI, 0.76-1.07; P = .22; I 2 = 53%), a dominant model (OR, 0.96; 95% CI, 0.82-1.12; P = .62; I 2 = 64%), or a recessive model (OR, 1.14; 95% CI, 0.93-1.38; P = .22; I 2 = 0%). CONCLUSION: Our meta-analysis found that the rs4998386 polymorphism of the GRIN2A gene is not associated with risk of PD in either Europeans or white Americans. However, large sample studies with different ethnicities should be conducted to establish the role of the rs4998386 polymorphism in PD pathophysiology.