Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1002/JLB.MR0318-102R

The pathogenesis of tuberculous meningitis

Introduction: The coronavirus disease-2019 (COVID-19) pandemic has been the most significant event in 2020, with ~86.8 million cases and 1.88 million deaths worldwide. It is a highly infectious disease, wherein the virus (severe acute respiratory syndrome coronavirus 2) rapidly multiplies and spreads to all parts of the body. Therefore, COVID-19 is not only respiratory disease but also a multisystem disease. Many people, including physicians, incorrectly believe that the disease affects only the respiratory tract. In this study, we aimed to describe COVID-19 manifestations and the underlying pathophysiology to provide the readers with a better understanding of this disease to achieve good management and to control the spread of this disease. Methods: Secondary data were obtained from PubMed, Google Scholar, and Scopus databases. The keywords used for the search were as follows: COVID-19, COVID-19 pulmonary manifestations, COVID-19 extra pulmonary manifestations, and pathophysiology of COVID-19. We collected secondary data from systemic reviews, metaanalyses, case series, and case reports in the form of public data that was published on websites of the government, medical corporations, medical peer-reviewed journals, and medical academies, all of which were indexed in PubMed, Google Scholar, or Scopus. Our questions were as follows: Is COVID-19 a respiratory disease only? and What are the extrapulmonary manifestations of COVID-19? Results: From our data, we found that a patient with COVID-19 may be either asymptomatic or symptomatic. Symptomatic cases may have either pulmonary or extrapulmonary manifestations. Pulmonary manifestations occur as mild, moderate, or severe cases. In mild and moderate cases, extrapulmonary manifestations such as gastroenteritis, fever, or vomiting may present alone. Some of these cases may be missed for diagnosis, and the patient may receive symptomatic treatment without a COVID-19 diagnosis, leading to increased spread of the infection. Extrapulmonary manifestations may occur in severe and critical cases as complications of severe infections (high viral overload) or the cytokine storm, such as in acute kidney injury (AKI), heart failure (HF), and venous thromboembolic (VTE) manifestation. Conclusion: COVID-19 is not a respiratory disease alone; rather, it is a multisystem disease. Pulmonary and extrapulmonary manifestations should be considered for early diagnosis and to control the spread of the infection.

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COVID-19: Pulmonary and Extra Pulmonary Manifestations.

Importance Tuberculous meningitis is associated with high frequency of cerebral salt wasting. There is a paucity of objective information regarding the best method of treatment of this condition. Objective To evaluate the efficacy and safety of fludrocortisone in the treatment of cerebral salt wasting in patients with tuberculous meningitis. Design, Setting, and Participants This is a single-center, open-label, randomized clinical trial conducted from October 2015 to April 2017 in India. Patients were randomized in a 1:1 ratio to arms receiving saline only or saline plus fludrocortisone, in addition to a standard treatment of 4 antitubercular drugs, prednisolone, and aspirin. The 2 arms were matched for demographic, clinical, and magnetic resonance imaging findings. The patients were followed up for at least 6 months. Interventions Patients were randomized to a 0.9% solution of intravenous saline with 5 to 12 g per day of oral salt supplementation, with or without the addition of 0.1 to 0.4 mg of fludrocortisone per day. Main Outcomes and Measures The primary end point was the time needed to correct serum sodium levels; secondary end points were in-hospital deaths, disability at 3 months, disability at 6 months, occurence of stroke, and serious adverse reactions. Results Ninety-three patients with suspected tuberculous meningitis were recruited; 12 did not meet the inclusion criteria, including 4 with alternate diagnoses. A total of 37 patients with cerebral salt wasting were eligible for the study. One refused to participate, and therefore 36 patients were included, with 18 randomized to each group. The median (range) age was 30 (20-46) years, and 19 were male (52.8%). Those receiving fludrocortisone regained normal serum sodium levels after 4 days, significantly earlier than those receiving saline only (15 days;P = .004). In an intention-to-treat analysis, hospital mortality, disability at 3 months, and disability at 6 months did not differ significantly, but fewer infarcts occurred in the deep border zone in the group receiving fludrocortisone (1 of 18 [6%]) vs those in the control arm (6 of 18 [33%];P = .04). Fludrocortisone was associated with severe hypokalemia and hypertension in 2 patients each, and pulmonary edema occurred in 1 patient. These adverse reactions necessitated discontinuation of fludrocortisone in 2 patients. Conclusions and Relevance Fludrocortisone results in earlier normalization of serum sodium levels, but did not affect outcomes at 6 months. Fludrocortisone had to be withdrawn in 2 patients because of severe adverse effects. This study provides class II evidence on the role of fludrocortisone in treatment of hyponatremia associated with cerebral salt wasting in patients with tuberculous meningitis. Trial Registration Clinical Trials Registry of India (ctri.nic.in) Identifier:CTRI/2017/10/010255

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Safety and Efficacy of Fludrocortisone in the Treatment of Cerebral Salt Wasting in Patients With Tuberculous Meningitis: A Randomized Clinical Trial.

Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model.

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

A structurally simple dielectric barrier discharge based mercury-free plasma UV-light source has been developed for efficient water disinfection. The source comprises of a dielectric barrier discharge arrangement between two co-axial quartz tubes with an optimized gas gap. The outer electrode is an aluminium baked foil tape arranged in a helical form with optimized pitch, while the inner electrode is a hollow aluminium metallic rod, hermetically sealed. Strong bands peaking at wavelengths 172 nm and 253 nm, along with a weak band peaking at wavelength 265 nm have been simultaneously observed due to plasma radiation from the admixture of xenon and iodine gases. The developed UV source has been used for bacterial deactivation studies using an experimental setup that is an equivalent of the conventional house-hold water purifier system. Deactivation studies for five types of bacteria, i.e., E. coli, Shigella boydii, Vibrio, Coliforms and Fecal coliform have been demonstrated with 4 log reductions in less than ten seconds.

/pdf/dielectric-barrier-discharge-based-mercury-free-plasma-uv-3bswnx7rtu.pdf

Dielectric Barrier Discharge based Mercury-free plasma UV-lamp for efficient water disinfection

SARS-CoV-2 infection, resulting in Coronavirus disease 2019 (COVID-19), has significantly affected the entire world. It was labelled a pandemic by World Health Organization. Although it commonly produces respiratory symptoms, neurological features have been described. Neurological manifestations may vary from non-specific symptoms such as headache, dizziness, myalgia and/or fatigue, olfactory or taste dysfunction to specific syndromes including meningitis, stroke, acute transverse myelitis and Guillain-Barre syndrome. This review describes potential pathogenetic mechanisms and neurological manifestations of COVID-19 along with its management. Considering structural and pathogenetic similarity of SARS-CoV-2 with SARS-CoV and MERS viruses, we compared their neurological manifestations and mentioned few features expected in COVID-19 in future. Interestingly, many COVID-19 cases may present with pure neurological manifestations at onset with non-neurological features manifesting few days later and we propose the term "Neuro-COVID syndrome" for such cases. Awareness of neurological manifestations may facilitate its management and improve outcome in such patients.

/pdf/neurological-manifestations-of-coronavirus-disease-2019-oyqh1neh4g.pdf

Neurological manifestations of coronavirus disease 2019: exploring past to understand present.

Background Both stroke and cerebral salt wasting (CSW) are common in tuberculous meningitis (TBM), but there is paucity of studies evaluating their combined effect. Aim The present study has been undertaken to evaluate the spectrum of stroke in TBM and its relation to CSW. Design Hospital-based prospective cohort study. Methods Eighty-one patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid and magnetic resonance imaging (MRI) criteria were prospectively included. Stroke was diagnosed on the basis of clinical, MRI findings or both. Stroke risk factors were noted. Patients with hyponatremia were categorized into CSW and other causes. Three and 6 months outcome was defined using modified Rankin Scale (mRS) as good (<2) or poor (≥2). Results Out of 81 patients with TBM, 32 (39.5%) had ischemic stroke. CSW was the commonest cause of hyponatremia and occurred in 34 (42%) patients. Stroke occurred in tubercular zone in 10, ischemic zone in 15 and both in 7 patients. The patients with ischemic zone infarction were older and had stroke risk factors such as diabetes mellitus, hypertension and hyperlipidemia. Out of 16 (47%) patients with CSW, 10 (62.5%) had stroke during the polyuric phase. The patients with CSW had more frequent deep white matter infarcts (P = 0.01) which were in internal border zone in 4 (40%). Conclusion In TBM, stroke occurred in 39.5% of the patients, 50% of whom had CSW. Volume contraction due to CSW may contribute to stroke.

/pdf/hypovolemia-due-to-cerebral-salt-wasting-may-contribute-to-2bmlgh2isk.pdf

Hypovolemia due to cerebral salt wasting may contribute to stroke in tuberculous meningitis

Serial single breath count is a reliable tool for monitoring respiratory functions in Guillain-Barré Syndrome.

A single barrier dielectric barrier discharge tube of quartz with multi-strip Titanium-Gold (Ti-Au) coatings have been developed and utilized for ultraviolet-B (UV-B) radiation production peaking at wavelength 308 nm. The observed radiation at this wavelength has been examined for the mixtures of the Xenon together with chlorine and air admixtures. The gas mixture composition, chlorine gas content, total gas pressure, and air pressure dependency of the UV intensity, has been analyzed. It is found that the larger concentration of Cl2 deteriorates the performance of the developed source and around 2% Cl2 in this source produced optimum results. Furthermore, an addition of air in the xenon and chlorine working gas environment leads to achieve same intensity of UV-B light but at lower working gas pressure where significant amount of gas is air.

Ultraviolet-B radiation enhancement in dielectric barrier discharge based xenon chloride exciplex source by air

Introduction: Stroke is a leading cause of long-term disability and loss of productive life in developing countries, including India. Ischemic stroke accounts for 85% of all types of stroke with a prevalence of 5%–15% among acute stroke incidents. The prevalence of poststroke depression among acute stroke survivors is varied from 5 to 54%. The study focused on depression among stroke survivors who actively involved in a home-based rehabilitation. Materials and Methods: A descriptive cross-sectional survey was conducted by enrolling 138 stroke survivors consecutively at tertiary care public hospital, North India. A sociodemographic and clinical profile sheet was used to seek information on personal and clinical variables. Information on disability, depression, performance in the activity of daily living, and degree of stroke severity was ascertained by using the Modified Rankin Scale (MRS), Physical Health Questionnaire (PHQ-9), Barthel Index, and National Institutes of Health Stroke (NIHSS). After binary logistic regression model, a multivariate logistic regression was applied to detect the independent predictor of depression. Results: Over 86% (119) of the stroke survivors had no symptoms of depression, and only 14% (19) were reported to have symptoms of depression. Poststroke depression found significant association with disability (P = 0.029) and functional independence (P = 0.0001). A significant difference was observed in the gender (P = 0.018), types of stroke (P = 0.0001), and location of lesion (P = 0.0001) with depression. Binary logistic regression model shows that disability (MRS) status of stroke survivor (P

Mritunjai Kumar

Papers

Neurological manifestations of coronavirus disease 2019: exploring past to understand present.

Hypovolemia due to cerebral salt wasting may contribute to stroke in tuberculous meningitis

Serial single breath count is a reliable tool for monitoring respiratory functions in Guillain-Barré Syndrome.

Ultraviolet-B radiation enhancement in dielectric barrier discharge based xenon chloride exciplex source by air

Poststroke depression among stroke survivors in Sub-Himalayan region.