The Spectrum of Intracranial Arteriopathies and Ischemic Strokes in Pediatric Tubercular Meningitis: A Tricentric Study From Eastern India.

INTRODUCTION: Addressing the need to uniformly classify arteriopathies among patients with arterial ischemic stroke (AIS) due to tubercular meningitis (TBM), we used the Childhood AIS Standardised Classification and Diagnostic Evaluation (CASCADE) criteria. METHODS: This tri-centric prospective study included children aged 0.5-12 years with TBM and AIS. Magnetic resonance angiographies (MRAs) were done during admission and repeated 3 and 12 months after discharge. Arteriopathies were classified according to the primary CASCADE criteria. We used the modified Pediatric Alberta Stroke Programme Early Computed Tomography Score as an ordinal measure of infarct volume. The severity of arteriopathies was graded using the focal cerebral arteriopathy severity score (FCASS). The final outcomes were measured at the 12-month follow-up visit using the Pediatric Stroke Outcome Measure (PSOM). RESULTS: Out of 55 patients, 64% had MRA-evidenced arteriopathies and 84% had multiple infarcts. The middle cerebral (46%) and internal carotid arteries (22%) were most commonly affected. The basal ganglia (70%) and the cerebral cortex (61%) were most commonly infarcted. CASCADE categories included 3b (40%), 1d (38%), 2b (16%), 2c (5%), progressive (32%), and stable (44%) arteriopathies. Younger age, hypertrophic pachymeningitis, cortical infarcts, recurrent strokes, progressive arteriopathies, EEG abnormalities, and mortality were significantly higher among patients with MRA-proven arteriopathies. Patients with progressive arteriopathies had a significantly higher prevalence of hypertrophic pachymeningitis, cortical infarcts, and recurrent strokes. FCASS correlated positively with outcomes measured by the Pediatric Stroke Outcome Measure and modified Pediatric Alberta Stroke Programme Early Computed Tomography Score. CONCLUSION: The CASCADE classification clarified the arteriopathy patterns, enabling us to correlate them with the characteristics of the infarcts. FCASS is useful to grade the arteriopathy severity and progression in TBM.

Case Report on Mycobacterium tuberculosis Presenting As Lemierre's Syndrome: A Reemerging Catastrophe.

Lemierre's syndrome is characterized by internal jugular vein thrombophlebitis and bacteremia, primarily from anaerobic organisms. The condition usually arises after a recent oropharyngeal infection. Young, healthy people with prolonged pharyngitis that progresses into septicemia, pneumonia, or lateral neck stiffness should be suspected of having Lemierre's syndrome. Identifying internal jugular vein thrombophlebitis and developing anaerobic bacterial growth on blood culture are frequently used to confirm the diagnosis. Treatment consists of long-term antibiotic treatment, sometimes in conjunction with anticoagulant medication. In this case report, we describe the unique case of a 29-year-old male with Mycobacterium tuberculosis with pulmonary tuberculosis, tubercular meningitis, tuberculosis-related acute ischemic stroke with septic thrombophlebitis. The patient presented with sudden onset altered sensorium for 4 hours. Magnetic resonance imaging of the brain was done, which suggested obstructive hydrocephalus with periventricular ooze. The patient was started on antibacillary treatment, antibiotics, anticoagulants, and systemic steroids. The patient was vitally stable when he was discharged. Therefore, it is crucial to consider the likelihood of such atypical tuberculosis presentations while providing a prompt and relevant diagnosis and recommending the right course of therapy.

Targeted Six-Week Intensive Physiotherapy for a Case of Tuberculous Meningitis With a Syndrome of Inappropriate Antidiuretic Hormone Secretion.

Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis (TB) characterized by the invasion of Mycobacterium tuberculosis into the meninges surrounding the brain and spinal cord. It triggers an intense inflammatory response, leading to neurological complications if not promptly and adequately managed. TBM often precipitates muscle weakness, neurological deficits, respiratory challenges, swallowing difficulties, joint contractures, and pain. Physiotherapy intervention is essential in treating these problems by personalized treatment strategies and treatment plans to enhance muscle strength, motor control, coordination, and overall mobility. This case report aims to highlight the significant role of physiotherapy in improving the quality of life (QOL) and functional abilities of patients with TBM. The current case report reviews the case of a 73-year-old male who presented with complaints of generalized weakness and difficulty in swallowing. The patient had a history of fever for the last six months. Magnetic resonance imaging (MRI) and high-resolution computed tomography (HRCT) diagnosed the case as TBM with miliary TB. Six weeks of targeted intensive rehabilitation program was designed according to the patient's impairments initiated from the intensive care unit (ICU) phase. The main goals of physiotherapy were to start early bed mobility, maintain joint integrity, improve postural strength and swallowing, and make the patient independent in transfer and activities of daily living (ADLs). After a six-week intensive physiotherapy (TIP-6) program, the patient exhibited significant improvements in muscle strength and independence in ADLs. This case highlights the critical role of physiotherapy in enhancing the QOL and functional abilities of patients with severe TB-related conditions.

The Role of Early Rehabilitation in Better Outcomes in a Rare Presentation of Tuberculous Meningitis With Broca's Aphasia.

There is a complex link between tuberculous meningitis (TBM) and aphasia, in which a language impairment is caused by an injury to the cortical language centre. The parts of the brain that function for speech and language production are the Wernicke's, Broca's, and arcuate fasciculus regions. This case report mainly highlights the neurological consequences of TBM, and how it affects language and speech functioning. It outlines a comprehensive physiotherapy rehabilitation program that targets a range of issues for the patient, such as verbal output, weakness, motor deficits, articulation issues in speech, and coordination issues. Various treatment modalities can help correct weakness, improve balance and coordination, increase flexibility and range of motion (ROM), and make speech more fluent. The case report emphasizes the necessity of using an integrated approach that combines speech-language therapy (SLT), melodic intonation therapy (MIT), constraint-induced aphasia therapy (CIAT), medication treatments, and physical therapy to address the multifaceted impacts of TBM-induced aphasia on a patient's quality of life (QOL).

The Neuro-Ophthalmology of Tuberculosis.

Tuberculosis (TB) is a global health concern and central nervous system (CNS) TB leads to high mortality and morbidity. CNS TB can manifest as tubercular meningitis, tuberculoma, myelitis, and arachnoiditis. Neuro-ophthalmological involvement by TB can lead to permanent blindness, ocular nerve palsies and gaze restriction. Visual impairment is a dreaded complication of tubercular meningitis (TBM), which can result from visual pathway involvement at different levels with varying pathogenesis. Efferent pathway involvement includes cranial nerve palsies and disorders of gaze. The purpose of this review is to outline the various neuro-ophthalmological manifestations of TB along with a description of their unique pathogenesis and management. Optochiasmatic arachnoiditis and tuberculomas are the most common causes of vision loss followed by chronic papilloedema. Abducens nerve palsy is the most commonly seen ocular nerve palsy in TBM. Gaze palsies with deficits in saccades and pursuits can occur due to brainstem tuberculomas. Corticosteroids are the cornerstone in the management of paradoxical reactions, but other immunomodulators such as thalidomide and infliximab are being explored. Toxic optic neuropathy caused by ethambutol necessitates careful monitoring and immediate drug discontinuation. Cerebrospinal fluid diversion through ventriculo-peritoneal shunting may be required in patients with hydrocephalus in stage I and II of TBM to prevent visual impairment. Early diagnosis and prompt management are crucial to prevent permanent disability. Prevention strategies, public health initiatives, regular follow-up and timely intervention are essential in reducing the burden of CNS TB and its neuro-ophthalmological complications.

The spectrum of cerebrospinal fluid findings in tuberculous meningitis and their relation to severity, radiological features, and outcome.

Objectives: The aim of the study was to evaluate cerebrospinal fluid (CSF) findings in tuberculous meningitis (TBM) and correlate it with severity, radiological features, and outcome of TBM. Materials and Methods: In a retrospective study, data from admitted TBM patients were analyzed, and findings of CSF examinations were recorded. The CSF was categorized as typical (protein 50-500 mg/dL, cells 50-500/mm3, and glucose 50% or lower of blood sugar); those above and below these values were categorized as increased or decreased, respectively. The CSF findings were correlated with stage of TBM, and 3-month outcome and radiological features. Paradoxical response was also noted. Results: There were 111 patients with TBM (definite 34, highly probable 77). On admission, 20 patients were in Stage I, 63 in Stage II, and 28 in Stage III TBM. CSF cells were in typical range in 73, low in 27 and increased in 11 patients. Protein was in typical range in 92 patients decreased in 11 patients and increased in eight patients. Sugar was normal in 41 and reduced in 70 patients. CSF cells, glucose, and protein did not correlate with the severity of meningitis. Fifteen patients had normal initial magnetic resonance imaging (MRI). Tuberculomas were present in 53 patients, hydrocephalus in 43 patients, basal exudates in 43 patients, and infarction in 44 patients. Mixed findings were present in 65 patients. The MRI features did not correlate with CSF. Second CSF was available after a median duration of 26 (13-276) days in 50 patients. The CSF cells were decreased in 20 and increased in 30 patients, protein increased in 30 and sugars decreased in 16 patients. Paradoxical worsening occurred in 27 patients. Fifty-one patients recovered completely, 41 partially, 15 had poor, three patients were lost to follow-up, and one died. CSF parameters did not correlate with 3-month outcome or paradoxical worsening. CSF parameters do not differ significantly between baseline and 1 month CSF, but cells and lymphocytes changed significantly between 1st month and 3rd month CSF. Conclusion: Typical CSF findings were present in 66% and did not correlate severity of TBM, radiological features paradoxical worsening or 3-month outcome. CSF cell count decreased within 3 months of treatment.

Diagnostic challenges in tuberculous meningitis: a case report with negative genexpert result.

Introduction: Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting the meninges, primarily caused by Mycobacterium tuberculosis. Diagnosis of TBM poses numerous challenges due to its nonspecific clinical presentation and the limitations of diagnostic tests like GeneXpert. Case presentation: The authors report a case of a 22-year-old female from Eastern Nepal presenting with acute-onset fever, headache, vomiting, and neck pain. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, low glucose levels, and cobweb coagulum indicative of TBM. However, the GeneXpert test revealed negative results. Discussion: In resource-limited settings like Nepal, where access to GeneXpert MTB/Rif is limited, CSF analysis and clinical algorithms play a crucial role in diagnosing TBM. Relying solely on GeneXpert results may lead to false negatives, so a high level of suspicion based on patient risk factors is essential. Prompt initiation of empirical antitubercular therapy is vital for a favorable outcome in TBM cases. Conclusion: Negative MTB PCR results from CSF can be misleading in diagnosis of tubercular meningitis. Therefore, comprehensive evaluations, including detailed patient history, physical examination, and CSF fluid analysis, are crucial in high tuberculous prevalence countries to ensure accurate and timely diagnosis.

A Rare Diagnosis of Aseptic Hypertrophic Pachymeningitis: A Case of Mycobacterial Tuberculosis Origin.

Tubercular meningitis is a rare yet devastating type of extrapulmonary tuberculosis (TB) posing great diagnostic challenges due to the nonspecific clinical presentation of the patients. Here, we present a rare diagnosis of hypertrophic pachymeningitis due to Mycobacterium tuberculosis. A 36-year-old male presented with a history of headaches and giddiness for one month. Neurological examination revealed hypo-reflexive triceps and ankle reflexes. Routine blood tests and autoimmune workup were normal. Brain MRI with contrast revealed diffuse dural thickening, focal leptomeningeal enhancement in the right temporal sulci, and enhancement in both the frontal and parietal convexity and the falx cerebri and along the tentorium cerebelli. Cerebrospinal fluid (CSF) analysis revealed elevated proteins, suggestive of aseptic meningitis. Meningeal biopsy revealed a chronic ill-formed granulomatous inflammatory lesion with occasional acid-fast bacilli, consistent with tubercular pachymeningitis. The patient was administered intravenous (IV) methylprednisolone for five days, following which the symptoms subsided. He was advised tablet prednisolone on discharge, and immunomodulation with rituximab was recommended as outpatient treatment. Hypertrophic pachymeningitis is a rare diagnosis characterized by the inflammation and fibrosis of the dura matter due to a diverse etiology. Tubercular etiology must be considered when the routine laboratory tests are negative, and the diagnosis should be confirmed by meningeal biopsy. The treatment of the underlying cause and corticosteroids remain the mainstay management of hypertrophic pachymeningitis. Hence, mycobacterial tuberculosis should be considered as a possible differential diagnosis while evaluating hypertrophic pachymeningitis, especially when the routine laboratory tests and immunological workup are negative.

Intracranial Microhemorrhages in a Patient With Tubercular Meningitis (TBM): A Case Report.

Intracranial tuberculosis (TB) is the most serious form of systemic TB and constitutes an important cause of morbidity and mortality in underdeveloped countries. Central nervous system TB is a difficult diagnosis to make, and treat, especially in the developing nations. Intracranial hemorrhage is one of the rare complications of intracranial TB. We are reporting a case of a 70-year-old male patient who presented to the neurology ward with complaints of persistent high-grade fever associated with significant weight loss, night sweats, and hemolysis for two months. Cerebrospinal fluid analysis was suggestive of tubercular meningitis. He was started on first-line antitubercular therapy. After two weeks, he developed respiratory distress, and invasive mechanical ventilation was started. He was then referred to the Intensive Care Unit of the Critical Care Medicine department. Susceptibility weighted images magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhancing lesions with multifocal areas of microhemorrhages in the brain parenchyma, and leptomeningeal enhancement in bilateral sylvian, perimesencephalic, prepontine and cerebellopontine angles. A tracheostomy was performed. He also developed septic shock for 72 hours, secondary to Pseudomonas aeruginosa and Acinetobacter baumannii ventilator-associated pneumonia, and Klebsiella bacteremia for which intravenous noradrenalin, Carbapenem and Colistin were administered. The patient improved within eight weeks. Our case presented with altered sensorium for the past three to four days but generally, there are other common features like headache, seizures, focal neurological deficit, and raised intracranial pressure. MRI findings of caseating tuberculomas reveal isointense to hypointense signals on both T2 and T1 weighted images with ring enhancement, which are in resemblance with the MRI findings of our case.

Tubercular meningitis and cortical venous thrombosis: A rare but potentially lethal combination-A case report and literature review.

Key Clinical Message: Cortical venous thrombosis is a rare but severe complication of TBM that requires a high index of suspicion for early diagnosis. The treatment of CVT in TBM is based on anticoagulant therapy, which is known to improve the outcomes of the patients. Abstract: The case report describes an 18-year-old male in India with symptoms of tubercular meningitis complicated by cortical venous thrombosis. Tubercular meningitis is a rare but severe form of meningitis caused by tuberculosis bacteria and is a significant public health concern in India. The patient presented to the emergency department with a history of fever, headache, and vomiting for the past month, with a positive Mycobacterium tuberculosis test. The patient was started on standard antitubercular therapy and was diagnosed with cortical venous thrombosis via an MRI scan. Treatment included antitubercular therapy, anticoagulation therapy, dexamethasone, and antiemetic drugs. The patient's symptoms improved over 2 weeks of therapy. The case highlights the importance of early detection, treatment, and prevention strategies, such as the National Tuberculosis elimination program, in controlling the spread of tuberculosis in India. It also emphasizes the importance of close monitoring for complications in patients with tubercular meningitis, such as cortical venous thrombosis, which can be life-threatening.

Cerebral venous thrombosis (CVT) complicating tubercular meningitis.

BACKGROUND: Tuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further. METHODS: Among those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. "Tuberculous meningitis" and "cerebral venous thrombosis" were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition. RESULTS: Among 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent. CONCLUSIONS: CVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs.

Acute Ischemic Stroke in Tubercular Meningitis Patients Without Conventional Vascular Risk Factors: A Retrospective Case Control Study.

Objective: Ischemic stroke is a common complication in patients with tubercular meningitis (TBM). However, the risk factors for Ischemic stroke in TBM patients are not fully understood, especially in those patients without conventional vascular risk factors. The aim of the present study was to explore the clinical features and independent risk factors for tubercular meningitis-related Ischemic stroke (TBMRIS). Methods: Tubercular meningitis patients with acute Ischemic stroke without conventional vascular risk factors were recruited between July 2010 and July 2020 as the TBMRIS group. Patients who solely had tubercular meningitis were recruited as the control group (TMB group). Demographic characteristics, clinical presentations, and cerebrospinal fluid (CSF) examinations were collected, and multiple logistic regression analysis was applied to analyse the independent risk factors for TBMRIS. Results: A total of 70 TBMRIS patients and 70 TMB patients were enrolled. Most (82.86%) of the TBMRIS patients experienced Ischemic stroke events within 3 months after the diagnosis of tubercular meningitis. The multiple logistic regression analysis revealed that variation in red blood cell distribution width (RDW-CV), mean platelet volume (MVP), C-reactive protein (CRP), CSF glucose and Modified Research Council Grade II (MRC Grade II) were independent risk factors for TBRIS. The AUC of the identification model was 0.808, with a sensitivity of 68.60% and a specificity of 84.30%. Conclusion: This study revealed that RDW-CV, MVP, CRP, CSF glucose and MRC Grade II are potential independent risk factors for TBMRIS. The identification model established in this study may help monitor TBM patients who are at high risk of developing TBMRIS.

Clinical Features of Multicenter Autoimmune Glial Fibrillary Acidic Protein Astrocytosis / 罕见病研究

  Objective  To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.  Methods  We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers.  Results  The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle.  Conclusions  Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.

Predictors of Infarction in Tuberculous Meningitis in Indian Patients.

BACKGROUND: Stroke is a devastating complication of tuberculous meningitis (TBM) and is an important determinant of its outcome. We propose a model which would help to predict development of infarction or cerebrovascular events in patients of TBM. METHODS: A prospective study with n=129 patients of TBM were evaluated for predictors and outcomes of stroke. A diagnostic grid was formulated with clinical, laboratory and radiology as parameters to predict the vascular outcomes. All patients were followed up for mortality and disability on the basis of modified rankin score (mRS). MRI & CSF cytokines TNF-alpha, IFN- gamma & IL-6,8, 10 were measured at baseline and 3 months. The diagnosis of TBM included definite, probable & possible types and stage I & II with early and late onset of symptoms respectively. RESULTS: The mortality was 16.2% and 19.4% of all patients developed stroke. The mean GCS, barthel index and mRS at admission was 57.03± 9.5,10.2±2.3 & 3.3±0.03 respectively mild to moderate infection and functional limitation. Barthel index (BI) happened to be a strong predictor [F=32.6, p=0.001, t=15.5, ßeta coefficient =0.002] followed by biomarker TNF-α [F=18.9, p=0.02, t= -2.07, ßeta coefficient=-0.04]. N=25 patients developed stroke with TNF-α, IL-6, IFN -γ showing statistically significant increase in all the stroke affected TBM (95% CI; 4.5 to 1.2; p=0.003). At 3 months, it was observed that mRS was statistically significant between stage I & II (95% CI; 5.4 to 2.1; p=0.04). CONCLUSIONS: Our data revealed that 19.4% patients developed vascular events during the hospital stay or follow up. We recruited late onset TBM as compared to early onset. BI, TNF-α, IL6 are most potent predictors of stroke post TBM.

Characteristics and biomarkers of patients with central nervous system infection admitted to a referral hospital in Northern Vietnam.

BACKGROUND: Laboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis. METHODS: We conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA). RESULTS: Total number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31-58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2-14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1-212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0-882) was associated with tubercular meningitis. CONCLUSIONS: Addition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.

Efficacy and safety of aspirin as an adjunctive therapy in tubercular meningitis: A systematic review and meta-analysis.

BACKGROUND: Tubercular meningitis (TBM) is associated with high mortality and stroke with chronic neurological sequelae even with best of care and antitubercular therapy. Studies have shown that aspirin as an adjunctive therapy might play some role in management of TBM. This systematic review and meta-analysis has been planned to evaluate the efficacy and safety of aspirin as an adjunctive therapy in TBM patients. METHODS: We conducted a systematic search of randomized controlled trials in patients with tubercular meningitis published till October 2019 in all major clinical journals. Study was registered with PROSPERO with registration number: CRD42019136689. Articles were tested for eligibility and assessed for quality and various bias. Data synthesis and analysis was done using Review manager 5.3. The primary end point for assessment of efficacy was mortality at three months. The secondary end point was stroke or composite outcome of stroke and mortality at three months. Adverse effects were also assessed as secondary safety end point. FINDINGS: Overall, three eligible randomized controlled trials with 365 participants were included that provided quantitative data for this meta-analysis. The analysis of primary and secondary end points was done using fixed effect model. There was not significant reduction in mortality [hazard ratio 0.78 (95% CI 0.45-1.35, p = 0.37)] and composite outcome of mortality and new onset stroke [hazard ratio 0.86 (95% CI 0.60-1.24, p = 0.43)] in aspirin group as compared to placebo. However, aspirin as compared to placebo significantly reduced new onset stroke [hazard ratio of 0.51 (95% CI 0.29-0.87, p = 0.01)]. INTERPRETATION: We did not find significant reduction in mortality and composite outcome (mortality and new onset stroke) with aspirin as compared to placebo but there was significant reduction in new onset stroke in aspirin group as compared to placebo with Number Needed to Treat (NNT) = 10, which might be of clinical importance since stroke is responsible for high mortality and morbidity in these subset of patients. However, a large well conducted randomized controlled trial is required to put more light on the available evidence.

MR vessel wall imaging in tubercular meningitis.

PURPOSE: Tubercular meningitis (TBM) has the propensity to cause secondary vasculitis through various mechanisms leading to development of cerebrovascular complications. These vascular involvements can be detected by vessel wall imaging (VWI). In this study, we aimed to study detailed findings of vessel wall imaging in cases of tubercular meningitis. METHODS: All consecutive patients of suspected tubercular meningitis in whom diagnosis of TBM could be made according to diagnostic criteria given by Ahuja et al. were included in the study. High-resolution MR VWI and time of flight (TOF) magnetic resonance angiography (MRA) were done along with routine MRI sequences. Arteries up to second-order branches were studied, and statistical analyses were done with respect to stage of tubercular meningitis, infarctions and TOF MRA findings. RESULTS: Out of all 101 cases of TBM, infarctions were found in 49 cases (48.5%), and vessel wall enhancement was seen in 67 cases (66.3%). With increasing severity of disease, more severe vascular involvement was seen on VWI. There was significant association between enhancement of individual arteries and infarctions in their territories. VWI had better sensitivity than the MRA, while MRA had better specificity than VWI for detection of vascular complications. CONCLUSION: Tubercular vasculitis can be detected by VWI in the form of nodular or smooth segmental enhancement of vessel wall with or without stenosis. Incorporation of VWI in routine MR imaging can play a greater role in early detection and management of cerebrovascular complications which can help to improve prognosis of the disease.

Post-Infective Hydrocephalus.

BACKGROUND: Post-infective hydrocephalus (PIH) arises as a complication of any CNS infection, and can be either communicating or noncommunicating. OBJECTIVE: The aim of this article is to study the various causes of PIH and its pathophysiology and treatment. MATERIAL AND METHODS: The literature was searched for articles describing the causes of PIH. RESULTS: Common causes of PIH are CNS tuberculosis (TB), neurocysticercosis, and perinatal or neonatal infection. TBM is most likely to result in hydrocephalus out of all these manifestations of CNS TB, and hydrocephalus is more likely to occur early in the course, typically 4-6 weeks after the onset of TBM, and is more common among children as compared to adults. A trial of medical management (antitubercular therapy, steroids, and decongestants) can be given to patients with communicating hydrocephalus. Ventriculoperitoneal shunt is the most employed method of CSF diversion in these patients. Though traditionally considered contraindicated, many recent studies have found ETV to be a reasonable option in patients with PIH. HCP in patients with neurocysticercosis can be associated with intraventricular cysts and racemose cysts in the basal subarachnoid cisterns. Surgical intervention is required either for cyst removal or CSF diversion. Endoscopic approaches can be used to remove the intraventricular cysts, which takes care of the HCP. PIH in infants can result either from antenatal infections (TORCH infections) or postnatal infections such as meningitis. CONCLUSIONS: Management of PIH can be challenging. Management has to be individualized.

Lumboperitoneal Shunts - Patient Selection, Technique, and Complication Avoidance: An Experience of 426 Cases.

BACKGROUND: Lumboperitoneal shunt is a known procedure for communicating hydrocephalus. Being an extracranial procedure, it can also be utilized in normal-sized ventricles. OBJECTIVE: To report our experience of lumboperitoneal shunt done with a minimal follow-up of 12 months with an emphasis on patient selection, technique, and complication avoidance. METHODS: This was a retrospective analysis of patients who underwent LP shunt during October 2014-October 2019 at the authors' institute. Inclusion criteria were patients with communicating hydrocephalus due to tubercular meningitis, normal pressure hydrocephalus, idiopathic intracranial hypertension, and postoperative refractory cerebrospinal fluid leaks. Data were collected for demographics, Glasgow coma scale and Glasgow outcome scale, vision, gait, memory, urinary incontinence, failed attempts, and complications. RESULTS: A total of 426 patients underwent the LP shunt procedure. The commonest indication was tubercular meningitis followed by idiopathic intracranial hypertension and normal pressure hydrocephalus. Age ranged from 16 to 72 years. There were 255 male and 171 female patients. The mean follow-up was 41 ± 8 months. Overall, 301 patients (70.6%) had neurological improvement. Shunt-related complications occurred in 112 (26.29%) patients, of which shunt block was the commonest. Other complications were infection in 17 (3.9%) patients and extrusion in four (0.9%) patients. Transient postural headache was seen in 46 (10.7%) patients, which gradually improved. CONCLUSION: Lumboperitoneal shunt was found to be a safe and effective treatment in appropriately selected communicating hydrocephalus patients. A meticulous technique reduces the complication rate.

Tubercular meningitis presenting as cerebral salt wasting syndrome in an adult: A case report.

INTRODUCTION: Cerebral salt wasting syndrome (CSWS) is a cause of hyponatremia in the setting of intracranial pathologies such as Central Nervous System (CNS) trauma, infections, and tumors. It is important to differentiate CSWS from the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as their management differs. CSWS leads to hypovolemia as opposed to euvolemia or hypervolemia in SIADH. SIADH is managed with fluid restriction and this could worsen CSWS which is managed with adminstration of intravenous crystalloids to correct hyponatremia. CASE SUMMARY: A 42-year-old male was admitted after a week of low-grade fever with easy fatigability, hypersomnolence, and excessive thirst. He had polyuria which started 5 days before presentation, and unintentionally lost 3 kg of weight in the past month. He had orthostatic hypotension, and was dehydrated, but vital signs were normal with the exception of his temperature. Cerebrospinal fluid (CSF) analysis revealed a glucose of 42 mg/dl, protein 170 mg/dl, cell count 28/mm3 with 65% lymphocytes which was consistant with tubercular meningitis. CSF AFB culture was positive in addition to a positive CSF PCR for M. tuberculosis. DISCUSSION: Presentation of CNS infection with tuberculosis may be non-specific and its insidious onset could lead to delayed or missed diagnosis; however persistent constitutional symptoms and signs with history of weight loss and a close contact with tuberculosis may raise the possibility of tuberculosis. Early diagnosis and treatment has an excellent prognosis, but any delay contributes to death and disability despite anti-tubercular drug therapy.CSWS should be managed with salt and volume replacement, but more importantly, the causative CNS insult should also be confirmed and addressed.