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.

MR vessel wall imaging in cerebral bacterial and fungal infections.

PURPOSE: Central nervous system (CNS) bacterial and fungal infections can cause secondary vasculitis which worsens the prognosis due to development of complications like infarctions or hemorrhages. In this prospective study, we aim to study intracranial vessel wall imaging findings in bacterial and fungal infections. METHODS: We included 12 cases of nontubercular bacterial and fungal CNS infections each, in whom definitive microbiological diagnosis could be made. High-resolution vessel wall imaging (VWI) and time of flight MR angiography (TOF MRA) were incorporated in the routine imaging protocol. All cases were evaluated for the presence of vascular enhancement, pattern of enhancement, and stenosis on VWI. Statistical analysis was done to evaluate association between findings of vessel wall imaging and infarctions. RESULTS: We found infarctions in 5 out of 12 cases (41.7%) of the bacterial group and 7 out of 12 cases (58.3%) of the fungal group. Vessel wall enhancement was seen in 5 cases (41.7%) of the bacterial group and 9 cases (75%) of the fungal group. There was a significant association between infarctions and vessel wall enhancement in the fungal group. However, pattern of enhancement or stenosis on VWI was not significantly associated with presence of infarction. VWI detected more cases of vascular involvement than TOF MRA. CONCLUSION: Secondary infectious vasculitis in bacterial and fungal infections can be detected by VWI, which can play an important role in better patient management as detection of vascular involvement can prompt early treatment to prevent complications like infarctions or hemorrhages.

PGIMER, Chandigarh: A temple of holistic Neurology.

History helps us to become better students, judge wisely, understand change, and most importantly, it tells us who we are. It helps us to understand what happened, why it happened and what its ramifications are. Winston Churchill once said: "Study history, study history. In history lie all the secrets of statecraft." Here, we take this opportunity to pay our gratitude to our esteemed teachers who worked relentlessly for uplifting of the department of Neurology, PGIMER, Chandigarh; and, narrate chronicles of all those people who made this department reach the heights where it stands today.

Infiltrative Optic Neuropathies: Opening Doors to Sinister Pathologies.

Optic disc edema may be caused by a number of conditions. A commonly ignored but important aspect is the presence of "infiltration" of disc; that may closely mimic disc edema. Disc edema, optic nerve dysfunction and a normal appearing disc in any combination may occur in infiltrative optic neuropathies. Identifying disc infiltration can aid in diagnosis of many sinister pathologies even in the absence of other specific clinical features. We describe two patients presenting with optic nerve dysfunction and infiltrated disc appearance, which on investigations were found to have underlying malignancies thereby underscoring the importance of detecting infiltrative optic neurpathies.

Linezolid Induced Reversible Peripheral Neuropathy.

Linezolid has been increasingly used for several severe infections including multidrug-resistant tuberculosis. Peripheral neuropathy is a rare side effect of linezolid and is conventionally considered as irreversible. Here, we report a case of reversible neuropathy induced by linezolid.

Identification of novel pathogenic variants of Calpain-3 gene in limb girdle muscular dystrophy R1.

BACKGROUND: Limb Girdle Muscular Dystrophy R1 (LGMDR1) is an autosomal recessive neuromuscular disease caused by mutations in the calpain-3 (CAPN3) gene. As clinical and pathological features may overlap with other types of LGMD, therefore definite molecular diagnosis is required to understand the progression of this debilitating disease. This study aims to identify novel variants of CAPN3 gene in LGMDR1 patients. RESULTS: Thirty-four patients with clinical and histopathological features suggestive of LGMD were studied. The muscle biopsy samples were evaluated using Enzyme histochemistry, Immunohistochemistry, followed by Western Blotting and Sanger sequencing. Out of 34 LGMD cases, 13 patients were diagnosed as LGMDR1 by immunoblot analysis, demonstrating reduced or absent calpain-3 protein as compared to controls. Variants of CAPN3 gene were also found and pathogenicity was predicted using in-silico prediction tools. The CAPN3 gene variants found in this study, included, two missense variants [CAPN3: c.1189T > C, CAPN3: c.2338G > C], one insertion-deletion [c.1688delinsTC], one splice site variant [c.2051-1G > T], and one nonsense variant [c.1939G > T; p.Glu647Ter]. CONCLUSIONS: We confirmed 6 patients as LGMDR1 (with CAPN3 variants) from our cohort and calpain-3 protein expression was significantly reduced by immunoblot analysis as compared to control. Besides the previously known variants, our study found two novel variants in CAPN3 gene by Sanger sequencing-based approach indicating that genetic variants in LGMDR1 patients may help to understand the etiology of the disease and future prognostication.

Neuromyelitis Optica Spectrum Disorders in North Indian Population: Experience from a Tertiary Care Center.

Introduction: To understand neuromyelitis optica spectrum disorders (NMOSDs) better we need to study them in different populations. This prospective study was conducted to characterize clinical, serological, radiological, and therapeutic profile of NMOSDs in a North Indian population. Materials and Methods: This study included 81 patients with NMOSDs. All patients underwent detailed history and examinations and were followed at 3 monthly intervals. They were evaluated using standard investigations including gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and spine with thin section optic nerve cuts and treated as per the standard guidelines. Data were recorded meticulously. Results: The mean age was 33.7 ± 13.4 years. The mean age at disease onset was 31.2 ± 13.5 years. Female-to-male ratio was 1.9:1. About 32.1% of patients presented with optic neuritis (ON), 56.8% with transverse myelitis (TM), and 11.1% with both ON and TM. The mean time from disease onset to diagnosis was 16.17 ± 23.09 months. Muscle atrophy, Lhermitte symptom, and tonic spasms were common. Foster-Kennedy syndrome-like presentation was seen in 8.6%. NMO antibodies were positive in 41 patients. MRI revealed involvement of <4 vertebral segments in 16.4% of patients with TM. Patients were managed as per standard guidelines. The mean follow-up duration was 15.3 ± 6 months. Approximately 88.9% had good functional outcome. Conclusion: NMOSDs are a common cause of demyelinating illnesses in Northern India. The response to treatment is excellent and most patients recover without residual disability.

Comparative Evaluation of Diffusion Kurtosis Imaging and Diffusion Tensor Imaging in Detecting Cerebral Microstructural Changes in Alzheimer Disease.

OBJECTIVE: Comparative evaluation of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) using a whole-brain atlas to comprehensively evaluate microstructural changes in the brain of Alzheimer disease (AzD) patients. METHODS: Twenty-seven AzD patients and 25 age-matched controls were included. MRI data was analyzed using a whole-brain atlas with inclusion of 98 region of interests. White matter (WM) microstructural changes were assessed by Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), Kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK). Gray matter (GM) integrity was evaluated using KFA, MK, RK, AK and MD. Comparison of the DKI and DTI metrics were done using student t-test (p ≤ 0.001). RESULTS: In AzD patients widespread increase in MD, AD and RD were found in various WM and GM region of interests. The extent of abnormality for DKI parameters was more limited in both GM and WM regions and revealed reduced kurtosis values except in lentiform nuclei. Both DKI and DTI parameters were sensitive to detect abnormality in WM areas with coherent and complex fiber arrangement. Receiver operating characteristic curve analysis for hippocampal values revealed the highest specificity of 88% for AK <0.6965 and highest sensitivity of 95.2% for MD >1.2659. CONCLUSION: AzD patients have microstructural changes in both WM and GM and are well-depicted by both DKI and DTI. The alterations in kurtosis parameters, however, are more limited and correlate with areas in the brain primarily involved in cognition.

High-Dose Dexamethasone Versus Tocilizumab in Moderate to Severe COVID-19 Pneumonia: A Randomized Controlled Trial.

Background and objectives Recent randomized controlled trials (RCTs) have indicated potential therapeutic benefits with high-dose dexamethasone (HDD) or tocilizumab (TCZ) plus standard care in moderate to severe coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS). No study has compared these two against each other. We aimed to compare the efficacy and safety of HDD against TCZ in moderate to severe COVID-ARDS. Methods Patients admitted with moderate to severe COVID-19 ARDS with clinical worsening within 48 hours of standard care were randomly assigned to receive either HDD or TCZ plus standard care. The primary outcome was ventilator-free days (VFDs) at 28 days. The main secondary outcomes were 28-day all-cause mortality and the incidence of adverse events. Our initial plan was to perform an interim analysis of the first 42 patients. Results VFDs were significantly lower in the HDD arm (median difference: 28 days; 95% confidence interval (CI): 19.35-36.65; Cohen's d = 1.14;p < 0.001). We stopped the trial at the first interim analysis due to high 28-day mortality in the HDD arm (relative risk (RR) of death: 6.5; p = 0.007; NNT (harm) = 1.91). The incidence of secondary infections was also significantly high in the HDD arm (RR: 5.5; p = 0.015; NNT (harm) = 2.33). Conclusions In our study population, HDD was associated with a very high rate of mortality and adverse events. We would not recommend HDD to mitigate the cytokine storm in moderate to severe COVID-19 ARDS. TCZ appears to be a much better and safer alternative.

Magnetic resonance imaging (MRI) versus computed tomographic scan (CT scan) of brain in evaluation of suspected cavernous sinus syndrome.

BACKGROUND AND PURPOSE: The cavernous sinus is a unique region owing to anatomical factors and the pathologies affecting it. The diagnosis of cavernous sinus syndrome (CSS) predominantly relies on clinicoradiological correlation. We studied the utility of computed tomographic (CT) scan versus magnetic resonance imaging (MRI) in the diagnosis of CSS. METHODS: A prospective observational study was conducted in a tertiary care center in north India. All patients presenting with a clinical syndrome of cavernous sinus involvement with radiologically confirmed lesions were enrolled in the study. MRI and CT scan with cavernous sinus cuts were done and reviewed by experienced neuroradiologists for cavernous sinus lesions and compared with the final diagnosis. Sensitivity and specificity were calculated. RESULTS: We included 48 patients in our study. A final diagnosis was achieved in 41 out of 48 (85.6%) patients. Fungal infections (16 (33.3%)) constituted the commonest cause of CSS, followed by neoplastic involvement (13 (27.1%)) and Tolosa-Hunt syndrome (12 (25%)). Vascular involvement was seen in three (6.3%) patients. Other rare causes were seen in four (8.3%) patients. CT scan had an overall sensitivity of 14.6% in achieving a final diagnosis, whereas MRI had an overall sensitivity of 70.7%, with a statistically significant difference (p < 0.001). CONCLUSIONS: Although CT scan is a relatively cheap and accessible resource, its role in CSS diagnosis and management is limited because of poor yield. Hence, it is prudent to do an MRI as an initial investigation in cases of CSS.

Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study.

OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). PATIENTS AND METHODS: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). RESULTS: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. CONCLUSION: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.

Newer magnetic resonance imaging techniques in neurocysticercosis.

INTRODUCTION: The definitive diagnosis of neurocysticercosis continues to be challenging. We evaluate the role of newer magnetic resonance imaging techniques including constructive interference in steady state, susceptibility-weighted imaging, arterial spin labelling and magnetic resonance spectroscopy in the diagnosis of neurocysticercosis. AIMS AND OBJECTIVES: To study the utility of newer magnetic resonance imaging sequences in the diagnosis of neurocysticercosis. PATIENTS AND METHODS: Eighty-five consecutive patients with neurocysticercosis attending a tertiary care hospital and teaching centre in northern India were included in the study. The diagnosis of neurocysticercosis was made by the Del Brutto criteria. All patients received treatment according to standard guidelines and were followed at 3-month intervals. The following magnetic resonance sequences were performed at baseline: T1 and T2-weighted axial sequences; T2 fluid-attenuated inversion recovery axial sequences; diffusion-weighted imaging; susceptibility-weighted imaging; pre and post-contrast T1-weighted imaging; heavily T2-weighted thin sections (constructive interference in steady state); arterial spin labelling (n = 19); and magnetic resonance spectroscopy (n = 24). RESULTS: The mean (±SD) age was 29.4 ± 12.9 years and 76.5% were men. Seizures were the commonest symptom (89.4%) followed by headache (24.3%), encephalitis (9.4%) and raised intracranial pressure (9.4%). Scolex could be visualised in 43.7%, 55.5% and 61.2% of neurocysticercosis patients using conventional, susceptibility-weighted angiography and constructive interference in steady state imaging sequences, respectively. Susceptibility-weighted angiography and constructive interference in steady state images resulted in significantly higher (P < 0.01) visualisation of scolex compared to conventional sequences. CONCLUSION: Newer magnetic resonance imaging modalities have a lot of promise for improving the radiological diagnosis of neurocysticercosis.