Mycobacterium abscessus Complex-Associated Chronic Meningitis: Time to Think Beyond Tuberculosis.

Background: Mycobacterium abscessus complex (MabC) has emerged as an important cause of human infections, including meningitis. In the absence of correct microbiological identification, cases of MabC meningitis are treated with conventional anti-tubercular therapy, thereby worsening the outcome. Objective: The current study was conducted to determine the clinical features, antimicrobial susceptibility, and outcome of patients with MabC meningitis. Material and Methods: Cerebrospinal fluid specimens processed between 2011 and 2021 were subjected to smear, culture, MALDI TOF identification, hsp65 gene sequencing, and susceptibility testing using Sensititre™ RAPMYCOI plates along with a literature review. Results: 12 cases of MabC meningitis were identified between 2011 and 2021, 11 of which were M. abscessus subspecies abscessus on hsp65 gene sequencing. A pioneer case of meningitis with M. abscessus subspecies bolletii was also identified. The common predispositions were TB elsewhere, HIV positivity, and head injury. Two patients had dual infections, both MabC and TB. Ten patients succumbed to infection with a mean survival of 11 months. All isolates were susceptible to amikacin and tigecycline and subspecies bolletii had a higher minimum inhibitory concentration (MIC) than subspecies abscessus. A combined analysis with the available literature, reporting 19 more cases, revealed that the overall mortality of MabC meningitis was 61.3% (19/31) and that of shunt-associated/neurosurgical intervention-related MabC meningitis was 66.7% (12/20). To date, out of 20 MabC meningitis isolates in which subspecies identification was carried, 13 were M. abscessus, six were M. massiliense, and one was M. bolletii. Conclusion: MabC is an important differential diagnosis of chronic meningitis. Prompt identification and speciation are imperative for targeted therapy, thus improving the overall patient outcome.

Review of Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly. This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords "SARS-CoV-2" and "neurological illness" for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes. Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals' brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients' CSF post hoc SARS-CoV-2 infection. Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

Comparison of Protein B Polymerase Chain Reaction (PCR) With IS6110 PCR for Diagnosis of Tuberculous Meningitis Patients.

Purpose Tuberculous meningitis (TBM) is a diagnostic challenge. With the conventional staining and culture techniques being too insensitive and time-consuming, and the commercial detection systems being costly, polymerase chain reaction (PCR) seems lucrative for routine laboratories. The purpose of this study was to evaluate the diagnostic potential of protein b antigen polymerase chain reaction (Pab PCR) for TBM, in comparison to IS6110. Another purpose was to compute a cut-off at which adenosine deaminase (ADA) could diagnose TBM. Material and methods This is a prospective case-control study to measure the diagnostic accuracy of PCR, BACTEC culture, Lowenstein-Jensen (LJ) culture, ADA, and acid-fast bacilli (AFB) smear tests in TBM. CSF from 50 TBM patients (10 confirmed, 40 clinically suspected) and 40 controls was subjected to Pab PCR and IS6110 PCR, and performance was compared against culture and composite reference standards. Results The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Pab PCR in diagnosing TBM were 82%, 100%, 100%, and 81.63%, respectively, and that of IS6110 PCR were 74%, 100%, 100%, and 75.47%, respectively. Both PCRs outperformed culture (p<0.001). Though performance of both PCRs was comparable (p=0.335) with excellent agreement (k=0.86), Pab PCR detected four additional cases, one culture-positive and three culture-negative clinically suspected. ADA of 6.5 IU/L was able to differentiate between TBM and non-TBM with 86% sensitivity and 63% specificity. Conclusions Molecular tools such as PCR have the potential to increase the clinician's ability to diagnose tuberculous meningitis. Pab PCR is a rapid and reliable method for diagnosing TBM in routine microbiology laboratories.

The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review.

Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.

A Case of a 23-Year-Old Male With Leber Hereditary Optic Neuropathy With a Rare Mutation.

Mitochondrial DNA (mtDNA) is responsible for encoding 13 subunits of the respiratory chain. These subunits are crucial in providing reducing equivalents for the energy-intensive intracellular processes. Leber hereditary optic neuropathy (LHON) is a mitochondrial illness that causes carcinogenesis due to oxidative stress and painless loss of central vision as a result of selective degradation of retinal ganglion cells as well as their axons. We present a case of a 23-year-old male patient who was diagnosed with subacute LHON. The mutation in our patient was found in a less commonly mutated exon sequence of MT-NDL4, which codes for NADH (nicotinamide adenine dinucleotide hydrogen, reduced) dehydrogenase subunit 4L. The MT-ND4L exon is located immediately upstream of the MTD4 exon on the human mtDNA. The take-home message is to always perform a comprehensive mitochondrial genome analysis for identifying rare mutations when LHON is suspected.

Ataxia Telangiectasia Presenting as Cervical Dystonia.

The ataxia telangiectasia mutant (ATM) protein is a sensor and signal transducer that amplifies and communicates signals of DNA damage further to the mediators of cell cycle arrest, apoptosis, and senescence (p16, p19, p21, BAX etc.) which is modified by the strength of the cellular stress. They are able to act as recognition and signaling proteins because of their kinase activity. Classic ataxia telangiectasia is associated with homozygous mutations of the ATM gene, the complete absence of its kinase activity and/or deleterious ATM gene mutations such as truncation/nonsense mutations, loss of function mutation, non-conservative substitutions, frameshift, and deletions. On the other hand, variant ataxia-telangiectasia (A-T) is associated with the presence of residual kinase activity. We report a six-year-old male patient who presented to us with abnormal neck movements as his initial complaint. ATM gene analysis showed a rare pathogenic variant of the ATM gene. The variant was a homozygous nonsense mutation in exon 2 of the ATM gene that resulted in the formation of a stop codon and premature truncation of the protein at codon 23 in exon 2 (p.Arg23Ter). In conclusion, we report a case of an unusual presentation of classic A-T. We should pursue a long-term follow-up and maintain a low threshold for performing pedigree analysis and genetic testing in pediatric patients with movement disorders. In resource-limited settings where kinase enzyme assays are not universally available to patients, web-based mutation prediction tools may be beneficial to predict the deleterious effects of the mutation.

The Spectrum of MRI Findings in Dengue Encephalitis.

Background In this study, we aimed to describe eight cases of dengue encephalitis along with their magnetic resonance imaging (MRI) findings. Dengue encephalitis is caused by an arbovirus that has four strains DENV1-DENV4. The dengue virus is usually non-neurotropic but DENV2 & DENV3 are neurotropic. Dengue encephalitis is characterized by headaches, seizures, and altered consciousness. Methodology At our facility, we performed 3T MRI on eight suspected cases of dengue encephalitis using the criteria established by Varatharaj et al. We were able to diagnose dengue encephalitis based on the proposed criteria which included symptoms, serology, cerebrospinal fluid (CSF) analysis results, MRI findings, and routine blood laboratory workup in dengue encephalitis. Because numerous brain regions are potentially impacted in severe cases of dengue encephalitis, an MRI of the brain can reveal the severity of the condition. In deteriorating situations, it may detect whether or not further regions are being impacted. Hence, MRI should be done in all suspected cases of dengue encephalitis. Results The changes observed on MRI of the eight cases were in the supra-tentorium (deep periventricular white matter, subcortical white matter, and deep gray matter of the brain, which includes basal ganglia and thalami), infra-tentorium (cerebellar white matter and brainstem, which includes pons), and occasionally in cortical gray matter. The MRI showed mild-to-moderate hyperintensities on T2-weighted images and fluid-attenuated inversion recovery sequence (FLAIR); diffusion restriction is seen on diffusion-weighted images. The neurological clinical features included non-localizing signs and symptoms such as altered mental status, headache with vomiting, and fever. Conclusions The commonly affected areas of the brain in dengue encephalitis are the basal ganglia, thalamus, brainstem, cerebellum, cortical white matter, periventricular white matter, and cortical gray matter, which are all hyperintense on T2-weighted images and FLAIR. The lesions are iso or hypointense on T1-weighted images and micro-hemorrhages appear as blooming on susceptibility-weighted MRI. MRI is a crucial initial investigation in suspected cases of dengue encephalitis and known cases of dengue fever experiencing worsening neurological conditions.

Myelitis Following COVID-19 Illness.

COVID-19 occurs due to infection by the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2), which has caused havoc globally. It presents with a wide range of symptoms, mainly respiratory symptoms, but with time various neurological manifestations of the disease have also been noted, like myelitis. This case report aims to shed light on COVID-19-associated myelitis so that potential neurological complications of COVID-19 can be identified and treated timely. We report a case of a 41-year-old male who presented with weakness of all limbs with urinary complaints. He also had a cough and sore throat for the past few days. The MRI scan of the spine showed long segment myelitis in the cervical cord extending from the cervicomedullary junction to the upper end of the C4 vertebral body. COVID-19 myelitis is a rare but severe complication of COVID-19 infection and needs to be discussed.

Myelin Oligodendrocyte Glycoprotein Antibody Disease After COVID-19 Vaccination - Causal or Incidental?

A variety of neurological complications of COVID-19 vaccinations are reported with each passing day. We report a rare case of a patient who developed brain stem and spinal cord lesions 20 days after the first dose of the ChAdOx1 nCoV-19 coronavirus vaccine. On further investigation, anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies were strongly positive, and a diagnosis of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) was made. This case report aims to add a rare entity to the possible complications of COVID-19 vaccines and discuss symptoms, MRI findings, and the differential diagnosis of MOGAD. We also suggest that these patients undergo follow-up serological tests to recognize recurrences quickly.

An Interesting Case of CMV Retinitis in a Case of ALL on Maintenance Therapy.

Forty-five years old male, a known case of T cell acute lymphoblastic leukemia (ALL) on maintenance therapy presented with bilateral painless progressive diminution of vision. Evaluation revealed cytomegalovirus (CMV) retinitis with low CD4 counts. CMV retinitis is usually seen in HIV disease or in post allogenic stem cell transplant recipients. CMV retinitis occurring in ALL maintenance phase is very rare. The disease is aggressive and shows incomplete response to medical therapy.

Acute Marchiafava-Bignami disease presenting as reversible dementia in a chronic alcoholic.

Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism. Its clinical diagnosis has considerably changed during recent times, with MRI of the brain paving way for in life diagnosis. We believe that physicians need to have a high index of suspicion, because acute onset MBD is not always fatal and complete recovery is possible, provided the diagnosis is made early and treated appropriately. We report a case of MBD who was diagnosed early in the disease course with subsequent clinical and radiological recovery on institution of appropriate treatment.