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.

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.