A case series of post-infectious chikungunya myeloradiculoneuropathy.

Chikungunya fever is an arboviral illness caused by chikungunya virus (CHIKV) and transmitted by the bite of Aedes aegypti and Aedes albopictus. It is an RNA virus belonging to the genus Alphavirus and family Togaviridae. We present a case series of three patients with chikungunya illness developing para/post-infectious myeloradiculoneuropathy.These patients developed neurological symptoms in the form of bilateral lower limb weakness with sensory and bowel involvement after the recovery from the initial acute episode of chikungunya fever. Clinical examination findings suggested myeloradiculoneuropathy with normal Magnetic Resonance Imaging of the Spine, with the nerve conduction study showing sensorimotor axonal polyneuropathy. All the patients were treated with 1 g of methylprednisolone once a day for five days, and case 2 was given intravenous immunoglobulin also. In the follow-up, cases 1 and 2 showed complete recovery without recurrence, and case 3 did not show improvement at one month.

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.

Utilization of Truenat chips in defining XDR, pre-XDR and MDR in tuberculous meningitis.

SETTING AND OBJECTIVE: To develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB. DESIGN: 93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing. RESULTS: Against pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in ∼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA. CONCLUSION: The strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods.

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.

Role of vascular endothelial growth factor in tuberculous meningitis: A prospective study from a tertiary care center in North India.

INTRODUCTION: The status of vascular endothelial-derived growth factor (VEGF) in the pathogenesis of tuberculous meningitis (TBM) remains far from clear. We prospectively evaluated the role of serum and cerebrospinal fluid (CSF) VEGF in TBM. PATIENTS AND METHODS: This prospective study was conducted at a tertiary care center in North India from January 2018 to June 2019. Consecutive drug-naive patients (n = 82) of TBM diagnosed on the basis of modified Ahuja's criteria were included in the study. The results were compared with 49 control subjects (n = 49). Serum and CSF VEGF were done in all the cases and controls. Follow-up serum VEGF levels were done in 34 patients after 3 months of completion of antitubercular therapy. The VEGF levels were estimated using the human VEGF enzyme-linked immunosorbent assay kit. RESULTS: The mean age was 29.9 ± 13.1 years. The study group consisted of 33 (40.2%) men and 49 (59.8%) women. BACTEC MGIT960 was positive in 15 (18%) patients while multiplex tuberculosis polymerase chain reaction was positive in 73 (89%) patients. Levels of VEGF in serum and CSF of TBM patients were not elevated when compared to controls. There was no association between final outcome in TBM and decrease in serum levels of VEGF at follow-up. CONCLUSION: VEGF may not be playing a significant role in the pathogenesis of TBM. Future studies with larger sample size may clarify the status of VEGF further in TBM.

Endoscopic Ultrasound-Guided Transgastric Shunt Obliteration for Recurrent Hepatic Encephalopathy.

INTRODUCTION: Occlusion of spontaneous portosystemic shunts (SPSSs) in patients with cirrhosis may be required in recurrent or refractory hepatic encephalopathy. We describe a novel method for occlusion of SPSS using endoscopic ultrasound (EUS). METHODS: EUS-guided transgastric shunt obliteration was performed by injecting glue and coils directly into SPSS. RESULTS: EUS-guided transgastric shunt obliteration was performed for 7 patients in 9 sessions. Complete cessation of Doppler flow was achieved in 6/7 cases. Adequate clinical response was observed in 6/7 patients. No procedure-related severe adverse events were seen. DISCUSSION: This novel technique is a potentially effective and efficient method for shunt obliteration.

Determining the diagnostic potential of Truenat MTB Plus for Tubercular lymphadenitis and detection of drug resistance and a comparison with GeneXpert Ultra.

SETTING: Tubercular lymphadenitis (TBLA), the most common form of extrapulmonary tuberculosis, is a diagnostic challenge. OBJECTIVE: Truenat MTB Plus (TruPlus) along with Truenat Rif assay (TruRif) was evaluated for detection of TBLA and rifampicin resistance and compared with GeneXpert Ultra (Xpert Ultra). DESIGN: 100 fine-needle aspirated specimens [50 confirmed by culture/smear/cytology, 20 clinically suspected, and 30 controls], processed in the mycobacteriology division of department of microbiology were subjected to TruPlus and TruRif, Xpert Ultra and multiplex PCR. The results of TBLA detection were compared against composite reference standard (CRS) and those of rifampicin resistance were compared against phenotypic drug susceptibility testing and rpoB gene sequencing. RESULTS: In comparison to CRS, the diagnostic yield of TruPlus, Xpert Ultra and MPCR was 77.14%, 59.18% and 84.28%, respectively; with substantial agreement for TruPlus (k = 0.66) and MPCR (k = 0.76) and moderate for Xpert Ultra (k = 0.60). TruRif reported four cases as RifR and Xpert Ultra reported two. On comparing with phenotypic DST and gene sequencing, only two cases of RifR were confirmed, hence TruRif reported false-RifR in two cases. CONCLUSION: TruPlus could be used as a reliable tool for diagnosing TBLA. The reporting of RifR by TruRif should be confirmed by phenotypic DST or gene sequencing.

A Novel Wall Touch-Single Limb Stance Exercise for Dynamic Activation o f Gluteus Maximus - A Cross Sectional Study.

Objective: Gluteus maximus (GM) dysfunction is associated with spinal/lower extremity musculoskeletal conditions. Studies on weightbearing GM exercises that can be used earlier in rehabilitation is limited. Utilizing GM isometric contraction and load transmission to thoracolumbar fascia during trunk straightening under unilateral stance, we for the first time describe Wall Touch Single Limb Stance (WT-SLS) exercise. Specific exercise prescription may be rationalised using knowledge of how upper and lower fibres of GM (UGM, LGM) respond during novel WT-SLS. Methodology: Surface EMG signals from UGM and LGM were compared among WT-SLS, Step up (SU) and Unilateral wall squat (UWS) in healthy subjects (N = 24). Raw data was normalized and expressed as percentage of maximum voluntary isometric contraction (%MVIC). Relative easiness in performing the exercises was scored using Borg's CR10 scale. Statistical significance was defined as p < 0.05. Results: WT-SLS had the highest %MVIC for both UGM and LGM (p < 0.0001), suggesting maximum activation of GM in healthy adults by our novel exercise. WT-SLS generated more motor unit action potentials, and had significantly greater activity for UGM than LGM (p = 0.0429). Remaining exercises had no differential activation of UGM and LGM. WT-SLS was perceived as only 'slight' exertion. Conclusions: WT-SLS depicted the greatest muscle activation, suggesting possible better clinical and functional outcomes considering GM activation and strengthening. UGM was preferentially activated during WT-SLS, but not during SU and UWS. Therefore, targeting GM with our novel exercise may improve gluteal weakness and dysfunction in lumbar radiculopathy, knee ligament injuries; as preventive measure for injury; or for postural correction.

MPT51 and MPT64-based antigen detection assay for the diagnosis of extrapulmonary tuberculosis from urine samples.

In view of WHO's "End-TB" strategy, we developed a non-invasive, urine-based ELISA, targeting 2 Mycobacterium tuberculosis antigens namely MPT51 and MPT64 for extrapulmonary TB (EPTB) diagnosis. Suspected EPTB patients (n = 137) [Pleural TB, Abdominal TB and Tuberculous meningitis] were categorized in "Definite" EPTB (n = 10) [Xpert-MTB/RIF and/or culture-positive], "Probable" EPTB (n = 77) and "Non-EPTB" (n = 50) groups using defined composite reference standards. ROC-curves were generated using ELISA results of "Definite" EPTB and "Non-EPTB" groups for both antigens independently and cut-off values were selected to provide 86.3% (95%CI:73.3-94.2) specificity for MPT51 and 92% (95%CI:80.8-97.8) for MPT64. The sensitivity of MPT51-ELISA and MPT64-ELISA was 70% (95%CI:34.7-93.3) and 90% (95%CI:55.5-99.7) for "Definite" EPTB group and 32.5% (95%CI:22.2-44.1) and 30.8% (95%CI:20.8-42.2) for "Probable" EPTB group, respectively. Combining the results of both ELISAs showed a 100% (95%CI:69.1-100) sensitivity in "Definite" EPTB group and 41.6% (95%CI:30.4-53.4) in "Probable" EPTB group, with an 80% (95%CI:66.3-89.9) specificity. The results demonstrated the potential of urine-based ELISAs as screening tests for EPTB diagnosis.

Molecular diagnosis of Tuberculous meningitis: sdaA-based multi-targeted LAMP and GeneXpert Ultra.

SETTING: Nucleic acid amplification techniques like GeneXpert and GeneXpert Ultra (Xpert Ultra), the first-line tests for diagnosing Tuberculous meningitis (TBM), are expensive and depend on sophisticated equipment. OBJECTIVE: The diagnostic potential of multitargeted loop-mediated isothermal assay (MLAMP), a low-cost simple test using novel gene combination, was evaluated for TBM. DESIGN: 300 CSF specimen (200 TBM patients, 100 controls) processed between January 2017 and December 2021 were subjected to MLAMP (using sdaA, IS1081 and IS6110 gene targets), sdaA PCR and Xpert Ultra. The performance was evaluated against uniform case definition as per Marais criteria, and against culture. RESULTS: Uniform case definition classified 50 as definite TBM and 150 as probable or definite TBM. Against this uniform case definition, the sensitivity and specificity of MLAMP was 88% and 100%, respectively. The sensitivity was 96% against culture-positive cases and 85.3% against culture-negative cases. The sensitivity of sdaA-LAMP, IS1081-LAMP, IS6110-LAMP, Xpert Ultra and sdaA-PCR was 82.5%, 80.5%, 85.3%, 67% and 71%, respectively against uniform case definition. sdaA-LAMP detected additional two cases and IS1081-LAMP detected nine. 11 of 134 (8.2%) cases were reported rifampicin resistant by Xpert Ultra. CONCLUSION: MLAMP, incorporating sdaA and IS1081, is a cheap, easy and accurate first-line diagnostic test for TBM.

Extensive Multifocal Emphysematous Osteomyelitis of Spine: A Rare Case and a Review of Literature.

BACKGROUND: Emphysematous osteomyelitis (EO) is an extremely rare form of osteomyelitis which is complicated mainly by infection with gas-forming organisms. The common causative agents of this disease are mainly members of Enterobacteriaceae family, the most common are Escherichia coli and Klebsiella pneumoniae along with anaerobes. A total of 48 cases of EO have been reported in the literature till now globally and none have documented the isolation of Corynebacterium amycolatum. CASE PRESENTATION: We report a rare case of emphysematous osteomyelitis of the spine and pelvis due to Escherichia coli along with the isolation of Corynebacterium amycolatum from the same pus samples on two consecutive occasions in a 50-year-old female with uncontrolled diabetes mellitus, who was successively treated with antibiotics and drainage of pus. We also did a brief review of the literature of all cases reported till now. CONCLUSION: The role of Corynebacterium amycolatum in the etiology of emphysematous osteomyelitis needs to be evaluated further in future studies as we cannot completely ignore its isolation in two consecutive samples as a mere contaminant.

Utility of cell-free transrenal DNA for the diagnosis of Tuberculous Meningitis: A proof-of-concept study.

Tuberculous Meningitis (TBM) diagnosis remains a grave challenge. We evaluated the utility of extracellular vesicles (EVs) as a source of cell-free transrenal-mycobacterial DNA (cf-Tr-MTB DNA) for TBM diagnosis from urine samples. We developed a qPCR-assay targeting a highly repetitive 36-bp sequence specific to Mycobacterium tuberculosis complex. EVs were isolated from urine samples of suspected TBM groups (n = 44) [categorized using composite reference standard as 'Definite' TBM (n = 8), 'Probable' TBM (n = 15), 'Possible' TBM (n = 21)] and 'Non-TBM' group (n = 26). cf-Tr-MTB DNA-based qPCR assay was applied to DNA isolated from EVs (EV-DNA) and EV-free-fraction (EV-free DNA). ROC-curves were generated using qPCR results of 'Definite' TBM and 'Non-TBM' category in both EV-DNA and EV-free DNA samples and cut-off values were selected to provide 100% (95%CI:69.1-100) specificity. The cf-Tr-MTB DNA assay gave a sensitivity of 54.5% (95%CI:38.8-69.6) for EV-DNA and 77.3% (95%CI:62.1-88.5) for EV-free DNA in the TBM group (n = 44). The combination of EV-DNA and EV-free DNA results (corresponding to performance cf-Tr MTB DNA assay in urine), gave an overall sensitivity of 81.8% (95%CI:67.2-91.8) in the TBM group. Our results confirmed EVs as one of the sources of cf-Tr-MTB DNA and we believe the cf-Tr-MTB DNA-based qPCR assay has a potential application for TBM diagnosis.

Impact of the COVID-19 Pandemic on the Frequency, Clinical Spectrum and Outcomes of Pediatric Guillain-Barré Syndrome in India: A Multicentric Ambispective Cohort Study.

Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75-11.25] years versus 5 (2.5-8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1-3.5) versus 3 (2-4); P = 0.042) and GBS disability score at 3 months (median 0 (0-0.75) versus 2 (0-3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.

Oculomotor Cranial Neuropathies: Diagnosis and Management.

Ocular nerve palsies are among the most common cranial neuropathies in neurological practice. Nerves can get affected anywhere along their path from the brainstem to the orbit. There can be isolated involvement of multiple cranial nerves together. The etiologies differ according to the type of presentation. The steps toward the diagnosis need to be strategically planned and must be based on clinical localization. It is crucial to make proper localization to plan further investigations and thus treatment of the etiology. This review covers the approach toward the diagnosis, etiologies involved, and management of ocular cranial neuropathies.

Impact of COVID-19 on Guillain-Barre Syndrome in India: A Multicenter Ambispective Cohort Study.

Introduction/Aims: Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic have reported varied data regarding the incidence of Guillain-Barre syndrome (GBS). The present study investigated demographic and clinical features, management, and outcomes of patients with GBS during a specified period of the COVID-19 pandemic, and compared these features to those of GBS in the previous year. Methods: A multicenter, ambispective cohort study including 26 centers across India was conducted. Data from a pre-COVID-19 period (March 1 to August 31, 2019) were collected retrospectively and collected ambispectively for a specified COVID-19 period (March 1 to August 31, 2020). The study was registered with the Clinical Trial Registry India (CTRI/2020/11/029143). Results: Data from 555 patients were included for analysis: pre-COVID-19 (n = 334) and COVID-19 (n = 221). Males were more commonly affected during both periods (male:female, 2:1). Gastroenteritis was the most frequent antecedent event in 2019 (17.4%), whereas fever was the most common event in 2020 (10.7%). Paraparesis (21.3% versus [vs.] 9.3%, P = 0.001) and sensory involvement (51.1% vs. 41.3%; P = 0.023) were more common during COVID-19 in 2020, whereas back pain (26.3% vs. 18.4%; P = 0.032) and bowel symptoms (20.7% vs. 13.7%; P = 0.024) were more frequent in the pre-COVID period. There was no difference in clinical outcomes between the two groups in terms of GBS disability score at discharge and 3 months after discharge. Independent predictors of disability in the pre-COVID period included areflexia/hyporeflexia, the requirementfor intubation, and time to bulbar weakness; in the COVID-19 period, independent predictors included time from onset to admission, intubation, and intubation requirement. The mortality rate was 2.3% during the entire study period (13/555 cases). Discussion: Results of this study revealed an overall reduction in the frequency of GBS during the pandemic. The lockdown likely reduced the risk for antecedent infections due to social distancing and improved hygiene, which may have resulted in the reduction of the frequency of GBS.