Diagnostic Utility of Multiplex Polymerase Chain Reaction in Patients of Clinically Suspected Pure Neuritic Leprosy by Identifying Mycobacterium leprae in Skin Biopsy Samples and Nasal Swabs.

Pure neuritic leprosy (PNL) often remains underdiagnosed due to the lack of simple, reliable diagnostic tools to detect Mycobacterium leprae. This study aimed to investigate the utility of multiplex polymerase chain reaction (MPCR) in easily accessible and less invasive biopsy sites, including skin biopsy samples and nasal swabs (NSs), to detect M. leprae. A total of 30 (N = 30) clinically suspected and untreated patients with PNL were recruited. Nasal swabs and skin biopsy samples from the innervation territory of an "enlarged nerve" were collected. DNA was extracted and subjected to MPCR (targeting leprae-specific repetitive element [RLEP], 16S rRNA, and SodA genes) and RLEP-PCR (individual gene PCR). The PCR products were analyzed by 3% agarose gel electrophoresis. In 30 patients with clinically suspected PNL, 60% (N = 18) of skin biopsy samples and 53% (N = 16) of NSs were found positive for M. leprae DNA by MPCR, whereas only 23.3% (N = 7) of skin biopsy samples and 10% (N = 3) of NSs were found positive by RLEP-PCR. MPCR demonstrated a greater positivity rate than did RLEP-PCR for detection of M. leprae. Serologic positivity for anti-natural disaccharide-octyl conjugated with bovine serum albumin (ND-O-BSA) antibodies was 80% (16/20), including 35% (7/20) of PNL patients for which the skin MPCR was negative. Both serologic positivity and skin MPCR positivity were observed in 65% of patients (N = 20). Multiplex polymerase chain reaction is a useful tool for detection for M. leprae in skin biopsy samples and NSs in clinically suspected cases of PNL, with the added advantages of being less invasive and technically easier than nerve biopsy.

Circulating cell-free DNA as a biomarker for molecular diagnosis of Neurocysticercosis.

Taenia solium is a widespread zoonotic tapeworm that predominantly affects regions of Latin America, South and South-East Asia, and Sub-Saharan Africa. Neurocysticercosis (NCC), the presence of T. solium cysts in the brain is associated with diverse clinical manifestations, such as epilepsy, seizures, and neurological deficits. It is a significant cause of preventable epilepsy globally, accounting for approximately 30% of cases in endemic regions. The diagnosis of neurocysticercosis relies on neuroimaging techniques, but these resources are often limited in low-income countries, resulting in an underestimation of the disease burden. The present study enrolled 141 patients who were clinically suspected and radiologically confirmed for NCC at the Neurology OPD of PGIMER, Chandigarh. Additionally, 98 control subjects attending the PGIMER OPD for investigation were also included. Plasma and urine samples were collected from all participants for further analysis. Cell-free DNA extraction was performed using specific kits, and the quality of the extracted DNA was assessed. The RT-LAMP assay targeted the cox1 gene. Real-time RT-LAMP results were evaluated using a fluorescence graph obtained with the Genei III fluorimeter. Among a group of patients diagnosed with NCC, the gene was identified in 74.4% of plasma samples and 67.3% of urine samples. In comparison, the T. solium cox1 gene was found in 6.1% of control subjects in plasma and urine samples using the LAMP assay. In conclusion, the study emphasises the need for improved diagnostic methods for NCC and presents promising alternatives, such as RT-LAMP and urine-based cell-free DNA analysis. These approaches offer advantages in terms of cost-effectiveness, simplicity, and diagnostic accuracy.

A mobile application-based post-stroke care strategy for survivors and their caregivers for prevention and management of post-stroke complications - "Stroke Home Care:" Development and feasibility.

Objectives: In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. Materials and Methods: The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. Results: The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. Conclusion: The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.

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.

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.

Role of MicroRNAs as post transcription regulators of matrix metalloproteinases and their association in tuberculous meningitis.

Matrix metalloproteinases (MMPs) have a role in driving neuroinflammation in infectious as well as non-infectious diseases; however, recent reports have potentiated the role of microRNAs in regulating MMPs at post-transcriptional levels, leading to dysregulation of crucial MMP functions like tissue remodelling, blood brain barrier integrity, etc. In present study, microRNAs regulating MMPs (MMP2 and MMP3) were selected from database search followed by literature support. Expression of these microRNAs i.e., hsa-miR-495-3p, hsa-miR-132-3p and hsa-miR-21-5p was assessed by RT-PCR and the protein levels of MMPs were assessed by ELISA in the cerebrospinal fluid (CSF) of tuberculous meningitis (TBM) patients, healthy controls (HC) and non-infectious neuroinflammatory disease (NID) patients. The expression of hsa-miR-495-3p and hsa-miR-132-3p showed downregulation in TBM while hsa-miR-21-5p was overexpressed as compared to healthy controls. Moreover, MMP levels were found to be deranged with a significant increase in MMP3 levels in the TBM and NID patients compared to HC group. These observations highlight dysregulated microRNAs (hsa-miR-495-3p, hsa-miR-21-5p and hsa-miR-132-3p) levels might impair the levels of MMPs (MMP2 and MMP3) leading to neuroinflammation in TBM and NID population. These findings can further be applied to target these microRNAs for developing newer treatment modalities for better complication management.

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.

Neurocognitive Functions After 6-Month Buprenorphine (Naloxone)-Based Opioid Agonist Maintenance Treatment: A Controlled Prospective Study.

BACKGROUND: Medications for opioid use disorder (OUD) may influence neurocognitive functions. Inadequate power, confounders, and practice effects limit the validity of the existing research. We examined the change in cognitive functions in patients with OUD at 6-month buprenorphine (naloxone) posttreatment and compared the cognitive performance of the buprenorphine-treated group with control subjects. METHODS: We recruited 498 patients with OUD within a week of initiating buprenorphine. Assessments were done twice-at baseline and 6 months. Those abstinent from illicit opioids and adherent to treatment (n = 199) underwent follow-up assessments. Ninety-eight non-substance-using control subjects were recruited from the community. The neurocognitive assessments comprised the Wisconsin Card Sorting Test, Iowa Gambling Task, Trail-Making Tests A and B (TMT-A and TMT-B), and verbal and visual N-Back Test. We controlled for potential effect modifiers. RESULTS: Twenty-five of the 32 test parameters significantly improved with 6 months of buprenorphine treatment; 20 parameters withstood corrections for multiple comparisons (P < 0.001). The improved test domains spread across cognitive tests: Wisconsin Card Sorting Test (perseverative errors and response, categories completed, conceptual responses), TMTs (time to complete), verbal and visual N-Back Tests (hits, omission, and total errors). After treatment, OUD (vs control subjects) had less perseverative response and error (P < 0.001) and higher conceptual response (P = 0.004) and took lesser time to complete TMT-A (P < 0.001) and TMT-B (P = 0.005). The baseline neurocognitive functions did not differ between those who retained and those who discontinued the treatment. CONCLUSION: Cognitive functions improve in patients with OUD on buprenorphine. This improvement is unlikely to be accounted for by the practice effect, selective attrition, and potential confounders.

Neurocognitive Dysfunctions in People with Concurrent Cannabis Use and Opioid Dependence: A Cross-Sectional, Controlled Study.

Cannabis and opioid co-dependence is independently associated with cognitive impairments. We examined neurocognitive dysfunctions in people with concurrent opioid dependence with cannabis dependence (OD+CD) or cannabis use (OD+CU) compared to those with only opioid dependence (OD) and healthy controls (HC). We selected adult participants, any sex, who met the diagnosis of OD (N = 268), OD+CU (N = 58), and OD + CD (N = 115). We recruited 68 education-matched HC. We administeredStandard progressive matrices (SPM), Wisconsin card sorting test (WCST), Iowa gambling task (IGT), Trail making tests A and B (TMT), and verbal and visual working memory 1-, 2-backtests. 496 (97.5%) were men, and 13 (2.5%) were women. In WCST, OD and OD+CD had significantly higher non-perseverative errors than HC. OD+CD group completed significantly lesser categories than HC. In verbal working memory 2-back, HC scored significantly fewer errors than OD and OD +CD. All patient groups, OD, OD+CU, and OD+CD, scored higher commission errors than HC in visual working memory 1-back. OD and OD+CD scored higher commission and total errors than the controls. OD+CU showed lesser error score than HC in TMT B. Cannabis and opioid co-dependence contribute to cognitive impairments, especially in working memory and executive functions.

"Comparative evaluation of different chemical agents induced Autism Spectrum Disorder in experimental Wistar rats".

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with uncertain etiology and pathophysiology. Several studies revealed that the commonly used animal models like Valproic Acid (VPA) and Propionic Acid (PPA) do not precisely represent the disease as the human patient does. The current study was conducted on different chemically (VPA, PPA, Poly I:C, Dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)) & Chlorpyrifos (CPF)) induced ASD-like animal models and validated the best suitable experimental animal model, which would closely resemble with clinical features of the ASD. This validated model might help to explore the pathophysiology of ASD. This study included rat pups prenatally exposed to VPA, PPA, Poly I:C, Dioxin & CPF within GD9 to GD15 doses. The model groups were validated through developmental and behavioral parameters, Gene Expressions, Oxidative Stress, and Pro-inflammatory and Anti-inflammatory cytokines levels. Developmental and neurobehavioral parameters showed significant changes in model groups compared to the control. In oxidative stress parameters and neuro-inflammatory cytokines levels, model groups exhibited high oxidative stress and neuro-inflammation compared to control groups. Gene expression profile of ASD-related genes showed significant downregulation in model groups compared to the control group. Moreover, the Poly I:C group showed more significant results than other model groups. The comparison of available ASD-like experimental animal models showed that the Poly I:C induced model represented the exact pathophysiology of ASD as the human patient does. Poly I:C was reported in the maternal immune system activation via the inflammatory cytokines pathway, altering embryonic development and causing ASD in neonates.

Study of fingolimod, nitric oxide inhibitor, and P-glycoprotein inhibitor in modulating the P-glycoprotein expression via an endothelin-sphingolipid pathway in an animal model of pharmacoresistant epilepsy.

BACKGROUND: The overexpression of P-glycoprotein (P-gp) contributes to drug resistance in patients with epilepsy, and the change of P-gp expression located at the blood-brain barrier alienates the anti-seizure effects of P-gp substrates. Thus, the present study explored the effect of fingolimod (FTY720) acting through an endothelin-sphingolipid pathway on P-gp-induced pentylenetetrazol (PTZ)-kindled phenobarbital (PB)-resistant rats. MATERIALS AND METHODS: PTZ kindling (30 mg/kg; i.p.) and PB (40 mg/kg; orally) were used to develop an animal model of refractory epilepsy. The effect of Fingolimod on seizure score (Racine scale), plasma and brain levels of PB (high-performance liquid chromatography), and blood-brain barrier permeability (Evans blue dye) was determined. Further, Fingolimod's neuroprotective effect was determined by measuring the levels of various inflammatory cytokines, oxidative stress parameters, and neurotrophic factors in rat brain homogenate. The Fingolimod's effect on P-gp expression was estimated by reverse transcriptase-polymerase chain reaction and immunohistochemistry in rat brain. The H and E staining was done to determine the neuronal injury. RESULTS: Fingolimod significantly (P < 0.001) reduced the seizure score in a dose-dependent manner and alleviated the blood-brain barrier permeability. It decreased the P-gp expression, which further increased the brain PB concentration. Fingolimod significantly (P < 0.01) reduced oxidative stress as well as inflammation. Moreover, it attenuated the raised neuronal injury score in a resistant model of epilepsy. CONCLUSION: The modulation of the P-gp expression by Fingolimod improved drug delivery to the brain in an animal model of refractory epilepsy. Therefore, S1P signaling could serve as an additional therapeutic target to overcome refractoriness.

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.

Association Between CYP2C19 Genotypes With Clinical Phenotypes and Adipokine Levels Among Ischemic Stroke Patients: A Prospective Observational Study.

Background Cytochrome P450 system is implicated in vascular pathologies, including stroke. Besides its role as a drug metabolizer, it also plays an important role in the metabolism of several endogenous substances like fatty acids, arachidonic acid, etc., which have pro-inflammatory effects. On the other hand, leptin and adiponectin are two of the most common adipose tissue-derived cytokines (adipokines), which are pro-inflammatory and anti-inflammatory in nature, respectively. Both of them are implicated in the pathogenesis of stroke. Methods We prospectively recruited ischemic stroke patients (within three months of occurrence of an attack of stroke). The occurrence of composite outcome (recurrence of transient ischemic attack/ischemic stroke or death) was evaluated for association with genetic variants of CYP2C19 (allele *2, *17, *3, and *4, i.e., single nucleotide polymorphism (SNP) 1/2/3/4, identified using TaqMan assays and DNA sequencing). Adiponectin and leptin levels were determined using an enzyme-linked immunosorbent assay. Comparisons were made between stroke vs. control patients and between CYP2C19 intermediate metabolizer (IM)/poor metabolizer (PM) vs. extensive metabolizer (EM)/ultra metabolizer (UM) (PM: *2/*2; IM: *1/*2 vs. EM: *1/*1; UM: *1/*17). P < 0.05 was taken as the threshold for statistical significance. Results A total of 204 patients and 101 controls were recruited. With regard to the occurrence of stroke, SNP2 showed a significant positive association. Haplotypes (SNP1/SNP2) AC (OR = 1.75 (1.08-2.83), p = 0.024) and GT (OR = 3.33 (1.53-7.22), p = 0.0026) were strongly associated with the occurrence of ischemic stroke even after adjustment for age and sex (global haplotype association p-value: 0.0062). Haplotype phenotype gender interaction was evident. Among stroke patients, with regard to composite outcome, only SNP1 showed a positive association. The AC haplotype was significantly associated with the occurrence of composite outcome (OR = 2.27 (1.17-4.41), p = 0.016). Among stroke patients, a significant positive association was seen between death and SNP1 (OR = 2.35 (1.13-4.90), p = 0.021) and AC haplotype (OR = 2.73 (1.20-6.22), p = 0.018). However, none of the SNPs or haplotypes showed any association with recurrence. Significant higher leptin and lower adiponectin levels were observed among stroke patients compared to controls. Leptin levels were higher in IM/PM group. IM/PM phenotypes showed a higher incidence of occurrence of composite outcome (hazard ratio = 2.07 (0.96-4.47), p = 0.056). Conclusion CYP2C19 polymorphisms may play a significant role in the pathogenesis of stroke. Leptin could serve as a prominent biomarker of atherosclerosis and inflammation in the early post-stroke period; however, further study is warranted with a larger sample size.

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.

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.

Heroin use and neuropsychological impairments: comparison of intravenous and inhalational use.

BACKGROUND AND OBJECTIVES: Injection and inhalational heroin use are associated with different levels of brain exposure to heroin and its metabolites and differences in the severity of dependence, which might lead to differential impacts on neuropsychological functions. We examined the difference and the magnitude of difference in the neuropsychological functions between inhalational and injection heroin-dependent subjects and also compared them with healthy controls. METHODS: The study sample comprised three groups: 73 subjects with injection heroin dependence, 74 with inhalational heroin dependence, and 75 healthy controls (HC). We excluded patients with HIV, head injury, epilepsy, and severe mental illness. Neuropsychological assessments were done by Standard Progressive Matrices, Wisconsin Card Sorting Test (WCST), Iowa Gambling Task, Trail-Making Tests A and B (TMT), and Verbal and Visual Memory 1 and 2 Backtests (NBT). We estimated independent effects of the groups on various neuropsychological test parameters, adjusted for age and duration of dependence. RESULTS: In the WCST, the inhalational heroin-dependent group took more trials to complete the first category and had higher scores in the failure to maintain set than controls. The intravenous group had higher total errors than controls in verbal working memory tests and Visual Working Memory 2 Backtest. This group scored higher commission errors in the Verbal 2 Backtest than the controls. The two groups of heroin users differed in failure to maintain set and Verbal Working Memory 2 Backtests. The effect sizes of the group differences were modest. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Either route of heroin use is associated with cognitive impairments; inhalational and injection use involve different cognitive domains.

Complex neurocysticercosis lesions on imaging: Explained through correlative histomorphology.

OBJECTIVES: Neurocysticercosis, the commonest neuro-parasite, sometimes presents as complex ring enhancing lesion causing diagnostic dilemma. We aim to establish radio-histo-morphological equivalents of early events in degeneration of the parasite to explain such imaging phenotypes. METHODS: We compared patterns of degeneration in 23 randomly selected complex NCC on MRI with histo-morphology in 30 cysts obtained from an unrelated post mortem brain. RESULTS: The anatomy of the parasite and the degenerative patterns of the scolex (hydropic changes, calcification, evagination, and fragmentation) and the cyst wall (undulation, accessory loculi, and frank disruption) were well demonstrated on both. The intact scolex remarkably resembled head of intestinal Taenia. The complex lesions were conglomeration of multiple communicating cysts with a single parent cyst and multiple daughter cysts. The parent cysts contained a solitary variably degenerated scolex, had thicker walls and associated chronic inflammation. The remaining cysts of the lesion complex contained no scolex, had poorly organized walls, turbid contents, and florid perilesional enhancement with leakage of contrast. Three lesions assumed a multi-cystic pseudo-tumorous pattern, of which two resolved into solitary calcific remnants on follow up. CONCLUSION: Complex lesion in NCC result from degeneration of solitary parasite with perilesional gliosis, surrounded by multiple non-larval daughter cysts inciting acute intra and perilesional inflammation due to enhanced antigenic challenge. Possibly, attempted abortive asexual reproduction by the cellulose cyst as a preterminal event results in a "limited Racemose like transition." Correct interpretation has diagnostic and therapeutic implications as active lesions and their fibrocalcific residue may have greater epileptogenic potential.

Novel therapeutic mechanism of action of metformin and its nanoformulation in Alzheimer's disease and role of AKT/ERK/GSK pathway.

INTRODUCTION: Brain Insulin-resistance plays a critical role in pathogenesis of Alzheimer's disease (AD). Current study explored the therapeutic mechanism of metformin (insulin sensitizer) and its solid-lipid nanoformulation (SLN) in rat-model of AD. In our study, SLN was prepared using microemulsion method. AD was induced with ICV-Aß whereas the control-group (sham) received ICV-NS. Treatment arms included, disease-control (no treatment), Metformin (50 mg/kg, 100 mg/kg and 150 mg/kg), SLN-metformin 50 mg/kg and memantine 1.8 mg/kg (positive-control). Animals were tested for cognitive performance (EPM, MWM) after 21 days of therapy and sacrificed. Aß (1-42), hyperphosphorylated tau, pAKTser473, GSK-3ß, p-ERK (ELISA), metformin level(HPLC), neuronal injury score(H&E), Bcl2 and Bax(IHC) was evaluated in isolated brain. In our study, metformin-SLN were of spherical shape (size<200 nm) with 94.08% entrapment efficiency. Metformin was detectable in brain. Compared to sham, the disease-control group showed significantly higher (p ≤ 0.05) memory impairment(MWM and EPM), hyperphosphorylated tau, Aß(1-42), neuronal-injury, Bax and lower Bcl-2 expression. Treatment with metformin and nanoformulation significantly reverse these parameters. AKT-ERK-GSK3ß-Hyperphosphorylated tau pathway was found to be involved in the protective efficacy of metformin. To conclude, both metformin and its SLN were found to be effective as therapeutic agents in AD which act through the AKT-ERK-GSK3ß-Hyperphosphorylated tau pathway. We need population based studies to confirm the same.

Age correlation in upper brachial plexus injury patients undergoing nerve transfer surgeries.

•A patient's age can be a critical factor influencing the outcome following upper brachial plexus injury (BPI) reconstruction.•The favorable factor being younger patients with short denervation period.•In older patients early and more aggressive management for an optimal outcome.•This study supports the various correlation of age with the outcomes of upper brachial plexus reconstruction surgery.