Efficiency of Cysticidal Therapy Impacted by the Host's Immune Response in Neurocysticercosis Patients.

Neurocysticercosis (NCC) is a neurological condition caused by the presence of cysts of Taenia solium in the brain, which manifests with a range of clinical symptoms. The severity of NCC and its prognosis following anti-helminth drug (AHD) treatment are closely linked to peripheral and local inflammation. The study aimed to analyse the efficiency of cysticidal therapy impacted by the host's immune response in NCC patients. A total of 104 patients were screened in this study, and blood samples were collected from 30 patients. The follow-up samples within 3 to 6 months of treatment were collected. Patients were categorised as Responder (R) and Non-Responder (NR). Cytokines IL-6, IL-10, IFN-γ and TNF-α were estimated using ELISA kits in PBMC cells. T0 is the time point before the AHD treatment begins, and T1 is between 3 to 6 months after the treatment starts. The responder patients showed significantly lower IL-10 and IL-6 levels in the supernatants at T0 as compared to T1, while in non-responder patients, IL-10 and IL-6 levels were higher at T0 as compared to T1. The IFN-γ and TNF-α levels were found to be higher in the supernatants at T0 as compared to T1 in both the responder and non-responder patients. These observations imply that these cytokines might have an impact on the efficacy of AHD treatment in NCC patients.

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.

Changes in the Cutaneous Nerve Fiber Staining and Distribution of PGP9.5 in Clinically Uninvolved Skin in Leprosy Patients after Completion of Multidrug Therapy and Assessing PGP9.5 as a Marker of Treatment Response.

Background: Subclinical involvement of nerves may sometimes be present much before the overt clinical manifestations become apparent. Protein gene product (PGP) 9.5, a ubiquitin-C-terminal hydrolase, has been widely used as a marker to study the involvement of peripheral nerve fibers in many diseases. Aim and Objectives: To evaluate the change in cutaneous nerve fiber staining and distribution from pre-treatment and post completion of multidrug therapy through the expression of PGP9.5 and to assess PGP9.5 as a marker of treatment response. Materials and Methods: In this prospective single-center observational study, skin biopsy was taken in patients with leprosy, having areas of nerve function impairment (NFI), based on findings of nerve conduction studies (NCSs), but not having lesions or impaired tactile or thermal impairment clinically. The thin nerve fiber density in the clinically normal skin in areas supplied by nerve showing changes of sensory neuropathy was evaluated to study the density of the fibers. A second biopsy was taken at the end of treatment from a site near the previous site to assess the changes in intra-epidermal nerve fiber staining and distribution. Results: Thirty-three patients were recruited in the present study (24 males and 9 females). Pre-treatment, 27 patients had abnormal NCSs, while six patients did not have any evidence of neuropathy on NCSs. Staining for nerve fibers using PGP9.5; in the epidermis was positive in five patients pre-treatment and 11 patients post treatment (P = 0.181). Staining in the dermis revealed positivity in 14 pre-treatment, which increased to 18 post treatment (P = 0.342). Adnexae showed positivity in five patients pre-treatment and increased to 17 post treatment (P = 0.005). Conclusion: A reduced PGP9.5 staining in the epidermal, dermal, and adnexal regions was seen in leprosy patients, which improved post treatment. Thus, PGP9.5 may serve as a marker of NFI and treatment response.

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.

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.

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.

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.

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.

The neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies.

The preoptic area of the hypothalamus is the central hub of thermoregulation in mammals, coordinating autonomic heat-effector pathways in response to sensory information from the ambient and internal environment. This aims to maintain temperature homeostasis at a predetermined thermoregulatory set-point. However, hormonal and neuronal changes during the menopause, including estrogen deficiency, disrupt these normal thermoregulatory responses. This results in abnormal activation of heat dissipation effectors, manifesting clinically as hot flush symptoms. Neurokinin B (NKB) signaling via the neurokinin-3 receptor (NK3R) within the preoptic area is thought to play an important role in the pathophysiology of hot flushes. Therefore attenuation of the NKB/NK3R signaling pathway has garnered much interest as a novel therapeutic target for the amelioration of menopausal hot flushes. Recent clinical trials have demonstrated that NK3R antagonists can produce rapid and sustained improvements in hot flush frequency, severity, and quality of life, without the need for estrogen exposure. Therefore NK3R antagonists are fast emerging as a safe and efficacious alternative to hormone replacement therapy, the current gold standard of treatment.

Carbamazepine versus levetiracetam in epilepsy due to neurocysticercosis.

BACKGROUND: The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC. PATIENTS AND METHODS: This was an open-labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs. RESULTS: Fifteen (15.2%) patients [CBZ- 4(8.2%); LEV- 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug-related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow-up. CONCLUSION: CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group.

Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.

BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODSWe conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTSIn healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSIONTaken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATIONInternational Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDINGNational Institute for Health Research and NIH.

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.

Identification of Taenia solium DNA by PCR in blood and urine samples from a tertiary care center in North India.

BACKGROUND: NCC is a neglected zoonotic disease with high endemicity and disease burden. Neurocysticercosis is a frequent cause of seizures in endemic countries. Early diagnosis and therapy helps in reducing morbidity and DALYs (daily adjusted life years) lost. Definite diagnosis still relies on neuroimaging identification of scolex or by histopathological examination. Molecular method such as PCR (Polymerase Chain Reaction) is an emerging modality to supplement or complement these Gold standard methods. AIM: To determine the utility of PCR in detecting Taenia Solium DNA in NCC patients. METHODS: A total of 100 blood samples of cases of NCC and 50 control blood samples, 58 urine samples of NCC cases and 24 control samples were collected. Repetitive element PTsol9 of the Taenia Solium was targeted. RESULTS: The sensitivity and specificity of PCR in blood samples was 57% and 94%, while sensitivity and specificity in urine samples was 64% and 87%. CONCLUSION: PCR assay can be used as an adjunct for the diagnosis of NCC especially in ambiguous cases, this is relatively rapid and non-invasive diagnostic modality.

Use of rituximab in muscle-specific tyrosine kinase antibody-positive myasthenia gravis: Preliminary observations from a tertiary care center in Northern India.

OBJECTIVES: Approximately 10%-15% of patients with myasthenia gravis (MG) are refractory to standard treatment. A sizable chunk of these patients is due to muscle-specific tyrosine kinase (MuSK) antibody-positive MG which often runs a severe course with frequent relapses and poor response to conventional treatment. We report six patients with refractory MuSK-positive MG who responded well to the treatment with rituximab. PATIENTS AND METHODS: In this prospective institute-based observational study, we report six MuSK antibody-positive MG patients, who did not achieve remission with standard treatment and were later started on rituximab infusion. RESULTS: There was a significant clinical improvement in all patients after starting rituximab. CONCLUSION: Rituximab is an effective immunomodulatory therapy in MuSK antibody-positive MG patients who are not responding to the standard treatment.

Sorting out difficulties in immunological diagnosis of neurocysticercosis: Development and assessment of real time loop mediated isothermal amplification of cysticercal DNA in blood.

PURPOSE OF THE STUDY: Among various immunological tests available for diagnosis of neurocysticercosis (NCC), only EITB (Electroimmunotransfer blot for detection of anticysticercal antibodies) had gained widespread acceptance. However EITB is not available widely and is costly (Indian rupees 15,000/- approximately). We evaluated utility of Loop mediated isothermal amplification (LAMP) assay for detection of Taenia solium cox1 gene in blood of patients with NCC. PATIENTS AND METHODS: Current study included 100 consecutive patients of NCC at a tertiary teaching hospital in Northern India. All the patients underwent detailed history and examinations as well as gadolinium enhanced magnetic resonance imaging of brain. LAMP assay was performed in all the patients. The results were compared with 50 controls. RESULTS: LAMP detected Taenia Solium cox1 gene in 74% of all blood samples in patients of NCC.T he overall sensitivity of LAMP assay for detection of cox1 gene was 74% in all patients with NCC, 71.8% in patients with intraparenchymal brain cysts only and 86.7% of patients with extraparenchymal brain cysts with or without intraparenchymal brain cysts. The overall specificity of LAMP assay was 90% in all these three subgroups. The positive predictive value of real time LAMP assay was close to 93% for almost all forms of NCC- both solitary and multiple while negative predictive value ranged from 57 to 64%. CONCLUSION: Real time LAMP assay of blood for detection of Taenia solium cox1 gene appears to be a promising toll for diagnosis of NCC.

Neurological Manifestations Do not Affect Cumulative Survival in Indian Patients with Antineutrophil Cytoplasmic Antibody Associated Vasculitis.

BACKGROUND: Neurological manifestations are an important cause of morbidity in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It is not clear whether or not they are indicative of a severe disease course with multiple organ involvement and shortened survival. AIMS AND OBJECTIVES: To characterize the neurological manifestations of AAV and analyze their relationship with other organ system and cumulative survival. METHODS: This was a retrospective single-center cohort study of AAV patients at a tertiary care hospital in North India. Data was collected from medical records regarding clinical history, neurological examination, Birmingham Vasculitis Activity Score (BVAS), serology, electrophysiology, imaging, and histopathological examination findings of patients. RESULTS: Ninety-two patients of systemic vasculitis were identified, 67 with granulomatosis with polyangiitis (GPA), 14 with microscopic polyangiitis, 8 with Churg-Strauss syndrome (CSS), and 3 with undifferentiated AAV. The median BVAS at presentation was 18.0 (interquartile range (IQR): 12.0). The median duration of follow-up was 31.3 months (IQR: 40.5). A total of 45.7% patients had neurological manifestations among which 23.8% presented with neurological complaints. Peripheral neuropathy was the most common manifestation noted in 23.9% of the patients. Among patients with GPA, 40.3% had neurological involvement (seen in 33.3% patients at presentation). Patients with nervous system disease were more likely to have associated musculoskeletal manifestations (P = 0.046) and less likely to have renal involvement (P = 0.017). The estimated cumulative survival of the subgroup with neurological involvement was 95.1 months from the time of diagnosis, which was not significantly different from the cohort without neurological involvement (113.8 months, P = 0.631). CONCLUSION: Neurological morbidity commonly accompanies systemic vasculitis. Nervous system disease does not affect the survival significantly in these patients.

In-silico analysis of novel p.(Gly14Ser) variant of ATOX1 gene: plausible role in modulating ATOX1-ATP7B interaction.

Clinical heterogeneity is commonly observed in Wilson disease (WD), including cases with identical ATP7B mutations. It is thought to be an outcome of impairment in other genes involved in cellular copper homeostasis in addition to the mutations in the ATP7B gene. ATOX1, a copper chaperone that delivers copper to ATP7B, is a potential genetic modifier of WD. In the present study, we analyzed the genetic variations in the ATOX1 gene in 50 WD patients and 60 controls. We identified four novel variants, of which, the coding region variant c.40G > A, p.(Gly14Ser) was observed in 2% alleles. Interestingly, p.(Gly14Ser) was seen with an early onset age, reduced serum ceruloplasmin level and manifestations of liver and brain in a WD patient unlike the other having identical ATP7B mutation but normal ATOX1 alleles. Further, computational analysis predicted that p.(Gly14Ser) substitution, in the critical copper binding motif (MXCXG14C) of the protein, affects the protein-protein interaction involved in copper sharing and transfer between ATOX1 and ATP7B-MBD4. Our findings suggest that p.(Gly14Ser) variant of ATOX1 might play a role as a genetic modifier leading to phenotypic variation in WD.

Prevalence of Epilepsy and its Association with Exposure to Toxocara canis: A Community Based, Case-control Study from Rural Northern India.

OBJECTIVES: Many community-based and hospital-based studies across the world have yielded contradictory results regarding association of positive Toxocara canis serology and epilepsy. The present study was planned to analyze disease burden of epilepsy in rural community of North India and its association with exposure to T. canis in this part of the world. METHODS: A door-to-door screening survey was carried out in the rural community using a validated questionnaire for epilepsy by trained field workers, which was finally confirmed by trained neurologists. The risk factors for epilepsy and for predisposing infections were also enquired. The results were compared with an equal number of age- and sex-matched healthy controls enrolled from the same community. Serologic evaluation was carried out to detect antibodies against T. canis. RESULTS: A total of 41,973 persons from the rural community in 49 villages were enrolled in the study. Two hundred and eleven persons were confirmed to be suffering from active epilepsy, resulting in a crude prevalence of 5 per 1000 population. More than 50% of people with epilepsy were in the second or third decade of life. The prevalence of antibodies to T. canis was similar in people with epilepsy (13.7%; 29 of 211 individuals) and controls (9.95%; 21 of 211 individuals). Of the 151 persons with epilepsy, who underwent CT scan, 34 people (22.3%) had evidence of inflammatory granuloma, thereby confirming high incidence of this infestation in rural Northern India. SIGNIFICANCE: Our study does not support the association between epilepsy and exposure to T. canis in rural Northern Indian population.