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Mutations in TDP-43 are known to cause Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). TDP-43 binds to and regulates splicing of several RNA includingZmynd11. Zmynd11 is a transcriptional repressor and a potential E3 ubiquitin ligase family member, known for its role in neuron and muscle differentiation. Mutations inZmynd11have been associated with autism with significant developmental motor delays, intellectual disability, and ataxia. Here, we show thatZmynd11is aberrantly spliced in the brain and spinal cord of transgenic mice overexpressing a mutant human TDP-43 (A315T), and that these changes occur before the onset of motor symptoms.

Background There is an apparently high incidence of stroke mimics in the present-day stroke code era. The reason being is the intense pressure to run with time to achieve the “time is brain”-based goals. Methods The present study was a retrospective analysis of the data collected over a duration of 6 months from April 2019 to September 2019. We observed the incidence of stroke mimics among the patients for whom rapid response stroke code was activated during the study period. We also performed a logistic regression analysis to identify the clinical features which can act as strong predictors of stroke and mimics. Results A total of 314 stroke codes were activated of which 256 (81.5%) were stroke and 58 (18.5%) were the mimics. Functional disorders and epilepsy were the most common mimics (24.1% each). Female gender (p = 0.04; odds ratio [OR] 2.9[1.0–8.8]), isolated impairment of consciousness (p < 0.01; OR 4.3[1.5–12.6]), and isolated dysarthria (p < 0.001) were the strong independent predictors for a stroke mimic. Hemiparesis was the strong independent predictor for a stroke (p < 0.001; OR 0.0[0.0–0.1]). Conclusion In the present epoch of rapid response stroke management, a streamlined assessment by the emergency physicians based on the above clinical predictors may help in avoiding the misdiagnosis of a mimic as stroke.

Large vessel occlusion has a disproportionately large contribution to overall mortality and morbidity from stroke. The Society of Vascular and Interventional Neurology in the year 2016 announced the launch of Mission Thrombectomy 2020 (MT2020), with the aim of increasing access to stroke thrombectomy globally. Despite 4 years since the start of MT2020, India is falling short in acute stroke therapy including thrombolysis and mechanical thrombectomy (MT). Access to timely MT leads to substantial mitigation of adverse stroke outcomes. This in turn leads to an enormous health benefit in that population. MT as a treatment is unevenly and unfairly distributed and increasing access to it is in need of strategies targeting political, economic, and environmental factors. Such strategies are slowly being adopted. In this article, we attempt to look at the major hurdles we face in improving acute stroke care in our country and we also explore options to address them.

Background The Indian data concerning the endovascular mechanical thrombectomy (MT) in acute ischemic strokes (AIS) with large vessel occlusion (LVO) is still scarce and evolving. Tenecteplase (TNK) has been recently approved for intravenous stroke thrombolysis prior to the MT. Methods This study is a single-center retrospective study. We performed data analysis of the AIS patients who consecutively presented during the study period with LVO and underwent thrombectomy. Procedural success was defined by the post-thrombectomy angiographic picture of grades 2b and 3 on modified Thrombolysis in Cerebral Infarction (mTICI) scale. Primary efficacy outcome was defined as an improvement of ≥4 points in National Institute of Health Stroke Scale (NIHSS) score at 24 h. Secondary efficacy outcome was based on modified Rankin Scale (mRS) score at 90 days. We also performed a comparative analysis of TNK and alteplase subgroups. Results Successful recanalization (mTICI 2b/3) was achieved in 65 (86.67%) patients. There was a significant mean difference between the NIHSS scores on admission and at 24 h ( P < .001). Likewise, mRS score at 3 months also showed a significant mean difference as compared to baseline ( P < .001). A faster recanalization was observed in those who were thrombolyzed with TNK, needed fewer number of passes, and if the procedure was performed under conscious sedation. Conclusion This study further strengthens the Indian data on efficacy and safety of MT in LVO ischemic strokes. Besides, whether the observation of TNK resulting in a faster revascularization is due to some factors unaccounted in our study, or an actual effect on thrombus due to a high fibrin specificity, needs to be tested further in larger randomized studies with matched sample sizes.

Background Anterior tarsal tunnel syndrome (ATTS) is an uncommon entrapment neuropathy which occurs due to the compression of deep peroneal nerve under the inferior extensor retinaculum at the ankle. We observed a frequent occurrence of this syndrome in toddy palm tappers and hence, planned to study the association between the two. Materials and Methods We studied the prevalence of isolated deep peroneal neuropathy at the ankle among the asymptomatic toddy tappers enrolled over a period of 3 months. Results In our case series, 81% (17/21) of the study participants had ATTS of which 43% (9/21) had unilateral and 38% (8/21) had bilateral involvement. There was a strong inverse association (p < 0.001) of “duration of toddy tapping in years” with peroneal (extensor digitorum brevis) amplitudes on both the sides. Conclusion Our study confirms “palm tree climbing” to be an occupational etiology of ATTS.

Dyke-Davidoff-Masson syndrome (DDMS) is a rare disease which is clinically characterized by hemiparesis, seizures, facial asymmetry, and mental retardation. The classical radiological findings are cerebral hemiatrophy, calvarial thickening, and hyperpneumatization of the frontal sinuses. This disease is a rare entity, and it mainly presents in childhood. Adult presentation of DDMS is unusual and has been rarely reported in the medical literature. Key Messages: DDMS is a rare disease of childhood. However, it should be kept in mind as a diagnostic possibility in an adult who presents with a long duration of progressive hemiparesis with seizures and mental retardation. Cerebral hemiatrophy, calvarial thickening, and hyperpneumatization of the frontal sinuses are diagnostic for this illness on brain imaging.

Background: Anemia is a common complication of human immunodeficiency virus (HIV) infection. The role of iron, Vitamin B12, and folate deficiencies, which are otherwise most common causes of anemia, is not well-established in HIV patients. Several studies in India have shown that severe immunodeficiency is associated with higher grade of anemia, but correlation of CD4 cell counts with severity of anemia is not well-documented. Aims: The aims of the present study were: To estimate the point prevalence of anemia in HIV patients, to analyze the causative role of iron, Vitamin B12, and folate deficiencies in anemic HIV patients, and correlating the degree of severity of anemia with CD4 cell counts. Materials and Methods: This study was a cross-sectional study. The study group enrolled 103 consecutive HIV patients attending medical emergency, medical outpatient department, medical wards, and anti-retroviral therapy (ART) center at a tertiary care medical center in North India. Study participation consisted of a single visit during which relevant data, including medical history, current medications, CD4 T-lymphocyte count, complete hemogram with red blood cell indices, peripheral smear picture, iron studies, serum Vitamin B12, serum folate and bone marrow studies, were recorded on a case report form. Anemia was classified according to the World Health Organization criteria. Data analysis was carried out using Microsoft Excel and Statistical Package for the Social Sciences software. Results: 86.4% (89/103) patients were found to be anemic. There was no significant difference in prevalence of anemia in ART-naive patients from those who were on ART (P > 0.05). Pearson's correlation had shown a highly significant positive correlation of hemoglobin and CD4 cell counts in male patients (r = 0.418) as well as female patients (r = 0.565). Normocytic normochromic was the most common type of anemia in males (46%) as well as females (42%). Significant iron deficiency (P = 0.022) was observed in 42.85% of the patients having microcytic hypochromic anemia. Significant Vitamin B12 and folate deficiencies were observed in patients having macrocytic anemia (47.05%, P = 0.003 and 35.29%, P = 0.012, respectively). Conclusions: This study shows that anemia is highly prevalent in HIV patients and severity of anemia increases with decrease in CD4 cell counts. Nutritional deficiencies play a significant role in causing anemia in these patients.

Moyamoya disease (MMD) is a rare neurovascular disorder which pathologically, is a chronic cerebrovasculopathy. It is characterized by stenosis of the internal carotid artery (ICA) and the main branches within the circle of Willis with consecutive development of collateral vessels. There are a few cases in the literature which have described movement disorders as a manifestation of MMD; however these have been uncommonly reported in cases of moyamoya syndrome (MMS). We present a 10-year-old boy with dystonia, myoclonus and encephalopathy like features. These features in association with moyamoya, are rarely described.

Objective: Outcome assessment of intravenous (IV) thrombolysis with tenecteplase in acute ischemic stroke. Materials and Methods: We consecutively enrolled acute ischemic stroke patients who underwent IV thrombolysis with tenecteplase from October 2016 to May 2017. Primary clinical efficacy outcome was defined as an improvement in the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h (h). Secondary clinical efficacy outcome was the favorable outcome on modified Rankin scale at 90 days defined as a score of 0 or 1. The safety endpoints were death rate at 90 days and symptomatic intracranial hemorrhage (SICH). Results: Mean NIHSS scores at baseline and 24 h were 13 (±3.81) and 9.29 (±5.74), respectively, the difference being statistically significant (P = 0.016). In this study, nine patients (64%) met the primary clinical efficacy outcome and eleven (78.5%) patients met the secondary clinical efficacy outcome. Only 1 (7%) patient developed SICH and additionally, aspiration pneumonia with subsequent death. Conclusion: This study confirms the efficacy and safety of tenecteplase for stroke thrombolysis in our clinical setting. Tenecteplase appears to be a suitable option for stroke thrombolysis in resource-limited settings, considering its cost-effectiveness, and ease of administration.

Objective: To assess the frequency of diabetic retinopathy (DR) and correlation with HbA1C in newly diagnosed type 2 diabetic patients. Patients and research methods: The study was conducted at a tertiary care medical centre in north india.All patients of >30 to

Vitamin D is vital for musculoskeletal health and may be associated with subacute and chronic low back pain. The objective of this study was to estimate the prevalence of vitamin D deficiency among chronic low back pain (CLBP) and subacute low back pain (SLBP), and compare the same with healthy controls. This study was designed as triple-arm case-control study comprising of CLBP, SLBP, and controls. SLBP and CLBP cases were consecutively enrolled over 3 months of winter season from November 2016 to January 2017. Serum 25- (OH) vitamin D was estimated for the study subjects and categorical comparison of severity of vitamin D deficiency was done for the cases and controls. A total of 250 CLBP, 177 SLBP cases, and 248 controls were included in the study. Mean (± SD) serum vitamin D levels among CLBP, SLBP, and controls were 20.36 (± 12.56), 21.42 (± 13.20), and 20.84 (± 6.93) ng/ml respectively, the difference being statistically insignificant. There was no significant difference in the prevalence of vitamin D deficiency among CLBP, SLBP, and controls which was 53.6, 50.8, and 51.6% respectively, in the three arms. However, the categorical analysis revealed that CLBP and SLBP cases had a significantly higher prevalence of worse categories of vitamin D deficiency. Cases had significantly larger frequency (CLBP vs. controls, 43.6 vs 20.1%, P

Background The intracerebral hemorrhage (ICH) score is well established as a reliable prognostic score in ICH, whereas recently, Acute Physiology and Chronic Health Evaluation II (APACHE II) has been observed to have a better discrimination in predicting mortality in primary pontine hemorrhage. Further, physiological parameters of APACHE II have been associated with outcome in ICH. This study is the first to observe a direct comparison between APACHE II and ICH scores in predicting 30-day mortality in spontaneous intracerebral hemorrhage (SICH). Materials and Methods This study was a prospective observational study where we compared the receiver operating characteristic (ROCs) of baseline ICH and APACHE II scores in patients with SICH for predicting 30-day mortality outcome. Results We observed that both APACHE II and ICH scores were good for predicting 30-day mortality with both having an area under the ROC curve of more than .8 (.831 [95% confidence interval {CI}, .740-.922; P .001] and .892 [95% CI, .757-.932; P .001], respectively). However, the ICH score was better discriminative (area under the curve AUC, .892 versus .831; P = .040) and better calibrated ( P = .037 versus P = .089, Hosmer–Lemeshow goodness-of-fit test for logistic regression) for the same. Both APACHE II and ICH scores had a sensitivity of 87% at cutoff values of 19 and 3, respectively; however, the ICH score had a better specificity (90% versus 76.5%). Conclusion The ICH score was observed to have a better discrimination and calibration for predicting 30-day mortality in SICH.

Introduction: Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rt-PA) is the cornerstone of acute ischaemic stroke treatment. The number of stroke patients receiving thrombolytic therapy in India has improved over the recent years. However, Warangal despite being the second largest city in Telangana, witnesses stroke thrombolysis infrequently. Aim: To study the factors which prevent stroke thrombolysis at a tertiary care center in Warangal. Materials and Methods: The study was undertaken at Kakatiya Medical College (KMC) and its associate Mahatma Gandhi Memorial Hospital (MGMH), from October 2016 to March 2017. The study subjects were recruited from the patients presenting to medical emergency or neurology outpatient department (OPD).We enrolled the consecutive ischaemic stroke patients who presented within three days of the symptoms onset and fulfilled the inclusion and exclusion criteria for thrombolysis as defined by the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA study group. We included the patients arriving after time window for thrombolysis, so as to study the causes associated with pre-hospital delay. Thrombolysis therapy was given within four and a half hours of the stroke onset. Results: Among a total of 223 study subjects, only 13 (5.8%) arrived within the time window for rt-PA infusion and nine (4%) received thrombolytic therapy. The pre-hospital delay was the single most important constraint for providing timely stroke treatment. ‘Lack of awareness of patients and their relatives to recognize stroke as a medical emergency’ and ‘lack of awareness about thrombolysis’ were the most important factors associated with the pre-hospital delay. Non-affordability and in-hospital delays were the barriers for successful stroke treatment among the patients who presented to the medical emergency on time and could not get thrombolytic therapy. Conclusion: The results of our study suggest the need for a comprehensive stroke care program at our health center to escalate the rate of thrombolytic therapy. Stroke education and awareness modules should be incorporated in the stroke program.

Orofacial pain’ most commonly occurs due to dental causes like caries, gingivitis or periodontitis. Other common causes of ‘orofacial pain’ are sinusitis, temporomandibular joint(TMJ) dysfunction, otitis externa, tension headache and migraine. In some patients, the etiology of ‘orofacial pain’ remains undetected despite optimal evaluation. A few patients in the practice of clinical dentistry presents with dental pain without any identifiable dental etiology. Such patients are classified under the category of ‘atypical odontalgia’. ‘Atypical odontalgia’ is reported to be prevalent in 2.1% of the individuals. ‘Atypical orofacial pain’ and ‘atypical odontalgia’ can result from the neurological diseases like multiple sclerosis, trigeminal neuralgia and herpes infection. Trigeminal neuralgia has been frequently documented as a cause of ‘atypical orofacial pain’ and ‘atypical odontalgia’. There are a few isolated case reports of acute pontine stroke resulting in ‘atypical orofacial pain’ and ‘atypical odontalgia’. However, pontine stroke as a cause of atypical odontalgia is limited to only a few cases, hence prevalence is not established. This case is one, where a patient presented with acute onset atypical dental pain with no identifiable dental etiology, further diagnosed as an acute pontine infarct on neuroimaging. A 40 years old male presented with acute onset, diffuse teeth pain on right side. Dental examination was normal. Magnetic resonance imaging(MRI) of the brain had an acute infarct in right pons near the trigeminal root entry zone(REZ). Pontine infarct presenting with dental pain as a manifestation of trigeminal neuropathy, has rarely been reported previously. This stresses on the importance of neuroradiology in evaluation of atypical cases of dental pain.

Pachygyria is considered a subtype of lissencephaly which, in turn, is a spectrum of disorders caused by abnormal neuronal migration. Clinical presentation in this disorder may be varied including microcephaly, developmental delay, facial dysmorphism, seizures, and mental retardation. Magnetic resonance imaging (MRI) of brain identifies the exact nature and extent of the disease and helps in delineating further plan of management. A Tigroid pattern on axial MRI scan and leopard pattern on a sagittal plane has been classically reported in disorders of myelin formation such as metachromatic leukodystrophy and Pelizaeus–Merzbacher disease. We present here a case of pachygyria who presented to us with some atypical features including “tigroid-like stripes” and “leopard-like pattern” on MRI brain which has not been reported in the medical literature previously.

Japanese Encephalitis (JE), caused by Japanese encephalitis virus (JEV), a flavi-virus, is the most significant aetiology of arboviral encephalitis worldwide. It has resulted in epidemics of encephalitis in the Indian subcontinent. Here, we report a case of 36-year-old female who presented with a short history of fever and headache followed by altered sensorium. Funduscopic examination revealed Papilloedema. Pyogenic or viral meningoencephalitis along with complicated malaria were kept as initial differential diagnosis. Magnetic Resonance Imaging (MRI) of brain revealed involvement of posterior limb of internal capsule and bilateral thalami in the form of haemorrhagic encephalitis along with obstructive hydrocephalus. Cerebro Spinal Fluid (CSF) serology (IgM ELISA) showed JE as the causative agent. Despite extensive literature search, we could not find a case of JE reported with hydrocephalus as a complication. This case highlights the typical and atypical features of JE including imaging findings and exemplifies the way, how diversely JE can present and would thus help in preparing management paradigms accordingly.

Wegener’s granulomatosis or granulomatosis with polyangiitis is a necrotizing vasculitis affecting both arterioles and venules. The disease is characterized by the classical triad involving acute inflammation of the upper and lower respiratory tracts with renal involvement. However, the disease pathology can affect any organ system. This case presents Wegener’s granulomatosis presenting with facial nerve palsy as the first manifestation of the disease, which is rarely reported in medical literature.

Introduction Diabetes mellitus is a disease with a rapidly increasing prevalence, needs continue research for novel methods to both prevent and treat this disorder. Obesity and decreased physical activity are the major risk factor for the development of diabetes. Recently the emphasis is focused on oxidative stress in pathogenesis of this disease. Aim To assess the serum levels of Nitric Oxide (NO) among diabetic patients and its correlation with lipid profile as well as oxidative stress in north Indian setting. Materials and methods This was a cross-sectional study. Subjects suffering from type 2 diabetes for more than 1 year and age between 30 to 50 years with hyperuricaemia were included in the study. The patients were divided into three groups: Group I- Type 2 diabetics with dyslipidemia and hyperuricaemia, Group II- Type 2 diabetics with dyslipidemia and normouricaemia and Group III- Type 2 diabetics with normolipidemia and normouricaemia. Results The nitric oxide level was significantly lower in Group I and Group II than Group III. The oxidative stress parameters had poor correlation with NO level in all the groups. Conclusion Our data suggests that there is definite role of Nitric Oxide (NO) in pathogenesis of type -2 diabetes mellitus with dyslipidemia and hyperuricaemia.

Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such asTLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated serum vitamin D, and VDR and TLR-2 gene polymorphisms in patients with spinal tuberculosis. This study comprised of 3 groups: spinal tuberculosis, pulmonary tuberculosis, and controls (each with 106 subjects). Enzyme-linked immunosorbent assay was used to measure vitamin D levels, and polymerase chain reaction-sequencing method was used to analyze VDR and TLR-2 gene polymorphisms. Patients were followed up for 6 months. Vitamin D deficiency was significantly more prevalent in patients with spinal tuberculosis (P

Leptospirosis is a zoonosis having a worldwide prevalence and has recently emerged as a major public health problem, especially in tropical and subtropical regions. Likewise, dengue is one of the major endemic health problems in the Indian subcontinent. It is a mosquito-borne arboviral infection causing considerable morbidity and mortality. Epidemiologically, mixed infections of dengue and leptospirosis are possible because similar environmental conditions are needed for the transmission of both these infections. Still, their coinfection is rarely reported in medical literature. Here, we report three such cases of dengue and leptospirosis coinfection, encountered in clinical practice during the monsoon season at Kolkata, West Bengal, India.

Objective: To describe the clinical profile of hemophiliac patients and their quality of life (QoL) in Western Uttar Pradesh. Materials and Methods: This was an observational cross-sectional study. Patients of all age groups with hemophilia admitted in the medicine and pediatrics ward for factor/fresh frozen plasma transfusion or having history of such type of transfusion were consecutively enrolled. A detailed clinical history was elicited from the accompanying parent/guardian. The HAEMO-QoL questionnaire was used for the assessment of QoL of the patients. Results: Out of the total 71 hemophilia patients, 66.2% (51/77) were >18 years of age. Type A hemophilia was observed in 88.3% (68/71) patients. Majority of the patients had severe hemophilia (80.5%). The family history and joint involvement were present in 58.4% and 77.9% of the patients, respectively. Knee joint was observed to be as the target joint among 57.1% of the patients. 76.6% of the patients had joint swelling, resulting in compromised joint movement. Bleeding occurred in soft tissues and joints in 62.3% and 15.6% of the patients, respectively. The patients had poor QoL scores. Overall, hepatitis B and C infection were observed in 6.5% and 9.1% of the patients, respectively. Orthophysiotherapy was needed in 22/26 (84.6%) patients. Conclusion: The severe type of haemophilia Type A was more common than mild and moderate types. The study suggests that important determinants for QoL in haemophilia patients are availability of factor concentrate from the clinical perspective and social and psychological support to ensure a holistic care approach.

Cytoplasmic inclusions containing TDP-43 are a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP-43 is an RNA binding protein involved in gene regulation through control of RNA transcription, splicing and transport. However, the function of TDP-43 in the nervous system is largely unknown and its role in the pathogenesis of ALS is unclear. The aim of this study was to identify genes in the central nervous system that are regulated by TDP-43. RNA-immunoprecipitation with anti-TDP-43 antibody, followed by microarray analysis (RIP-chip), was used to isolate and identify RNA bound to TDP-43 protein from mouse brain. This analysis produced a list of 1839 potential TDP-43 gene targets, many of which overlap with previous studies and whose functions include RNA processing and synaptic function. Immunohistochemistry demonstrated that the TDP-43 protein could be found at the presynaptic membrane of axon terminals in the neuromuscular junction in mice. In conclusion, the finding that TDP-43 binds to RNA that codes for genes related to synaptic function, together with the localization of TDP-43 protein at axon terminals, suggests a role for TDP-43 in the transport of synaptic mRNAs into distal processes.

Background This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD. Methods One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory). Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT]) were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test. Results Significant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks. Conclusions The working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match–to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task.