Supriyo Choudhury

Polycomb group (PcG) protein-dependent histone methylation and ubiquitination drives chromatin compaction leading to reduced tumor suppressor expression and increased cancer cell survival. Green tea polyphenols and S -adenosylhomocysteine (AdoHcy) hydrolase inhibitors are important candidate chemopreventive agents. Previous studies indicate that (-)-epigallocatechin-3-gallate (EGCG), a potent green tea polyphenol, suppresses PcG protein level and skin cancer cell survival. Inhibition of AdoHcy hydrolase with 3-deazaneplanocin A (DZNep) inhibits methyltransferases by reducing methyl group availability. In the present study, we examine the impact of EGCG and DZNep cotreatment on skin cancer cell function. EGCG and DZNep, independently and in combination, reduce the level of PcG proteins including Ezh2, eed, Suz12, Mel18 and Bmi-1. This is associated with reduced H3K27me3 and H2AK119ub formation, histone modifications associated with closed chromatin. Histone deacetylase 1 level is also reduced and acetylated H3 formation is increased. These changes are associated with increased tumor suppressor expression and reduced cell survival and are partially reversed by vector-mediated maintenance of Bmi-1 level. The reduction in PcG protein level is associated with increased ubiquitination and is reversed by proteasome inhibitors, suggesting proteasome-associated degradation.

Alpha-synuclein and inflammatory pathology are evident in Parkinson's disease (PD) but, their link to disease pathogenesis needs further elucidation.To explore α-synuclein-mediated inflammation in the serum of PD patients and its link with disease severity.Serum levels of IL-1β, NLRP3, total and phosphorylated α-synuclein were compared.IL-1β, NLRP3 levels were significantly increased in PD. We also observed a linear correlation of NLRP3 with α-synuclein. Phosphorylated α-synuclein levels were significantly elevated in later stages of PD.The α-synuclein-NLRP3 mediated inflammation may underline the pathophysiology of PD and might serve as a novel therapeutic target in PD.

Since its introduction as a treatment for strabismus, botulinum toxin (BoNT) has had a phenomenal journey and is now recommended as first-line treatment for focal dystonia, despite short-term clinical benefits and the risks of adverse effects. To cater for the high demand across various medical specialties, at least six US Food and Drug Administration (FDA)-approved formulations of BoNT are currently available for diverse labelled indications. The toxo-pharmacological properties of these formulations are not uniform and thus should not be used interchangeably. Synthetic BoNTs and BoNTs from non-clostridial sources are not far from clinical use. Moreover, the study of mutations in naturally occurring toxins has led to modulation in the toxo-pharmacokinetic properties of BoNTs, including the duration and potency. We present an overview of the toxo-pharmacology of conventional and novel BoNT preparations, including those awaiting imminent translation from the laboratory to the clinic.

Chronic pancreatitis is characterized by progressive loss of exocrine and endocrine functions of the pancreas and is considered to be the single most important cause for development of pancreatic cancer. Recent evidence suggests that inflammation and oxidative stress play pivotal roles in the development of clinical conditions like pancreatitis, type 2 diabetes mellitus, and metabolic syndrome. Nonetheless, molecular signaling pathways linking inflammation, oxidative stress, and pancreatic cell death are not yet well defined. In this study, bacterial lipopolysaccharide (LPS) was used (injected twice a week for three weeks) to emulate a chronic systemic inflammatory state in experimental Swiss albino mice. Using this model, we traced the genesis of inflammation-induced pancreatic dysfunction and mapped the signaling events which contribute to the induction of this state. Histopathological studies revealed the appearance of cell injuries and increased collagen content in LPS-exposed group, indicative of fibrosis. Assays for intraperitoneal glucose tolerance, insulin levels, and insulin receptor mRNA expression signified inflammation-induced insulin insensitivity. For the first time we present evidence that cellular inflammation and subsequent oxidative stress modulate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/NF-E2-related factor 2 or Nuclear factor (erythroid-derived 2)-like 2 pathway and initiates pancreatic cell death by activation of stress-responsive Rho/stress-activated protein kinase or SAPK/Jun-N-terminal kinase (JNK) pathway. Scavenging of intracellular reactive oxygen species (ROS) by a standard antioxidant N-acetyl cysteine led to pancreatic cell survival. The data obtained strongly indicates that the LPS/toll-like receptor-4 or TLR-4/ROS/NF-κB pathway is critically involved in the initiation of inflammation, oxidative stress, and pancreatic cell death and might prove to be an excellent choice as a target for novel therapeutic strategies in the management of metabolic disorders.

Medical students feel a significant amount of stress due to a variety of factors. Few studies have explored the relative size of these various stressors to identify which are most important. This study was undertaken to quantify the magnitude of various sources of stress among students of a medical college at Kolkata, West Bengal, and also to assess the reliability of Medical Students' Stressor Questionnaire (MSSQ-40) in this context.We evaluated the degree of stress along various dimensions using the MSSQ-40, a scale to measure stress among medical students that has been validated in other countries. Differences in stress and its causal factors were analyzed across demographic subgroups. The reliability of the MSSQ-40 was evaluated using Cronbach's alpha.The overall prevalence of stress was 91.1% and the vast majority of students (94.9%) were stressed due to academic reasons. Academic related stress was found to be higher among students who are not conversant with the local language, experienced a change in medium of teaching from secondary school to medical school, and resided in a hostel. The MSSQ-40 in general, and its academic-related stress domain specifically, were found to be reliable in our setting.Early detection and remedying stressors will help to build physical and mental health in medical students. Language training early during the medical course might reduce academic stress among our students. Further studies should relate individuals' stress with their academic performance.

Background. Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. Methods. We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. Results. StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. Conclusion. We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

Movement DisordersVolume 34, Issue 6 p. 917-918 Letters: New Observations Noninvasive vagus nerve stimulation improves gait and reduces freezing of gait in Parkinson's disease Banashree Mondal MSc, Banashree Mondal MSc Department of Neurology and Ram Gopal Chamaria Medical Research Centre (RGC), Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorSupriyo Choudhury MD, Supriyo Choudhury MD Department of Neurology and Ram Gopal Chamaria Medical Research Centre (RGC), Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorBruce Simon PhD, Bruce Simon PhD ElectroCore LLC, Basking Ridge, New Jersey, USASearch for more papers by this authorMark R. Baker FRCP, Mark R. Baker FRCP Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK Department of Clinical Neurophysiology, Royal Victoria Infirmary, Newcastle, UK Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UKSearch for more papers by this authorHrishikesh Kumar DM, Corresponding Author Hrishikesh Kumar DM rishi_medicine@yahoo.com Department of Neurology and Ram Gopal Chamaria Medical Research Centre (RGC), Institute of Neurosciences, Kolkata, IndiaCorrespondence to: Dr. Hrishikesh Kumar, Department of Neurology, Institute of Neurosciences, Kolkata, 185/1 AJC Bose Road, Kolkata, West Bengal, India 700017; E-mail: rishi_medicine@yahoo.comSearch for more papers by this author Banashree Mondal MSc, Banashree Mondal MSc Department of Neurology and Ram Gopal Chamaria Medical Research Centre (RGC), Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorSupriyo Choudhury MD, Supriyo Choudhury MD Department of Neurology and Ram Gopal Chamaria Medical Research Centre (RGC), Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorBruce Simon PhD, Bruce Simon PhD ElectroCore LLC, Basking Ridge, New Jersey, USASearch for more papers by this authorMark R. Baker FRCP, Mark R. Baker FRCP Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK Department of Clinical Neurophysiology, Royal Victoria Infirmary, Newcastle, UK Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UKSearch for more papers by this authorHrishikesh Kumar DM, Corresponding Author Hrishikesh Kumar DM rishi_medicine@yahoo.com Department of Neurology and Ram Gopal Chamaria Medical Research Centre (RGC), Institute of Neurosciences, Kolkata, IndiaCorrespondence to: Dr. Hrishikesh Kumar, Department of Neurology, Institute of Neurosciences, Kolkata, 185/1 AJC Bose Road, Kolkata, West Bengal, India 700017; E-mail: rishi_medicine@yahoo.comSearch for more papers by this author First published: 14 March 2019 https://doi.org/10.1002/mds.27662Citations: 22 Funding agency: Noninvasive vagus nerve stimulation devices were provided by Dr. Bruce Simon (Electrocore [Basking Ridge, New Jersey]). Other research costs were covered by the research fund of Institute of Neurosciences, Kolkata. Relevant conflicts of interests/financial disclosures: Nothing to report. Correction added on March 21, 2019, after first online publication. The funding agency information for this article concerning the Institute of Neurosciences has been updated. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume34, Issue6June 2019Pages 917-918 RelatedInformation

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson's disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophins, inflammatory markers and markers of oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomized to either active nVNS or sham nVNS. After baseline assessments, patients were instructed to deliver six 2 min stimulations (12 min/day) of the active nVNS/sham nVNS device for 1 month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with active nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly ( p &amp;lt; 0.05) after active nVNS treatment. Here we present the first evidence of the efficacy and safety of nVNS in the treatment of gait in PD patients, and propose that nVNS can be used as an adjunctive therapy in the management of PD patients, especially those suffering from FOG. Clinical trial registration : identifier ISRCTN14797144.

Neurorehabilitation aims to induce beneficial neural plasticity in order to restore function following injury to the nervous system. There is an increasing evidence that appropriately timed functional electrical stimulation (FES) can promote associative plasticity, but the dosage is critical for lasting functional benefits. Here, we present a novel approach to closed-loop control of muscle stimulation for the rehabilitation of reach-to-grasp movements following stroke and spinal cord injury (SCI). We developed a simple, low-cost device to deliver assistive stimulation contingent on users' self-initiated movements. The device allows repeated practice with minimal input by a therapist, and is potentially suitable for home use. Pilot data demonstrate usability by people with upper limb weakness following SCI and stroke, and participant feedback was positive. Moreover, repeated training with the device over 1-2 weeks led to functional benefits on a general object manipulation assessment. Thus, automated FES delivered by this novel device may provide a promising and readily translatable therapy for upper limb rehabilitation for people with stroke and SCI.

Abstract View Supplementary Video 1 Background Spinocerebellar ataxia type 12 (SCA12) is a rare form of an autosomal‐dominant ataxic disorder associated with an expansion of CAG repeat length. Here, we present a large case series of patients with SCA12 and describe a wide range of typical and rare symptoms. Methods Twenty‐one consecutive patients with genetically proven SCA12 underwent detailed neurological examination. We assessed clinical characteristics using validated rating scales for evaluating motor features in SCA. Nonmotor symptoms and quality of life were assessed using appropriate, validated scales. Correlations of CAG repeat length with both severity score and age of onset were explored. Results The mean age of onset was 51 years, and most patients were descendants of a single, endogamous Indian community (Agarwal). Tremor was the most common initial presenting symptom (90%). Hand dystonia was present in 14 of 21 patients, and most patients in the cohort presented with gait disturbance. Neuropsychiatric manifestations were common coexisting features. The CAG repeat length was significantly correlated ( r = −0.760; P = 0.0001) with early age of onset, but not with disease severity. Tremor affected the quality of life in 18 of 21 patients, because they had difficulty in handling liquids. Conclusions Tremor was the most common, nonataxic symptom at initial presentation in patients with SCA12. Proximal upper limb tremor, typically with high amplitude and low frequency, can raise a strong diagnostic suspicion. Associated hand dystonia was a common coexisting motor feature. Various nonmotor features were also observed in several cases which require therapeutic attention.

Loneliness has been linked to negative health and economic outcomes across the life course. Health effects span both physical and mental health outcomes, including negative health behaviours, lower well-being, and increased mortality. Loneliness is however preventable with effective intervention. This systematic review aims to identify what has worked in interventions for loneliness to guide the development of future interventions.Eight electronic databases (Medline, Embase, PsycINFO, Social Policy and Practice, Social Sciences Citation Index, Epistemonikos, CINAHL, Cochrane Library) were systematically searched from inception to February 2022 using terms for intervention and loneliness to identify relevant interventions in the general population. No restrictions on age, socio-economic status, or geographic location were imposed. Studies were to measure loneliness as the primary outcome through a validated scale or single-item question. Case studies were excluded. Additional studies were identified through citation chasing. Extracted data included study and intervention characteristics, and intervention effectiveness for cross-study comparison. Critical appraisal was conducted using the Joanna Briggs Institute and Critical Appraisal Skills Programme tools before the studies were summarised in a narrative synthesis.Searches identified 4,734 hits, from which 22 studies were included in this review. Of these studies, 14 were effective in reducing loneliness. Additionally, five studies presented unclear findings, and three concluded no decrease in loneliness. Interventions varied between group vs. individual format, online vs. in person delivery, and regarding both intervention duration and individual session length. Furthermore, this review highlighted five key areas when considering designing an intervention for loneliness: use of between session interaction, inclusion of clear learning mechanisms, role of active participation, number of opportunities for group or facilitator interaction, and variation in teaching and learning styles.Group sessions seem preferred to individual formats, and interaction through active participation and group or facilitator contact appear beneficial, however studies also recognised the importance of a person-tailored approach to delivery. Studies suggest there is no 'quick fix' to loneliness, but that learnt practices, behaviours, and community connection should be built into one's lifestyle to achieve sustained intervention effectiveness. Future interventions should consider longer follow-up periods, male and populations with lower educational levels.

The concept of generic prescription is widely accepted in various parts of the world. Nevertheless, it has failed to gain popularity in India due to factors such as nonavailability and distrust on the product quality. However, since 2012, the Government of West Bengal, India, has initiated exclusive generic drug outlets called "fair price medicine shop" (FPMS) inside the government hospital premises in a "public-private-partnership" model. This study was undertaken to evaluate the experience and attitude of patients who were consuming generic drugs purchased from these FPMS.It was a questionnaire-based cross-sectional study where we have interviewed 100 patients each consuming generic and branded drugs, respectively. The perceived effectiveness, reported safety, medication adherence, cost of therapy, and availability of drugs was compared between two mentioned groups. Medication adherence was estimated through Drug Attitude Inventory-10.93% of generic and 87% branded drug users believed that their drugs were effective (P = 0.238) in controlling their ailments. No significant difference (9% generic, 10% branded drug users, P = 1.000) was observed in reported adverse effects between generic and branded drug users. 82% and 77% of patients were adherent generic and branded drugs, respectively (P = 0.289). As expected, a significantly lower cost of generic drugs was observed compared to its branded counterpart.The policy of FPMS implemented by the Government of West Bengal, India appeared to be promising in terms of perceived effectiveness, safety, and adherence of generic drugs from FPMS compared to drugs purchased from open market retailers. Therefore, this study might act as an impetus for the policy-makers to initiate similar models across the country.

Introduction Environmental enrichment during physical exercise was found beneficial in neurological disorders. Application of dance in a structured way could effectively enhance the environment of physical rehabilitation. Therefore, dance therapy can be an alternative exercise program with potential benefit in affect, cognition and social integration in various neurological disorders. Objective This pre-post experimental study without control was designed to assess the impact of dance movement therapy on cognition, quality of life and motor symptoms in PD patients. Methods A group of 10 mild-moderate PD patients from Movement Disorders Clinic; I-NK, participated in group sessions for a period of 2 months (twice a week). Each session involved verbal communication followed by warming up movements and concluded with target oriented physical activities, focused on physical symptoms, emotional and cognitive aspects. All the patients were assessed before and after the intervention using Unified Parkinson's Disease Rating Scale part III (UPDRS part III), Hoehn and Yahr Scale (H and Y), Parkinson's Disease Questionnaire 39 (PDQ-39) and Montreal Cognitive Assessment (MOCA). Results We observed a change in median MOCA score from 19.00 to 22.00 (p .027). PDQ 39 also showed change in median score from 59.50 to 30.00 (p .027). The change in UPDRS III (0.08) and H and Y (0.157) failed to reach significant limit. Conclusion Dance Movement Therapy was found beneficial in overall cognition and quality of life in patients with mild-moderate PD. Studies with larger sample size will assess the long-term safety and effectiveness of this alternative therapy in future.

There is some evidence regarding the role of LAG-3, TLR mediated neuroinflammation in PD.sLAG-3, TOLLIP, NLRP3 levels were measured in PD and healthy controls.These markers were significantly higher in PD and were associated with progression.sLAG3 and TOLLIP are involved in the NLRP3 mediated inflammatory activation in PD.

ABSTRACT: Background: Pathophysiology of levodopa-induced dyskinesia (LID) remains obscure. Increased dopamine metabolism due to prolonged levodopa treatment can exacerbate oxidative damage and neuroinflammatory pathology in Parkinson’s disease (PD). Association of novel peripheral markers with LID severity might provide insight into LID pathomechanisms. Objective: We aimed to study specific peripheral blood inflammatory-oxidative markers in LID patients and investigate their association with clinical severity of LID. Method: Motor, non-motor and cognitive changes in PD with and without LID compared to healthy-matched controls were identified. Within the same cohort, inflammatory marker (sLAG3, TOLLIP, NLRP3 and IL-1β) levels and antioxidant enzyme activities were determined by ELISA and spectrophotometric methods. Results: LID patients showed distinctly upregulated TOLLIP, IL-1β levels with significant diminution of antioxidant activity compared to controls. Significant negative association of cognitive markers with oxidative changes was also observed. Conclusion: To our understanding, this is the first study that indicates the involvement of toll-like receptor-mediated distinct and low-grade inflammatory activation in LID pathophysiology.

In the past couple of decades, with the widespread application of computerized medical records, data harmonization in biomedical and health research has become increasingly important. Data harmonization methods transform discordant data collected from various sources into a single cohesive format. Data collected from multicentric studies are typically large and some could be considered “big data”, which require data harmonization. Similar research procedures are also followed in genomic studies and biobanks. Unlike standard research techniques, big data studies often analyze the data without prior hypotheses. They frequently use data from patients collected in routine clinical practice and in this context, investigators exercise extreme care to protect the privacy of the patients while data harmonization and all other steps of analysis are completed. In addition to maintaining confidentiality, there are several ethical aspects that require special attention in the curation of such digital data. This is particularly important because ethical standards and guidelines are not uniform across countries. The ethical aspects which require special mention are data sharing and ownership, informed consent, international collaboration, transfer of biospecimens, return of research results to participants, benefit sharing and the roles of ethics committees. Consensus guidelines are required to strengthen ethical standards of data harmonization. In this chapter, we have given a brief overview of data harmonization and associated ethical considerations.

Levodopa-induced dyskinesia (LID) is a debilitating motor feature in a subset of patients with Parkinson's disease (PD) after prolonged therapeutic administration of levodopa. Preliminary animal and human studies are suggestive of a key role of dopamine type 3 (D3) receptor polymorphism (Ser9Gly; rs6280) in LID. Its contribution to development of LID among Indian PD patients has remained relatively unexplored and merits further investigation.200 well-characterised PD patients (100 without LID and 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata. MDS-UPDRS (Unified Parkinson's Disease Rating Scale from International Movement Disorder Society) Part III and AIMS (abnormal involuntary movement scale) were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analysed for the presence of Ser9Gly single nucleotide variant (SNV) (rs6280) by polymerase chain reaction followed by restriction fragment length polymorphism techniques.The frequency of AA genotype (serine type) was more frequently present in PD patients with LID compared to PD patients without LID (50 % vs 28 %; P = 0.002; OR = 2.57, 95 % CI: 1.43 - 4.62). The abnormal involuntary movement scale score was significantly higher in PD patients with AA genotype compared to carriers of glycine allele (AG + GG) (4.08 ± 3.35; P = 0.002).We observed a significant association of serine type SNV (rs6280) in D3 receptor gene in a cohort of PD patients with LID from India. More severe motor severity was found in patients with glycine substitution of the same SNV. The current study emphasised the role of D3 receptor in the pathogenesis of LID.

A 52-year-old hypertensive female presented with a lancinating pain in right side of face for 15 years, frequently affecting her daily life activity. Chewing food or brushing teeth would precipitate into severe facial pain, which radiated towards forehead and ears. Her sleep was also severely affected due to facial pain. She was initially treated with carbamazepine 100 mg/day that was later increased up to 400 mg/day. Her pain was controlled inadequately despite the additional administration of gabapentin at 450 mg/day. As a result of difficulty in taking food, she had lost a lot of weight in the past 1 year. The pain was distributed in all the three zones of trigeminal nerve. Routine blood tests and MRI of the trigeminal nerve were done. The trigger of pain was found to be confined to zone 2. We planned to perform transcutaneous transovale radiofrequency ablation (RFA) of the trigeminal root entry zone. Patient was counselled for possible complications, and her consent was taken. The whole procedure was done under sedation with propofol, and vitals were constantly monitored. Oxygen was given through a nasal cannula. The position of the patient was supine with head-end raised up to 30°. The procedure was performed in a cathlab under C-Arm. C-Arm was focused on sub-mental view, and ipsilateral foramen ovale was identified. The RFA cannula was then introduced approximately 2 cm lateral to ipsilateral angle of mouth and directed towards the foramen of ovale. Upon penetration of foramen ovale, the patient experienced extreme pain. The RF lesion generator was checked, and ground electrode was attached. RFA electrode was introduced through the cannula, and correct impedance was monitored to ensure its correct placement. Stimulation was given, and the patient experienced pain similar to her facial pain due to trigeminal neuralgia. Three consecutive lesions were made at 60, 70, and 80 centigrade for 60 s each. During lesioning, the corneal reflex was examined by the assistant. Ice pack was placed over the affected side of the face, and prophylactically, a single dose of 1 g of ceftriaxone was administered. In the first follow-up, 15 days after the intervention, the patient reported a reduction in pain and mild heaviness of the face, with no fever, an absence of Kernig's sign, and an intact corneal reflex. She did not report or notice any complications, for example, an increase in the threshold of pain, corneal anaesthesia, or anaesthesia dolorosa. The dose of the medication was tapered and gradually stabilised at carbamazepine 200 mg/day over a month. On her second follow-up (after 2 months), she was relatively free from facial pain.

<b>Context:</b> Mixed connective tissue disorder is an uncommon disease. Some scientists are reluctant to recognize it as a separate entity. Some others have defined this ailment. Cutaneous features of this condition are unique. Researchers from India have described these features to relate to those described in the studies from other parts of the globe. <b>Aims:</b> This study aims to delineate the skin manifestations of clearly defined mixed connective tissue disease (MCTD) patients, to compare them with those established as overlap syndrome, and to relate them with studies from other parts of the globe. <b>Settings and Design:</b> Successive patients who fulfilled the specific criteria for MCTD presenting in the skin outpatient department of a tertiary care hospital in eastern India were clinically examined from 2009 for 3 years. <b>Materials and Methods:</b> The number of participants was 23 and the dermatological features of these were compared with 22 patients with overlap syndrome. The antibody to uridine-rich U1 ribonucleoprotein was measured for all patients. <b>Statistical Analysis Used:</b> SPSS (Version 17) and MedCalc (Version 11.6). <b>Results:</b> The Male: Female ratio among the MCTD patients was 1:6.67 and that of the overlap syndrome was 1:10. Twenty patients of the MCTD group presented with synovitis as against only seven in the overlap group. Raynaud's phenomenon was present in some of the subjects. Puffy fingers were rare in our study. Facial numbness was reported by four of those suffering from MCTD. Antinuclear antibody (ANA) was essentially of a speckled pattern in this disease <b>Conclusions:</b> Cutaneous indicators of MCTD are distinct from overlap syndrome. Knowledge of these manifestations prevalent in a region may lead to early diagnosis of the disease.

Background. In monkey, reticulospinal connections to hand and forearm muscles are spontaneously strengthened following corticospinal lesions, likely contributing to recovery of function. In healthy humans, pairing auditory clicks with electrical stimulation of a muscle induces plastic changes in motor pathways (probably including the reticulospinal tract), with features reminiscent of spike-timing dependent plasticity. In this study, we tested whether pairing clicks with muscle stimulation could improve hand function in chronic stroke survivors. Methods. Clicks were delivered via a miniature earpiece; transcutaneous electrical stimuli at motor threshold targeted forearm extensor muscles. A wearable electronic device (WD) allowed patients to receive stimulation at home while performing normal daily activities. A total of 95 patients >6 months poststroke were randomized to 3 groups: WD with shock paired 12 ms before click; WD with clicks and shocks delivered independently; standard care. Those allocated to the device used it for at least 4 h/d, every day for 4 weeks. Upper-limb function was assessed at baseline and weeks 2, 4, and 8 using the Action Research Arm Test (ARAT), which has 4 subdomains (Grasp, Grip, Pinch, and Gross). Results. Severity across the 3 groups was comparable at baseline. Only the paired stimulation group showed significant improvement in total ARAT (median baseline: 7.5; week 8: 11.5; P = .019) and the Grasp subscore (median baseline: 1; week 8: 4; P = .004). Conclusion. A wearable device delivering paired clicks and shocks over 4 weeks can produce a small but significant improvement in upper-limb function in stroke survivors.

The etiopathogenesis of Parkinson's disease (PD) is not clear. Yet, it seems likely that inflammation as well as oxidative stress plays a major role in the disease pathogenesis. Based on our previous findings, we aimed to investigate prospective changes in peripheral inflammasome and oxidative modulators in relation to the progression of motor symptoms and severity of PD.Levels of inflammatory and oxidative markers in the serum of PD patients and healthy controls were estimated by quantitative ELISA and spectrophotometric methods at the baseline and at the end of one year.In PD patients, serum NLRP3 inflammasome and IL-1β levels increased significantly over a year, compared to the baseline. The average enzymatic activity of serum SOD1 was also augmented at one-year follow-up. Alongside these serummarker changes, the mean motorseverity of this patient cohort worsened over the time period.This pioneering study identified a novel association of peripheral inflammatory and oxidative markers with the progression of PD. Correlation of these serum proteins with the central pathological changes in PD and disease severity in a prospective manner might be useful not only for prognostication, but for understanding disease mechanisms and for planning future therapeutic strategies.

What is known and objective Drugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. Methods This is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. Results and discussion 21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naïve patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR = 1.82, 95% CI for OR: 1.36-2.45, P < .001). What is new and conclusion There was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects.

We reported a series of patients who presented with LSP-induced movement disorders specifically, dyskinetic movements. We have presented one case of LSP-induced parkinsonism and summarized ten cases of LSP-induced dyskinesia. The causality of the adverse drug reaction was assessed systematically using a validated rating system, and we extensively qualified the clinical presentation of each case of dyskinesia using a clinical rating scale. We described an unusual case of acute onset LSP-induced parkinsonism in a 56-year-aged female. The mean age of ten patients of LSP-induced dyskinesia was 65.3 years (standard deviation 10.4), and 25% of patients were female. They were consuming suspected medication for a median duration of 13 months (range 1-60 months). We noted LSP-induced dyskinesia was challenging to treat as its resolution is often incomplete even with adequate treatment.

Background: Writer's cramp (WC) is a task-specific focal hand dystonia presenting with pain, stiffness and/or tremor while writing. We explored the involvement of cortical and brainstem circuits by measuring intermuscular coherence (IMC) and pre-pulse inhibition (PPI) of the blink reflex. Methods: IMC was measured in 10 healthy controls and 20 WC patients (10 with associated tremor) while they performed a precision grip task at different force levels. Blink responses were evaluated in 9 healthy controls and 10 WC patients by stimulating the right supraorbital nerve and recording surface EMG from the orbicularis oculi muscles bilaterally. PPI involved conditioning this stimulation with a prior shock to the right median nerve (100 ms interval), and measuring the reduction in the R2 component of the blink reflex. Results: Significant IMC at 3-7 Hz was present in WC patients, but not in healthy controls. Compared to healthy controls, in WC patients the R2 component of the blink reflex showed significantly less PPI. IMC at 3-7 Hz could reliably discriminate WC patients from healthy controls. Conclusion: Cortical or sub-cortical circuits generating theta (3-7 Hz) oscillations might play an important role in the pathogenesis of WC. Moreover, the lack of PPI implicates abnormalities in brainstem inhibition in the emergence of WC. IMC may merit further development as an electrodiagnostic test for focal dystonia.

By virtue of being a specialized field by itself, the science of clinical trials (CTs) may not be well understood by doctors who are not specifically trained in it. A lack of knowledge may translate to a negative perception toward CT. With the idea of getting a situational snapshot, we estimated the knowledge and perception of CTs among doctors from government medical colleges of West Bengal who are not trained on CT in their postgraduate curriculum. Several determinants of knowledge and perception regarding CT were also evaluated.We have quantified the knowledge and perception of CTs by a structured validated questionnaire. Development and validation of the questionnaire was performed prior to the study.Among 133 participants, 7.5% received focused training on CT and 16.5% participated in CTs as investigators. Majority of the doctors were unfamiliar with the basic terminologies such as, "adverse event" and "good clinical practice." Encouragingly, 93.3% doctors advised that a detailed discussion of CT methodology should be incorporated in the under graduate medical science curriculum. They had an overall positive attitude toward CTs conducted in India, with a mean score that is 72.6% of the maximum positive score. However, a large number of the doctors were skeptical about the primary motivation and operations of pharmaceutical industry sponsored CTs, with 45% of them believing that patients are exploited in these sponsored CTs.Participant doctors had a basic knowledge of CT methodology. The study has revealed specific areas of deficient knowledge, which might be emphasized while designing focused training on CT methodology.

The incidence of Type 2 diabetes is increasing worldwide and diabetes is four times more common among ethnic minority groups than among the general Caucasian population. This study reflects on the specific issues of engaging people and evaluating interventions through written questionnaires within older ethnic minority groups.The original protocol set out to evaluate an adapted version of the X-PERT patient program http://www.xpert-diabetes.org.uk/ using questionnaires and interviews.Questionnaires, even verbally completed, were unsuccessful and difficult to administer as participants found the questionnaire structure and design difficult to follow and did not perceive any benefit to completing the questionnaires. The benefits of attending the course were also poorly understood by participants and in many cases people participated in coming to the course as a favour to the researcher. Engaging participants required word of mouth and the involvement of active members of the community.Peer led courses and their evaluation in older ethnic minority communities needs a very different approach for that in younger Caucasian patients. A structured approached to evaluation (favoured by western educational system) is inappropriate. Engaging participants is difficult and the employment of local well known people is essential.

BACKGROUND: Gait instability is one of the disabling clinical features of majority of patients suffering from Parkinson’s disease (PD). It is partially responsive to dopamine replacement therapy. Precise evaluation of distinct l-DOPA-sensitive and l-DOPA-resistant gait profiles might help in planning therapy of PD patients with gait disorder.METHOD: In this cross-sectional analytical study, we measured the gait parameters of 70 patients and 37 healthy participants using a 6.1-m long electronic walkway containing thousands of pressure sensors embedded in a carpet. The patients were evaluated in their OFF and ON phases of l-DOPA medication, and the data were compared with age- and gender-matched healthy controls.RESULTS: Except for the cadence, most gait parameters including velocity, stride length, and step length were deranged in PD patients. The mean velocity was significantly higher among healthy volunteers (99.19cm/s) compared to PD patients (73.90cm/s, P value 0.0001). However, the mean cadence was comparable between healthy and patient groups (103.29 vs. 103.39, P value 0.966). Certain temporal parameters (cadence, cycle time, and swing time) were nonresponsive to the dopaminergic therapy.CONCLUSION: On the basis of the findings, we propose that l-DOPA treatment improves most of the spatiotemporal gait parameters but cannot completely eliminate the risk of fall.

Movement Disorders Clinical PracticeVolume 10, Issue 5 p. 856-857 LETTERS: PUBLISHED ARTICLES Pattern Specific Dysgraphia—Beyond Letter Specificity Jacky Ganguly MD, DM, PDF, Jacky Ganguly MD, DM, PDF orcid.org/0000-0002-5098-3311 Movement Disorder Centre, Institute of Neurosciences Kolkata, Kolkata, IndiaSearch for more papers by this authorSupriyo Choudhury MD, Supriyo Choudhury MD Movement Disorder Centre, Institute of Neurosciences Kolkata, Kolkata, IndiaSearch for more papers by this authorHrishikesh Kumar MD, DM, PDF, Corresponding Author Hrishikesh Kumar MD, DM, PDF [email protected] orcid.org/0000-0002-9789-7832 Movement Disorder Centre, Institute of Neurosciences Kolkata, Kolkata, India Correspondence to: Dr. Hrishikesh Kumar, Movement Disorder Centre, Institute of Neurosciences Kolkata, 185, Acharya Jagadish Chandra Bose Rd, Elgin, Kolkata, West Bengal, 700017, India; E-mail: [email protected]Search for more papers by this author Jacky Ganguly MD, DM, PDF, Jacky Ganguly MD, DM, PDF orcid.org/0000-0002-5098-3311 Movement Disorder Centre, Institute of Neurosciences Kolkata, Kolkata, IndiaSearch for more papers by this authorSupriyo Choudhury MD, Supriyo Choudhury MD Movement Disorder Centre, Institute of Neurosciences Kolkata, Kolkata, IndiaSearch for more papers by this authorHrishikesh Kumar MD, DM, PDF, Corresponding Author Hrishikesh Kumar MD, DM, PDF [email protected] orcid.org/0000-0002-9789-7832 Movement Disorder Centre, Institute of Neurosciences Kolkata, Kolkata, India Correspondence to: Dr. Hrishikesh Kumar, Movement Disorder Centre, Institute of Neurosciences Kolkata, 185, Acharya Jagadish Chandra Bose Rd, Elgin, Kolkata, West Bengal, 700017, India; E-mail: [email protected]Search for more papers by this author First published: 13 March 2023 https://doi.org/10.1002/mdc3.13721Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Prasad S, Pal PK. Letter specific dysgraphia: a silent stutter. Mov Disord Clin Pract 2018; 5(6): 640–642. https://doi.org/10.1002/mdc3.12650. 10.1002/mdc3.12650 PubMedWeb of Science®Google Scholar 2Shamim EA, Chu J, Scheider LH, Savitt J, Jinnah HA, Hallett M. Extreme task specificity in writer's cramp. Mov Disord 2011; 26(11): 2107–2109. https://doi.org/10.1002/mds.23827. 10.1002/mds.23827 PubMedWeb of Science®Google Scholar 3Lang AE, Prashanth LK, Ghosh S, Elahi B, Chen R. Extreme task specificity: is it dystonia or another form of motor programming abnormality? Mov Disord 2012; 27(9): 1202–1203. https://doi.org/10.1002/mds.25023. 10.1002/mds.25023 PubMedWeb of Science®Google Scholar Citing Literature Volume10, Issue5May 2023Pages 856-857 ReferencesRelatedInformation

Objective: Environmental influence and dietary variations are well-known risk factors for various diseases including neurodegenerative disorders. Preliminary evidence suggests that diet in early-life and living environment might influence the incidence of Parkinson’s disease (PD) in later phase of life. There have been limited epidemiologic studies on this aspect especially in India. In this hospital-based case-control study, we intended to identify dietary and environmental risk factors of PD. Methods: Patients with PD (n = 105), Alzheimer’s disease (AD) (n = 53) and healthy individuals (n = 81) were recruited. Dietary intake and environmental exposures were assessed using a validated Food-Frequency and Environmental Hazard Questionnaire. Their demographic details and living environment were also recorded using the same questionnaire. Results: Pre-morbid consumption of carbohydrate and fat was significantly higher whereas dietary fiber and fruit content was significantly lesser in PD as compared to AD and healthy age-matched controls. Meat and milk intake was the highest among all the food groups in PD patients. Rural living and their habitation near water bodies were significantly more frequent in PD patients. Conclusion: We found that past intake of carbohydrate, fat, milk, and meat are associated with increased risk of PD. On the other hand, rural living and habitat near water bodies might be associated with incidence and severity of PD. Hence, preventive strategies related to dietary and environmental modulators in PD might be clinically useful in the future.

Abstract Patients with Parkinson’s disease and focal dystonia have difficulty in generating and preventing movement. Reaction time (RT) and stop signal reaction time (SSRT) measure the speed to initiate and stop a movement respectively. We developed a portable device to assess RT and SSRT. This incorporated a novel analysis to measure SSRT more efficiently (optimal combination SSRT, ocSSRT). After validation ocSSRT was measured in Parkinson’s disease patients without dyskinesia (PD), cervical dystonia (CD) and writer’s cramp. We also assessed how ocSSRT responded to L-dopa in PD patients and botulinum toxin injections in CD patients. Participants were instructed to release a button following a green LED flash on the device. On 25% of trials, a red LED flashed 5–195 ms after the green LED; participations were instructed to abort the button release on these trials. ocSSRT and RT were significantly prolonged in patients with Parkinson’s disease and focal dystonia (one-way ANOVA p &lt; 0.001). Administration of L-dopa significantly improved ocSSRT and RT in PD patients (p &lt; 0.001). Administration of botulinum toxin significantly improved ocSSRT, but not RT, in CD patients (p &lt; 0.05). ocSSRT is an easily-administered bedside neuro-physiological tool; significantly prolonged ocSSRT is associated with PD and focal dystonia.

Estimation of facial aging has assumed growing importance due to the advent of several antiaging therapies. Evidence-based estimation of global facial aging is often necessary, especially for validation of these treatment modalities. Most available methods are expensive and have been used in fair skinned individuals.We attempted to develop a clinical rating scale for the estimation of global facial aging applied on an Indian population which has brown to black skin. We have also measured the association of this rating scale score with the chronological age.Initially, a 14- item summated rating scale was developed with inputs from five dermatologists and a clinical pharmacologist. The rating scale was applied to 105 consenting subjects with healthy facial skin between 30 to 90 years of age. Intra- and inter-rater reliability was assessed.The summated rating score showed a significant positive correlation with the chronological age (Pearson's correlation coefficient 0.834, P < 0.001). We omitted one item from the scale due to a low inter-rater agreement. The resulting 13-item rating scale was internally consistent (Cronbach's alpha: 0.905), with substantial inter- and intra-rater reliability (intraclass correlation coefficient: 0.973 and 0.788, respectively). Principal components and predictive equation for perceptible age were identified on further computation.Participants of this study were limited to a particular ethnic group from West Bengal and other neighboring states of Eastern India.We have developed and validated a 13-item rating scale for the quantification of global facial aging suitable for Indian (brown to black) skin type. This scale can be utilized effectively for clinical estimation of global facial aging.

Mirror movements (MM) have been previously reported in patients with Parkinson's disease (PD). Despite being potentially relevant in PD, MM as a neurological sign have remained less recognized. In this study we critically evaluated the characteristic features of MM and their attributes among a cohort of PD patients from a tertiary care center of eastern part of India.In this analytical cross-sectional study, 70 patients with PD were evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) and a previously used scale to score MM in the OFF and ON phases of l-Dopa therapy. MM was video-recorded for 4 motor tasks (finger- tapping, hand-movement, pronation-supination, rapid ankle-flexion-extension) and scored for the MM attributes i.e. amplitude, distribution and proportion.A vast majority of PD patients (95.7%) exhibited MM and there was a trend of higher MM score with lesser severity of disease affection. Marked differences in amplitude, distribution and proportion of MM in the upper and lower limbs were evident in response to l-Dopa therapy in certain motor tasks. In addition, less involved limbs exhibited higher MM and the MM scores were higher for lower limb tasks in the ON phase.The high prevalence of MM in PD patients and its correlation to disease severity echoed previous studies across the globe. In addition, this study provides evidence for a differential response of MM attributes to l-Dopa. To our knowledge, this is the first study that characterized MM in a cohort of PD patients from India. Our findings suggest the significance of MM as a clinical neurological sign in PD.

<h2>Abstract</h2><h3>Background</h3> Inflammation along with oxidative stress alters neuroplasticity which might contribute to neurodegeneration in Parkinson's disease (PD). <h3>Objectives</h3> We aimed to explore the correlation of inflammatory-oxidative and neurotrophic changes in PD and their association with clinical staging and motor severity. <h3>Methods</h3> Serum oxidative markers, pro and anti-inflammatory cytokines and BDNF levels were estimated by spectrophotometric and ELISA techniques. <h3>Results</h3> Redox-Inflammatory and neurotrophic markers significantly altered in PD and strongly correlated with motor severity and stagings of PD. <h3>Conclusion</h3> This study establishes a link between peripheral immune-neurotrophic markers and disease severity in PD. This can lead to novel future therapeutics.

Aborting an ongoing motor response (response inhibition) is controlled through a complex network, critically involving the hyper-direct pathway from supplementary motor area to the subthalamic nucleus (STN) [[1]Aron A.R. Poldrack R.A. Cortical and subcortical contributions to stop signal response inhibition: role of the subthalamic nucleus.J Neurosci. 2006; 26: 2424-2433Crossref PubMed Scopus (1223) Google Scholar]. Logan and Cowan first described the Stop Signal Reaction Time (SSRT), a measure of stopping efficiency [[2]Logan G.D. Cowan W.B. On the ability to inhibit thought and action: a theory of an act of control.Psychol Rev. 1984; 91: 295Crossref Scopus (1828) Google Scholar]. Since then SSRT has been investigated in various neurological disorders. Parkinson’s disease (PD) patients have deficient response inhibition, which is independent of the severity of bradykinesia [[3]Gauggel S. Rieger M. Feghoff T. Inhibition of ongoing responses in patients with Parkinson’s disease.J Neurol Neurosurg Psychiatr. 2004; 75: 539-544Crossref PubMed Scopus (230) Google Scholar]. Levodopa and bilateral STN deep brain stimulation (DBS) both improve response inhibition in Parkinson’s patients [[4]Ray N. Jenkinson N. Brittain J. Holland P. Joint C. Nandi D. et al.The role of the subthalamic nucleus in response inhibition: evidence from deep brain stimulation for Parkinson’s disease.Neuropsychologia. 2009; 47: 2828-2834Crossref PubMed Scopus (105) Google Scholar,[5]Choudhury S. Roy A. Mondal B. Singh R. Halder S. Chatterjee K. et al.Slowed movement stopping in Parkinson’s disease and focal dystonia is improved by standard treatment.Sci Rep. 2019; 9: 1-9Crossref PubMed Scopus (4) Google Scholar]. Recently, our group has developed a portable device to measure reaction time and response inhibition, which is easy to use at the bedside or in the clinic. We have also introduced an improved measure (optimum combination SSRT; ocSSRT) which uses a Bayesian statistical approach to enhance reproducibility [[5]Choudhury S. Roy A. Mondal B. Singh R. Halder S. Chatterjee K. et al.Slowed movement stopping in Parkinson’s disease and focal dystonia is improved by standard treatment.Sci Rep. 2019; 9: 1-9Crossref PubMed Scopus (4) Google Scholar]. In this pilot study we recruited Parkinson’s patients from our movement disorders clinic, and compared ocSSRT with standard bedside clinical assessments during optimisation of bilateral STN-DBS parameters. We included 16 patients with STN-DBS (Medtronic Activa stimulators), in whom DBS electrodes had been implanted at least six months prior to optimisation. All patients reported motor complaints with existing programming, and attended clinic to optimize simulation parameters using the N’vision 8840 physician programmer. Measurements of Movement Disorder Society- Unified Parkinson’s disease Rating Scale Part III (MDS-UPDRS III, Motor score for PD patients) and ocSSRT were made three times: with the initial DBS setting (when the patients had motor symptoms), after turning off the DBS and lastly after reprogramming, when both programmer and subject felt that the settings were optimal. The ocSSRT box has a screen to display instructions and test results. A green and red LED act as the go and stop cues respectively (Fig. 1A). Patients started a trial by pressing and holding a button. They were told to release this quickly if the green LED illuminated (go trial), but to keep the button pressed if the red LED illuminated (stop trial). Responses to 192 trials were recorded (inter-trial interval 1–2.638s), in three blocks of 64 trials separated by a 60 s rest. Within each block, there were 48 go trials and 16 stop trials. The stop trials presented the red LED at four different delays (5–195 ms) after the green LED. The device measured the distribution of reaction times in the go trials, and the proportion of stop trials where a response was produced inappropriately. We assume that on a stop trial, two processes are initiated within the nervous system by the go and stop cues respectively, and that these race to completion. If the go process completes first, an inappropriate response is produced; if the stop process wins the race, the response is successfully inhibited. SSRT is computed from the proportion of inappropriate responses and the distribution of the reaction times in go trials. ocSSRT optimises this calculation using knowledge of the response statistics, as we have previously described [[5]Choudhury S. Roy A. Mondal B. Singh R. Halder S. Chatterjee K. et al.Slowed movement stopping in Parkinson’s disease and focal dystonia is improved by standard treatment.Sci Rep. 2019; 9: 1-9Crossref PubMed Scopus (4) Google Scholar]. Cohen’s kappa statistic was used to assess the strength of agreement between clinical assessments and reaction times. As expected, the UPDRS III worsened after turning off DBS and improved significantly after optimising the programming. Similarly, ocSSRT also prolonged significantly after turning off DBS and shortened after optimising the programming parameters (Fig. 1BC). Interestingly, the reaction time did not show a similar trend (Fig. 1D). All 16 patients demonstrated a clinical improvement after optimising the DBS program and also showed a reduction in ocSSRT (Fig. 1E). This pilot experiment shows that ocSSRT estimated through a portable device could be used as a tool for optimising DBS settings: there was perfect agreement between improvement on a subjective clinical rating scale widely used for evaluating the severity of the movement disorder in PD patients and ocSSRT (Cohen’s kappa = 1, p < 0.0001). This may be important for the objective documentation of the effects of treatment on motor function in PD, particularly where several different assessors are involved in optimising settings over time. It may also aid the selection of optimum settings when used in conjunction with standard clinical scales in cases where there is ambiguity. However, multi-centre studies with larger sample sizes are essential if this promising observation is to be validated. Since making these observations, we have solved some technical challenges and successfully implemented the method as a mobile phone application (app) which measures ocSSRT as effectively as our custom device. This could open the way for ocSSRT and similar measures to aid remote supervision of DBS programming or be used as a tool to support programming by the patients’ care giver. Akash Roy: Study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. Supriyo Choudhury: Study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. Purba Basu: Acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. Mark R. Baker: Study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content. Stuart N. Baker: Study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content. Hrishikesh Kumar: Study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content, study supervision. Funding for study was provided by Institutional research fund, Institute of Neurosciences Kolkata (I-NK) of H.K, MRC Confidence in Concept grant number MC/PC/17168 and by MRC project grant number MR/P012922/1 to SNB. The fellowship of AR is supported by DST-INSPIRE of Government of India [IF-170628].

A putative spinal circuit with convergent inputs facilitating human wrist flexors has been recently described. This study investigated how central nervous system lesions may affect this pathway. We measured the flexor carpi radialis H-reflex conditioned with stimulation above motor threshold to the extensor carpi radialis at different intervals in fifteen patients with stroke and nine with spinal cord injury. Measurements after stroke revealed a prolonged facilitation of the H-reflex, which replaced the later suppression seen in healthy subjects at longer intervals (30-60 ms). Measurements in patients with incomplete spinal cord injury at cervical level revealed heterogeneous responses. Results from patients with stroke could represent either an excessive facilitation or a loss of inhibition, which may reflect the development of spasticity. Spinal cord injury results possibly reflect damage to the segmental interneuron pathways. We report a straightforward method to assess changes to spinal circuits controlling wrist flexors after central nervous system lesion.

Background: Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. Methods: In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Results: Significant improvement in knowledge (P < 0.001) was noted in the pre- to post-test knowledge scores, while a high gain in class average normalized score was evident. In Likert scale analysis, most students (93%) expressed that role-play was an acceptable way of teaching. In a thematic analysis, themes of both strengths and weaknesses of the session emerged. Discussion: Role-play can be effectively utilized while teaching selected topics of molecular pharmacology in undergraduate medical curricula.

Progressive supranuclear palsy (PSP) is a large-scale network disease resulting in variable signs and symptoms including gait impairment and higher order cognitive dysfunction. Despite few studies showing the association of falls and cognitive dysfunction, the existing literature is yet to establish the exact relationship of discrete characteristics of gait with cognitive function in PSP.In this cross-sectional study, we aimed to characterize and explore the relationship of these two apparently distinct physiological phenomena in patients with PSP and across its different variants.Quantitative assessment of two-dimensional gait parameters was measured using an electronic walkway (GAITRite®). Dementia Rating Scale-2 was used to assess global as well as higher order cognitive functions.A regression model was used to interpret results.We observed that the variability domain of gait was significantly impaired in PSP patients with severe cognitive impairment compared to that of intact cognition. Moreover, initiation/perseveration (I/P), a higher order cognitive process, and one of its specific components, i.e., complex verbal task (β = 2.39, P < 0.001), significantly predict gait velocity in PSP [F (1, 40) = 16.102, P < 0.001].Our findings indicate that the severity of cognitive functions affects gait variability, which might lead to frequent falls as observed in PSP. Furthermore, semantic fluency task of I/P function may act as a predictor of gait velocity. We suspect that higher order cognitive dysfunction through the damage of frontal lobe structure including dorsolateral prefrontal cortex or related network may influence gait in PSP.

<b>Objectives:</b> Chronic venous insufficiency (CVI) in lower limbs manifest as stasis dermatitis. The anti-collagenase, anti-inflammatory and immunomodulatory effects of doxycycline and the T-cell inhibitory effects of tacrolimus could theoretically modify the disease pathophysiology. This study was undertaken to evaluate the efficacy and safety of four weeks combination therapy of oral doxycycline 100 mg with topical tacrolimus 0.1% for stasis dermatitis associated with CVI. <br> <b>Materials and Methods:</b> A single-arm, interventional pilot study was conducted on subjects with CVI of C4 to C6 category (CEAP classification: clinical, etiology, anatomical, pathophysiology). Treatment duration was four weeks with fortnightly follow-ups. Primary efficacy was assessed as changes from baseline of pigmentation, erythema, edema, itching and hair loss of the affected area evaluated on Likert scale scores. Secondary efficacy parameters were percentage improvement of the dermatitis area and changes in ulcer dimensions (maximum length and breadth), if present. Safety evaluation included all treatment emergent clinical signs and symptoms reported by the patients and/or observed by the physician. <br> <b>Results:</b> Out of 19 recruited subjects, 15 completed the study for analysis. Significant (P<0.01) improvement in pain, edema, pigmentation, erythema and exudation were observed. Reduction of ulcer dimensions was also statistically significant (P<0.01). 86.6% showed improvement of the dermatitis area, 6.7% patients failed to show any improvement and 6.7% showed worsening. Adverse effects were observed in only two subjects.<br> <b>Conclusion:</b> This pilot study suggests efficacy of this combination therapy in controlling features of stasis dermatitis but further studies are needed for validation.

The extent of gait abnormality is non-uniform across motor phenotypes of Parkinson's disease (PD). The biological basis of this heterogeneity remains intriguing. Moreover, the relationship of gait impairment with various neurodegenerative protein markers in PD is not well established.Here, we aimed to explore the interplay between gait parameters and specific serum protein markers in PD.A total of 62 PD patients were consecutively recruited. Blood samples and gait data were acquired from 37 and 34 patients respectively. Two-dimensional spatio-temporal gait parameters were estimated using an electronic walkway (GAITRite®, CIR Systems Inc., USA). Serum phosphorylated alpha synuclein (p-Ser129-a-syn) and total a-syn levels were measured using commercially available ELISA kit. Data was analyzed using SPSS Version 20 (IBM).We found that phosphorylated a-syn levels were significantly higher in PD patients with postural instability and gait difficulty compared to tremor dominant variant. Significant reduction in gait velocity was also observed with increasing levels of this pathological form of a-syn. Regression modelling showed that phosphorylated a-syn is an independent predictor of gait velocity.Our findings indicate that concentrations of peripheral p-Ser129-a-syn but not total a-syn could be a potential contributor of gait impairment in PD. Further investigation on the systemic role of phosphorylated a-syn on gait would bridge the gap between central and peripheral mechanisms underlying phenotypic variability in PD.

Objective: To assess the extent, pattern and determinants of non-prescription medicine use in an urban area of eastern India.Methods: A descriptive cross-sectional survey with total 392 subjects was carried out for 3 months by a structured questionnaire to assess the extent, pattern and determinants of non-prescription medicine use amongst the patients at a community retail medicine shop and a pharmacy running in Public-Private Partnership (PPP) model in a government hospital.Results: Our study found that 61.4% of the consumers indulged in the practice of self-medication.The commonest reason for self medication was a prevailing tendency in the community followed by cost-saving and convenience.The most commonly used medicines were antacids (43.4%) followed by analgesics-antipyretics (42.6%).It was found that only 12.5% completed an ongoing course of antibiotics.Consumption of ORS was commoner in diarrhoea than vomiting and only a few (13%) of the patients dissolved the ORS powder as directed.Only 9.7% of the subjects thought non-prescription medicine use is safe.Regarding the various types of medicine preparations used by them from the two types of pharmacy, a significant difference was noted only for eye drops (p = 0.003).This result might have been obtained due to prevailing ocular infections in the selected study population and underreporting at the Ophthalmology OPD of the nearest hospital.Conclusion: The current study has documented the extent of, factors associated with, and the pattern of non-prescription medicine use resulting in a surge of self-medication practice in urban area. Key words: Non-

Spinocerebellar Ataxia 12(SCA12) is a rare form of SCA, predominantly reported in the ethnic Agarwal population originating from North India. It generally presents with late onset upper limb tremor followed by ataxia.1 Tremor in SCA12 remains poorly studied to date. Since action tremor is the most common and earliest sign in SCA12, it is often mis-diagnosed as Essential tremor.2 In SCA12, CAG repeat associated neuro-toxic protein accumulation accelerates degeneration in the cerebello-cortical region.3 Since toxic protein associated neuro-degeneration is a diffuse process, one may expect appendicular features of SCA12 to reflect symmetry. But asymmetrical hand tremor was documented in one patient of Indian origin by Kalia et al.4 They stated that previous reports did not comment about tremor symmetry, this remains largely true to date. In this paper we have tried to explore if asymmetry of symptoms in SCA12 is an exception or a common finding. We studied 22 cases of SCA12 with a focus on laterality and associated phenomenology of symptoms. Mean disease duration in our study population was 8.2 (±4.7) years. Tremor was clinically analyzed by a movement disorders neurologist. The findings have been summarized in Table 1. When we look into upper limb findings, all 22 (100%) patients had intention tremor, 21 (95%) had dysmetria, 21 (95%) patients had postural tremor and 12 had rest tremor. Interestingly, postural tremor did not depict re-emergence, which is commonly seen in Parkinson's disease. Twenty (91%) patients had asymmetrical upper limb tremor and 10 (45%) had asymmetrical dysmetria. Out of these 20 patients, 19(90%), 10 (83%) and 5 (29%) had asymmetry in postural, rest and intention tremor respectively. Notably, postural tremor showed the highest rate of asymmetry. Only two patients had symmetry in upper limb tremor at presentation but their symptoms started 14 and 16 years ago respectively. Even in these two patients, tremor began on one side and took 5–7 years to equally involve the upper limbs. Twelve patients had simultaneous rest, postural and action tremor, which is defined as Holmes' tremor (HT).5 When analyzing lower limb data, only one patient had action tremor and it was symmetrical. Sixteen patients had dysmetria, all of which was symmetrical. Our findings suggest that asymmetry is a commonly found character of upper limb tremor in SCA12, which can be seen in the representative video segments (Video 1), provided as a supplement to this manuscript. Written informed consent was obtained and ethical approval was taken. Theoretically, HT can be found in any cerebellar outflow tract disorder, but we duly document it in SCA12 for the first time.5 Lower limb tremor was found in only one patient, and it was symmetrical. Dysmetria was more common in lower limbs as compared to tremor, and that too was symmetrical. The clear incongruence in upper and lower limb symptoms in tremor disorders is well reported but unexplained. Well-developed laterality in the upper limbs might make central oscillations manifest better on one side. These oscillations may be dampened in the lower limb due to more crosstalk between bilateral neural tracts. Through our preliminary observation, we conclude that asymmetrical upper limb tremor is a hallmark of SCA12. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique; (4) Supervision. S.B.: 1A, 1B, 1C, 2C, 3A, 3B S.C.: 2A, 2C, 3B U.S.: 1C, 2C, 3C P.B.: 1C, 2C, 3C H.K.: 1A, 1B, 1C, 2A, 3B, 4 This study was approved by the Institute of Neurosciences Kolkata, Institutional Ethics Committee. Written informed consent to publish case reports and videos was obtained from all participants. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Institutional research fund of HK was used for this study. The authors declare no conflicts of interest relevant to this work. The authors declare that there are no additional disclosures to report.

To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) and compared values with data from healthy controls.Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm.The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022).Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.

<b>Objectives:</b> Lafutidine is a new H ₂ -blocker in India claimed to be more potent and effective than existing H ₂ -blockers. Proton pump inhibitors (PPIs), by virtue of their mechanism of action, have greater efficacy than H ₂ -blockers in gastric acid suppression. However, clinical trials comparing H ₂ -blockers directly with PPIs are limited. We carried out a head-to-head comparison of the effectiveness of lafutidine versus the PPI pantoprazole in uninvestigated dyspepsia [CTRI/2013/12/004261].<br> <b>Materials and Methods:</b> A prospective, open label, randomized, controlled trial was conducted in a tertiary care hospital. Ambulatory adult patients with dyspepsia, not yet subjected to endoscopy, were recruited if they had at least moderately severe symptoms, defined as a score of ≥ 4 on a 7-point Global Overall Symptom (GOS) Scale. Those with alarm features or significant comorbidity were excluded. Subjects received either once daily lafutidine 10 mg or pantoprazole 40 mg, orally, for 8 weeks. Reflux, dysmotility and pain scores were assessed by Modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSGERD), and quality of life (QoL) by SF-8 scale. The latter had physical and mental components summarized by physical component summary score (PCS) and a mental component summary score (MCS). <br> <b>Results:</b> Of 122 patients enrolled, data of 57 on lafutidine and 60 on pantoprazole were analyzed. At 4 weeks, proportion of subjects responding (GOS score ≤ 2) in the two arms (lafutidine 45.61% vs. pantoprazole 48.33%, <i>P</i> = 0.854) or showing symptom resolution (GOS score ≤ 1) (lafutidine 12.28% vs. pantoprazole 5.00%; <i>P</i> = 0.197) were comparable. Similarly at 8 weeks, both responder (lafutidine 52.63% vs. pantoprazole 56.67%; <i>P</i> = 0.712) and symptom resolution proportions (lafutidine 33.33% vs. pantoprazole 30%; <i>P</i> = 0.843) were comparable. Total score on mFSSGERD scale, as well as all its three component scores, and PCS and MCS scores on QoL SF-8 scale showed improvement but no statistically significant difference between the two arms. Tolerability of both drugs was excellent.<br> <b>Conclusions</b> : Lafutidine is well-tolerated and there is no clinically worthwhile difference between the two drugs in the empirical treatment of uninvestigated dyspepsia.

Parkinson’s Disease (PD) and vitamin D share a unique link as Vitamin D deficiency (VDD) prevails in PD. Thus, an in-depth understanding of Vitamin D biology in PD might be crucial for therapeutic strategies emphasizing Vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D-associated genes in PD, like VDR (Vitamin D Receptor) or GC (Vitamin D Binding Protein), may aid the process along with polymorphisms of Vitamin D metabolizing genes (e.g., CYP2R1, CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to Vitamin D levels [GC (GC1-rs7041, GC2-rs4588), CYP2R1, CYP24A1, CYP27B1] and Vitamin D function [VDR (FokI - rs2228570, ApaI - rs7976091, BsmI-rs1544410, TaqI-rs731236)] was conducted to explore their relationship with PD severity globally. Furthermore, the DisGeNET database was utilized to explore the gene-disease associations in PD, and STRING alongside Cytoscape was utilized to identify critical genes associated with PD. VDR-FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese, and Japanese populations, whereas VDR-ApaI polymorphism was found to affect PD in the Iranian population. However, VDR-TaqI and BsmI polymorphisms had no significant association with PD severity. Conversely, GC1 polymorphisms reportedly affected Vitamin D levels without influencing the disease severity. CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD. Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D-rich food intake, enhancing inflammation, and thereby influencing PD pathophysiology. Knowledge of the polymorphisms associated with vitamin D appears promising for developing new therapeutic strategies against PD.

The ability to start and stop movements is impaired in movement disorders [ [1] Choudhury S. et al. Slowed movement stopping in Parkinson's disease and focal dystonia is improved by standard treatment. Sci. Rep. 2019; 9: 1-9 Crossref PubMed Scopus (5) Google Scholar ]. Measuring the ability to respond to a cue is relatively easy; stopping is a more hypothetical concept which is harder to quantify. One successful approach relies on the ‘horse race’ model. This conceptualises a Go and Stop process which race in parallel towards a finish line. If the Go process wins, the movement is executed; if the Stop process wins, movement is inhibited. This theoretical concept was given mathematical expression by Logan and Cowan (1984), leading to the stop signal reaction time (SSRT) [ [2] Logan G.D. Cowan W.B. On the ability to inhibit thought and action: a theory of an act of control. Psychol. Rev. 1984; 91: 295 Crossref Scopus (1877) Google Scholar ]. We measured SSRT through a simple task using a battery-operated portable box (Fig. 1B), ideal for bedside assessment. In the task, the subjects were requested to release a button in response to an intermittently flashing green LED (‘go signal’) as fast as they could but cease to release the button in a quarter of trials at random when the ‘stop signal’ (red LED) flashed immediately followed the ‘go signal’. The stop signals were delivered in four different delays (Fig. 1A), leading to different proportions of trials where the button was released inappropriately. The probability of error and reaction time during a stop-signal task are used to compute SSRT. Recently, we improved SSRT estimation reliability using a Bayesian mathematical approach (optimum combination stop signal reaction time, ocSSRT) [ [1] Choudhury S. et al. Slowed movement stopping in Parkinson's disease and focal dystonia is improved by standard treatment. Sci. Rep. 2019; 9: 1-9 Crossref PubMed Scopus (5) Google Scholar ]. Essentially, this measure was derived from mean posterior probabilities of SSRTs in four different stop-signal delays and summarised as one mean and 95% confidence interval for individual subjects. Subsequently, we applied ocSSRT to movement disorders patients through a portable battery-operated box with a digital display. We observed that patients with movement disorders e.g. Parkinson's Disease (PD), cervical dystonia (CD), and writer's cramp demonstrated significantly prolonged ocSSRT compared to healthy control [ [1] Choudhury S. et al. Slowed movement stopping in Parkinson's disease and focal dystonia is improved by standard treatment. Sci. Rep. 2019; 9: 1-9 Crossref PubMed Scopus (5) Google Scholar ] (Fig. 1C). Thus, this neurophysiological index may have potential use for classification of various types of movement disorders including psychogenic movement disorders. The prolonged ocSSRT was partially normalised after intake of l-dopa in PD patients and after one month of injecting therapeutic doses of botulinum toxin in the affected muscles in CD patients (Fig. 1D). We also used this box to optimise the settings for deep brain stimulation (DBS) in patients from our Movement Disorders clinic [ [3] Roy A. et al. Stop Signal Reaction Time measured with a portable device validates optimum STN-DBS programming. Brain Stimul.: Basic Translat. Clin. Neuromodul. 2020; 13: 1609-1611 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar ] and potentially this could be further validated as a tool for DBS programming remotely (Fig. 1EF). We also showed that ocSSRT is useful in discriminating between Alzheimer's and Parkinson's disease [ [4] Rahman S. et al. Comparing stop signal reaction times in Alzheimer's and Parkinson's disease. Can. J. Neurol. Sci. 2021; : 1-26 Google Scholar ] (Fig. 1G). SSRT could thus be used for screening and classification of neurodegenerative conditions. Against this backdrop, there is a need for greater accessibility of this tool to movement disorders neurologists and researchers interested in exploring the clinical utility of SSRT. We therefore developed and validated an android application to measure simple visual reaction time (RT) and ocSSRT.

Gait differentiation in progressive supranuclear palsy (PSP) and vascular parkinsonism (VaP) is sometimes difficult to detect with the naked eye. Here, we compared specific gait parameters, neuro-morphometric indices, and their associations between patients with PSP Richardson's syndrome (PSP-RS) and VaP. A total of 18 PSP-RS and 13 VaP patients were recruited. Spatio-temporal gait parameters (GAITRite®) and neuroanatomical morphometry (FreeSurfer pipeline) were assessed. The groups were compared using unpaired t-tests involving 10000 random permutations after statistically controlling for total UPDRS-III and H&Y scores. Statistically significant differences between the groups were decided at < 5% Benjamini-Hochberg False Discovery Rate (FDR) for multiple-comparison related corrections. Spearman's correlations were performed to assess the significant associations (p < 0.05) between the gait parameters and morphometry indices. Among all the spatio-temporal gait parameters, PSP-RS patients displayed greater stride time, step time, swing time, and stance time variabilities compared to VaP. Morphometric analyses showed that thalamus, and caudate volumes were significantly lower, but cerebellar cortex, hippocampus, amygdala, accumbens, and putamen volumes were higher in PSP-RS than VaP. Moreover, the bilateral insula was significantly thinner in VaP than in PSP-RS. Correlation analyses support the involvement of limbic structures besides cerebellum in postural control during self-paced walking of PSP-RS patients. Our findings underline the importance of examining individual brain regions to understand the association of cortical and subcortical morphometric estimates and gait variability parameters in PSP-RS and VaP. This study suggests the involvement of the limbic system in addition to the classical neural structures for motor control and gait.

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Abstract Parkinson's disease (PD) and vitamin D share a unique link as vitamin D deficiency (VDD) prevails in PD. Thus, an in‐depth understanding of vitamin D biology in PD might be crucial for therapeutic strategies emphasising vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D‐associated genes in PD, like VDR (vitamin D receptor) or GC (vitamin D binding protein) may aid the process along with polymorphisms of vitamin D metabolising genes (e.g., CYP2R1 and CYP27A1 ) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to vitamin D levels [ GC (GC1‐rs7041 and GC2‐rs4588), CYP2R1 , CYP24A1 and CYP27B1] and vitamin D function [ VDR (FokI ‐ rs2228570 and rs10735810; ApaI ‐ rs7976091, rs7975232BsmI and rs1544410; and TaqI ‐ rs731236)] was conducted to explore their relationship with PD severity globally. VDR ‐FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese and Japanese populations, whereas VDR ‐ApaI polymorphism was found to affect PD in the Iranian population. However, VDR ‐TaqI and BsmI polymorphisms had no significant association with PD severity. Conversely, GC1 polymorphisms reportedly affected vitamin D levels without influencing the disease severity. CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD. Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D‐rich food intake, enhancing inflammation, there by influencing PD pathophysiology. Knowledge of the polymorphisms associated with VDD appears promising for developing precision vitamin D‐dosing therapeutic strategies against PD.

Abstract Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophins, inflammatory markers and oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver six 2 minute stimulations (12 minutes/day) of the nVNS/sham device for one month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly (p &lt; 0.05) after nVNS treatment. Here we present the first evidence of the efficacy and safety of nVNS in the treatment of gait in PD patients, and propose that nVNS can be used as an adjunctive therapy in the management of PD patients, especially those suffering from FOG. Clinical trial registration number : ISRCTN14797144 Date of Registration: 11 May, 2020

Introduction: Freezing of gait (FOG) and other gait disturbances are common disabling symptoms in Parkinson’s disease (PD). Trans-cranial Direct Current Stimulation has shown to improve gait in some stud- ies. In the same vein, we hypothesize that non invasive vagus nerve stimulation (nVNS) could improve FOG in PD patients by modulating cortico-subcortical interactions.

Parkinson's disease (PD) has been reported from single gene mutation among both familial and sporadic forms of the disease. In PD, SNCA (PARK 1 and 4), LRRK2 (PARK8) follow autosomal dominant mode of inheritance. On the other hand, autosomal recessive homozygous or compound heterozygous mutations have been identified in genes like PARK2 (Parkin), PARK6 (PINK1), PARK7 (DJ-1), ATP13A2 (PARK9) and PARK14 (PLA2G6) etc. Besides the relatively rare occurrence of these genes in PD population, few of them appear to be responsible for a substantial proportion of early-onset PD (EOPD) or atypical PD since their clinical presentation is distinct from classical PD. PARK9 is classically linked to Kufor-Rakeb syndrome (KRS), a form of EOPD [ [1] Behrens M.I. Brüggemann N. Chana P. Venegas P. Kägi M. Parrao T. Orellana P. Garrido C. Rojas C.V. Hauke J. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Mov. Disord. 2010; 25: 1929-1937 Google Scholar ]. KRS is an autosomal recessive parkinsonism, generally presents with signs of pyramidal degeneration, dementia, levodopa-responsive parkinsonism and supranuclear gaze paresis. Generalized brain atrophy and iron accumulation in the basal ganglia are also found in imaging studies. Mutation in Parkin (PARK2) is also responsible for EOPD usually characterizing by dystonia, sleep benefit and early complications from levodopa treatment. At least 28 mutations of ATP13A2 gene and over 100 mutations in PARK2 gene have been found to be associated with Parkinsonism [ [2] Park J.S. Blair N.F. Sue C.M. The role of ATP13A2 in Parkinson's disease: clinical phenotypes and molecular mechanisms. Mov. Disord. 2015; 30: 770-779 Google Scholar , [3] West A. Periquet M. Lincoln S. Lücking C.B. Nicholl D. Bonifati V. Rawal N. Gasser T. Lohmann E. Deleuze J.F. Complex relationship between Parkin mutations and Parkinson disease. Am. J. Med. Genet. 2002; 114: 584-591 Google Scholar ]. The PARK2 gene encodes cytosolic ubiquitin-E3-ligase (the Parkin protein), which acts as neuroprotection in the survival of dopaminergic neurons upon exposure to various neurotoxins. The protein encoded by ATP13A2 is a member of subfamily P5 of the P-type superfamily of ion pumps, provides protection from Mn2+, Zn2+toxicity and alpha-synuclein aggregation which are all associated with PD. Although the commonest mode of inheritance is homozygous, simple or compound heterozygous mutations are also described in patients with Parkinsonism. To our knowledge, this is the first report of coexisting unique heterozygous PARK9 and PARK2 mutations in a case of EOPD.

Introduction: The ability to stop the execution of a movement in response to an external cue requires intact executive function. The effect of psychotropic drugs on movement inhibition is largely unknown. Movement stopping can be estimated by the Stop Signal Reaction Time (SSRT). In a recent publication, we validated an improved measure of SSRT (optimum combination SSRT, ocSSRT). Here we explored how diazepam, which enhances transmission at GABAA receptors, affects ocSSRT. Methods: Nine healthy individuals were randomized to receive placebo, 5 mg or 10 mg doses of diazepam. Each participant received both the dosage of drug and placebo orally on separate days with adequate washout. The ocSSRT and simple reaction time were estimated through a stop-signal task delivered via a battery-operated box incorporating green (Go) and red (Stop) light-emitting diodes. The task was performed just before and one hour after dosing. Result: The mean change in ocSSRT after 10mg diazepam was significantly higher (+27ms) than for placebo (-1ms; p=0.012). By contrast, the mean change in simple response time remained comparable in all three dosing groups (p=0.419). Conclusion: Our results confirm that a single adult therapeutic dose of diazepam can alter motor inhibition in drug naïve healthy individuals. The selective effect of diazepam on ocSSRT but not simple reaction time suggests that GABAergic neurons may play a critical role in movement-stopping.

Spinocerebellar ataxia type 12 (SCA 12) is characterized by late onset tremor, ataxia and pyramidal signs. Parkinsonism and cognitive decline may appear with time. It is considered as slowly progressive but temporal evolution of symptoms has not been reported.We report the evolution of symptoms in three SCA12 patients followed over a range of 5-6 years. We focused on the evolution of gait abnormality as it becomes the most disabling symptom as disease advances. Two-dimensional gait parameters were studied using an electronic walkway at various time points to measure objective changes in gait.All patients presented with tremor in the upper extremity at baseline which progressed non-uniformly over the years. Progression of gait variability measures of step length, stance time and step time were also observed.Gait characteristics such as variability may precede clinical gait abnormality and could serve as a sensitive marker for disease progression for better therapeutic intervention in disease management. Future studies with larger sample size should be undertaken to conclusively validate this observation.

To describe the spectrum of hospitalized NeuroCOVID on admission in a tertiary neurology centre in Kolkata, the largest and most populated metropolitan city in Eastern India.We retrospectively studied confirmed COVID-19 patients admitted with a neurological condition from 1st May 2020 to 30th January 2021. Neurological diagnoses and their temporal relationship to respiratory features along with clinicodemographic profile for such patients was ascertained.228 patients were diagnosed with NeuroCOVID at our centre. Of the 162 included population (median age was 59 (50-70) and 62.3% (101) were male) and 73.5% were diagnosed with NeuroCovid before any respiratory or febrile features. 46 patients (28.8%) had a pre/co-existing neurological illness, and 103 (63.6%) had systemic comorbidities. No significant difference was observed when comparing demographics and comorbidities of NeuroCOVID patients presenting with and without fever and respiratory features. Moreover, no individual NeuroCOVID diagnosis was more prone to present with respiratory or febrile features. Diabetes mellitus was the only comorbidity which was significantly higher in the ischemic stroke group, all other comorbidities and characteristics were evenly distributed between stroke and non-stroke NeuroCOVID patients and encephalopathy non encephalopathy NeuroCOVID patients.Stroke and encephalopathy are the most prevalent parainfectious neurological conditions occurring with COVID-19 in the Indian population. This study demonstrates seemingly low-risk individuals (i.e. people without pre-existing systemic and neurological comorbidities) may develop neurological conditions. Moreover, NeuroCOVID may manifest independent of respiratory features and fever.

Objective: To identify the presence of subclinical therosclerosis by measuring carotid intima medial thickness (IMT) in patients with psoriasis attending the dermatology clinic of a tertiary care hospital. Methods: 30 patients who fulfilled the exclusion and inclusion criteria were recruited. 5 healthy persons devoid of known cardiovascular risk factors were registered as controls. Intima medial thickness of common carotid and vertebral arteries of both sides were measured by B mode ultrasound. Results: Result showed that IMT and velocity of left common carotid artery and velocity in right vertebral artery were significantly greater in psoriatic patients than control group and psoriatic patients had 0.8 times greater risk of developing  atherosclerosis than control group. Conclusion: Subclinical atherosclerosis remains undiagnosed in patients of psoriasis who usually lack the established risk factors for cardiovascular disease.

Parkinson's disease (PD) lacks a definitive diagnosis due to a lack of pathological validation of patients at antemortem. The risk of misdiagnosis is high in the early stages of PD, often eluded by atypical parkinsonian symptoms. Neuroimaging and laboratory biomarkers are being sought to aid in the clinical diagnosis of PD. Nigrosome imaging and neuromelanin (NM)-sensitive magnetic resonance imaging (MRI) are the new emerging tools, both technically simple plus cost-effective for studying nigral pathology, and have shown potential for authenticating the clinical diagnosis of PD. Visual assessment of the nigrosome-1 appearance, at 3 or 7 Tesla, yields excellent diagnostic accuracy for differentiating idiopathic PD from healthy controls. Moreover, midbrain atrophy and putaminal hypointensity in nigrosome-1 imaging are valid pointers in distinguishing PD from allied parkinsonian disorders. The majority of studies employed T2 and susceptibility-weighted imaging MRI sequences to visualize nigrosome abnormalities, whereas T1-weighted fast-spin echo sequences were used for NM imaging. The diagnostic performance of NM-sensitive MRI in discriminating PD from normal HC can be improved further. Longitudinal studies with adequate sampling of varied uncertain PD cases should be designed to accurately evaluate the sensitivity and diagnostic potential of nigrosome and NM imaging techniques. Equal weightage is to be given to uniformity and standardization of protocols, data analysis, and interpretation of results. There is tremendous scope for identifying disease-specific structural changes in varied forms of parkinsonism with these low-cost imaging tools. Nigrosome-1 and midbrain NM imaging may not only provide an accurate diagnosis of PD but could mature into tools for personally tailored treatment and prognosis.

Levodopa-induced dyskinesia (LID) is one of the most disabling complications of long-term pharmacotherapy of Parkinson's disease (PD). The objective of our study was to examine the clinical profile and determinants of severity of LID in Indian PD patients on levodopa therapy.Retrospective analysis of records of PD patients with LID was performed. All patients were on levodopa and carbidopa combination. Records of subjects with complete information about disease profile, drug intake, and dyskinesia were analyzed. Characterization of LID was based on responses to part IV of unified Parkinson's disease rating scale (UPDRS).Records of 42 patients (M∶F = 4·6∶1) were analyzed. The median Hoehn and Yahr (H&Y) stage was 2·5 while median duration of levodopa therapy was 6·16 years (range: 1·91-14·58). Early morning dystonia was reported by 97·6% of the patients. Patients treated with ≧2 concomitant PD medication reported a significantly lower median UPDRS IV A score compared to patients treated with <2 number of concomitant drugs. A trend toward a lower UPDRS IV A score was associated with use of dopamine agonists (DA). Patients with H&Y score ≧3 had a significantly higher median total UPDRS IV A score than patients with H&Y score <3.Early morning dystonia might be more common among Indian patients of LID. Use of a higher number of concomitant PD medications alongside levodopa is associated with a reduced severity of dyskinesia, even on prolonged use. Levodopa-induced dyskinesia is not only a drug-related phenomenon but the stage of PD itself also affects the dyskinesia severity.

Movement Disorders Clinical PracticeVolume 10, Issue 4 p. 683-686 CASE REPORT Cervical Dystonic Tremor and Dysphonia—Rare Presentation of Anti–N-Methyl-D-Aspartate Encephalitis and Its Management Sakhi Bhansali MBBS, Sakhi Bhansali MBBS Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorChetana Sen Chatterjee MD, DM, MRCP, Chetana Sen Chatterjee MD, DM, MRCP Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorUmmatul Siddique MSc,, Ummatul Siddique MSc, Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorPurba Basu MBBS, MPhil, Purba Basu MBBS, MPhil Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorSupriyo Choudhury MBBS, MD, Supriyo Choudhury MBBS, MD Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorMona Tiwari MBBS, DMRD, DNB, FRCR, Mona Tiwari MBBS, DMRD, DNB, FRCR Department of Neuroradiology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorHrishikesh Kumar MD, DM, Corresponding Author Hrishikesh Kumar MD, DM [email protected] orcid.org/0000-0002-9789-7832 Department of Neurology, Institute of Neurosciences, Kolkata, India Correspondence to: Dr. Hrishikesh Kumar, Head, Department of Neurology, In Charge, Parkinson's Disease and Movement Disorders Program, Director, RGCM Research Centre, Vice Chairman, Institute of Neurosciences Kolkata, 185/1 AJC Bose Road, Kolkata, West Bengal 700017, India; E-mail: [email protected]Search for more papers by this author Sakhi Bhansali MBBS, Sakhi Bhansali MBBS Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorChetana Sen Chatterjee MD, DM, MRCP, Chetana Sen Chatterjee MD, DM, MRCP Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorUmmatul Siddique MSc,, Ummatul Siddique MSc, Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorPurba Basu MBBS, MPhil, Purba Basu MBBS, MPhil Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorSupriyo Choudhury MBBS, MD, Supriyo Choudhury MBBS, MD Department of Neurology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorMona Tiwari MBBS, DMRD, DNB, FRCR, Mona Tiwari MBBS, DMRD, DNB, FRCR Department of Neuroradiology, Institute of Neurosciences, Kolkata, IndiaSearch for more papers by this authorHrishikesh Kumar MD, DM, Corresponding Author Hrishikesh Kumar MD, DM [email protected] orcid.org/0000-0002-9789-7832 Department of Neurology, Institute of Neurosciences, Kolkata, India Correspondence to: Dr. Hrishikesh Kumar, Head, Department of Neurology, In Charge, Parkinson's Disease and Movement Disorders Program, Director, RGCM Research Centre, Vice Chairman, Institute of Neurosciences Kolkata, 185/1 AJC Bose Road, Kolkata, West Bengal 700017, India; E-mail: [email protected]Search for more papers by this author First published: 24 September 2022 https://doi.org/10.1002/mdc3.13579Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1Barry H, Byrne S, Barrett E, Murphy KC, Cotter DR. Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull 2015; 39(1): 19–23. 2Irani SR, Bera K, Waters P, et al. N-methyl-D-aspartate antibody encephalitis: Temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 2010; 133(Pt 6): 1655–1667. 3Josep Dalmau, Amy J Gleichman, Ethan G Hughes, JeffreyE Rossi, Xiaoyu Peng et al. Anti-NMDA-receptor Encephalitis: case series and analysis of the effects of antibodies. 4Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15(4): 391–404. 5Dawit S, Okazaki E, Grill M. Isolated dysarthria due to immune-mediated brainstem encephalitis associated with anti-glutamate acid decarboxylase 65 antibodies (P2.2-038). Neurology 2019; 92(15 Supplement):P2. 2-038. 6Rubio-Agustí I, Dalmau J, Sevilla T, Burgal M, Beltrán E, Bataller L. Isolated hemidystonia associated with NMDA receptor antibodies. Mov Disord 2011; 26(2): 351–352. 7Baizabal-Carvallo JF, Stocco A, Muscal E, Jankovic J. The spectrum of movement disorders in children with anti-NMDA receptor encephalitis. Mov Disord 2013; 28(4): 543–547. 8Zheng F, Ye X, Shi X, Poonit ND, Lin Z. Management of refractory orofacial dyskinesia caused by anti-N-methyl-d-aspartate receptor encephalitis using botulinum toxin. Front Neurol 2018; 9(p.81). 9Balu R, McCracken L, Lancaster E, Graus F, Dalmau J, Titulaer MJ. A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology 2019; 92(3): e244–e252. 10Lange DJ, Rubin M, Greene PE, et al. 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Background: Writer’s cramp (WC) is a task specific focal hand dystonia, where patients present with pain, stiffness and/ or tremor while writing. WC might develop due to reduced inhibition of motor output at various anatomical levels.We took an initiative to explore the intermuscular coherence (IMC) pattern, cortico-muscular coherence (CMC) and pre-pulse inhibition of blink reflex to explore the involvement of brainstem in WC patients. The appropriateness of the characteristic IMC pattern as a diagnostic test was also evaluated.

Background: Simulation is a realistic representation of real-world dynamics or processes that reflect or parallel patient scenarios. Simulation-based medical education enables knowledge, skills and attitudes to be acquired by all health-care professionals. It has been widely adopted as a training and assessment tool in medical education. The aim of the study was to compare simulation-based versus apprenticeship-based teaching-learning tool on patient. Patients and Methods: In this prospective randomised interventional study, 30 interns were randomly assigned to perform laryngoscopy and endotracheal intubations (L and EI) on patients (Group 1) or on an airway mannequin (Group 2) up to 5 times over 3 successive days. Following this, all interns regardless of their group allocation performed up to 10 intubations on patients. They were assessed and scored by two observers using a rating scale and every attempt scored as 'Success' (1 point) or 'Failure' (0 point). Average scores of intubations of two groups were compared using the paired t-test. Results: Average scores of intubations on 10 patients by two independent observers were 6.220 (standard deviation [SD] 1.1428) in Group 1 and 7.147 (SD 0.6520) in Group 2 and 6.307 (SD 1.1317) in Group 1 and 7.193 (SD 0.6170) in Group 2, respectively (P = 0.012 and 0.014 for Observers A and B, respectively). The score of attempt 1 and attempt 10 was observed by a single observer between groups, and significant difference (P = 0.021) was found at attempt 1 between groups with the mannequin group scoring better. At attempt 10, there was no significant difference between the groups. Conclusion: The mannequin group acquired better skills in airway management with respect to L and EI.

Objective: Inflammation-derived oxidative stress and its impact in neuronal plasticity significantly contributes to nigrostriatal degeneration in Parkinson's disease (PD). The aim of this study was to identify whether peripheral blood of PD patients show a distinctive oxidative and inflammatory profile compared to healthy subjects and to determine if alterations could relate to their disease severity.

Applause sign (AS) is a clinical phenomenon observed in several neurological disorders including progressive supranuclear palsy (PSP). We investigated the factors associated with AS in patients with PSP. PSP patients with AS showed greater motor impairment compared to those with negative AS. Global cognition including attention and memory were affected more in patients with positive AS. We also observed that gait variability, a known marker for unstable gait is pronounced in those who presented with positive AS. Hence, the clinician might expect a more severe disease and an unstable gait in a PSP patient presenting with AS.

Introduction: One of the hallmark symptoms of Parkinson’s disease (PD) is gait instability. As an overall clinical outcome the gait stability improve following levodopa (L-dopa) therapy but the response remains inconsistent. We have undertaken this study for a precise gait analysis among PD patients in ON and OFF phase. We also intended to identify gait variables which respond and those which do not respond to L-dopa therapy.

The present study was conducted to explore the relationship between academic anxiety and academic performance among upper primary Muslim students with respect to their gender and locale. Students of class VIII from fifteen schools from the three districts of West Bengal [North 24 Parganas, South 24 Parganas, and Kolkata], under the West Bengal Board of Secondary Education were treated as the population of this research. The Academic Anxiety Scale (AASC) consisted of twenty items developed for Indian culture was adopted and translated into the Bengali language (1). Mean, SD, correlation and t-test were used as statistical techniques for analyzing the collected data. The study found that there is a significant difference in academic anxiety and performance with respect to gender and locale. The present study explored the negative correlation between the academic anxiety and academic performance of the students.

In 2016, studies reported that 6.1 million individuals globally had Parkinson’s disease (PD). An exponential rise in disease prevalence associated with increased economic burden is expected to persist. The neurobiology of PD and other movement disorders still remains partially unknown. The incongruence between our knowledge of the disease process and its prevalence makes movement disorders a favored area of research for basic scientists. Advances have been made to understand the disease pathophysiology. Curative therapies for some conditions are still under trial and several are in more preliminary stages of development. Neuroprotective therapies are the need of the hour, but these may require administration before disease onset in susceptible individuals. This heralds the age of biomarkers, which predict the disease before their clinical onset. Translational research fills the lacunae of both bench work and bedside, therefore playing a pivotal role in unraveling the mysteries of movement disorders.

Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson's Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity.The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist.SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI.Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.

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Objective: In movement disorders the ability to initiate a movement in response to a cue is often im- paired. However, the neurobiology of movement is believed to be a balance between, the process of initia- tion (go signal) and efficiency of stopping (stop signal) in response to external stimuli. Technically, quan- tification of the latency of ‘go signal’ is very much possible through electromyograph unlike the efficiency of stopping process. ‘Stop signal reaction time (SSRT)’ is a validated statistical measure, which quantifies hypothetical idea of efficiency of stopping. The clear understanding of fundamentals of SSRT is far from complete. Therefore, we undertook this study to compare the SSRT among Parkinson’s disease (PD), cervi- cal dystonia (CD) and healthy participants.

Introduction: Cervical dystonia (CD) is a focal dystonic disorder, yet it may present with various features suggestive of wider neural network involvement. Earlier studies have demonstrated gait and postural ab- normalities in CD suggesting dysfunction beyond the classical dystonia pathways of basal ganglia. Pain is one of the major associated clinical features of CD. We hypothesize the extent of pain could be one of the important determinant of gait abnormality in this group.

Background: One of the prominent pathogenic mechanism of cervical dystonia is disinhibition of motor outputs at various levels of nervous system. Disinhibition at the level of brainstem has been investigated through startle response and blink reflex phenomenon before. Startle response was found to be less fre- quent despite comparable reflex latency in patients with cervical dystonia (CD) in literature. We investigat- ed a related but distinct experimental paradigm- StartReact, in patients with symptomatic CD (torticollis), to validate the hypothesis of disinhibition at the level of brainstem in CD patients.

Introduction: Antimicrobials are the mainstay treatment in neonatal septicemia (NS). National treatment guidelines for antimicrobial use in infectious diseases issued by the Government of India has paved the way for rationalizing antibiotic use, but it needs tailoring according to the prevalent local microbiota and individual patient's needs. A periodic surveillance of the microbial etiology and antibiotic use patterns in NS may be useful in rational selection of empirical antimicrobial therapy. Aims and Objectives: We observed the utilization pattern of antimicrobials and quantified the same in neonates admitted to neonatal intensive care unit (NICU) with septicemia along with the prospective follow-up of the clinical response to individual regimen. Materials and Methods: This hospital-based prospective observational study was conducted from January 2017 to June 2017 on 102 consecutive cases of NS admitted to NICU. Data regarding demographic parameters, antimicrobials used, and outcome were collected through a predesigned case record form. Antimicrobial usage was quantified as days of therapy (DOT) per 1000 patient days. Results: Common antimicrobials used in descending order of DOT were amikacin, colistin, and meropenem. Ampicillin, cefotaxime, and gentamicin were rarely found suitable for use based on the reported antibiograms. Piperacillin-tazobactam + amikacin regimen was the most commonly used empirical regimen. The case fatality rate was 4% in our study sample. Conclusion: Ampicillin, cefotaxime, and gentamicin had limited effectiveness in the majority of cases. Although there is a need of alignment with national treatment guidelines in NS, yet, the concurrent scope of periodic survey and research must be available for changeover to evidence-based local individualization of empirical antimicrobial therapy wherever required.

Background : India accounts for about a quarter of the global TB burden. Worldwide India is the country with the highest burden of both TB and MDR TB. Smoking and alcohol use results in sub-optimal response to anti tuberculosis treatment as well as poor prognosis Alcoholism and Nicotine abuse contribute significantly to the development and treatment course of tuberculosis in patients. Aim of the Study: To assess the Prevalence of Nicotine and Alcohol Addiction among Tuberculosis Patients and to monitor the effect of Brief Counselling Sessions for the De-addiction of Alcohol and Nicotine in the management of Tuberculosis Patients. Material &amp; Methods: We had taken the tuberculosis patients coming to the OPD of Medicine and Respiratory Medicine Departments of DrRMLIMS, Lucknow. We used questionnaires for assessing the Nicotine Dependence and Alcohol dependence among the tuberculosis patients (Fagerstrom Tolerance Questionnaire), The Alcohol use disorders Identification Test (AUDIT). Results: Prevalence of Addiction among tuberculosis patient-54 cases out of 447 total cases (April to October). In our study, we found addiction in 45 males and 9 females, Smoking addiction was seen in 13 tuberculosis patients, alcohol addiction was found in 17 tuberculosis patients, and both smoking and alcohol addiction was seen in 24 patients. Conclusion: Nicotine and Alcohol Addiction problem in Tuberculosis patients should be effectively assessed through the nicotine addiction and AUDIT scales and Brief Cognitive Therapy should be introduced along with regular ATT for effective management of such patients.

Truncal dystonia leads to significant distress to the patient and poses difficult therapeutic challenge to clinicians. Truncal dystonia is not rare but surprisingly, there is not enough data available to guide an approach to diagnosis or treatment. Camptocormia (flexion dystonia of trunk) was found in 7% of patients with Parkinson’s disease and the prevalence increases with the severity of the disease.[1] As high as 26% of patients with multiple system atrophy reportedly present with Pisa syndrome (lateral truncal flexion).[2] 17% of progressive supranuclear palsy patients reported to have axial dystonia in extension.[3] Patients with tardive syndrome, Wilson’s disease, neurodegeneration with brain iron accumulation, and some other genetic form of dystonia may have prominent truncal involvement. A subset of patients presents with isolated idiopathic truncal dystonia. Does this phenomenon need a special mention?—the answer would be a clear “yes”; there is no doubt that truncal dystonia causes fair share of disability and distress when present. Unfortunately, the response to medications is generally not satisfactory. Since the availability of botulinum toxin for the treatment of dystonia, truncal dystonia has been treated with the injection with variable result. The groups of Cynthia L. Comella and Joseph Jankovic, respectively, published their experience on the safe and effective use of botulinum toxin injection for this condition.[45] After more than a quarter century of usage, truncal dystonia still remains an off-label indication for botulinum toxin injection. The onus is on the neurologists and industry to generate enough data to help regulatory approval of botulinum toxin injection in truncal dystonia. In this issue of Annals of Indian Academy of Neurology, Mehta et al. shared their experience with truncal dystonia and treatment with botulinum toxin injection.[6] The varied etiology of the patients in their series reflects the need for proper evaluation when one deals with truncal dystonia. Promising improvement in the patient-perceived subjective outcome following the treatment was observed without any adverse effect. The degree of improvement in their patients has clinical value as these patients were refractory to medicines. Moreover, the injection procedure required focusing on only two muscles: paraspinals and recuts abdominis. These are large muscles and injecting them is not challenging at all. It is difficult to standardize the dose of botulinum toxin in truncal dystonia (or any other dystonia). The dosage needs to be individualized depending upon the clinical severity and degree of muscle hypertrophy. Usage of various formulations of botulinum toxins in available studies also makes the comparison difficult. Abobotulinum toxin has been reported to have greater spread than Onabotulinum or Incobotulinum toxin.[7] Whether this leads to better clinical efficacy in treating large muscles remains unknown. To sum up, the findings of the study by Mehta et al.[6] are clinically relevant and will encourage the clinicians to use botulinum toxin injection in the treatment of truncal dystonia and document their experience.

Introduction: Functional movement disorders are a spectrum of neurological disorders associated with medically unexplained symptoms which resemble movement disorders. Common clinical features include Tremor, Gait difficulty, Dystonia, Myoclonus and Parkinsonism. The symptoms may have overlapping features. Anxiety, Depression acts as a co -morbidity to the illness. The incidence of the disease varies with socio-demographic profile. The medications used included antidepressants, benzodiazepines or a combination of both.

Objective: Patients with Parkinson's disease (PD) show marked heterogeneity in their clinical features in relation to motor phenotype, rate of progression, and development of cognitive impairment. Tremor dominant (TD) and postural instability and gait difficulty (PIGD) are two broad clinical phenotypes of PD. The biomolecular basis of such phenotypic variation in PD is completely unknown. We aimed to investigate if TD and PIGD phenotypes could be discriminated based on altered levels of peripheral blood total and phosphorylated α-synuclein, a potential biomarker for PD.

Objective: Deep brain stimulation (DBS) of subthalamic nucleus (STN) is increasingly used in the treatment of Parkinson's disease (PD). The hyper-direct pathway connecting the frontal cortex and STN is strongly implicated in the control of motor response inhibition. We explored the possibility of using an automated bed side test of motor response inhibition - Stop Signal Reaction Time (SSRT) while optimizing DBS parameters.

Background: Number of disorders slows the ability of movement-stopping. Estimation of movement-stopping is possible through - Stop Signal Reaction Time (SSRT). The effect of neurotropic drugs on SSRT is elusive till now.

Introduction: Disorders of gait and falls are common in patients with Parkinson's disease (PD). Research efforts have therefore focused on neurostimulation to address the PD gait disorders. Evidence from animal experiments has shown that VNS might treat some of the motor and non-motor features of PD. In our open label pilot study, we found an encouraging result in treatment of freezing of gait in PD patients.

Introduction: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide and associated with multiple systemic involvements. Long-term hypoxia leads to impaired cognitive function and hand dexterity. With the background of few previous researches, we have aimed to assess cognitive function and hand dexterity in the patients with COPD as well as correlation between them and with oxygen saturation (SpO2). Materials and Methods: Data were collected and compared between 52 stable mild-to-moderate hypoxemic COPD patients defined by the Global Initiative for Obstructive Lung Disease Guidelines and 48 age- and sex-matched healthy volunteers attending the outpatient department of a government hospital Kolkata, using a validated questionnaire Mini-Mental State Examination (MMSE) tool for the assessment of cognitive function and the Nine-Hole Peg Test for assessment of hand dexterity. Results: The median (interquartile range [IQR]) value of Hand Dexterity Test for the dominant hand for the test group was 22 (20–24) s, and for the control group, 19 (18–20) s (P

Objective: Stop signal reaction time (SSRT) is a measure of the executive control of movement whereas cognitive control is a critical executive function of the human brain. Several studies have reported the involvement of the cerebral cortex, basal ganglia & thalamus in response inhibition. Through our study we wished to compare the motor response inhibition in patients with Parkinson's disease (PD) and Alzheimer's disease (AD).

Objective: Aborting an ongoing movement in response to external stimulus, is a relatively complex task and involve multiple brain regions. The relative contribution of various anatomical substrates controlling movement-stopping is yet to be understood completely. Cerebro-cerebellar interaction was found essential for response inhibition. In this study we estimated the movement-stopping performance in patients with Spinocerebellar Ataxia-12 (SCA12) and explored any association with severity of disease.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a significant cause of morbidity and mortality globally. COPD is a systemic disease, cardiovascular and Peripheral Arterial Disease (PAD) are common entities in COPD. Asymptomatic, undiagnosed PAD can lead to impaired functional exercise capacity, increased morbidity and mortality. Aim: To find out the occurrence of PAD in COPD and relative contribution of PAD, severity of COPD, and Health Related Quality of Life (HRQL) on functional exercise capacity. Materials and Methods: The present study was a prospective, cross-sectional, analytical study carried out in the Department of Respiratory Medicine of a teaching institution in eastern India over a period of six months. All COPD patients diagnosed as per Global Initiative for Obstructive Lung Diseases (GOLD) criteria were recruited for the study after obtaining written informed consent. HRQL was assessed by Clinical COPD Questionnaire (CCQ). Exercise capacity was assessed by Six Minute Walk Test (6MWT) and PAD was evaluated by Ankle Brachial Index (ABI) on Ultrasound (USG) Doppler. Data were analysed using appropriate statistical tests. Mean, Standard Deviation (SD) and percentages were calculated for descriptive frequencies, p-value was calculated using Fischer’s-exact test or Chi-square test for categorical data and independent sample t-test and Kruskal Wallis test for parametric and non parametric data, respectively. Results: Out of 75 COPD patients, PAD was present in 18 (24%) patients. Majority of COPD patients (n=35; 46.6%) were in GOLD group D. There was no statistically significant difference in age, Body Mass Index (BMI) and smoking index between COPD with and without PAD. Most PAD patients were asymptomatic. In comparison to COPD without PAD, severe PAD cases had significantly less Six Minute Walk Distance (6MWD), more episodes of leg cramps and needed to stop more frequently during 6MWT. Apart from PAD, increasing severity in COPD was associated statistically significant changes in Forced Expiratory Volume in the first second (FEV1), CCQ score, 6MWD, post 6MWT Heart Rate (HR), Respiratory Rate (RR), Borg score, fatigue, Oxygen Saturation (SpO2). Conclusion: The PAD is a frequent entity in COPD and can be diagnosed easily by measuring ABI. Increasing COPD severity affect HRQL and exercise capacity significantly.