Guillain-barré syndrome (GBS) with antecedent chikungunya infection: a case report and literature review.

Guillain-Barré Syndrome (GBS) is an autoimmune neuropathy. Antecedent infections have been seen to be significant triggering factors for developing GBS. Among them, arboviral infections are rapidly gaining importance as significant triggers, especially in the areas where they are endemic. Chikungunya, an arboviral infection that usually causes a self-limiting acute febrile illness can lead to GBS as one its severe complications. Herein, we describe a case of a 21-year-old female who presented with weakness in all four limbs and paresthesia. Nerve conduction study and cerebrospinal fluid (CSF) analysis showed axonal, demyelinating motor and sensory neuropathy with albuminocytological dissociation indicating Acute Motor and Sensory Axonal Neuropathy (AMSAN) variant of GBS. Serum IgM antibodies against ganglioside GM1 were detected. Anti-Chikungunya IgM antibodies were found in both serum and CSF samples. The patient was initiated with Intravenous Immunoglobulin (IVIG) therapy. In view of hypoxia, she was intubated and was on mechanical ventilation. After 2 weeks of being comatose, the patient gradually improved and was discharged with no sequelae.A literature review on antecedent infections in GBS is presented alongside the case report to better understand the association of GBS with antecedent infections, especially the endemic arboviral infections like Chikungunya, Dengue and Zika. This will help in reinforcing the significance of having robust surveillance and public health control measures for infectious diseases.

Effectiveness of an Intensive, Functional, and Gamified Rehabilitation Program on Upper Limb Function in People With Stroke (EnteRtain): A Multicenter Randomized Clinical Trial.

BACKGROUND1: Despite a growing interest in gaming rehabilitation for upper limb (UL) recovery post-stroke, studies investigating the effects of game-based rehabilitation incorporating functional games are lacking. OBJECTIVE: To investigate the efficacy of an intensive, functional, gamified rehabilitation program compared to task-based training on UL motor function in acute/sub-acute stroke survivors. METHODS: This randomized, multicenter, single-blind, clinical trial comprises 120 participants with unilateral stroke who were randomized to receive either gamified training (n = 64) using the ArmAble™ [experimental group (EG)] or task-based training (n = 56) in conjunction with conventional therapy for 2 hours per day, 6 days per week for 2 weeks, followed by UL rehabilitation for another 4 weeks at home. Primary outcomes evaluated by a blinded assessor included the Fugl-Meyer Assessment-Upper Extremity (FM-UE), and Action Research Arm Test (ARAT). Data were analyzed using a linear mixed-effect regression model. RESULTS: The mean (standard deviation) age of the participants was 54.4 ± 11.7 years (78.1% men) in the EG and 57.7 ± 10.9 years (73.2% men) in the comparator group (CG). The median (interquartile range) time since stroke was 30.0 (54.0) days in the EG and 22.5 (45.0) days in the CG. Following the 2-week intervention, a statistically significant improvement was observed in the EG for the FM-UE [between-group mean differences (95% confidence interval): -3.9 (-6.5, -1.3); P = .003]; but not for the ARAT [-2.9 (-5.8, 0.0); P = .051]. Gains at 6 weeks were significantly greater in the EG for both FM-UE [-3.9 (-6.5, -1.3); P = .003]; and ARAT [-3.0 (-5.9, -0.0); P = .046]. CONCLUSION: Gamified rehabilitation using the ArmAble™ device has shown immediate and short-term improvement in UL function after acute/sub-acute stroke. CLINICAL TRIALS REGISTRY NUMBER: CTRI/2020/09/027651.

Do kinematic measures, added to clinical measures, better predict upper extremity motor impairments at three months post-stroke?

OBJECTIVE: Predicting post-stroke recovery through prediction models is crucial for choosing appropriate treatment options. However, the existing models predominantly incorporate clinical measures although measurement of movement quality using kinematic measures is essential for distinguishing various types of recovery. Thus, this study aimed at determining if, by considering varied aspects of recovery, adding kinematic measurements over clinical measures would better predict upper extremity (UE) motor impairments at three months post-stroke. MATERIALS AND METHODS: Eighty-nine stroke survivors (58.9 ± 11.8 years) were assessed for clinical predictors between 4 and 7 days, kinematic predictors within 1 month, and the impairment outcome of the Fugl Meyer Assessment of the UE (FM-UE) at three months post-stroke. Significant predictors (p<0.05) with a variation inflation factor (VIF) <10 were selected for model development. After performing further step-wise selection, three models incorporating clinical outcomes, kinematic measurements, and a combination of these two, respectively, were formulated. RESULTS: The clinical model (R2 = 0.70) included shoulder abduction finger extension (SAFE) scores, the National Institutes of Health Stroke Scale (NIHSS), and the Montreal Cognitive Assessment (MoCA). The kinematic model (R2 = 0.34) included total displacement, total time, and reaction time. The combined model (R2 = 0.72) comprised of SAFE score and shoulder flexion. All the models had a minimal mean squared error on cross validation, which indicated a good validity. CONCLUSION: The performance of clinical and combined prediction models for predicting three-month post-stroke UE motor recovery was nearly similar. However, in order to detect minimal changes over time and to understand all aspects of motor recovery, there is a need to add instrument-based kinematic measures.

A comprehensive review of protein misfolding disorders, underlying mechanism, clinical diagnosis, and therapeutic strategies.

INTRODUCTION: Proteins are the most common biological macromolecules in living system and are building blocks of life. They are extremely dynamic in structure and functions. Due to several modifications, proteins undergo misfolding, leading to aggregation and thereby developing neurodegenerative and systemic diseases. Understanding the pathology of these diseases and the techniques used to diagnose them is therefore crucial for their effective management . There are several techniques, currently being in use to diagnose them and those will be discussed in this review. AIM/OBJECTIVES: Current review aims to discuss an overview of protein aggregation and the underlying mechanisms linked to neurodegeneration and systemic diseases. Also, the review highlights protein misfolding disorders, their clinical diagnosis, and treatment strategies. METHODOLOGY: Literature related to neurodegenerative and systemic diseases was explored through PubMed, Google Scholar, Scopus, and Medline databases. The keywords used for literature survey and analysis are protein aggregation, neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, systemic diseases, protein aggregation mechanisms, etc. DISCUSSION /CONCLUSION: This review summarises the pathogenesis of neurodegenerative and systemic disorders caused by protein misfolding and aggregation. The clinical diagnosis and therapeutic strategies adopted for the management of these diseases are also discussed to aid in a better understanding of protein misfolding disorders. Many significant concerns about the role, characteristics, and consequences of protein aggregates in neurodegenerative and systemic diseases are not clearly understood to date. Regardless of technological advancements, there are still great difficulties in the management and cure of these diseases. Therefore, for better understanding, diagnosis, and treatment of neurodegenerative and systemic diseases, more studies to identify novel drugs that may aid in their treatment and management are required.

Serum Inflammatory Markers in Patients with Guillain Barre Syndrome.

Background: Guillain Barre syndrome (GBS) is an immune-mediated peripheral neuropathy characterized by the demyelination and axonal damage of the peripheral neurons. The pathogenesis of GBS involves the breakdown of the blood-brain barrier after which pro inflammatory cytokines attack the neurons in the peripheral nervous system. Aims: This study aims to evaluate five markers, namely matrix metalloproteinase (MMP)-2 and MMP-9, vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factor (bFGF), and SFLT-1, which could have a role in the inflammatory response in patients with GBS and healthy controls. Settings and Design: In this prospective study, patients diagnosed with GBS at the department of neurology, Kasturba Medical College, Manipal, Karnataka were enrolled. Methods and Material: The markers selected for this study were analyzed using the ELISA method and expressed as given in the kit provided by the company. Ethical clearance was obtained from the Institutional Ethical Committee. Statistical Analysis: Results were evaluated using SPSS version 17.0 and expressed as mean ± SD. Error bars for each were drawn. Results: The levels of all five parameters showed a significant increase in patients as compared to controls. Conclusions: Disruption of the basement membrane of endoneurium by MMP-2 and MMP-9, recruitment and migration of macrophages and other cytokines by VEGF-A, bFGF, and soluble fms-like tyrosine kinase-1 (SFLT-1) are plausible, which leads to inflammation process and thus neuronal damage leading to the development of GBS.

Predicting post-stroke motor recovery of upper extremity using clinical variables and performance assays: A prospective cohort study protocol.

BACKGROUND AND PURPOSE: Measurement of movement quality is essential to distinguish motor recovery patterns and optimize rehabilitation strategies post-stroke. Recently, the Stroke Recovery and Rehabilitation Roundtable Taskforce (SRRR) recommended four kinetic and kinematic performance assays to measure upper extremity (UE) movements and distinguish behavioral restitution and compensation mechanisms early post-stroke. The purpose of this study is to develop and validate a prediction model to analyze the added prognostic value of performance assays over clinical variables assessed up to 1-month post stroke for predicting recovery of UE motor impairment, capacity and quality of movement (QoM) measured at 3 months post-stroke onset. METHODS: In this prospective cohort study, 120 stroke survivors will be recruited within seven days post-stroke. Candidate predictors such as baseline characteristics, demographics and performance assays as per SRRR recommendations along with tonic stretch reflex threshold will be measured up to 1-month post-stroke. Upper extremity motor recovery will be evaluated in terms of motor impairment (Fugl-Meyer assessment for UE), UE capacity measured with Action Research Arm Test (ARAT) and QoM (movement smoothness in the form of peak metrics [PM]) assessed with a reach-to-grasp-to-mouth task (mimicking a drinking task) at 3 months post-stroke. Three multivariable linear regression models will be developed to predict factors responsible for the outcomes of Fugl-Meyer assessment for upper extremity (FM-UE), ARAT and movement quality. The developed models will be internally validated using a split-sample method. DISCUSSION: This study will provide a validated prediction model inclusive of clinical and performance assays that may assist in prediction of UE motor recovery. Predicting the amount of recovery and differentiating between behavioral restitution and compensation (as reflected by the FM-UE, QoM and ARAT) would enable us in realistic goal formation and planning rehabilitation. It would also help in encouraging patients to partake in early post-stroke rehabilitation thus improving the recovery potential.

Activity monitoring of stroke patients by physiotherapist and caregivers in a hospital setting: A pilot study.

Background: Activity monitoring is a necessary technique to ensure stroke survivors' activity levels in the hospital are within optimal levels as this is important for enhanced motor recovery. However, this could be time-consuming for healthcare professionals like physiotherapists. Activity monitoring by caregivers could be an alternate option. Therefore, our aim was to compare the activity monitoring of stroke survivors by caregivers and physiotherapists during early phase in a hospital setting. Methods: An observation study was carried out in the neuroscience ward in a tertiary care hospital among 17 stroke survivors. Physiotherapist and caregivers were instructed to use an activity log chart that was developed during previous research conducted by the same authors for observing the activities performed by the patients every 15 minutes from 8 AM to 5 PM across one day. Data collected were analysed using Stata 15. Kappa statistics were carried out to determine the agreement of the observations between the two raters. Results: A total of 10 male and seven female caregivers of stroke survivors with a mean age of 40.11 ± 9.2 years and a trained physiotherapist participated in the study. A total of 272 observations of caregivers were in agreement with that of the physiotherapist. Inter-rater Kappa statistics showed 60% agreement between the physiotherapist and the caregivers (p<0.05). Conclusions: There was moderate agreement between the physiotherapist and caregiver for activity monitoring of stroke survivors. This suggests behavioural mapping by caregivers may be a potential alternative solution in healthcare settings.

Evaluation of clinical, diagnostic features and therapeutic outcome of neurobrucellosis: a case series and review of literature.

AIM: In this study, we aimed to discuss the clinical features, laboratory findings, treatment and outcome of seven cases of neurobrucellosis from a tertiary care center and review the available global literature. MATERIALS AND METHODS: The diagnosis of neurobrucellosis was established using the following criteria in our setting: (1) signs and symptoms of neurological infection with examination of cerebrospinal fluid (CSF) revealing signs of meningitis, (2) isolation of Brucella spp. from blood and/or CSF and/or antibody titer ≥1:160 in serum using standard agglutination test (SAT) and/or the presence of anti-Brucella antibodies in CSF and/or detection of Brucella spp.-specific DNA from CSF using PCR. A literature search was performed to review previous cases of neurobrucellosis published worldwide during the last 30 years. RESULTS: The proportion of neurobrucellosis was 2.8% in our setting. Fever with headache and altered sensorium were the major presenting complaints. Brucella melitensis was isolated from blood culture in 6 patients. From the literature search, a total of 221 cases of neurobrucellosis were reviewed and analyzed. Meningitis (32.6%), loss of hearing (25.8%) and encephalitis (14.9%) were the most common clinical features. Involvement of cranial nerves, polyradiculopathy and paraplegia were the major complications found in patients with neurobrucellosis. CONCLUSIONS: Neurobrucellosis should always be considered in the differential diagnosis of befitting neurological, rheumatological, and neuropsychiatric presentations in endemic regions for brucellosis. To prevent morbidity and mortality associated with neurobrucellosis, a multimodal diagnostic approach is essential for early and accurate diagnosis and effective treatment.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Clinical Spectrum and Complications of Polycythemia, in Patients presenting at Tertiary Care Centre at Goa.

BACKGROUND: Polycythemia is characterized by rise in hemoglobin and hematocrit, either as a result of hematopoietic clonal expansion (Vera) or secondary to hypoxic stimuli (secondary polycythemia).It is of great importance to detect early and identify the type of polycythemia and also asses the thrombotic risk so that timely and appropriate treatment can be given. The present study aims to characterize the different presentations and complications of polycythemia, evaluate genetic factors and differences between the two categories of polycythemia in ethnic Goan subjects. AIMS AND OBJECTIVES: 1. To identify common presentations and etiologies of polycythemia 2. To evaluate and compare the differences in clinical features, hematological parameters and complications of polycythemia in primary (vera) and secondary polycythemia 3. To study the profile of JAK 2 V617F mutation in Goan patients with polycythemia Vera. MATERIALS AND METHODS: This was a retrospective observational cohort study, conducted at the Department of Internal Medicine, Goa Medical College, a tertiary care, teaching institute in the state of Goa. We analysed clinical and laboratory data of patients of polycythemia due to all causes (polycythemia Vera and secondary causes) previously admitted or following up at the hospital from January 2014 to December 2017. In each of these 2 groups, we studied the various clinical parameters including the age at presentation,sex,residence, symptomatology and clinical findings,presence of hypertension, as well as complications arising due to polycythemia (past and at present) hematological data including Hb,HCT, total WBC count, absolute neutrophil count, RBC and platelet count, ESR, rouleaux formation, EPO levels and JAK 2 V617F mutation analysis (done by real time PCR technique) and requirement of phlebotomies in the last 4 years. Commonest clinical presentations and complications arising due to polycythemia, in each group were analysed and compared. RESULTS: A total of 44 patients were included in the study out of which 33 were males. Polycythemia Vera was seen in 43.18% while secondary causes were seen in 56.8 % patients. Patients with Vera were found to be more symptomatic with higher levels of mean Hb, HCT, cell counts and with a higher requirement of phlebotomy and more thrombotic complications. Amongst Vera group, patients having high WBC count, increased Rouleau formation, and JAK2 positivity were found to be more prone for thrombosis. Hypertension was frequently seen to be associated with both groups. Obstructive sleep apnea followed by COPD was found to be the commonest causes of secondary polycythemia. CONCLUSION: Our study revealed that patients with polycythemia Vera are more symptomatic and have a higher requirement of phlebotomy and a higher thrombotic tendency (arterial being more common than venous) as compared to the secondary polycythemia owing to a higher hyperviscocity in the former. Leukocytosis and JAK 2 617F positivity were found to be important predictors of thrombotic risk. Hypertension was found to be frequently associated with Vera as well as in secondary causes due to OSA.

Randomized controlled trial on the effectiveness of a multicomponent intervention on migraine: A study protocol.

AIM: To describe a randomized controlled trial protocol that evaluates the effectiveness of a multicomponent intervention in improving the outcomes (quality of life, disability, intensity, frequency and duration) of patients with migraine. BACKGROUND: Migraine affects various facets of Quality of Life and results in moderate to high levels of disability among migraineurs. Migraine pain can be intense and unremitting that can interfere with the daily routine and reduce the ability to think and function normally. Many people can lower their risk of a migraine by simply avoiding stress, getting enough sleep, eating regularly and by avoiding triggers. Hence, the present study aims at evaluating the effectiveness of a multicomponent intervention in managing migraine headaches. The multicomponent intervention includes behavioural lifestyle modification program and sessions of pranayama (a form of yogic breathing exercise). DESIGN: The study is a prospective, randomized, controlled, single-blinded trial with parallel arms. METHODS: The study participants are randomized to intervention and control arms. The participants randomized to the intervention arm would receive the specific multicomponent intervention based on the protocol. The participants in the control arm would receive routine care. They are followed up for 24 weeks and the outcomes are assessed. DISCUSSION: Various studies report that non-pharmacological therapies and integrative therapies play a major role in the management of migraine headaches. The findings of the study are expected to open up new horizons in health care arena emphasizing the use of non-pharmacological therapy for less focused areas of primary care health problems such as migraine. TRIAL REGISTRATION: The trial is registered with the Clinical Trials Registry India (CTRI). The CTRI India is one of the primary registries in the WHO registry network (Ctri.nic.in, ). CTRI reference ID: CTRI/2015/10/006282.

Role of albumin in cirrhosis: from a hospitalist's perspective.

Albumin, a negatively charged globular protein encoded on chromosome 4, is one of the most abundant proteins in the plasma and accounts for approximately 75% of plasma oncotic pressure. The role of albumin in the management of various disease states has shown to be beneficial historically. Low serum albumin is a predictor of mortality and poor outcomes. In cirrhotics undergoing paracentesis, albumin infusion prevents rapid re-accumulation of ascitic fluid while simultaneously decreasing the risk of post-paracentesis related circulatory dysfunction. Additionally, albumin is utilized in patients with hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP). Overall, albumin appears to be an effective pharmacological agent in the management of cirrhosis and its complications.

Clinical profile and functional disability of patients with migraine.

BACKGROUND: Migraine is a common disabling primary headache disorder. Globally, migraine was ranked as the seventh highest cause of disability. AIM: The aim of the study was to explore the clinical profile and functional disability of patients with migraine. SETTINGS AND DESIGN: A cross-sectional survey was conducted at the neurology outpatient department of a tertiary care hospital in Karnataka. MATERIALS AND METHODS: Using a consecutive sampling technique, 60 patients were recruited for the study. Descriptive and inferential statistics were used to analyze the data. RESULTS: Majority of the participants were in the age group of 18-40 years with a mean age 35.22 years. There was a female preponderance with 70% of study participants being females. The various symptoms experienced by patients include throbbing pain (90%), photophobia (93.3%), phonophobia (85%), nausea (76.7%), and vomiting (41.7%). Most of the subjects (73.3%) under the study belonged to moderate to severe levels of functional disability. About 53.3% of patients were in the category of episodic migraine and 46.7% were in the category of chronic migraine. CONCLUSION: Migraine is associated with moderate to severe functional disability. Frequency of migraine has a positive correlation with the levels of disability/migraine disability assessment scores of migraineurs.

Engel's Model as a Conceptual Framework in Nursing Research: Well-being and Disability of Patients With Migraine.

Exploring, selecting, and utilizing an appropriate conceptual framework is a vital step in development of a research work. This article discusses the application of "Engel's model on biopsychosocial well-being," in exploring the relationship between biopsychosocial well-being and disability of patients with migraine headaches.

Pathophysiology and diagnosis of Guillain-Barré syndrome - challenges and needs.

Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy which presents with acute onset and rapid progression of flaccid, hyporeflexi quadriparesis. Both sensory and autonomic nerve involvement is seen. GBS has various subtypes that vary in their pathophysiology. The pathogenesis involves an immune response triggered by a preceding event which may be an infection, immunisation or surgical procedure. Clinical diagnosis has been largely the primary diagnosing criterion for GBS along with electrodiagnosis, which has several pitfalls and is supported by ancillary testing of cerebrospinal fluid (CSF) analysis and Nerve Conduction Studies. Measurement of anti-ganglioside antibodies is also an effective tool in its diagnosis. Further understanding of pathophysiology and better diagnostic methods are required for better management of GBS.

Bilateral medial medullary syndrome secondary to Takayasu arteritis.

Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA.

Calcified embolism: a rare cause of cerebral infarction.

Calcified cerebral emboli (CCE) are a rare cause of stroke and these emboli can be identified on a CT scan of the brain performed for the initial evaluation of stroke. In this report we present a patient who developed a CCE following cardiac catheterisation that lodged in the left middle cerebral artery with resultant right hemiparesis and aphasia. The calcified embolus was seen on CT but could not be identified on MRI. Predisposing factors for CCE include angiography and valve or vessel wall calcification. The natural history and response to standard therapy in patients with CCE as compared with stroke of other aetiologies have not been studied until now. Increased awareness and ability to identify calcified emboli will help us to have an improved understanding of strokes resulting from CCE.

Antihypertensive therapy: nocturnal dippers and nondippers. Do we treat them differently?

Hypertension is a major independent risk factor for cardiovascular diseases. Management of hypertension is generally based on office blood pressure since it is easy to determine. Since casual blood pressure readings in the office are influenced by various factors, they do not represent basal blood pressure. Dipping of the blood pressure in the night is a normal physiological change that can be blunted by cardiovascular risk factors and the severity of hypertension. Nondipping pattern is associated with disease severity, left ventricular hypertrophy, increased proteinuria, secondary forms of hypertension, increased insulin resistance, and increased fibrinogen level. Long-term observational studies have documented increased cardiovascular events in patients with nondipping patterns. Nocturnal dipping can be improved by administering the antihypertensive medications in the night. Long-term clinical trials have shown that cardiovascular events can be reduced by achieving better dipping patterns by administering medications during the night. Identifying the dipping pattern is useful for decisions to investigate for secondary causes, initiating treatment, necessity of chronotherapy, withdrawal or reduction of unnecessary medications, and monitoring after treatment initiation. Use of this concept at the primary care level has been limited because 24-hour ambulatory blood pressure monitoring has been the only method for documenting dipping/nondipping status so far. This monitoring technique is expensive and inconvenient for routine usage. Simpler methods using home blood pressure monitoring systems are evolving to document basal blood pressure in the night, which would help in greater acceptance and use of the concept of dipper/nondipper in managing hypertension at the primary care level.