Understanding Psychosocial Functioning, Caregiver Burden, and Neuropalliative Care in Parkinson's Disease - A Mixed-Methods Study.

BACKGROUND: Despite advancements in treatment, patients with Parkinson's disease (PD) experience a range of symptoms that affect their quality of life. There is a need to integrate neuropalliative care into standard care. The aim of the study is to understand the psychosocial functioning in persons with PD and explore their caregivers' burden. METHODS: The study utilizes a mixed-methods design where 50 patient-caregiver dyads attending the outpatient services of the movement disorder clinic at a tertiary care hospital were measured on psychosocial functioning and caregiver burden and palliative care outcomes for a period of 6 months. Focus group discussions were conducted with 18 patient-caregiver dyads to understand the needs of palliative care. RESULTS: It was found that caregiver burden was positively correlated with palliative care outcomes scores of patients ( r = 0.586) and caregivers ( r = 0.675) and psychosocial functioning was positively correlated with palliative care outcomes of patients ( r = 0.708). The psychosocial functioning score was higher among female patients (indicating worse functioning) than males, and female caregivers experienced significantly higher caregiver burden. The qualitative findings reveal that there is a substantial gap in awareness about palliative care, lack of information, presence of stigmatizing beliefs, and lack of adequate accessibility to palliative facilities. CONCLUSION: The study lays the foundation for future PD neuropalliative care research, guiding interventions, and exploration of regional variations in PD experiences in India. There is a need to address caregiver burden in PD in India.

Cryptococcal infection causing longitudinal extensive transverse myelitis in an immunocompetent individual: Case report and literature review.

Cryptococcal CNS infections in immunocompetent individuals are occasionally reported in literature. The spinal manifestations of cryptococcal CNS infections are epidural abscess, chronic arachnoiditis, intramedullary granuloma, myelitis and vasculitis. We report a rare case of CNS cryptococcal infection presenting as a longitudinal extensive transverse myelitis (LETM) in an immunocompetent male. This report highlights cryptococcus as an important etiology among infectious causes in acute LETM patients in-spite of the immunocompetent status of the patient and the utility of CRAG (cryptococcal antigen) for diagnosis in such patients. We also present a literature review of all reported cases of cryptococcal myelitis.

Osteo-Cutaneous Trophic Changes in Complex Regional Pain Syndrome and their Reversal with Steroids.

Background: Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by autonomic and inflammatory features. There is paucity of data regarding sustained benefits of any treatment modality. We aimed to document the effect of steroids in CRPS on long-term basis. Materials and Methods: We came across five patients of CRPS in Out Patient clinics of super-speciality Institutes in North India. All five cases fulfilled the Budapest criteria for the diagnosis of CRPS. All of them received prednisolone and were prospectively followed up for 2 years. Treatment outcome was carefully recorded in all affected modalities. Results: All five cases were found to have excruciating neuropathic pain in defined regions along with cutaneous manifestations. Osseous changes in the form of surface erosion of underlying bones in four cases and marked marrow edema leading to considerable increase in bone thickness in one case were noted. All these features improved considerably following steroid therapy. Bone marrow edema and bone resorption showed improvement on serial imaging. Conclusion: Apart from pain relief, steroids therapy is capable of reversing the osteo-cutaneous autonomic changes of CRPS type I.

Autoimmune polyglandular syndrome type II presenting as subacute combined degeneration of spinal cord: a neuroendocrinology crossroad.

Introduction: Autoimmune polyglandular syndrome (APS) is a condition having multiple endocrine abnormalities. It is divided into three types depending on the involvement of various endocrinopathies. It is also associated with other systemic involvement. The basic pathophysiology of this syndrome revolves around autoimmunity.Case presentation: We discuss the case of a 50-year-old gentleman who presented to us in emergency with subacute onset progressive weakness of both lower limbs followed by upper limbs. On examination, patient was confused and disoriented. General examination findings include hypotension, pallor, facial puffiness and vitiligo. Neurological examination revealed spasticity and motor weakness in all four limbs with extensor planter response. Sensory examination during hospital course revealed posterior column involvement. Laboratory and radiological investigations confirmed subacute combined degeneration of spinal cord secondary to pernicious anaemia, Addison's disease and autoimmune thyroid disease. The final diagnosis of autoimmune polyglandular syndrome type II was made after fulfilment of the required criteria.Conclusion: Autoimmune polyglandular syndrome type II can rarely present to neurologist as subacute combined degeneration of spinal cord. This syndrome and its systemic association should be kept in mind in order to reach the final diagnosis.

Development of a Trigger Tool to Identify Adverse Events and Harm in a Neuropsychiatry Setting.

BACKGROUND OBJECTIVES: Adverse drug events (ADEs) present the greatest risk of harm to patients in hospitals, especially those receiving neuropsychiatric treatment. The objective of the present record-based study was to test the appropriateness of the neuropsychiatry trigger tool (NPTT) to identify and measure harm due to adverse events (AEs). METHODS: A total of 1324 clinical case notes of discharged patients from 2017 to 2018 with a hospital stay >24 hours to <70 days were examined. RESULTS: One hundred forty-four (10.88%) patients experienced 166 AEs. A total of 854 triggers (range, 1-12 triggers per patient) were identified in 296 (22.36%) and 39 (2.94%) patients presented with triggers at admission. The overall AE rate per 1000 patient days was 12.73 (intensive care unit, 21; inpatient department, 11.54). Triggers at admission were altered sensorium and abnormal behavior followed by headache, ataxia, and aspiration pneumonia. A small number of triggers accounted for most AEs (laxative, rising liver function test (LFT), hypokalemia, hyponatremia, health care-associated infections, intubation, abnormal behavior/sensorium, hepatic encephalopathy, antiemetics), although type of AE reported differed by level of care. Most AEs caused minor harm, and relatively fewer patients experienced temporary harm requiring intervention (110; 8.29%), permanent harm (45; 3.39%), harm requiring initial/prolonged hospitalization (10; 0.75%), interventions to sustain life (24; 1.81%), and death (109; 8%). The higher the number of AEs, the longer was the length of stay (average increased from 9.32 to 17.33 days). The NPTT identified 30 times more AEs compared with 5 AEs reported by voluntary method. Medication-related ADEs were found in 130 (90%) of 144 patients who experienced AEs. Antitubercular drugs caused most ameliorable AEs (visual disturbance, drug-induced vomiting, deranged LFT, constipation). Care is needed in attributing harm because some triggers (abnormal sensorium/behavior, intubation, headache/dizziness, laxatives) may overlap with neurological illnesses (cerebrovascular accident [CVA]/meningitis/stroke). If the triggers are identified early, harm/discomfort to the patients can be reduced. The NPTT can be used in patient safety improvement projects. Harm occurred in 296 (22.28%) patients (temporary, 120 [9%]; permanent, 178 [13%]). Adverse events prolonged hospital stay (14.29 days) compared with 9.32 days in patients without AEs. CONCLUSIONS: A higher number of triggers per patient (≥5), trigger nature (intubation, cardiac arrest/shock), or the presenting illness (CVA/neuroinfections/status epilepticus/prolonged seizures) were correlated with the highest harm, that is, death. Because some triggers (abnormal sensorium/behavior, headache/dizziness, laxatives, intubation) may overlap with neurological illness (CVA/meningitis/stroke), care is needed in attributing harm. The NPTT identified 30 times more AEs compared with 5 AEs reported by voluntary method. Antitubercular drugs caused ameliorable AEs (visual disturbance, drug-induced vomiting, deranged LFT, constipation) and, if identified early, can reduce harm/discomfort to the patients.

Genetics of Ataxias in Indian Population: A Collative Insight from a Common Genetic Screening Tool.

Cerebellar ataxias (CAs) represent a group of autosomal dominant and recessive neurodegenerative disorders affecting cerebellum with or without spinal cord. Overall, CAs have preponderance for tandem nucleotide repeat expansions as an etiological factor (10 TREs explain nearly 30-40% of ataxia cohort globally). The experience of 10 years of common genetic ataxia subtypes for ≈5600 patients' referrals (Pan-India) received at a single center is shared herein. Frequencies (in %, n) of SCA types and FRDA in the sample cohort are observed as follows: SCA12 (8.6%, 490); SCA2 (8.5%, 482); SCA1 (4.8%, 272); SCA3 (2%, 113); SCA7 (0.5%, 28); SCA6 (0.1%, 05); SCA17 (0.1%, 05), and FRDA (2.2%, 127). A significant amount of variability in TRE lengths at each locus is observed, we noted presence of biallelic expansion, co-occurrence of SCA-subtypes, and the presence of premutable normal alleles. The frequency of mutated GAA-FRDA allele in healthy controls is 1/158 (0.63%), thus an expected FRDA prevalence of 1:100 000 persons. The data of this study are relevant not only for clinical decision making but also for guidance in direction of genetic investigations, transancestral comparison of genotypes, and lastly provide insight for policy decision for the consideration of SCAs under rare disease category.

Validating a Genomic Convergence and Network Analysis Approach Using Association Analysis of Identified Candidate Genes in Alzheimer's Disease.

Previously, we demonstrated an integrated genomic convergence and network analysis approach to identify the candidate genes associated with the complex neurodegenerative disorder, Alzheimer's disease (AD). Here, we performed a pilot study to validate the in silico approach by studying the association of genetic variants from three identified critical genes, APOE, EGFR, and ACTB, with AD. A total of 103 patients with AD and 146 healthy controls were recruited. A total of 46 single-nucleotide polymorphisms (SNPs) spanning the three genes were genotyped, of which only 19 SNPs were included in the final analyses after excluding non-polymorphic and Hardy-Weinberg equilibrium-violating SNPs. Apart from our previously reported APOE ε4, four other SNPs in APOE (rs405509, rs7259620, -rs769449, and rs7256173), one in EGFR (rs6970262), and one in ACTB (rs852423) showed a significant association with AD (p < 0.05). Our results validate the reliability of genomic convergence and network analysis approach in identifying the AD-associated candidate genes.

Autoimmune Encephalitis versus Creutzfeldt-Jakob disease in a patient with typical Facio-brachial dystonic seizures: A case report with Diagnostic challenges.

BACKGROUND: Diagnosis of rapidly progressive dementia (RPD) is very challenging. There are many conditions that fall into category of RPD ranging from autoimmune causes to neurodegenerative causes. Autoimmune encephalitis should be readily diagnosed and treated because of its response to immunomodulators. However there is no treatment available for conditions like Creutzfeldt-Jakob disease (CJD). CASE PRESENTATION: Here we present a case of anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis who presented with only typical facio-brachial dystonic seizures at presentation. On follow up, patient had a rapid cognitive decline with development of myoclonic jerks, akinetic mute state and ultimately death. Neuroimaging showed presence of hyperintensities in two cortical regions namely parietal and occipital on fluid-attenuated inversion recovery (FLAIR) sequence. Electroencephalogram showed diffuse slowing with occasional periodic sharp wave complexes. Thus a diagnosis of probable CJD was made. CONCLUSION: Autoimmune encephalitis mimicking CJD or vice versa is not a very commonly encountered phenomenon. This case discusses the clinical overlap of these two conditions and its diagnostic dilemmas. This case presented with typical LGI1 encephalitis and in spite of therapy with immunomodulators had a rapid decline and ultimately turned out to be CJD. This has been rarely described in literature.

Clinical profile and outcome of non-COVID strokes during pandemic and the pre pandemic period: COVID-Stroke Study Group (CSSG) India.

BACKGROUND: As the health systems around the world struggled to meet the challenges of COVID-19 pandemic, care of many non-COVID emergencies was affected. AIMS: The present study examined differences in the diagnosis, evaluation and management of stroke patients during a defined period in the ongoing pandemic in 2020 when compared to a similar epoch in year 2019. METHODS: The COVID stroke study group (CSSG) India, included 18 stroke centres spread across the country. Data was collected prospectively between February and July 2020 and retrospectively for the same period in 2019. Details of demographics, stroke evaluation, treatment, in-hospital and three months outcomes were collected and compared between these two time points. RESULTS: A total of 2549 patients were seen in both study periods; 1237 patients (48.53%) in 2019 and 1312 (51.47%) in 2020. Although the overall number of stroke patients and rates of thrombolysis were comparable, a significant decline was observed in the month of April 2020, during the initial period of the pandemic and lockdown. Endovascular treatment reduced significantly and longer door to needle and CT to needle times were observed in 2020. Although mortality was higher in 2020, proportion of patients with good outcome were similar in both the study periods. CONCLUSIONS: Although stroke admissions and rates of thrombolysis were comparable, some work flow metrics were delayed, endovascular stroke treatment rates declined and mortality was higher during the pandemic study period. Reorganization of stroke treatment pathways during the pandemic has likely improved the stroke care delivery across the globe.

Evidence-Based Discriminant Analysis: A New Insight into Iron Profile for the Diagnosis of Parkinson's Disease.

INTRODUCTION: Parkinson's disease is the second most common neurodegenerative disorder. Neurochemical studies have implicated metals in pathogenesis of PD. OBJECTIVES: To examine the association of serum iron, transferrin, ferritin, transferrin saturation and UIBC in PD patients and to derive the Discrimination Function with scores of these variables to correctly classify PD cases and healthy controls. METHODS: In the present study, identification of biomarker pool in case-control study involving 79 PD cases and 80 healthy controls were performed. RESULTS: The results of independent t-test analysis showed that PD cases presented significantly higher (P < 0.01) level of transferrin, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and urea than controls. As only one-third of transferrin is saturated with iron, so the transferrin present in serum has the extra binding capacity (67%), this is called UIBC. Discriminant analysis was performed to determine the factors that best discriminate between the categories of an outcome variables (Disease status = PD and Control) and total of five biochemical independent variables (UIBC, transferrin, iron, transferrin saturation, and copper) were taken into consideration. UIBC has emerged out to be highest discriminating, powerful and independent variable among considered independent variables, which indicates iron deficiency. After development of Discriminant Function (Z) and calculation of discriminant function cut points, a cross-validation analysis of PD cases and controls were conducted. The sensitivity of the developed model was 98.73% and specificity 83.75%. Receiver operating characteristics (ROC) was plotted, and the findings of ROC curve corroborated with the results obtained from discriminant function analysis. CONCLUSION: Prospective validation of Discriminant model in large cohort is warranted in future studies.

Systematic Review of Different Neuroimaging Correlates in Mild Cognitive Impairment and Alzheimer's Disease.

Alzheimer's disease (AD) is a heterogeneous progressive neurocognitive disorder. Although different neuroimaging modalities have been used for the identification of early diagnostic and prognostic factors of AD, there is no consolidated view of the findings from the literature. Here, we aim to provide a comprehensive account of different neural correlates of cognitive dysfunction via magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI) (resting-state and task-related), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) modalities across the cognitive groups i.e., normal cognition, mild cognitive impairment (MCI), and AD. A total of 46 meta-analyses met the inclusion criteria, including relevance to MCI, and/or AD along with neuroimaging modality used with quantitative and/or functional data. Volumetric MRI identified early anatomical changes involving transentorhinal cortex, Brodmann area 28, followed by the hippocampus, which differentiated early AD from healthy subjects. A consistent pattern of disruption in the bilateral precuneus along with the medial temporal lobe and limbic system was observed in fMRI, while DTI substantiated the observed atrophic alterations in the corpus callosum among MCI and AD cases. Default mode network hypoconnectivity in bilateral precuneus (PCu)/posterior cingulate cortices (PCC) and hypometabolism/hypoperfusion in inferior parietal lobules and left PCC/PCu was evident. Molecular imaging revealed variable metabolite concentrations in PCC. In conclusion, the use of different neuroimaging modalities together may lead to identification of an early diagnostic and/or prognostic biomarker for AD.

Burden of Stroke in India During 1960 to 2018: A Systematic Review and Meta-Analysis of Community Based Surveys.

BACKGROUND: Stroke is a heterogeneous disorder comprising of clinical subtypes and many risk factors, also alluded to as cerebrovascular disorders (CVDs). Increase in the global burden of stroke in developed and developing countries has been alarming. To galvanize the efforts towards the prevention and treatment, there is a need for robust data on the burden of stroke. OBJECTIVE: The aim of this study was to estimate the burden of stroke, a systematic review of community-based studies was conducted. MATERIAL AND METHODS: Systematic search of PubMed and Google Scholar for studies from January 1960 to December 2018 was done. The articles were screened and the data was retrieved and sorted into incidence, prevalence and mortality rates. Meta-analysis was done on Medcalc statistical software version 19.2.6. RESULTS: Prevalence rate of stroke for total population inclusive of urban and rural population, varied from 44.54 to 150/100000.For the urban population prevalence rate was 45 to 487/100000 and 55 to 388.4/100000 for rural population. The incidence rate varied from 33 to 123/100000 in the urban population and in the rural population it was estimated to be 123.57/100000. The 30 days case fatality rate of stroke varied from 41.08% to 42.06% in urban population and 18% to 46.3%.in the rural population. CONCLUSIONS: Systematic review and meta-analysis reveal that the stroke burden in India is quite high.

Clinical Features and Outcome of Stroke with COVID-19. COVID-19 Stroke Study Group (CSSG), India.

BACKGROUND AND PURPOSE: Occurrence of stroke has been reported among patients with COVID-19. The present study compares clinical features and outcomes of stroke patients with and without COVID-19. METHODS: The COVID-19 Stroke Study Group (CSSG) is a multicentric study in 18 sites across India to observe and compare the clinical characteristics of patients with stroke admitted during the current pandemic period and a similar epoch in 2019. The present study reports patients of stroke with and without COVID-19 (CoVS and non-CoVS, respectively) seen between February 2020 and July 2020. Demographic, clinical, treatment, and outcome details of patients were collected. RESULTS: The mean age and gender were comparable between the two groups. CoVS patients had higher stroke severity and extent of cerebral involvement on imaging. In-hospital complications and death were higher among CoVS patients (53.06% vs. 17.51%; P < 0.001) and (42.31% vs. 7.6%; P < 0.001), respectively. At 3 months, higher mortality was observed among CoVS patients (67.65% vs. 13.43%; P < 0.001) and good outcome (modified Rankin score [mRS]: 0-2) was seen more often in non-CoVS patients (68.86% vs. 33.33%; P < 0.001). The presence of COVID-19 and baseline stroke severity were independent predictors of mortality. CONCLUSIONS: CoVS is associated with higher severity, poor outcome, and increased mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and baseline stroke severity are independent predictors of mortality.

Neurological Associations of COVID-19-Do We Know Enough: A Tertiary Care Hospital Based Study.

The neurotrophic potential of SARS-CoV-2 virus is manifesting as various neurological disorders in the present pandemic. Nervous system involvement can be due to the direct action of the virus on the brain tissue or due to an indirect action through the activation of immune-mediated mechanisms. This study will discuss the detailed systematically evaluated clinical profile and relevant investigations and outcome of 14 laboratory confirmed SARS-CoV-2 positive patients presenting with neurological signs and symptoms. The patients were further categorized into confirmed, probable, and possible neurological associations. The probable association was found in meningoencephalitis (n = 4), stroke (n = 2), Guillain-Barré syndrome (n = 1), and anosmia (n = 1). The other six patients had coexisting neurological diseases with SARS-CoV-2. One patient with a large artery stroke succumbed to the illness due to respiratory complication. Memory impairment as a sequela is present during follow up of one encephalitis patient. Presently the early recognition and diagnosis of neurological manifestations remains a challenge for clinicians as the SARS-CoV-2 related neurological manifestations are in evolution. A long-term correlation study of clinical profile, radiological and laboratory investigations, along with neuropathological studies is needed to further understand the pathophysiology behind the SARS-CoV-2 neurological manifestations. Further understanding will facilitate timely recognition, therapeutic intervention, and possible prevention of long-term sequalae.

Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment.

Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood absence epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy and epilepsy with generalized tonic-clonic seizure on awakening and focal epilepsy like temporal lobe epilepsy and cryptogenic focal epilepsy. In 70% of the epilepsy cases, genetic factors are responsible either as single genetic variant in rare epilepsies or multiple genetic variants acting along with different environmental factors as in common epilepsies. Genetic testing and precision treatment have been developed for a few rare epilepsies and is lacking for common epilepsies due to their complex nature of inheritance. Precision medicine for common epilepsies require a panoramic approach that incorporates polygenic background and other non-genetic factors like microbiome, diet, age at disease onset, optimal time for treatment and other lifestyle factors which influence seizure threshold. This review aims to comprehensively present a state-of-art review of all the genes and their genetic variants that are associated with all common epilepsy subtypes. It also encompasses the basis of these genes in the epileptogenesis. Here, we discussed the current status of the common epilepsy genetics and address the clinical application so far on evidence-based markers in prognosis, diagnosis, and treatment management. In addition, we assessed the diagnostic predictability of a few genetic markers used for disease risk prediction in individuals. A combination of deeper endo-phenotyping including pharmaco-response data, electro-clinical imaging, and other clinical measurements along with genetics may be used to diagnose common epilepsies and this marks a step ahead in precision medicine in common epilepsies management.