Yoga as an Add-on Therapy in Parkinson's Disease: A Single Group Open-label Trial.

OBJECTIVE: We aimed to evaluate the effect of yoga on motor and non-motor symptoms and cortical excitability in patients with Parkinson's disease (PD). METHODS: We prospectively evaluated 17 patients with PD at baseline, after one month of conventional care, and after one month of supervised yoga sessions. The motor and non-motor symptoms were evaluated using the Unified Parkinson's disease Rating Scale (motor part III), Hoehn and Yahr stage, Montreal Cognitive Assessment, Hamilton depression rating scale, Hamilton anxiety rating scale, non-motor symptoms questionnaire and World Health Organization quality of life questionnaire. Transcranial magnetic stimulation was used to record resting motor threshold, central motor conduction time, ipsilateral silent period (iSP), contralateral silent period (cSP), short interval intracortical inhibition (SICI), and intracortical facilitation. RESULTS: The mean age of the patients was 55.5 ± 10.8 years, with a mean duration of illness of 4.0 ± 2.5 years. The postural stability of the patients significantly improved following yoga (0.59 ± 0.5 to 0.18 ± 0.4, p = 0.039). There was a significant reduction in the cSP from baseline (138.07 ± 27.5 ms) to 4 weeks of yoga therapy (116.94 ± 18.2 ms, p = 0.004). In addition, a significant reduction in SICI was observed after four weeks of yoga therapy (0.22 ± 0.10) to (0.46 ± 0.23), p = 0.004). CONCLUSION: Yoga intervention can significantly improve postural stability in patients with PD. A significant reduction of cSP and SICI suggests a reduction in GABAergic neurotransmission following yoga therapy that may underlie the improvement observed in postural stability. CLINICALTRIALSGOV IDENTIFIER: CTRI/2019/02/017564.

Pediatric neurobrucellosis: a systematic review with case report.

Pediatric neurobrucellosis represents a common anthropozoonosis in endemic areas but only anecdotal reports are available till date. Using appropriate search terms in the database platforms of MEDLINE, SCOPUS and Web of Sciences, we performed a systematic review of all the cases of pediatric neurobrucellosis published in the medical literature till date, in the light of a case report. The protocol was registered under PROSPERO (CRD42022333907). Our search strategy yielded 187 citations of which 51 citations were included. A total of 119 cases were reviewed. Of these cases, eight of them had insufficient data. The most common presentation was meningitis with or without encephalitis (n = 79, 71.2%). A high prevalence of cranial neuropathies (n = 22, 20.7%) was observed in the pediatric population in which abducens palsy was the most common (n = 9, 8.1%). Diagnosis was based on multimodal investigations including standard agglutination test (n = 44, 39.6%), Rose Bengal test (n = 37, 33.3%), blood culture (n = 23, 20.7%), serology (n = 20, 18.0%) and cerebrospinal fluid (CSF) culture (n = 11, 9.9%). Rifampicin-based triple drug regimen was the most commonly employed (83/102, 81.4%). Pediatric neurobrucellosis was associated with greater frequency of sequalae (5.4%), deafness (2.7%) and mortality (2.7%), when compared to that of general population. Neurobrucellosis mimics neuro-tuberculosis in various aspects. The review highlights several unique aspects of this entity in children. A high index of suspicion can ensure prompt diagnosis, timely initiation of management and favorable outcomes.

Pediatric neurobrucellosis represents a common zoonosis in endemic areas but only anecdotal reports are available till date. Using appropriate search terms in the database platforms of MEDLINE, SCOPUS and Web of Sciences, we performed a systematic review of all the cases of pediatric neurobrucellosis published in the medical literature till date, in the light of a case report. Our search strategy yielded 187 citations of which 51 citations were included. A total of 119 cases were reviewed. When compared to the largest series in neurobrucellosis, a higher frequency of meningitis was observed in the pediatric age group (71.2% vs. 37%). A high prevalence of cranial neuropathies (n = 22, 20.7%) was observed in the pediatric population in which abducens palsy was the most common (n = 9, 8.1%). Diagnosis was based on multimodal investigations including standard agglutination test (n = 44, 39.6%), Rose Bengal test (n = 37, 33.3%), blood culture (n = 23, 20.7%), serology (n = 20, 18.0%) and CSF culture (n = 11, 9.9%). Rifampicin-based triple drug regimen was the most commonly employed (83/102, 81.4%). Our systematic review highlighted the wide and heterogeneous spectrum of manifestations of neurobrucellosis in the pediatric population. A high index of suspicion can ensure prompt diagnosis, timely initiation of management and favorable outcomes.

Review of tremor in Parkinson's disease and atypical parkinsonian disorders.

Rest tremor (RT), a cardinal feature of Parkinson's disease (PD) is often accompanied by other types of tremor such as action tremor, which includes postural tremor, kinetic tremor, re-emergent tremor (ReT), and orthostatic tremor (OT). Literature on other tremors of PD, especially ReT and OT, is scarce. Tremor can be present in any of the atypical parkinsonian disorders such as progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. RT can even be the presenting symptom of these disorders. The objective of this review is to provide a comprehensive review of lesser known tremors in PD and to critically look at the prevalence of tremor in atypical Parkinsonian disorders.

Role of Optical Coherence Tomography in Predicting Visual Outcome after Surgery for Sellar and Supra-Sellar Tumors.

BACKGROUND: Almost one-fifth of patients undergoing surgery for sellar/supra-sellar tumors do not gain a significant improvement in their vision. Various methods have been described to predict prospective visual outcomes in them, although they lack uniformity. OBJECTIVE: The study was conducted to predict visual outcomes following surgery for sellar and supra-sellar tumors compressing the anterior optic pathway based on pre-operative optical coherence tomography (OCT) parameters. METHODS AND MATERIALS: This was a record-based observational descriptive longitudinal study done in a tertiary care center in India. Thirty-seven patients (74 eyes) diagnosed with sellar supra-sellar lesions were included in the study. Patients' ophthalmic evaluations, done pre-operatively and 3 months post-operatively, were reviewed. Spectral-domain OCT and segmentation were done using the automated segmentation technology of Spectralis software. The thickness of the respective layers was measured. RESULTS AND CONCLUSIONS: The mean age of the study population was 42.68 years. Eyes with a pre-operative visual acuity component of VIS (visual impairment score) ≤61, pre-operative ganglion cell layer thickness ≥26.31 um, a pre-operative inner plexiform layer thickness of ≥25.69 um, a pre-operative ganglion cell inner plexiform layer thickness of 52.00 um, pre-operative ganglion cell complex thickness ≥84.47 µm, and a pre-operative inner retinal layer thickness of ≥205.25 µm were more likely to have an improved visual outcome. Eyes with a pre-operative duration of visual symptoms of ≥15 months, VIS ≥126.50, a pre-operative decimal visual acuity of <0.035, a pre-operative visual field index of ≤8%, a pre-operative macular thickness of ≤287.06 um, a pre-operative macular RNFL (retinal nerve fiber layer) thickness ≤66.00 µm, and a pre-operative peri-papillary RNFL thickness ≤64.62 µm were unlikely to have visual improvement.

Progressive multifocal leukoencephalopathy (PML) associated with HIV Clade C--is not uncommon.

Progressive multifocal leukoencephalopathy (PML) is a rare, subacute, demyelinating disease of the central nervous system caused by JC virus. Studies of PML from HIV Clade C prevalent countries are scarce. We sought to study the clinical, neuroimaging, and pathological features of PML in HIV Clade C patients from India. This is a prospective cum retrospective study, conducted in a tertiary care Neurological referral center in India from Jan 2001 to May 2012. Diagnosis was considered "definite" (confirmed by histopathology or JCV PCR in CSF) or "probable" (confirmed by MRI brain). Fifty-five patients of PML were diagnosed between January 2001 and May 2012. Complete data was available in 38 patients [mean age 39 ± 8.9 years; duration of illness-82.1 ± 74.7 days). PML was prevalent in 2.8 % of the HIV cohort seen in our Institute. Hemiparesis was the commonest symptom (44.7 %), followed by ataxia (36.8 %). Definitive diagnosis was possible in 20 cases. Eighteen remained "probable" wherein MRI revealed multifocal, symmetric lesions, hypointense on T1, and hyperintense on T2/FLAIR. Stereotactic biopsy (n = 11) revealed demyelination, enlarged oligodendrocytes with intranuclear inclusions and astrocytosis. Immunohistochemistry revelaed the presence of JC viral antigen within oligodendroglial nuclei and astrocytic cytoplasm. No differences in clinical, radiological, or pathological features were evident from PML associated with HIV Clade B. Clinical suspicion of PML was entertained in only half of the patients. Hence, a high index of suspicion is essential for diagnosis. There are no significant differences between clinical, radiological, and pathological picture of PML between Indian and Western countries.

Cortical excitability changes in patients of vascular parkinsonism with cognitive impairment.

INTRODUCTION: Vascular parkinsonism (VaP), type of lower body parkinsonism, occurs in relation to ischemic cerebrovascular disease. It can be associated with cognitive impairment. We aimed to study the cortical excitability changes in these patients using transcranial magnetic stimulation (TMS). METHODS: We included 20 patients with VaP and 22 healthy controls (HC). All subjects underwent TMS over left motor cortex with recording of resting motor threshold (RMT), central motor conduction time (CMCT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), contralateral and ipsilateral silent period (SP) along with RMT and CMCT in the contralateral lower limb. Cognitive assessments were done using Montreal cognitive assessment (MoCA) and Addenbrooke's cognitive evaluation III (ACE III). RESULTS: Mean age of patients (63.90 ± 7.36 years) was comparable with controls (59.77 ± 6.94 years; p = 0.07). Duration of disease was 2.58 ± 2.57 years. The upper and lower limb RMT of patients (32.45 ± 4.81%; 57.20 ± 11.54%) was significantly low compared to HC (43.64 ± 7.73%; 69.18 ± 14.27%; p < 0.001). There was a significant reduction in SICI in patients (1.87 ± 2.03) compared to HC (0.38 ± 0.29; p < 0.001). In addition, there was a significant prolongation of ipsilateral SP in patients (48.49 ± 24.49) compared to controls (32.04 ± 12.26, p = 0.01). However, there was no significant difference in contralateral SP (p = 0.66) and ICF (p = 0.25) between the two groups. There was a significant prolongation of lower limb CMCT in patients (p < 0.01). There was a positive correlation of SICI with MoCA (r = 0.45, p < 0.05) and ACE-III (r = 0.33, p < 0.05) scores. CONCLUSION: Reduction in RMT and SICI in patients with VaP suggests abnormalities in GABAergic neurotransmission that may underlie cognitive impairment observed in them.

A systematic review and meta-analysis of optical coherence tomography studies in schizophrenia, bipolar disorder and major depressive disorder.

OBJECTIVES: Due to the common neurodevelopmental origin and easy accessibility, the retina serves as a surrogate marker for changes in the brain. Hence, Optical Coherence Tomography (OCT), a tool to examine the neuronal layers of retina has gained importance in investigating psychiatric disorders. Several studies in the last decade have reported retinal structural alterations in schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). However, the findings are inconsistent. Hence, we conducted a meta-analysis to investigate alterations in OCT parameters in patients with SCZ, BD and MDD. METHODS: We searched electronic databases for studies that examined OCT parameters in patients with SCZ, BD and MDD published up to January 2023. The primary outcome measures were thickness and volumes of the retinal Nerve Fibre Layer (RNFL). We conducted meta-analysis using a random effects model. RESULTS: The searches yielded 2638 publications of which 43 studies were included in the final analysis across all disorders. Compared to controls, the RNFL was thinner in SCZ patients (SMD = -0.37, p = <0.001) and BD patients (SMD = -0.67, p = < 0.001), but not in MDD patients (SMD = -0.08, p = 0.54). On quadrant wise analysis, temporal quadrant RNFL was thinner in SCZ but not in BD, while all other quadrants were thinner in both SCZ and BD. CONCLUSION: We found significant reductions in RNFL thickness in SCZ and BD, but not in MDD. The differential involvement in various quadrants and parameters across the disorders has potential implications for using retinal parameters as a diagnostic biomarker.

Looking beyond the brain: Insights into vascular parkinsonism with optical coherence tomography.

BACKGROUND: Vascular Parkinsonism (VP) is characterized by rigidity and bradykinesia predominantly affecting the lower limbs. Optical Coherence tomography (OCT) facilitates the visualization of retina and choroid and may help in delineating differential involvement of retina and choroid in patients with VP. In this study, we report the pattern of changes in the retinal and choroidal layers in patients with VP with the help of spectral domain OCT (SD-OCT). METHODS: We adopted a case-control design and evaluated 24 patients with VP with complete history, clinical examination, Montreal Cognitive Assessment (MOCA), Unified Parkinson's Disease Rating Scale (UPDRS) motor part in OFF state, and retinal and choroidal imaging with SD-OCT. The peripapillary retinal nerve fiber layer (RNFL) thickness, peripapillary choroidal layer thickness (PPChT), central macular thickness (CMT) and subfoveal choroid thickness (SFChT) were assessed. Twenty-two age and gender-matched healthy control subjects were also recruited. RESULTS: The peripapillary RNFL, in most of the segments and CMT were significantly thinner in patients with VP compared to controls. The subfoveal and peripapillary ChT did not differ significantly between patients and controls. CONCLUSION: This is the first study that has evaluated the role of OCT in patients with VP and these patients have significant involvement of the retina. In addition to providing pathophysiological insights, OCT parameters may serve as disease biomarkers in VP. This study lays the foundation for carrying out future studies with larger sample sizes and a longitudinal design.

Collagen XII-Related Myopathy: An Emerging Spectrum of Extracellular Matrix-Related Myopathy.

Collagen XII, a member of a protein family called fibril associated collagen with interrupted triple helices (FACIT), is an important component of extracellular matrix and is essential for bridging the neighbouring fibrils. Mutations in collagen XII have been recently described to cause a rare extracellular matrix-related myopathy in those whose phenotype resembles collagen VI-related dystrophies and were negative for pathogenic variants in COL6A genes. The authors report a 4-year old girl presented with a phenotype mimicking Ullrich congenital muscular dystrophy and genetically confirmed to have pathogenic variants in COL12A1 gene thus, expanding the phenotypic spectrum of COL12A1-related myopathy.

Ayurveda for management of migraine: A narrative review of clinical evidence.

Migraine is a primary headache disorder characterized by recurrent attacks. The economic and societal burden of migraine is substantial, affecting patients' quality of life in terms of work, social activities, and family life. This article attempts to review the available literature for clinical evidence of Ayurveda in the management of migraines. We performed a literature search from January 2000 to July 2020 on popular search engines such as Pub Med, Google Scholar, and AYUSH Research Portal using the keywords "Complementary and Alternative Medicine (CAM) and Migraine", "Ayurveda and Migraine" and "Panchakarma and Migraine". The selection criteria involved published clinical trials, including pilot studies, whereas review articles, concept papers, letters to the editor, and studies published in languages other than English were excluded. Out of 77 studies that were screened, 12 articles that satisfied the selection criteria consisted of six Randomized controlled Trials (RCTs), five non-RCTs, and one pilot study. Among them, ten studies used polyherbal and Herbo mineral formulations, two studies contained no oral medications, three trials utilized external therapies, and ten studies used panchakarma procedures. Eleven studies found Ayurveda to be clinically beneficial as monotherapy, while one study demonstrated the usefulness of Ayurveda as an add-on to conventional management. This review reveals the beneficial role of Ayurveda in the management of migraines without many side effects. Yet several limitations exist, like small sample size, short follow up, and lack of better outcome measures for pre and post-assessments. Future research should overcome these limitations and follow a robust methodology so that definitive conclusions can be drawn.

Retinal Changes in Parkinson's Disease: A Longitudinal Follow-up Study.

Background: There is definite evidence for the involvement of retina in Parkinson's disease (PD). However, a specific pattern has not been clear due to the cross-sectional nature of the majority of the previous studies. Objective: The aim of this work was to study the pattern of changes in the retinal layers in patients with PD on longitudinal follow-up. Materials and Methods: Twelve patients with PD (23 eyes) were evaluated at baseline with complete history, clinical examination, Unified Parkinson's Disease Rating Scale (UPDRS) motor part, visual acuity, and retinal imaging with spectral-domain Optical Coherence Tomography. After a mean duration of 3.7 ± 0.46 years, patients were re-evaluated. Results: The Central Macular Thickness (CMT) of the right eye was found to be significantly thicker during the follow-up (P = 0.002). The outer retinal layer in the temporal quadrant at 0.5 centimeters from the fovea of the left eye was found to be significantly thinner (P = 0.001). Conclusion: The serial evaluation of the retinal layers in patients with PD suggests a progressive loss of thickness of the outer retinal layer. The involvement of non-dopaminergic mechanisms, especially glutamatergic pathways, may be responsible for these changes.

The Spectrum of Neuro-COVID: A Study of a Comprehensively Investigated Large Cohort from India.

Background: Though reports of neurological manifestations of COVID-19 have emerged from various parts of the world, the cohorts reported are from the West and mostly derived from electronic databases. Much remains unknown regarding neuro-COVID in developing countries. India is the second-worst affected country, and this study reports the neurological manifestations of COVID-19 in a comprehensively evaluated cohort. Objective: The aim of this study was to describe the range of neurological manifestations of COVID-19 in India with an emphasis on the risk factors, laboratory and imaging findings and short-term outcome. Methods: Retrospective review of hospital records of all confirmed COVID-19 patients with neurological manifestations, receiving inpatient care in two neurology referral hospitals were done. All demographic, clinical details, investigations, and treatment were analysed. Results: A total of 120 confirmed COVID-19 cases presenting with neurological symptoms were included. The mean age of illness and duration of illness was 48.03 ± 17.3 years and 10.9 ± 17.3 days respectively. New onset of neurological symptoms occurred in 100 cases while 20 patients had worsening of pre-existing neurological illness. Stroke was the commonest neurological disorder (43%), followed by encephalopathy (23%) and Guillain-Barre syndrome (10%). Other unusual neurological manifestations included new-onset headache (7%), seizures including denovo status epilepticus (5%) and meningo-encephalitis (5%). Nearly half of the patients had preceding COVID-19 symptoms. Poor outcome at discharge was seen in 40% and mortality occurred in 15%. Conclusion: Stroke and encephalopathy constitute the most common neurological manifestations. The absence of preceding COVID-19 symptoms in nearly half the cases is striking. Poor outcome was seen in nearly 50% despite early recognition and management.

Smartphone-Based Telestroke Vs"Stroke Physician" led Acute Stroke Management (SMART INDIA): A Protocol for a Cluster-Randomized Trial.

Background: One of the major challenges is to deliver adequate health care in rural India, where more than two-thirds of India's population lives. There is a severe shortage of specialists in rural areas with one of the world's lowest physician/population ratios. There is only one neurologist per 1.25 million population. Stroke rehabilitation is virtually nonexistent in most district hospitals. Two innovative solutions include training physicians in district hospitals to diagnose and manage acute stroke ('Stroke physician model') and using a low-cost Telestroke model. We will be assessing the efficacy of these models through a cluster-randomized trial with a standard of care database maintained simultaneously in tertiary nodal centers with neurologists. Methods: SMART INDIA is a multicenter, open-label cluster-randomized trial with the hospital as a unit of randomization. The study will include district hospitals from the different states of India. We plan to enroll 22 district hospitals where a general physician manages the emergency without the services of a neurologist. These units (hospitals) will be randomized into either of two interventions using computer-generated random sequences with allocation concealment. Blinding of patients and clinicians will not be possible. The outcome assessment will be conducted by the blinded central adjudication team. The study includes 12 expert centers involved in the Telestroke arm by providing neurologists and telerehabilitation round the clock for attending calls. These centers will also be the training hub for "stroke physicians" where they will be given intensive short-term training for the management of acute stroke. There will be a preintervention data collection (1 month), followed by the intervention model implementation (3 months). Outcomes: The primary outcome will be the composite score (percentage) of performance of acute stroke care bundle assessed at 1 and 3 months after the intervention. The highest score (100%) will be achieved if all the eligible patients receive the standard stroke care bundle. The study will have an open-label extension for 3 more months. Conclusion: SMART INDIA assesses whether the low-cost Telestroke model is superior to the stroke physician model in achieving acute stroke care delivery. The results of this study can be utilized in national programs for stroke and can be a role model for stroke care delivery in low- and middle-Income countries. (CTRI/2021/11/038196).

Medication Overuse Headache.

BACKGROUND: Medication overuse headache (MOH) is one of the highly disabling headache disorder and affects about 1% of the population of the world. It is associated with the development of headache for 15 days or more, with consumption of acute symptomatic medications for 10-15 days (depending on the class of drug, like, simple analgesics, triptans, and opioids) in a month, used for relief of headache for three or more months, in a known patient of primary headache disorder. OBJECTIVE: The aim of this study was to review the topic of MOH and present the details of this disorder with an emphasis on recent updates in the field of pathophysiology and treatment. MATERIAL AND METHODS: Literature search was performed in the PubMed/MEDLINE and Cochrane database with appropriate keywords and relevant full-text articles were reviewed for writing this article. RESULTS: Over the years, the concept of MOH has evolved, although the exact pathophysiology is still being explored. In a susceptible individual interplay of genetics, change in pain pathways, changes in areas of the brain associated with the perception of pain, and changes in the neurotransmitters have been implicated. It has to be differentiated from other secondary chronic daily headache disorders, by a careful history, targeted examination, details of intake of medications. Treatment predominantly involves patient education, removal of the offending agent, and initiation of prophylactic medications for primary headache disorder in the outpatient or inpatient services. CONCLUSIONS: MOH is a secondary headache disorder, which should be considered in any chronic headache patient. There are various pathophysiological mechanisms attributed to its development. Management includes educating the patients about the disorder, detoxification, and prophylactic therapy.

DNAJC6 mutation causing cranial-onset dystonia with tremor dominant levodopa non-responsive parkinsonism: A novel phenotype.

DNAJC6 mutation causes two types of phenotypes: slowly progressive parkinsonism with levodopa response and rapidly progressive parkinsonism with additional manifestations like intellectual disability, epilepsy etc. We report a new phenotype wherein an adolescent girl developed blepharospasm followed by jaw opening, lingual and cervical dystonia followed by tremors of limbs (rest and action) with rigidity, bradykinesia. The dystonia-parkinsonism phenotype has not been described. She had novel homozygous missense mutation in DNAJC6 gene.

The Rationale of Yoga in Parkinson's Disease: A Critical Review.

BACKGROUND: Patients with Parkinson's disease (PD) commonly use complementary and alternative medications. Yoga is a mind-body intervention that is being increasingly explored as a tool in the therapeutic armamentarium of PD. OBJECTIVE: To critically evaluate the studies and summarize the utility of Yoga in PD. MATERIAL AND METHODS: We performed a systematic literature search in the Medline and Cochrane databases and included randomized controlled trials (RCT) of Yoga in PD. The studies were evaluated for internal validity and the relevant data were extracted. RESULTS: A total of seven studies were included in the analysis. We collated the data on the changes in motor function, gait and balance parameters, anxiety, depression and quality of life scores observed after intervention (Yoga) in patients with PD and highlighted the limitations of these studies. CONCLUSION: Anxiety, depression, and balance issues in PD may benefit from Yoga. Yoga has potential as an add-on therapy in PD.