An Individualized Multi-Modal Approach for Detection of Medication "Off" Episodes in Parkinson's Disease via Wearable Sensors.

The primary treatment for Parkinson's disease (PD) is supplementation of levodopa (L-dopa). With disease progression, people may experience motor and non-motor fluctuations, whereby the PD symptoms return before the next dose of medication. Paradoxically, in order to prevent wearing-off, one must take the next dose while still feeling well, as the upcoming off episodes can be unpredictable. Waiting until feeling wearing-off and then taking the next dose of medication is a sub-optimal strategy, as the medication can take up to an hour to be absorbed. Ultimately, early detection of wearing-off before people are consciously aware would be ideal. Towards this goal, we examined whether or not a wearable sensor recording autonomic nervous system (ANS) activity could be used to predict wearing-off in people on L-dopa. We had PD subjects on L-dopa record a diary of their on/off status over 24 hours while wearing a wearable sensor (E4 wristband®) that recorded ANS dynamics, including electrodermal activity (EDA), heart rate (HR), blood volume pulse (BVP), and skin temperature (TEMP). A joint empirical mode decomposition (EMD) / regression analysis was used to predict wearing-off (WO) time. When we used individually specific models assessed with cross-validation, we obtained > 90% correlation between the original OFF state logged by the patients and the reconstructed signal. However, a pooled model using the same combination of ASR measures across subjects was not statistically significant. This proof-of-principle study suggests that ANS dynamics can be used to assess the on/off phenomenon in people with PD taking L-dopa, but must be individually calibrated. More work is required to determine if individual wearing-off detection can take place before people become consciously aware of it.

Sepsis or sympathetics? Paroxysmal sympathetic hyperactivity after pontine stroke.

A 64-year-old man from nursing home with a pontine stroke 3 months ago, ventilator-dependent, presented with episodic fever, tachycardia and tachypnoea occurring several times a day. He was evaluated for sepsis and pulmonary embolism and was treated empirically with broad-spectrum antibiotics. But these episodes persisted. Due to the episodic nature and typical symptoms of sympathetic overactivity, in the setting of prior brain injury, paroxysmal sympathetic hyperactivity was considered. His antibiotics were discontinued, and he was treated symptomatically with baclofen and bromocriptine, which resulted in a partial reduction of these episodes.

Rare case of rapidly reaccumulating ascites.

Eosinophilic ascites is a rare type of exudative ascites most commonly caused by eosinophilic gastroenteritis. Here, a 57-year-old man presents with sudden-onset abdominal distension associated with nausea, vomiting and decreased appetite for 10 days. Physical examination revealed significant abdominal distention and fluid wave. Initial labs showed leucocytosis and mild peripheral eosinophilia. Imaging of his abdomen revealed severe ascites, no features of cirrhosis and diffuse inflammatory changes involving the jejunum and ileum. Diagnostic paracentesis showed exudative, ascitic fluid with predominant eosinophilia. Cytology of the ascitic fluid and blind biopsies taken during oesophagogastroduodenoscopy and enteroscopy were both negative for malignancy. The ascites reaccumulated rapidly, requiring five rounds of large-volume paracentesis during hospitalisation. Empiric treatment for suspected eosinophilic gastroenteritis with intravenous steroids improved and stabilised the patient's ascites for discharge. Parasitic workup resulted positively for Toxocara antibodies on ELISA. On 2-week outpatient follow-up, a course of albendazole resolved all gastrointestinal symptoms.

Stroke in COVID-19: a single-centre initial experience in a hotspot of the pandemic.

BACKGROUND: COVID-19, caused by SARS-CoV-2, is a global pandemic that has been an immense burden on healthcare systems all over the world. These patients may be at higher risk for acute ischaemic stroke (AIS). We present our experience with AIS in patients with COVID-19. METHODS: We reviewed all patients admitted to our hospital during a 6-week period with a positive nasopharyngeal swab test for SARS-CoV-2. Among these patients, we identified AIS. We reviewed the demographics, clinical, laboratory, imaging characteristics, treatments received and outcomes of AIS in patients with COVID-19. RESULTS: We identified 683 patients admitted with COVID-19 during the study period, of which 20 patients had AIS. Large-vessel occlusion (LVO) was noted in 11 patients (55%). Intravenous alteplase was administered in four patients (20%) and mechanical thrombectomy was performed in five patients (25%). Respiratory symptoms preceded the onset of AIS in most of the patients (70%) by 1 to 21 days. Mortality in patients with AIS was 50% compared with 26% of all COVID-19 admissions. Most of these patients died due to non-neurological causes (70%). Three patients with AIS had clinical and imaging findings consistent with COVID-19, but were negative for multiple nasopharyngeal swab tests. INTERPRETATION: LVO was more common in patients with AIS and COVID-19. They had more severe disease and higher mortality rates. Most of the patients had respiratory symptoms preceding AIS by days to weeks. This could explain certain patients with clinical picture of COVID-19 but negative nasopharyngeal swab tests.

Experience of pallidal deep brain stimulation in dystonia at a tertiary care centre in India: An initial experience.

INTRODUCTION: Dystonia is one of the most prevalent forms of movement disorders and is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonia causes significant morbidity with an adverse impact on the quality of life. When dystonia is medically refractory, causing severe pain and impairment in activities of daily living, deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a potential option to reduce disability. MATERIALS AND METHODS: This is a chart review of patients who underwent DBS for dystonia (from 2009 to 2015) at our tertiary referral centre. A total of ten patients (7 males, 3 females) underwent DBS for non-parkinsonian conditions. The patients were selected after failure of adequate medical management. All the patients had a severe disability with normal cognitive (Mini-Mental State Examination) and psychiatric profile. They also had to have a suitable GPi for DBS based on magnetic resonance imaging. RESULTS: The mean baseline Burke-Fahn-Marsden dystonia movement score of the 10 patients selected for surgery was 60.3 ± 27.3 (ranging from 19 to 104). On repeated-measures analysis of variance, there was significant difference in the different time points (pre-DBS, post-DBS at 3 months, 6 months, and 1 year) F (3, 5) = 7.68, P = 0.026. The data showed that there was a maximum improvement after 1 year of stimulation (pre-DBS vs. 3 months 12.9 ± 1.9 vs 8.8 ± 2.1, P = 0.01; pre-DBS vs. 6 months 12.9 ± 1.9 vs 7.4 ± 1.6, P = 0.04; pre-DBS vs. 1 year, 12.9 ± 1.9 vs. 7 ± 2.4. CONCLUSION: In medically refractory primary or secondary dystonia patients, bilateral GPi DBS can be considered as an option. Patients with disabling symptoms that significantly deteriorate activities of daily life may consider DBS before these symptoms become fixed.

Prescribing Pattern for Parkinson's Disease in Indian Community before Referral to Tertiary Center.

BACKGROUND: Several factors determine the choice of medications in patients with Parkinson's disease (PD). We aimed to analyze the pattern of prescription of drugs in patients with PD before attending a tertiary-care center. METHODS: The study included chart review of 800 PD patients attending the Department of Neurology of the National Institute of Mental Health and Neurosciences in Bangalore, India. RESULTS: The mean age at onset was 51.1±11.8 years. The mean duration of illness was 41.7±43.6 months. At first visit, 79.4% (group 1, n=635) of patients were on medications, 10% (group 2, n=80) were on medications but later discontinued, and 10.6% (group 3, n=85) were drug-naïve. Overall, levodopa was prescribed in 94.8%, trihexyphenidyl in 40.4%, dopamine agonists in 23.2%, and amantadine in 17.2% either as monotherapy or in combination. In group 1, 37.8% were on monotherapy, with levodopa being the most commonly used agent (33.1%), followed by trihexyphenidyl (2.2%), dopamine agonists (1.6%), and amantadine (0.6%). Among those on polytherapy, levodopa plus trihexyphenidyl was the preferred combination (23.9%). In group 2, levodopa monotherapy was also most common (72.5%), followed by trihexyphenidyl monotherapy (7.5%). CONCLUSIONS: Levodopa and trihexyphenidyl were the most commonly prescribed drugs in our patients. A higher use of trihexyphenidyl could be due to its easy availability, low cost, and better tolerability in our patients, who were relatively young at the time of onset of their disease. The choice of antiparkinsonian medications at the primary and secondary care levels in India may be inappropriate, and newer guidelines tailored to the Indian context are warranted.

Research in Parkinson's disease in India: A review.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting patients in large numbers throughout the world. In this article, we review all the published data on PD based on studies in Indian population. We have tried to consolidate the contribution of Indian studies in PD research. We found 95 articles, of which 92 were original research papers. This is a relatively less number, but in the last decade, there has been an increase in research on PD from this country. But most of them seem to be restricted to only a few research institutes. The nonmotor symptoms and genetics are the most commonly studied aspects. The systematic review of the articles reveals that the epidemiology in India may be different with relatively lesser incidence here. Most of the genetic mutations found to cause PD in other population are not found in India, revealing that other genetic factors may be involved. Further research needs to be encouraged to understand the disease in Indian patients better, as all the results cannot be extrapolated from the Western literature to this heterogeneous Indian population. There need to be more studies on therapeutic aspects of the disease.

Bilateral pallidal deep brain stimulation in idiopathic dystonic camptocormia.

INTRODUCTION: Camptocormia is seen with Parkinson's disease (PD), segmental or generalized dystonia, extensor myopathies, anterior horn cell disorders, and muscle disorders. In severe selected cases of PD with camptocormia and dystonic camptocormia, deep brain stimulation (DBS) has been tried with variable success. In this paper, the first case report of its kind from India, we report a case of dystonic camptocormia who underwent DBS and review the available literature. METHODS: A 42-year-old male, presented with dystonia of 5-year duration, that initially started with cervical dystonia and later progressed to severe disturbance of posture causing involuntary truncal flexion induced by standing or sitting. The camptocormia was completely relieved when sitting on a chair or lying down on the bed. Routine blood testing was normal. The workup for secondary dystonia including slit lamp examination for Kayser-Fleischer ring and serum copper studies did not reveal any abnormality. Magnetic resonance imaging of the brain was unremarkable. The electromyogram of the lumbar and thoracic paraspinal muscles was also normal. RESULTS: The patient was initially treated with multiple drugs and Botulinum A toxin which were ineffective. He underwent bilateral globus pallidus interna (GPi) DBS Over a period of 2 weeks; there was a mild reduction in the dystonia of the trunk and neck. The maximum improvement in dystonia, approximately 30% over baseline, was noted at 2 weeks postsurgery and over a further long-term follow-up, the improvement was 50% as determined by the sub-item (trunk) assessment of the Burke-Fahn-Marsden (BFM) dystonia score. Cervical dystonia improved by >90% in sub-item (neck) assessment of BFM scale. CONCLUSIONS: In this report, we have shown the efficacy of GPi DBS in the treatment of drug refractory dystonia associated camptocormia. Although only reported for PD associated camptocormia, evaluation for truncal extensor myopathy is mandatory in these cases also to achieve a good outcome.