Real-life benefits of intrajejunal levodopa infusion therapy in four patients with the parkinsonian variant of progressive supranuclear palsy: A 1-year follow-up data report.

BACKGROUND: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative condition presenting with different clinical endophenotypes. The parkinsonian variant of PSP (PSP-P) is characterised by early but fading responsiveness to high-dose levodopa therapy; however, high-dose oral therapy is often associated with intolerance due to dopaminergic side effects and so doses may have to be capped despite clinical benefits. Evidence from animal models and real-life registries suggest far higher doses of levodopa can be tolerated if given in a continuous drug delivery (CDD) manner. We investigated tolerance and possible clinical benefits in patients with PSP-P still responsive to levodopa after initiating CDD in the form of intrajejunal levodopa infusion (IJLI) therapy as part of a compassionate usage program (CU). METHODS: This is an observational clinical data report from the IJLI implementation program undertaken in regional tertiary referral Parkinson's centres in India and at King's College Hospital London, Dubai as part of a CU. Four patients with PSP-P receiving IJLI as a part of a CU underwent evaluations of liver and renal function, motor and nonmotor function, quality of life, sleep dysfunction, fatigue, anxiety and depression, and cognitive impairment at baseline and 6 and 12 months post-IJLI initiation. RESULTS: In total, three out of four patients successfully completed 12 months of treatment (6 months in one patient). All four patients showed good tolerability to IJLI even at higher doses (1400 and 1960 mg at 6 and 12 months, respectively) when compared to oral levodopa (812.5 ± 103 levodopa equivalent daily dose [LEDD]) and presented with overall persistent improvements in motor and nonmotor scores and quality-of-life scores at 6 and 12 months post-IJLI. All patients showed improvement in estimated glomerular filtration rate (43.50 ml/min/1.73 m2 to 67.5 ml/min/1.73 m2 and 79.5 ml/min/1.73 m2 at 6 and 12 months, respectively). CONCLUSIONS: IJLI led to persistent beneficial effects on motor and some nonmotor aspects in patients with PSP-P at up to 12 months after treatment with associated improvement in overall renal function.

Clinical and Molecular Spectrum of Degenerative Cerebellar Ataxia: A Single Centre Study.

Background: Cerebellar ataxia is a disabling neurological symptom with extreme clinical and etiological heterogeneity. Objective: To study the clinical and molecular characteristics in patients with degenerative cerebellar ataxia. Materials and Methods: In this study, 150 South-Indian patients with degenerative cerebellar ataxia underwent a phenotype guided, sequential tiered testing. Phenotypic features studied included cerebellar symptoms, pyramidal and extrapyramidal features, and ophthalmic and systemic findings. Tier one included conventional tests such as short PCR/fragment analysis for spinocerebellar ataxia (SCA) subtypes 1, 2, 3, 6, 7, 8, 12, 17, and 36 and TP-PCR for Friedreich ataxia (FA). Tier two testing comprised next-generation sequencing (NGS)-based strategies reserved for select undiagnosed cases. Results: The clinical features were highly overlapping and had limited specificity, except in autosomal recessive ataxias and SCA 34. The overall diagnostic yield of our study was 49.3%. SCA 1, 2, and 3 were noted in 13 (12.6%), 12 (11.6%) and 14 (13.5%), respectively, out of the 103 tested, and FA was noted in 17/55 (30.9%) patients. SCA subtypes 6, 7, 8, 12, 17, and 36 were absent in the cohort studied. Targeted Sanger sequencing and NGS revealed some rare diagnoses in 17 among the 18 patients tested. Whole exome sequencing uncovered a novel genotype-phenotype association in a sibling-pair with ataxia, dysmorphism, and retinopathy. Conclusion: SCA 1, 2, 3 and FRDA were the most common causes of ataxia. SCA 6, 7, 8, 12, 17, and 36 were absent in the cohort studied. NGS testing revealed several rare forms of ataxia. Clinical features based testing is cost-effective, achieves good genotype-phenotype correlation, and prioritizes variants for further studies.

Parkinson's Disease: Personalized Pathway of Care for Device-Aided Therapies (DAT) and the Role of Continuous Objective Monitoring (COM) Using Wearable Sensors.

Parkinson's disease (PD) is a chronic, progressive neurological disorder and the second most common neurodegenerative condition. Advanced PD is complicated by erratic gastric absorption, delayed gastric emptying in turn causing medication overload, and hence the emergence of motor and non-motor fluctuations and dyskinesia, which is initially predictable and then becomes unpredictable. As the patient progresses to the advanced stage, advanced Parkinson's disease (APD) is characterized by refractory motor and non motor fluctuations, unpredictable OFF periods, and troublesome dyskinesias. The management of APD is a complex affair. There is growing recognition that GI dysfunction is common in PD, with virtually the entire GI system (the upper and lower GI tracts) causing problems from dribbling to defecation. The management of PD should focus on personalized care addressing both motor and non-motor symptoms, ideally including not only dopamine replacement but also associated non-dopaminergic circuits, particularly focusing on noradrenergic, serotonergic, and cholinergic therapies bypassing the gastrointestinal tract (GIT) by infusion or device-aided therapies (DAT), including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, which are available in many countries for the management of the advanced stage of Parkinson's disease (APD). The PKG (KinetiGrap) can be used as a continuous objective monitoring (COM) aid, as a screening tool to help to identify advanced PD (APD) patients suitable for DAT, and can thus improve clinical outcomes.

Association of 25-Hydroxyvitamin D Deficiency in Pediatric Epileptic Patients.

OBJECTIVE: Epilepsy is a chronic neurological disorder requiring long-term therapy using antiepileptic medications. Reports have incriminated long-term antiepileptic drugs use in deficiency of vitamin D and bone diseases in all age groups. We aimed to investigate the association between serum 25-hydroxyvitamin D levels and pediatric epilepsy in Indian patients. MATERIALS & METHODS: We prospectively recruited 100 pediatric epilepsy patients, on monotherapy for minimum one-year duration, and 50 age and sex matched controls. This study was carried out at Yashoda Hospital, India from 2011-2014. All cases and controls underwent tests for serum 25-hydroxyvitamin D, alkaline phosphatase, serum calcium and phosphorus levels. RESULTS: Patients with 25-hydroxyvitamin D deficiency were significantly higher among cases (45%) than controls (24%). Mean alkaline phosphatase was significantly higher in cases and mean serum calcium was significantly lower (8.3±1.5) in cases. Amongst antiepileptic drugs, carbamazepine and sodium valproate were significantly associated with 25-hydroxyvitamin D deficiency. Risk of vitamin D deficiency was highest with sodium valproate usage (odds:4.0;95%CI 1.4-11.6) followed by carbamazepine use (odds: 2.7; 95%CI 1.0-6.8). After adjustment using multiple logistic regression, antiepileptic drugs showed independent association with 25-hydroxyvitamin D deficiency (odds:2.2;95%CI 0.9-4.5). CONCLUSION: 25-hydroxyvitamin D deficiency was significantly associated with use of carbamazepine and sodium valproate in pediatric epilepsy.

Association of Helicobacter pylori with Parkinson's Disease.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a major neurological disorder that requires lifelong treatment, and the combined presence of Helicobacter pylori (H. pylori) infection can increase the required anti-PD medications. We aim to investigate the effect of H. pylori infection in Indian PD patients. METHODS: We prospectively recruited 36 PD patients from December 2007 to January 2011. All patients underwent a detailed neurological evaluation and serological examination for H. pylori infection. Seropositive and seronegative patients were considered to be the cases and controls, respectively. All patients who were seropositive received triple therapy for 2 weeks. Outcome measures of the mean 'off' Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean 'on' UPDRS-III score, mean onset time, mean 'on' duration, and mean daily 'on' time were measured at baseline and at a 3-week follow-up. RESULTS: H. pylori-IgG positivity was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%), mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose (824 mg vs. 707 mg) were significantly higher among H. pylori positive patients than in controls (p<0.0001). Controls had a significantly longer 'on' duration and daily 'on' time, and better 'on' UPDRS-III scores. Seropositive patients took a significantly longer time to turn 'on' after a levodopa challenge. At the 3-week follow-up, H. pylori eradication significantly improved the mean 'on' UPDRS-III score, onset time, 'on' duration, and daily 'on' time. CONCLUSIONS: H. pylori infection was present in 50% of Indian PD patients. H. pylori seropositivity was associated with a poor response to levodopa and increased medication usage, while eradication therapy was associated with better patient outcomes.

Adult-onset Leigh's disease: A rare entity.

Leigh syndrome (LS) is a heterogeneous familial or sporadic neurodegenerative disorder. It is typically seen in infancy or childhood, although rare cases of adult onset have been described. The authors describe a 37-year-old woman who presented with protracted gastrointestinal symptoms followed by acute brain stem syndrome with severe metabolic acidosis and who subsequently showed dramatic clinical and neuroradiological improvement.

Development of global rating instruments for pediatric patients with ataxia telangiectasia.

INTRODUCTION: Ataxia telangiectasia (AT) is a neurodegenerative disorder with cerebellar and extrapyramidal features. Interventional and epidemiological studies in AT should rely on specific scales which encompass the specific neurological features, as well the early progressive course and the subsequent plateau. The aim of this study was to build a scale of the CGI type (Clinical Global Impression) which is disease specific, as well as to check the feasibility of the ICARS scale for ataxia in this population. METHODS: We recruited 63 patients with ataxia, aged 10.76 ± 3.2 years, followed at 6 international AT centers, 49 of them (77.8%) with classical AT. All patients were evaluated for ataxia with ICARS scale. In patients with AT, two CGI scales were scored, unstructured as structured for which separate anchors were provided. RESULTS: Mean ICARS score was 44.7 ± 20.52, and it's severity positively correlated with age (Spearman correlation, r = 0.46, p < 0.01). Mean CGI score was 2 (moderately involved). There was a high correlation between the structured and unstructured CGIs (Spearman correlation, r = 0.87, p < 0.01). Both CGI scales showed positive correlation between severity and increasing age (Spearman correlation r = 0.59, p < 0.01 for structured CGI and r = 0.61, p < 0.01 for unstructured). DISCUSSION: We succeeded to build two CGI scales: structured and unstructured, which are disease specific for AT. The unstructured scale showed better connection to disease course; the sensitivity of the unstructured scale could be improved by adding anchors related to extrapyramidal features. In addition we showed that ataxia can be reliably measured in children with AT by using ICARS.

Outcome of acute ischemic stroke after intra-arterial thrombolysis: A study from India.

Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is the currently standard treatment of acute ischemic stroke within 4.5 hours of the onset of stroke. Recent studies have looked at the benefits of administration of intra-arterial (IA) rt-PA within 8 hours onset of symptoms. Our objective was to assess the outcome of stroke after administration of IA rt-PA in patients with acute ischemic stroke. Methods: We recruited 10 consecutive acute ischemic stroke patients with onset of stroke from 4.5 hours to 6.5 hours. The present study was conducted at Yashoda Hospital, Hyderabad, India, between January 2008 and December 2013. All patients underwent stroke subtyping and were administered rt-PA. We measured the thrombolysis in cerebral infarction (TICI) score after thrombolysis and functional outcomes at time of admission, after 24 hours, 30, 60, and 90 days. A good outcome was defined as modified Rankin Scale (mRS) ≤ 2 after 90 days. Results: Out of 10 patients 9 were men, mean age 56.3 ± 1.8 years and age range from 35-68 years. On stroke subtyping, 6 (60%) patients had large artery atherosclerosis, 3 (30%) had a stroke of indeterminate etiology and 1 (10%) had a stroke of other etiologies. Mean time of recanalization was 6.2 ± 0.5 hours, 7 (70%) patients showed major neurological improvement with a mRS score of ≤ 2 at 90 days and one patient was lost to follow-up. Conclusion: Our study established good outcome at 90 days after administration of IA thrombolysis rt-PA in acute ischemic stroke.

Association of plasma brain natriuretic peptide levels in acute ischemic stroke subtypes and outcome.

BACKGROUND: Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascular diseases, including atrial fibrillation (AF). Recent studies have incriminated BNP as a marker of cardioembolic stroke. We aimed at investigating association of plasma BNP levels in acute ischemic stroke subtypes and their outcome in Indian patients. METHODS: We recruited 270 acute ischemic stroke patients within 48 hours of symptom onset and compared with 110 age- and sex-matched control subjects. This study was carried out at Yashoda Hospital, Hyderabad, India between April 2011 and March 2013. Serum BNP levels were estimated in stroke patients and control subjects. Good functional outcome at 3 months was defined as modified Rankin score (mRS) 2 or less. RESULTS: Elevated BNP levels was significantly more in patients with acute ischemic stroke patients 119 (44%) compared with controls 4 (3.6%; P < .0001). Among stroke subtypes, elevated BNP levels were observed in 75% of cardioembolic strokes, 45.8% of small artery disease, 43.1% of larger artery atherosclerosis, and 34.5% of stroke of undetermined etiology. On multiple logistic regression analysis, elevated BNP levels were significantly associated with acute ischemic stroke (odds ratio [OR], 13.0; 95% confidence interval [CI], 8.1-15.4). Among stroke subtypes, significant association was seen with cardioembolic stroke (OR, 3.5; 95% CI, 2.2-7.2). Elevated BNP levels were independently associated with poor outcome (OR, 3.4; 95% CI, 1.2-13.7; P < .0001) and higher mortality (OR, 3.4; 95% CI, 1.2-13.7; P < .0001). CONCLUSIONS: Elevated BNP level is an independent marker for cardioembolic stroke and poor outcome at 90 days follow-up. No significant association was seen with other stroke subtypes.

Mild cognitive impairment: clinical and imaging profile in a memory clinic setting in India.

BACKGROUND: Despite the increasing burden of dementia in developing countries, mild cognitive impairment (MCI) continues to be underexplored. MCI has conventionally been identified based on clinical profile, but recently, biomarkers suggestive of Alzheimer's disease pathology have been included in the revised National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria. In this study, we evaluated the profile of MCI in a memory clinic in India and explored the applicability of the revised NIA-AA criteria in a limited resource setting. METHODS: Consecutive subjects evaluated at the memory clinic for mild memory complaints were included and underwent clinical and neuropsychological examination as well as standard brain imaging. A subset of patients was subjected to imaging biomarker studies as a part of routine clinical practice. RESULTS: Among the 1,190 patients evaluated during the study period, 226 (19.0%) presented with mild memory complaints. Cerebrovascular disease was a common secondary cause. Nearly half of the patients (109 of 226) had MCI according to the modified Petersen criteria. All MCI subjects were educated and the majority were male. A total of 12% of the cohort was classified by imaging biomarkers as having MCI with intermediate likelihood of AD according to the NIA-AA criteria. CONCLUSION: In the setting of urban India, MCI is an emerging problem; therefore, it was feasible to operationalise the revised NIA-AA criteria in identifying subjects with MCI with intermediate likelihood of AD.

High sensitivity C-reactive protein levels in Acute Ischemic Stroke and subtypes: A study from a tertiary care center.

BACKGROUND: Stroke is a heterogeneous disease with several risk factors. High sensitivity C-reactive protein (hsCRP) is a marker for cardiovascular and cerebrovascular diseases. Recent studies have shown that high hsCRP level is a risk factor for ischemic stroke. The objective of our study was to investigate the association of high hsCRP (> 3 mg/L) levels with ischemic stroke and its subtypes in Indian patients. METHODS: We recruited 210 consecutive acute stroke patients and 150 age and sex matched controls. Stroke patients were admitted within 72 hours of onset, at Yashoda Hospital, Hyderabad, India. The study period was from January 2011 to December 2012. All patients underwent tests as per standard protocol for stroke workup. Serum hsCRP level was assessed in all stroke patients and controls on the day of admission. RESULTS: The mean hsCRP was significantly higher in stroke patients (3.8 ± 2.5) than controls (1.8 ± 1.5) (P < 0.001). High hsCRP had higher frequency in stroke patients 130 (61.9%) compared to controls 10 (6.6%), P < 0.001. High hsCRP level was more prevalent in the stroke subtypes of cardioembolic stroke (83.3%) and large artery atherosclerosis (72%). High hsCRP level was significantly associated with hypercholesterolemia (P = 0.001), age (P = 0.01), and mortality (0.04). After adjustment of regression analysis it was observed that high level hsCRP is independently associated with acute ischemic stroke (Odds 4.5; 95% CI: 2.5-12.2); especially the stroke subtypes of cardioembolic stroke, (odds ratio 3.4, 95% CI: 1.9-10.5) and large artery atherosclerosis (odds ratio 2.1, 95% CI: 1.5-3.8). CONCLUSION: High hsCRP level is strongly associated with and an independent predictor of acute ischemic stroke. The association was found in all ischemic stroke subtypes.