Mohit Bhatt

Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson's disease

Subthalamic nucleus stimulation is emerging as an effective surgical therapy for Parkinsons disease. It is considered to be a safe procedure with little morbidity, the most common complications being intracranial haemorrhage and hardware failure. We report on three cases of depression, one of whom attempted suicide after bilateral subthalamic nucleus stimulation.

Botulinum toxin in the treatment of writer's cramp A double‐blind study

We treated 20 patients with writers cramp in a double-blind, placebo-controlled study. Each patient received two treatments in tandem, one with botulinum-A toxin (BTX-A) injections and another with normal saline, separated by 3 months. Treatment order was randomized and unknown to the patient and physician. Patients were assessed before each treatment and 2 and 6 weeks after each treatment by objective measurements of pen control. Twelve patients had improvement in pen control after treatment with BTX-A, but only four had significant improvement in writing. BTX-A injections are effective in relieving symptoms in selected cases of writers cramp, particularly in those with significant wrist-joint deviation.

Acute and reversible parkinsonism due to organophosphate pesticide intoxication Five cases

Objective: To describe five patients who developed acute and reversible parkinsonism following organophosphate (OP) pesticide exposure, and to consider whether this syndrome represents a rare sequela of such exposure in genetically susceptible individuals. Background: Several toxins are known to produce parkinsonism following acute exposure. Although case–control studies have implicated OP pesticides in the etiology of PD, acute parkinsonism following brief pesticide exposure has never been reported. Methods: The authors describe the clinical syndrome affecting five patients who presented with recent OP exposure and symptoms of an acute akinetic–rigid syndrome. Results: All patients developed parkinsonism that resembled PD clinically except for poor response to levodopa. Three genetically related patients were exposed to pesticides in a common environment before onset of parkinsonism; other family members remained unaffected. Other secondary causes of parkinsonism were excluded. Four patients recovered completely without treatment, and one patient was lost to follow-up. One patient experienced repeated episodes of parkinsonism with inadvertent reexposure to a pesticide-contaminated environment. Conclusion: The clinical course of these five patients suggests their syndrome represents a heretofore undescribed toxic effect of OP pesticides. Our observations strengthen epidemiologic studies implicating OP pesticides in the etiology of PD. A genetic susceptibility to OP pesticide-induced parkinsonism may account for three family members developing this syndrome.

Severe tongue protrusion dystonia Clinical syndromes and possible treatment

We describe intermittent or sustained severe involuntary tongue protrusion in patients with a dystonic syndrome. Speech, swallowing, and breathing difficulties can be severe enough to be life threatening. Causes include neuroacanthocytosis, pantothenate kinase–associated neurodegeneration, Lesch–Nyhan syndrome, and postanoxic and tardive dystonia. The pathophysiology of intermittent severe tongue protrusion remains unknown. Tongue protrusion dystonia is often unresponsive to oral drugs but may benefit from botulinum toxin injections into the genioglossus muscle. Bilateral deep brain pallidal stimulation was beneficial in two cases.

Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations.

Levodopa is effective for the motor symptoms of Parkinsons disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add‐on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double‐blind, placebo‐controlled, parallel‐group study was to evaluate the efficacy and safety of safinamide, an α‐aminoamide with dopaminergic and nondopaminergic mechanisms, as add‐on to l‐dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinsons Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression‐Change (CGI‐C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI‐C were significantly greater in both safinamide groups versus placebo. There were no significant between‐group differences for incidences of treatment‐emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l‐dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease

In a 6‐month double‐blind, placebo‐controlled study of Parkinsons disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON‐time without increasing dyskinesia. Further long‐term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON‐time over 24 months. Other efficacy endpoints included change in ON‐time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P = 0.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2‐year, controlled study of add‐on safinamide in mid‐to‐late Parkinsons disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON‐time (without troublesome dyskinesia), OFF‐time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.

A Randomized, Double-Blind, Placebo-Controlled Trial of Safinamide as Add-on Therapy in Early Parkinson's Disease Patients

Safinamide is an α‐aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add‐on to dopamine agonist (DA) therapy in early‐stage PD. In this 24‐week, double‐blind study, patients with early PD receiving a stable dose of a single DA were randomized to once‐daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty‐nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were −3.90 for safinamide 200 mg, −6.0 for safinamide 100 mg and −3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: −0.4; 95% confidence interval (CI): −2.3–1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: −1.9; 95% CI: −3.7 to −0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation.

Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine.

To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.

A novel Global Assessment Scale for Wilson's Disease (GAS for WD)

Wilsons disease (WD) is an inherited disorder of copper metabolism. Despite being treatable, patients with WD suffer severe disabilities due to delay in initiation and difficulty in monitoring treatment. We propose a two tier, Global Assessment Scale for Wilsons Disease (GAS for WD) that grades the multisystemic manifestations of the disease. Tier 1 scores the global disability in four domains: Liver, Cognition and behavior, Motor, and Osseomuscular. Tier 2 is multidimensional scale for a fine grained evaluation of the neurological dysfunction. We prospectively validated this scale in 30 patients with WD. Both tiers had a high inter‐rater reliability (Intraclass correlation coefficient ICC (A, 2) = 0.96–1.0). Tier 2 items were internally consistent (Cronbachs α = 0.89) and factorial analysis showed that 90.3% of the Tier 2 total score variance was determined by seven factors. Scores of both tiers were commensurate with the disease burden as assessed by standard disability scales (Child Pugh, UPDRS, SS3, and CGI) and satisfied criteria for validity. Longitudinal follow‐up over 1.5 years showed that the scale was sensitive to clinical change. This suggests that GAS for WD is a practical tool with potential applications in management of patients, and in testing and comparison of treatment regimens.

Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: A report on three patients

We describe three patients who developed a rapidly evolving posttraumatic akinetic‐rigid syndrome (ARS), the clinical manifestations of which were similar to Parkinsons disease, including response to levodopa. Despite initial imaging studies showing traumatic damage to the substantia nigra, the ARS appeared after a delay of 1–5 months after the injury. We stress the importance of magnetic resonance imaging to illustrate nigral damage in all patients in whom head trauma precedes an ARS.