Double-blind, randomized and controlled trial of EPI-743 in Friedreich's ataxia.

AIM: To evaluate the safety and clinical effects of EPI-743 in Friedreich's ataxia patients. EPI-743 is a compound that targets oxidoreductase enzymes essential for redox control of metabolism. METHODS: We conducted a multicenter trial that evaluated EPI-743 during a 6-month placebo-controlled phase, followed by an 18-month open-label phase. End points included low-contrast visual acuity and the Friedreich's Ataxia Rating Scale. RESULTS/CONCLUSION: EPI-743 was demonstrated to be safe and well tolerated. There were no significant improvements in key end points during the placebo phase. However, at 24 months, EPI-743 treatment was associated with a statistically significant improvement in neurological function and disease progression relative to a natural history cohort (p < 0.001).

Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence regarding ataxia treatment. METHODS: A comprehensive systematic review was performed according to American Academy of Neurology methodology. CONCLUSIONS: For patients with episodic ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study). For patients with Friedreich ataxia or spinocerebellar ataxia (SCA), riluzole probably improves ataxia signs at 12 months (1 Class I study). For patients with SCA type 3, valproic acid 1,200 mg/d possibly improves ataxia at 12 weeks. For patients with spinocerebellar degeneration, thyrotropin-releasing hormone possibly improves some ataxia signs over 10 to 14 days (1 Class II study). For patients with SCA type 3 who are ambulatory, lithium probably does not improve signs of ataxia over 48 weeks (1 Class I study). For patients with Friedreich ataxia, deferiprone possibly worsens ataxia signs over 6 months (1 Class II study). Data are insufficient to support or refute the use of numerous agents. For nonpharmacologic options, in patients with degenerative ataxias, 4-week inpatient rehabilitation probably improves ataxia and function (1 Class I study); transcranial magnetic stimulation possibly improves cerebellar motor signs at 21 days (1 Class II study). For patients with multiple sclerosis-associated ataxia, the addition of pressure splints possibly has no additional benefit compared with neuromuscular rehabilitation alone (1 Class II study). Data are insufficient to support or refute use of stochastic whole-body vibration therapy (1 Class III study).

Longitudinal gait and balance decline in Friedreich's Ataxia: A pilot study.

INTRODUCTION: Friedreich's Ataxia (FA) is a devastating, progressive, neurodegenerative disease. Objective measures that detect changes in neurological function in FA patients are needed to facilitate therapeutic clinical trials. The purpose of this pilot study was to analyze longitudinal changes in gait and balance in subjects with FA using the GAITRite Walkway System® and Biodex Balance System™, respectively, and to test the ability of these measures to detect change over time compared to the Friedreich's Ataxia Rating Scale (FARS). METHODS: This was a 24-month longitudinal study comparing ambulatory FA subjects with age- and gender-matched, healthy controls. Eight FA subjects and 8 controls were tested at regular intervals using the GAITRite and Biodex Balance systems and the FARS. RESULTS: In the FA group, comfortable and fast gait velocity declined 8.0% and 13.9% after 12 months and 24.1% and 30.3% after 24 months, respectively. Postural stability indices increased in FA subjects an average of 41% from baseline to 24 months, representing a decline in balance. Subjects with FA also demonstrated a 17.7% increase in FARS neurological exam scores over 24 months. There were no changes in gait or balance variables in controls. In the FA group, multiple gait and balance measures correlated significantly with FARS neurological exam scores. CONCLUSIONS: The GAITRite and Biodex Balance systems provided objective and clinically relevant measures of functional decline in subjects with FA that correlated significantly with performance measures in the FARS. Gait velocity may be an important objective measure to identify disease progression in adults with FA.

Emerging therapies in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an inherited, progressive neurodegenerative disease that typically affects teenagers and young adults. Therapeutic strategies and disease insight have expanded rapidly over recent years, leading to hope for the FRDA population. There is currently no US FDA-approved treatment for FRDA, but advances in research of its pathogenesis have led to clinical trials of potential treatments. This article reviews emerging therapies and discusses future perspectives, including the need for more precise measures for detecting changes in neurologic symptoms as well as a disease-modifying agent.

Randomized, controlled pilot trial of solifenacin succinate for overactive bladder in Parkinson's disease.

OBJECTIVE: To evaluate the efficacy of solifenacin succinate in Parkinson's disease (PD) patients suffering from overactive bladder (OAB). BACKGROUND: Urinary dysfunction is a commonly encountered non-motor feature in PD that significantly impacts patient quality of life. DESIGN/METHODS: This was a double-blind, randomized, placebo-controlled, 3-site study with an open label extension phase to determine the efficacy of solifenacin succinate in idiopathic PD patients with OAB. Patients were randomized to receive solifenacin succinate 5-10 mg daily or placebo for 12 weeks followed by an 8-week open label extension. The primary outcome measure was the change in the mean number of micturitions per 24 h period. Secondary outcome measures included the change in the mean number of urinary incontinence episodes and the mean number of nocturia episodes. RESULTS: Twenty-three patients were randomized in the study. There was no significant improvement in the primary outcome measure in the double-blind phase, but there was an improvement in the number of micturitions per 24 h period in the solifenacin succinate group compared to placebo at a mean dose of 6 mg/day (p = 0.01). In the open label phase, the mean number of urinary incontinence episodes per 24 h period decreased (p = 0.03), as did the number of nocturia episodes per 24 h period (p = 0.01). Adverse events included constipation and xerostomia, which resolved after treatment was discontinued. CONCLUSIONS: In this pilot trial, solifenacin succinate treatment led to an improvement in urinary incontinence, despite persistence in other OAB symptoms.

Critical appraisal of rotigotine transdermal system in management of Parkinson's disease and restless legs syndrome - patient considerations.

Rotigotine (RTG) is a dopamine agonist that is used as mono and adjunct therapy to treat Parkinson's disease, and as therapy for moderate-to-severe restless legs syndrome. RTG is the only dopamine agonist currently available as a 24-hour/day transdermal system, providing once-a-day dosing. As a transdermal patch, RTG bypasses the gastrointestinal tract, making it a treatment option for patients with dysphagia. The use of RTG also avoids the need to schedule administration of medication around meals. This review provides a critical appraisal of RTG as treatment of Parkinson's disease and RLS.

Treatment of cerebellar ataxia.

Symptoms of cerebellar degeneration include ataxia or wide-based gait, visual and speech dysfunction, dysmetria, and dyscoordination. The etiology of cerebellar degeneration is vast and often complex, and requires neuroimaging, lab assessments, and a thorough family history to delineate its cause. There is currently no accepted treatment of hereditary cerebellar degeneration, although several pharmaceutical agents have shown potential promise.

Pilot program to improve self-management of patients with heart failure by redesigning care coordination.

Objectives. We tested both an educational and a care coordination element of health care to examine if better disease-specific knowledge leads to successful self-management of heart failure (HF). Background. The high utilization of health care resources and poor patient outcomes associated with HF justify tests of change to improve self-management of HF. Methods. This prospective study tested two components of the Chronic Care Model (clinical information systems and self-management support) to improve outcomes in the self-management of HF among patients who received intensive education and care coordination during their acute care stay. A postdischarge follow-up phone call assessed their knowledge of HF self-management compared to usual care patients. Results. There were 20 patients each in the intervention and usual care groups. Intervention patients were more likely to have a scale at home, write down their weight, and practice new or different health behaviors. Conclusion. Patients receiving more intensive education knew more about their disease and were better able to self-manage their weight compared to patients receiving standard care.

Update on treatment of essential tremor.

OPINION STATEMENT: Essential tremor is one of the most common movement disorders in the world. Although millions of people worldwide are affected by ET, only one medication, propranolol, is approved by the United States Food and Drug Administration to treat it. None of the medications currently used as ET therapy were developed specifically for this purpose, and select antihypertensive and antiepileptic medications remain at the forefront of ET therapy. Propranolol and primidone are considered "effective" agents that treat ET; topiramate, atenolol, and alprazolam are "probably effective", and nimodipine, nadolol, and clonazepam are "possibly effective". Medications that probably do not adequately treat ET include levetiracetam and pregabalin. Gabapentin appears to improve ET when used as monotherapy, but not when used as adjunct therapy. Sotalol has been found to be "probably effective" in treating ET in previous reviews, but it may be associated with arrhythmias and should not be routinely recommended. Botulinum toxin A may reduce limb tremor, but may cause dose dependent weakness. Deep brain stimulation (DBS) of the VIM is used as an alternative to pharmacological therapy of ET in patients who fail to adequately respond to medical therapy. The magnitude of effect from DBS is greater than from medical management, but more severe side effects are possible with surgery. Future treatment options for ET will depend on valid animal models, and a better understanding of its pathophysiology.