Amber M. Miller

A randomized trial of varenicline (chantix) for the treatment of spinocerebellar ataxia type 3.

Objective: The objective of this double-blind, placebo-controlled, randomized study was to evaluate the efficacy of varenicline (Chantix), a partial agonist at α4β2 neuronal nicotinic acetylcholine receptors used for smoking cessation, in patients with spinocerebellar ataxia (SCA) 3. Methods: Patients with genetically confirmed SCA3 were randomly assigned to receive either varenicline (4 weeks for titration and 4 weeks at a dose of 1 mg twice daily) or placebo. Outcome measures included changes in the Scale for the Rating and Assessment of Ataxia (SARA) scores at endpoint (8 weeks) compared with baseline, a timed 25-foot walk and 9-hole peg test, measurements of mood and anxiety, and adverse events. Results: Twenty patients with SCA3 (mean age = 51 ± 10.98 years; mean disease duration = 14 ± 9.82 years; mean SARA score = 16.13 ± 4.67) were enrolled in the study, and data on 18 patients were analyzed in period I. The most common side effect associated with varenicline was nausea. Improvements were noted in the SARA subsections for gait (p = 0.04), stance (p = 0.03), rapid alternating movements (p = 0.003), and timed 25-foot walk (p = 0.05) and Beck Depression Inventory scores (p = 0.03) in patients taking varenicline compared with those taking placebo at endpoint, with a trend toward improvement in the SARA total score (p = 0.06) in the varenicline group. Conclusions: In this controlled study, varenicline significantly improved axial symptoms and rapid alternating movements in patients with SCA3 as measured by SARA subscores and was fairly well tolerated. Classification of evidence: This study provides Class II evidence that varenicline improved the axial functions of gait, stance, and timed 25-foot walk but did not improve appendicular function, except for rapid alternating movements, in adult patients with genetically confirmed SCA3.

Overview of essential tremor

Essential tremor (ET) is one of the most common movement disorders in the world. Despite this, only one medication (propranolol) is approved by the Food and Drug Administration (FDA) to treat it. Fortunately, recent studies have identified some additional medications as treatment of ET. Surgical procedures, such as deep brain stimulation of the ventral intermediate nucleus of the thalamus, offer treatment for refractory tremor. The epidemiology, pathogenesis, and medical and surgical treatment of ET will be discussed in this paper.

Evaluation of humoral immune response in adaptive immunity in ALS patients during disease progression.

In ALS, evidence suggests immune reactions in disease pathogenesis. Although immunological changes point to adaptive immune response, whether humoral or cellular response dominates during disease course is unknown. The study aim was to evaluate humoral immune response in ALS patients during disease progression. Circulating immune complexes (CICs), IgG, and IgM in sera of ALS patients and matching controls were evaluated after each of two visits. Results showed significantly elevated CICs and IgG in ALS patient sera. CICs decreased to control levels at the second visit, yet IgG remained higher than controls. Serum IgM was within normal range. Results suggest a humoral immune response initiating adaptive immunity in ALS, however, cellular immune response needs verification.

Reduction of Circulating Endothelial Cells in Peripheral Blood of ALS Patients

Background Amyotrophic Lateral Sclerosis (ALS) treatment is complicated by the various mechanisms underlying motor neuron degeneration. Recent studies showed that the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are compromised in an animal model of ALS due to endothelial cell degeneration. A later study demonstrated a loss of endothelium integrity in the spinal cords of ALS patients. Since circulating endothelial cells (CECs) in the peripheral blood are associated with endothelium damage, being detached dysfunctional endothelial cells, we hypothesized that CEC levels may reflect endothelium condition in ALS patients. Methodology/Principal Findings CEC levels were estimated in whole blood smears from ALS patients with moderate stage (MALS), severe stage (SALS), and healthy controls by CD146 expression using immunocytochemistry. A significant reduction of CECs was detected in MALS and SALS patients. Conclusions/Significance CECs did not predict endothelium state in ALS patients; however, endothelial damage and/or impaired endothelium repair may occur in ALS leading to BBB/BSCB dysfunction. Reduced CECs in peripheral blood of ALS patients may indicate different mechanisms of endothelial damage and repair, rather than only detachment of dysfunctional endothelial cells. Although a potential mechanism of CEC reduction is discussed, establishing a reliable indicator of endothelial dysfunction/damage is important for evaluation of BBB/BSCB status in ALS patients during disease progression.

Multisite, double‐blind, randomized, controlled study of pregabalin for essential tremor

This prospective, double-blind, randomized, placebo-controlled crossover trial was approved by institutional review boards at participating institutions. Adult ET patients with a Fahn-Tolosa-Marin (FTM) postural tremor score of at least 2 in the dominant upper limb were enrolled. Patients with DBS, clinically significant liver, kidney, or cardiac abnormalities, previous lack of response to propranolol and primidone, or current treatment with gabapentin were excluded. Concomitant antitremor medications at a stable dose were permitted. Patients were randomized to pregabalin or matching placebo according to a 1:1 schedule generated using SAS 9.2 software (SAS Institute Inc., Cary, NC). Investigators, raters, participants, and caregivers were blinded. Medication was initiated at a dose of 75 mg twice-daily (BID), titrated to a maximum daily dose of 225 mg BID, and maintained at maximum dose for 40 days (see Supporting Appendix 1). After a 3-week washout, participants crossed over to the alternative treatment. Participants were allowed to down-titrate by one level if adverse events (AEs) occurred; titration could be halted if tremor completely resolved or if side-effects prevented an increase. The primary outcome measure was the FTM total score. The two spirals and three lines of the FTM were drawn on an electronic digitizing table (Wacom Intuos 3; www.wacom.com) and rated with the FTM and quantified for tremor using spectral analysis. As a result of technical difficulties at one center, tablet data were obtained from 23 of the 29 participants. Baseline characteristics were compared using the Student’s t test and chi-square test; treatment effects were assessed using the GLM procedure in SAS to account for treatment order and the crossover design. The analysis used an intention-to-treat approach, and last observation carried forward if patients withdrew prematurely. The study was powered to detect a 30% change in the FTM total score (required n 1⁄4 7, assuming a 1⁄4 0.05 and power 1⁄4 0.9).

Sleep disorders in Parkinson’s disease

Sleep disorders occur commonly in Parkinson’s disease (PD), and reduce quality of life. Sleep-related problems in PD include insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, parasomnias, excessive daytime sleepiness, and sleep attacks. This article reviews sleep disorders and their treatment in PD.

Fentanyl-induced bradykinesia and rigidity after deep brain stimulation in a patient with Parkinson disease.

A 58-year-old man with advanced Parkinson disease underwent battery replacement for a deep brain stimulator and experienced severe bradykinesia and rigidity postoperatively for 36 hours. The patient was administered fentanyl as an anesthetic during the procedure and as an analgesic periodically during the day after surgery. The severe bradykinesia and rigidity persisted despite reactivation of the deep brain stimulator and immediate reinstitution of Parkinson disease medications, but resolved completely several hours after discontinuation of fentanyl.

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor

Background Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. Methods We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Results Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. Discussion The data from this study indicate that medication cessation is common following unilateral DBS for ET.