Kelly L. Sullivan

Evidence-based guideline: Treatment of tardive syndromes Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? Methods: PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966–2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Results and recommendations: Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).

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.

Essential tremor. Epidemiology, diagnosis, and treatment.

Background:Essential tremor (ET) is the most common adult tremor disorder and is characterized by postural and kinetic tremor. Symptoms are typically progressive and potentially disabling, often forcing patients to change jobs or seek early retirement. Proper treatment is contingent on a correct diagnosis, and other possible causes of tremor must be excluded. Review Summary:Although primidone and propranolol have been regarded as the mainstays of pharmacologic therapy for ET, additional agents may be useful in reducing tremor. Surgical procedures are available that effectively ameliorate tremor that is refractory to medical management. This article reviews the epidemiology, pathophysiology, and treatment options for ET. Conclusions:Despite a range of treatment options currently available, further research is necessary to manage this syndrome most effectively. Double-blind, controlled trials are needed to determine whether primidone, propranolol, or a combination of these medications is superior in the initial management of ET. Other pharmacologic agents have shown potential to reduce tremor and should be investigated further. Additional studies are also needed to determine the best treatment of head and voice tremor with pharmacologic and surgical interventions. With proper treatment, tremor is sufficiently reduced in the majority of patients.

Social Security Disability Insurance (SSDI) in Parkinson's disease

Objective. Parkinsons disease (PD) causes significant economic burden for patients and caregivers. Social Security Disability Insurance (SSDI) provides insurance to workers in the United States who have been gainfully employed, but who are no longer able to work due to a medical condition. We performed a descriptive pilot study that examined PD patients experience with SSDI. Methods. PD patients who were diagnosed with PD prior to age 60 and were followed at an academic movement disorders center were consecutively invited to participate in a survey concerning their employment history and experience with SSDI. Results. All 68 invited patients participated in the study (mean age 58 years, mean disease duration 9.5 years). Eighty-two percent of patients felt that they were too disabled to work full time at a mean of 3.4 years after PD diagnosis. Patients applied for SSDI at a mean of 5 years after diagnosis, and two-thirds of PD patients who applied for SSDI obtained it on their first attempt. The primary debilitating symptom that subjectively contributed to work disability was fatigue (49% of patients). Patients who successfully acquired SSDI had extensive documentation of physician visits, and the aid of a disability lawyer. Conclusions. Patients felt they were too disabled to work full time at a mean of 3.4 years after diagnosis. Those who applied for SSDI did so at a mean of 5 years after diagnosis. Patients who obtained SSDI awards had extensive documentation of medical records or the help of a disability lawyer.

The controversy concerning plasma homocysteine in Parkinson disease patients treated with levodopa alone or with entacapone: effects of vitamin status.

Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). Although inhibition of COMT should theoretically prevent or reduce levodopa-induced HHcy, results from several prospective studies are conflicting. Our review of these studies suggests that the ability of COMT inhibition to reduce or prevent levodopa-induced HHcy in Parkinson disease patients may be attributed to differences in the vitamin status of the study participants. In patients with low or low-normal folate levels, levodopa administration is associated with a greater increase in homocysteine and concomitant entacapone administration is associated with a greater reduction in homocysteine.

Treatment of ataxia and imbalance with varenicline (chantix): report of 2 patients with spinocerebellar ataxia (types 3 and 14).

Two patients with spinocerebellar ataxia (types 3 and 14) experienced marked improvement in their cerebellar symptoms shortly after taking varenicline (Chantix).

Subjective improvement in proprioception in 2 patients with atypical Friedreich ataxia treated with varenicline (Chantix).

Two patients with atypical Friedreich ataxia (heterozygotes for a GAA expansion and a G130V point mutation) experienced modest proprioceptive improvements in their extremities within a month of taking varenicline (Chantix), a drug approved for smoking cessation.

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

OBJECTIVEnTo evaluate the efficacy of solifenacin succinate in Parkinsons disease (PD) patients suffering from overactive bladder (OAB).nnnBACKGROUNDnUrinary dysfunction is a commonly encountered non-motor feature in PD that significantly impacts patient quality of life.nnnDESIGN/METHODSnThis 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 5-10xa0mg 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 24xa0h period. Secondary outcome measures included the change in the mean number of urinary incontinence episodes and the mean number of nocturia episodes.nnnRESULTSnTwenty-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 24xa0h period in the solifenacin succinate group compared to placebo at a mean dose of 6xa0mg/day (pxa0=xa00.01). In the open label phase, the mean number of urinary incontinence episodes per 24xa0h period decreased (pxa0=xa00.03), as did the number of nocturia episodes per 24xa0h period (pxa0=xa00.01). Adverse events included constipation and xerostomia, which resolved after treatment was discontinued.nnnCONCLUSIONSnIn this pilot trial, solifenacin succinate treatment led to an improvement in urinary incontinence, despite persistence in other OAB symptoms.

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.