Does abnormal neuronal excitability exist in myotonic dystrophy)?�II. Effects of the antiarrhythmic drug hydroquinidine on apathy and hypersomnia

Abstract

An abnormal neuronal excitability in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine could ameliorate apathy and hypersomnia besides slow saccadic eye movements in these patients. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. Apathy was evaluated by means of the apathy evaluation scale (AES) and hypersomnia by a sleep diary. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. The drug significantly reduced AES scores and daily sleep time compared to placebo. Thus, hydroquinidine can ameliorate apathy and hypersomnia in MD. However, the possibility of proarrhythmia and the high frequency of cardiac disturbances in MD seriously limit the therapeutic perspective. The effects on eye movements are presented in a companion paper.

Prevalence and correlates of apathy in myotonic dystrophy type 1

“…Findings also confirm the absence of relationship between apathy and age, gender, disease duration, CTG repeats, functional impairment, and fatigue in DM1 patients [ 13 , 14 ]. The absence of a significant correlation between apathy and fatigue must be pointed out considering the conceptual proximity of lack of motivation and experienced fatigue [ 30 ].…”

“…In addition, they found that apathy did not vary with duration of illness, muscular weakness, depression, daytime sleepiness, and fatigue. The absence of relationship between apathy and depression was also noted in a subsequent smaller study ( n = 10 DM1 patients) looking at an anthiarrhytmic drug [ 14 ]. No study has though explored the relationship of apathy to cognitive abilities in DM1 patients.…”

Ocular motor function in relation to gross motor function in congenital and childhood myotonic dystrophy type 1

“…The global layer also includes myosine heavy chain isoforms of the same type as in the heart muscle (Alfa‐cardic myosi). Treatment for antiarrhythmia has shown to have an effect on slow saccades, and thus ocular motor analysis may be useful for follow up in patients with DM1 (Di Costanzo et al. 2000).…”

Report of the second Outcome Measures in Myotonic Dystrophy type 1 (OMMYD-2) international workshop San Sebastian, Spain, October 16, 2013

“…Caughey and Myrianthopoulos noted that affected individuals, even when mildly incapacitated physically, are often content to sit or lie idle for hours [55]. The prevalence of apathy in DM1 varies across studies (40-90%) [56][57][58].…”