N.P.1 01 Muscle excitability abnormalities in Machado-Joseph disease: Preliminary report

Abstract

Machado-Joseph disease (MJD) is a common autosomal dominant cerebellar ataxia caused by an unstable CAG trinucleotide repeat expansion. Muscle cramps and fasciculations are frequent and sometimes disabling manifestations. However, their frequency and pathophysiological mechanisms remain largely unknown. To estimate the frequency and characterize muscle excitability abnormalities in a large cohort of MJD patients. Symptomatic MJD patients with molecular confirmation were assessed. A standard questionnaire addressing clinical features of both muscle cramps and fasciculations was employed. Cramps Disability Scale (CDS) was used to quantify cramps-related disability. Patients underwent neurophysiological exams with routine techniques. F-waves of the right median nerves were obtained and persistence indexes calculated. Four muscles (deltoid, first dorsal interosseus, tibialis anterior and vastus lateralis) were examined by needle EMG. A semi-quantitative scale (0-no activity to 4-continuous activity) was used to determine frequency of rest activity in each muscle. Groups were compared by Student’s t-test. Forty seven MJD patients (28 men and 19 women) were included: mean age at examination of 46 years, age on onset of 35 and duration of disease of 11 years; (CAG)n varied from 59 to 75 repeats. Thirty-eight patients presented muscle cramps and in 7 it was the first symptom. Frequency of cramps varied between one to 90 episodes a week. For 12 patients, cramps were a chief complaint frequently disturbing sleep or work (CDS scores 2 or 3). Lower limbs were affected in 21 individuals, but unusual regions such as face and abdominal muscles were reported. Although not a significant complaint for any patient, fasciculations were found in 25, including facial muscles in 5. Median F-wave persistence was not different between patients with and without cramps (53% vs 40%, p = 0.3). There was a significant difference in persistence indexes between MJD patients with (43%) and without (60%) fasciculations (p = 0.05). Muscle excitability abnormalities were found in 80% of MJD patients and the presenting complaint in 14.8%. Muscle cramps were both more common and disabling than fasciculations. As suggested by F-wave findings, motor neuron damage may probably account for fasciculations in MJD. Further research is needed to correlate F-wave characteristics and neuromuscular manifestations in MJD. Support: FAPESP.