External anal sphincter electromyographic patterns in multiple system atrophy: implications for diagnosis, clinical correlations, and novel insights into prognosis
Multiple system atrophy (MSA) is a sporadic, progressive, adult-onset, neurodegenerative disorder characterized by autonomic dysfunction symptoms, parkinsonian features and cerebellar signs in various combinations. An early MSA diagnosis is of the utmost importance for a proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients. The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging markers supporting MSA diagnosis. Nonetheless, especially in the early disease stage, it can be challenging to differentiate MSA from mimic disorders, in particular Parkinson’s disease (PD). Electromyography (EMG) of the external anal sphincter (EAS) represents a useful neurophysiological tool for the differential diagnosis, since it can provide indirect evidence of Onuf’s nucleus degeneration, which is a pathological hallmark of MSA. However, the diagnostic value of EAS EMG has been a matter of debate for three decades due to controversial reports in the literature. After a brief overview on the electrophysiological methodology, we critically analyzed the available knowledge on the diagnostic role of EAS EMG and discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at EAS EMG. This study aimed to explore the diagnostic and prognostic value of a novel classification of EAS EMG patterns, and their correlations with clinical features and cardiovascular autonomic function in MSA. We retrospectively collected clinical data and EAS EMG findings in 72 patients with MSA and 21 with PD. Sixty-one and 56 MSA patients also underwent cardiovascular reflex tests and 24-hour blood pressure monitoring, respectively. We ascertained the survival times of 49 MSA patients who died during follow-up. Through evaluation of spontaneous activity, motor unit action potential (MUAP) duration and recruitment, we identified four EAS EMG patterns: normal findings (pattern I); mild neurogenic damage (pattern II); moderate neurogenic damage (pattern III); severe neurogenic damage (pattern IV). Pattern I was frequently observed in PD patients, while it was associated with prolonged survival when identified in a few MSA patients. Conversely, patterns II, III and IV were predominant in MSA. Subjects with MSA and EAS EMG abnormalities often showed fecal incontinence and urogenital symptoms, which were frequently present at disease onset when MUAP recruitment was impaired. Abnormal EAS EMG patterns correlated with MSA diagnosis (p < 0.001), with a sensitivity of 88.9%, specificity of 85.7%, and odds ratio of 48.0 (95% confidence interval: 11.5–199.8). Pattern IV was associated with the highest likelihood of MSA diagnosis (p < 0.001), and with the worst prognosis in the MSA cohort (vs. pattern I, p < 0.001; vs. pattern II, p = 0.001; vs. pattern III, p = 0.007). EAS EMG patterns were not related to motor impairment or cardiovascular autonomic function in MSA. In conclusion, the increasing severity of EAS EMG patterns paralleled diagnostic accuracy and survival in MSA. EAS EMG patterns correlated with symptom type at disease onset and with prevalence of urogenital symptoms and fecal incontinence. Prognostic findings of our novel classification of EAS EMG patterns could pave the way towards the implementation of this neurophysiological technique for survival prediction in MSA patients
