Diagnosing multiple system atrophy with greater accuracy: Combined analysis of the clonidine-growth hormone test and external anal sphincter electromyography

The clonidine-growth hormone test (CGHT) has been proposed as a means of differentiating multiple system atrophy (MSA) from idiopathic Parkinson's disease (PD). However, it is controversial whether the CGHT is valid. We sought to confirm the validity of the CGHT and to compare the diagnostic accuracy of the CGHT with that of external anal sphincter electromyelography (Sph-EMG) for MSA. We performed the CGHT and the Sph-EMG on 21 PD patients, 23 patients with probable MSA of parkinsonian type (MSA-p), and 22 patients with probable MSA of cerebellar type (MSA-c). We compared the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of CGHT, Sph-EMG, and a combination of the two tests. We also evaluated the correlations of Unified Parkinson's Disease Rating Scale (UPDRS) scores with the results of the two tests. There was no significant difference between the UPDRS scores for the PD and MSA-p groups. Serum growth hormone concentrations after clonidine significantly increased in PD (mean increase ± SEM, 4.19 ± 0.92 ng/ml; P < 0.0001), but remained unchanged in both MSA-p (0.83 ± 0.61 ng/ml) and MSA-c (1.45 ± 0.58 ng/ml). The growth hormone responses to clonidine in MSA-p were significantly different from those in PD (P < 0.05). Abnormal, denervated Sph-EMG was observed in 95.7% of MSA-p, 86.4% of MSA-c, and 33.3% of PD patients. Compared to Sph-EMG, the CGHT was less sensitive but more specific in both MSA-p and MSA-c. The result of neither test correlated with the severity of parkinsonism. Interestingly, combining the results of the CGHT and Sph-EMG markedly increased the specificity (85.7% in the CGHT and 66.7% in Sph-EMG vs. 95.2% in the combination study) and the PPV in both MSA-p (85.7% and 75.9% vs. 94.4%) and MSA-c (82.4% and 73.1% vs. 91.7%). We confirm that the CGHT can distinguish MSA-p from PD. Its sensitivity is lower and its specificity higher than Sph-EMG. Compared to either test alone, combined testing with the CGHT and Sph-EMG increased specificity and PPV, thereby enhancing accuracy the diagnosis of MSA.