Differences in Evoked Potential Findings between DRPLA Patients and Patients with Cortical Reflex Myoclonus

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Purpose: Although very rare, DRPLA is an important differential diagnosis in patients with progressive myoclonic epilepsy (PME). Recently, the diagnosis of DRPLA has become easier because of the widespread availability of DNA analysis. However, it is still important to develop tools for clinical diagnosis and to uncover the pathophysiology of DRPLA. The purpose of the present study was to investigate the usefulness of evoked potential recording for the clinical diagnosis of DRPLA and elucidation of its pathophysiology. Methods: Ten patients (9 pedigrees) with DRPLA (mean age = 29.9 ISD = 7.61) and 3 patients with Unverricht‐Lundborg disease (UL) (mean age = 35.3 [range: 16–55]) participated in the study. In 9 of the I0 patients, the diagnosis of DRPLA was genetically confirmed, based on a 62–75 CAG triplet repeat expansion on chromosome 12p; in the remaining case, the diagnosis was not genetically confirmed but the patient was clinically diagnosed as having DRPLA and was within the same pedigree as one of the 9 genetically confirmed patients. Two out of the 3 patients with UL who had been tested for dodecainer repeatexpansion in the cystatin B gene were genetically confirmed as having UL; the remaining case was also clinically diagnosed as having UL, but the patient did not have the aforementioned genetic abnormality. The subjects were receiving antiepileptic drugs, mainly sodium valproate, and all gave informed consent before participation in the study. Cortical somatosensory evoked potentials (SEPs) to median nerve stimulation and auditory brainstem responses (ABRs) were rccorded. Thc amplitudes of the SEPs were determined as the peak‐to‐peak amplitudes between P2 and N2 deflections, SEPs with amplitudes of over 10 pV were regarded as high‐amplitude SEPs. ABR was classified by simply as ABR‐positive (ABR+) or ABR‐negative (ABR‐). ABR (+) corresponded to ABRs containing all the peaks (I‐V) in response to both left and right ear stimulations; on the other hand, ABR (‐) corresponded to ABRs lacking peaks 111‐V in response to either left or right ear stimulation.Resu1ts: All of the DRPLA patients showed SEPs with amplitudes below 10 pV (mean: 3.6 c 2.2). Conversely, all of the UL patients showed high‐amplitude SEPs (10.9–28.4 pV; mean: 17.5 pV). The amplitudes in DRPLA patients were significantly lower than that in UL patients. The number of CAG repeats was significantly correlated with SEP amplitudes within the DRPLA patients. Five out of the 8 DRPLA patients showed ABRs lacking peaks Ill‐V in response to either left or right ear stimulation. Conversely, all of the 2 UL patients showed ABRs in which all peaks, from I‐V, were distinguishable. Patients in the ABR (‐) group had a tendency toward more expanded CAG repeats and lower SEP amplitudes than those in the ABR (+) patient group. Furthermore, the DRPLA patients were classified into 2 subgroups according to their severity of symptoms estimated simply based on their ability to walk. The differences in age at onset between the groups reached statistical significance, and duration of illness and the number of CAG repeats had a tendency toward significant difference. Conclusions: In the present study, DRPLA and UL were clearly differentiated by the SEP and the ABR, suggesting differences in pathophysiology between DRPLA, which predominantly affects the brainstem and subcortical regions, and PME, characterized by cortical hyperexcitability. Thus, evoked potential measurements may be a useful adjunst for differentiating DRPLA patients from those with cortical reflex myoclonus.