Authors :
Presenting Author: Matthew Hoerth, MD – Mayo Clinic Arizona
Marcus Callister, MD – Mayo Clinic Arizona; John Caviness, MD – Mayo Clinic Arizona; Amir Mbonde, M.B., Ch.B. – Mayo Clinic Arizona; Shyamal Mehta, MD, PhD – Mayo Clinic Arizona; Jonathon Parker, MD. PhD – Mayo Clinic Arizona
Rationale:
Myoclonus in progressive myoclonic epilepsy (PME) can be disabling and refractory to medication management. Limited case series have reported myoclonus improvement with deep brain stimulation (DBS) of targets including the border of the subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) [1-2] and the SNr alone [3], however the neurophysiology has not yet been described.
Methods:
A 22-year-old female with Unverricht-Lundborg PME presented intractable myoclonus limiting walking and activities of daily living, despite treatment with valproate, perampanel, clonazepam, and levetiracetam. She had a movement neurophysiology study including EEG, surface EMG, and limb accelerometry, which showed frequent 25-30 msec EMG discharges correlating with high amplitude accelerometry deflection consistent with myoclonus. EEG-EMG back-averaging of 103 myoclonus EMG discharges confirmed cortical myoclonus with a clear focal contralateral EEG transient with positive-negative peak to peak amplitude of 11 uV, beginning 15 msec before the averaged myoclonus EMG discharge, consistent with cortical myoclonus. After multidisciplinary evaluation/discussion, DBS was implanted. Bilatareral directional stimulation DBS leads were implanted using a direct targeting approach, refined with asleep intoperative microelectrode recording. The distal electrode contact was placed immediately deep to the STN–SNr electrographic transition zone based on microelectrode recording (Figure 1). 2 weeks after DBS implantation, a repeat movement neurophysiology study was performed with DBS OFF and with DBS ON trialing several monopolar stimulation settings at each contact bilaterally: (1) 2.0 mA, 145 Hz, 60 uS pulse width, (2) 2.5 mA, 145 Hz, 60 uS, (3) 2.0 mA 130 Hz, 90 uS, (4) 2.5 mA, 130 Hz, 90 uS, (5) 2.7 mA, 130 Hz, 90 uS, and (6) 3.0 mA, 130 Hz, 90 uS.
Results:
During the movement neurophysiology study with DBS OFF, myoclonus duration and frequency were similar to the pre-DBS study. With DBS ON at settings (1) - (3) at the distal contacts, there was no change in myoclonus. With setting (4) in the distal contacts, there was broadening of the myoclonus EMG discharge duration and more fusion of EMG discharges. This was less apparent with setting (4) at the next most proximal contacts, and myoclonus returned to baseline with setting (4) in the next most proximal contacts. Settings (5) - (6) increasing the voltage at in the distal contacts showed longer duration phasic EMG discharges similar to setting (4), but resulted in paresthesias. The patient was left with DBS ON at setting (4) in the distal contacts. One month later, she reported improvement in myoclonus with decreased need for assistance with walking and request to increase stimulation parameters further.
Conclusions:
In this patient, initial results of electrophysiologic changes and clinical improvement are encouraging and consistent with previous reports of beneficial effects of SNr DBS on myoclonus in PME. To our knowledge, this is the first report of the electrophysiologic response of DBS. This concludes that movement neurophysiology studies may be useful in guiding DBS programming and evaluating response to treatment in epileptic myoclonus.
Funding: None