Epileptic Negative Myoclonus with Lateralized Periodic Discharges: Insights into Pathophysiology

Introduction: Negative myoclonus is a jerky movement characterized by a sudden, brief, and involuntary interruption of sustained muscle activity known as a silent period (SP). ENM is defined by the SP being time-locked to an epileptiform discharge, e.g. a spike. ENM has been described in chronic epilepsy syndromes but not in acutely epileptogenic neurological conditions with LPDs.

Objective: To report two cases of epileptic negative myoclonus (ENM) associated with lateralized periodic discharges (LPDs).

Materal & Methods: We identified two patients admitted to the neurological ICU at University Hospitals Cleveland Medical Center with acute brain injuries (subdural hematoma and viral encephalitis). Both patients were noted to have negative myoclonus on bedside examination. Both patients were monitored with video-EEG. Surface-EMG (sEMG) electrodes were placed on the agonist and antagonistic muscle pairs of the arm affected by the negative myoclonus. EEG-SP latency was calculated using freely available software, BacAv.

Results: Both patients had contralateral facial clonic seizures on presentation. The facial clonic contractions were time-locked to LPDs with superimposed fast activity (LPD+F) at ≥2 Hz frequency. As the seizures subsided by day five-six, the LPDs became blunt with a reduced frequency of 0.5-1Hz. With sustained muscle contraction, brief type I SPs were noted on sEMG electrodes of the contralateral arm (Fig.1). These SPs were time-locked to the LPDs. The maximum initial negativity of the LPDs localized to the parieto-central region. The LPD-SP latency varied from 20-25 ms to 50-60 ms.

Conclusions: ENM can occur in acute epileptogenic neurological insults like subdural hematoma and encephalitis with the SPs being time-locked to LPDs. The most likely generator is post-central (S1) as indicated by the localization of the LPDs and SPs being type I only. ENM tends to develop late in the course as the LPDs become less frequent and the superimposed fast activity disappears ("improved epileptogenicity"). The appearance of ENM with improvement in LPDs is likely related to inhibition of deeper cortical layers, producing the SPs. Superimposed faster frequencies with LPDs can overcome this inhibition, thus producing a descending pyramidal tract volley (I-waves) causing a muscle twitch (Fig.2).

Figure legends

Fig.1 EEG with right parasagittal bipolar chain (top four channels) and surface EMG channels—flexor (blue) and extensor (red). EEG channels demonstrate LPDs with maximum negativity at C4 (double head arrow). The EMG channels demonstrate brief SPs, time-locked to the LPDs (black arrows).

Fig.2 Schematic showing pathophysiology of + myoclonus and – myoclonus. Left panel- LPDs with superimposed faster frequencies: Depolarization of superficial and deep cortical neurons leading to descending pyramidal I-waves, thus leading to a positive muscle twitch. Right panel- LPDs without superimposed faster frequencies: Depolarization of superficial neurons with hyperpolarization of deeper neurons, thus leading to inhibition of ongoing muscle activity.