Negative Myoclonic Status Due to Antiepileptic Drug Tapering: Report of Three Cases

Abstract

Summary: Purpose: Epileptic negative myoclonus (ENM) has been increasingly recognized in different epilepsies, but the reasons for its appearance and prognosis remain uncertain. We report 3 patients who developed de novo, almost continuous ENM, triggered by antiepileptic drug (AED) tapering, that resolved with treatment.Methods: Three patients aged 16, 19, and 65 years with a 13-to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA). None had previously had ENM. Forty-eight to 72 h after CLB or VPA withdrawal, the habitual seizures recurred. The patient also began to report repetitive postural lapses of one or more limbs that interfered with eating or writing. At this time, each patient underwent polygraphy with simultaneous surface electromyography (EMG) of deltoid, biceps, and triceps muscles and of the wrist extensor and flexor bilaterally.Results: In all patients, EEGs demonstrated almost continuous epileptiform discharges whose spatial distribution was similar to that observed before ENM appearance. Polygraphic recordings showed repetitive loss of postural EMG activity in one or more limbs, 100400 ms in duration, which occurred in conjunction with the spike-waves. One milligram of clonazepam intravenously always terminated ENM status, which has not recurred in the ensuing 9-36 months.Conclusions: ENM may emerge as a new type of seizure due to tapering of AED therapy. This effect is possibly related to the great activation of epileptiform activity with consequent interference with cortical activity.

Epileptic negative myoclonus in a case of atypical benign partial epilepsy of childhood: a detailed video-polygraphic study

“…In respect of the clinical evaluation, although the antiepileptic medication reduced the number of the seizures and decreased the epileptiform activity on the EEG, these effects were transitory, fluctuating and unpredictable. Our observation is in keeping with the proposal that the treatment response remains uncertain when ictal epileptiform discharges form part of the natural history of the underlying condition as in the case of ABPE 6 .…”

“…Similarly Oguni et al 11 reported, in a patient with ENM associated with contralateral rolandic spikes, a rough coincidence between the interruption of the EMG activity and the slow component of the spike-and-wave discharges. Other authors have reported similar findings 6,[11][12][13][14] .…”

“…In these cases and in our observation, ENM may be more likely due to a transient inhibition of cortical motor function 6,13 . However, not all studies have obtained these results, and some investigations have pointed out a significant association between the contralateral centroparietal spike component and ENM 4,13,[15][16][17][18] suggesting a cortical excitatory mechanism.…”

“…ENM is a rare epileptic condition whose exact physiopathology remains unresolved. It has been associated with very diverse clinical situations, such as ABPE, cortical malformations, antiepileptic drug tapering, or more recently hemimegalencephaly 2,3,[5][6][7] . The intensity of the clinical manifestations may be markedly variable, and it may oscillate from slight focal atonia to severe gait disturbances originating pseudoataxia 8 .…”

Epileptic negative myoclonus and brief asymmetric tonic seizures. A supplementary sensorimotor area involvement for both negative and positive motor phenomena

“…According to previous interpretations of ENM as the result of an elective disruption of motor cortex output [5,6,10,13), we suggest that such disruption could be caused not only by discharges originating in the sensory parietal areas, but also from premotor areas such as the SMA [8][9][10]. In our patient, we can hypothesise that during the "interictal" period, a frontomesial epileptic focus could produce a paroxysmal negative motor phenomena through selective interference with the left arm motor output.…”