Abnormalities of the balance between inhibition and excitation in the motor cortex of patients with cortical myoclonus

Abstract

Patients with cortical myoclonus may have purely focal or multifocal jerks, or they may have additional bilateral or generalized jerks, suggesting the spread of excitatory myoclonic activity between the cerebral hemispheres and across the sensorimotor cortex. The factors contributing to this spread of activity were investigated in 10 patients with multifocal cortical myoclonus and eight patients with multifocal and bilateral or generalized cortical myoclonus. The two groups were termed 'non- spreaders' and 'spreaders' respectively. Eight of the patients were also epileptic. Motor thresholds to single transcranial magnetic shocks at rest were higher in 'non- spreaders' (median 88%, range 45-100% of stimulator output) than either 'spreaders' (50%, range 26-90%, P=0.023) or health controls (38%, range 28-53%, P<0.001). This pathological elevation in motor threshold was not simply an effect of treatment with antiepileptic drugs. Paired transcranial magnetic stimuli were used to investigate ipsilateral cortico-cortical and transcallosal inhibition, There was less (MANOVA, P<0.05) ipsilateral inhibition at interstimulus intervals (ISIs) of 1-6 ms in 'spreaders' (mean 107+/-SEM 23% of control) compared with 'non- spreaders' (75+/-15%) or healthy subjects (59+/-10%). There was also less (P<0.05) transcallosal inhibition across inhibitory timings (10, 12 and 14 ms) in the 'spreaders' (98+/-6% of control) compared with the 'non-spreaders' (64+/-8%) or healthy subjects (59+/-6%). There was no relationship between ipsilateral cortico-cortical and transcallosal inhibition and the presence or absence of epilepsy, although non-epileptic patients did have higher motor thresholds (median 85%, range 32-100% of stimulator output) than either epileptic patients (50%, range 26-90%, P<0.001) or healthy controls (38%, range 28-53%, P=0.002). Abnormalities in ipsilateral and transcallosal inhibition appear to facilitate the spread of the cortical myoclonic activity responsible for bilateral and generalized jerks. However, these abnormalities in inhibition do not play a major role in the development of generalized seizures in patients with cortical myoclonus.

Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy

“…The reduction in early ICI without changes in ICF in our JME patients provides further evidence to support the hypothesis that inhibitory mechanisms may be altered in JME (19)(20)(21). This finding is in agreement with previous paired TMS investigations on the excitability of motor areas in epilepsy (15)(16)(17). However, in those studies, paired TMS was performed in progressive, severe myoclonic epilepsy (16,17), whereas paired TMS using short ISIs has been investigated only unilaterally in a small number of JME patients (1 5).…”

“…Intraoperative monitoring has shown that the MEP amplitude at long ISIs (100 to 150 milli-seconds) occurs at the cortical level (13). Paired TMS has been used as a research tool to investigate motor cortex excitability in different forms of epilepsy (14)(15)(16)(17) and in several neurological diseases (1 6,lS). Reduced cortical inhibition was observed in progressive myoclonic epilepsy (15,16) and in partial epilepsy (14).…”

Effects of antiepileptic drugs on motor cortex excitability in humans: A transcranial magnetic stimulation study

“…Patients with cortical myoclonus [42] of the human motor cortex in epilepsy indicate that it may be possible to characterize the disordered cortex excitability in a given patient on the basis of altered threshold or intracortical excitability. In the future, the technique of noninvasive TMS may facilitate the prediction of optimal AED treatment (ion channel blockers versus neurotransmitter modulators) for a given patient.…”

Epilepsia partialis continua (Koshevnikov): a preliminary case report

“…In our case, both waking and sleep EEGs were normal. However, SSEP were abnormal and consistent, with a decrease in local cortico-cortical inhibition and expression of hyperexcitability of motor cortex 22 . Moreover, the remission of myoclonies in a few months gives additional support to the hypothesis of an idiopathic form.…”