G. Zanette

Hyperexcitable cortical responses in progressive myoclonic epilepsy A TMS study

Objective: Transcranial magnetic stimulation (TMS) has allowed investigators to study intracortical inhibition and facilitation and sensorimotor integration in motor disorders and epilepsy. The authors used TMS to elucidate the pathophysiology of reflex myoclonus with giant somatosensory evoked potentials (SEP). Methods: The authors studied four patients with progressive myoclonic epilepsy. All patients had giant SEP elicited by mixed and digital nerve stimulation. They studied the response to paired-pulse TMS at interstimulus intervals (ISI) ranging from 1 to 15 ms and the conditioning effect of digital electrical stimulation at ISI ranging from 10 to 100 ms on the motor evoked potential amplitude to TMS. Results: Digital stimulation markedly facilitated conditioned motor evoked potentials at ISI ranging from 25 to 40 ms in all patients. This pattern was significantly different from the inhibition observed in controls (n = 12) at the same ISI. In the patients, paired-pulse TMS showed a decrease in intracortical inhibition in the motor cortex in comparison with controls. Conclusions: These findings suggest cortical and subcortical components of abnormal sensorimotor integration in addition to hyperexcitability of the sensory and motor cortex in our myoclonic patients.

Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy

Summary: Purpose: We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy.

Effects of sleep deprivation on cortical excitability in patients affected by juvenile myoclonic epilepsy : a combined transcranial magnetic stimulation and EEG study

Objective: To investigate the effect of sleep deprivation on corticospinal excitability in patients affected by juvenile myoclonic epilepsy (JME) using different transcranial magnetic stimulation (TMS) parameters. Methods: Ten patients with JME and 10 normal subjects underwent partial sleep deprivation. Motor threshold (MT), motor evoked potential amplitude (MEP), and silent period (SP) were recorded from the thenar eminence (TE) muscles. Short latency intracortical inhibition (SICI) and short latency intracortical facilitation (SICF) were studied using paired magnetic stimulation. TMS was performed before and after sleep deprivation; EEG and TMS were performed simultaneously. Results: In patients with JME, sleep deprivation induced a significant decrease in SICI and an increase in SICF, which was associated with increased paroxysmal activity. A significant decrease in the MT was observed. No significant changes in any TMS parameters were noted in normal subjects after sleep deprivation. The F wave was unchanged by sleep deprivation in both control subjects and in patients with JME. Conclusions: In patients with JME, sleep deprivation produces increases in corticospinal excitability in motor areas as measured by different TMS parameters.

Transient deafferentation in humans induces rapid modulation of primary sensory cortex not associated with subcortical changes: a somatosensory evoked potential study

Human somatosensory cortex (S1) is capable of rapid modification after temporary peripheral deafferentation but it is not known whether subcortical changes contribute to this modulation. We recorded spinal, brainstem and cortical somatosensory evoked potentials (SEPs) to median nerve stimulation following anaesthetic block of the ipsilateral ulnar nerve. Spinal N13 and subcortical P14, N18 potentials remained unchanged during the experiment. N20/P20, P27 and N30 cortical potentials, which are generated in different subareas of the S1 (N20/P20, N30 in area 3b; P27 in area 1), showed different increases in amplitude during the anaesthesia, which were more marked for N20/P20 and N30 than for P27 potentials. These results suggest that changes in S1 neural activity induced by transient deafferentation may be primarily intracortical in origin and appear to be segregated within the different subareas of the somatosensory cortex. Unmasking of pre-existing thalamo-cortical projections from median nerve territories, induced by ipsilateral ulnar nerve deafferentation, may be the mechanism underlying cortical SEP enhancement.

Crossed and direct effects of digital nerves stimulation on motor evoked potential: a study with magnetic brain stimulation

We studied the influence of contralateral and ipsilateral cutaneous digital nerve stimulation on motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation (TMS). We tested the effect of different magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE) muscles of the right hand while an electrical conditioning stimulus was delivered to the second finger of the same hand with an intensity four times above the sensory threshold. Amplitude decrement of conditioned MEPs as a function of magnetic stimulus intensity was observed. The lowest TMS stimulus intensity produced the largest decrease in conditioned MEPs. Moreover, we investigated the effects of ipsilateral and contralateral electrical digital stimulation on MEPs elicited in the right TE and biceps muscle using an intensity 10% above the threshold. Marked MEP inhibition in TE muscles following both ipsilateral and contralateral digital stimulation is the main finding of this study. The decrease in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of unconditioned MEP amplitude with the circular coil and 30% with the focal coil. The amplitude of conditioned MEPs to contralateral digital stimulation showed a decrease of 60% with the circular coil and more than 50% with the focal coil. The onset of the inhibitory effect of contralateral stimulation using the focal coil occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP inhibition was observed when recording from proximal muscles. Ipsilateral and contralateral digital stimulation had no effect on F wave at appropriate interstimulus intervals, where the main MEP suppression was noted. We stress the importance of selecting an appropriate test stimulus intensity to evaluate MEP inhibition by digital nerves stimulation. Spinal and cortical sites of sensorimotor integration are adduced to explain the direct and crossed MEP inhibition following digital nerves stimulation.

Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

Summary: Purpose: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti‐convulsant drugs (AEDs) on the excitability of motor cortico‐spinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment.

Decrease in motor cortical excitability in human subjects after sleep deprivation

The effect of sleep deprivation on human motor cortical excitability was investigated by evaluating the changes in motor evoked potentials from the thenar eminence muscles of the right hand in seven subjects. Motor threshold, motor evoked potential amplitude, silent period, intracortical inhibition, intracortical facilitation and F wave were studied. Recordings were performed every 6 h during the day-time (from 09.00 to 21.00 h) and every 3 h during the night-time (from 21.00 to 09.00 h). Significant increases in motor threshold, intracortical inhibition and silent period were noted in the recordings during the night associated with a return to baseline values in the morning. No significant changes were observed in any of the other parameters. Enhancement of intracortical motor inhibition is suggested to explain the effect of sleep deprivation.

Peripheral and segmental spinal abnormalities of median and ulnar somatosensory evoked potentials in Hirayama’s disease

Objectives: To investigate the origin of juvenile muscle atrophy of the upper limbs (Hirayama’s disease, a type of cervical myelopathy of unknown origin). Subjects: Eight male patients were studied; data from 10 normal men were used as control. Methods: Median and ulnar nerve somatosensory evoked potentials (SEP) were recorded. Brachial plexus potentials at Erb’s point (EP), dorsal horn responses (N13), and subcortical (P14) and cortical potentials (N20) were evaluated. Tibial nerve SEP and motor evoked potentials (MEP) were also recorded from scalp and spinal sites to assess posterior column and pyramidal tract conduction, respectively. Results: The most important SEP findings were: a very substantial attenuation of both the EP potentials and the N13 spinal responses; normal amplitude of the scalp N20; and normal latency of the individual peaks (EP-N9-N13-P14-N20). Although both nerves were involved, abnormalities in response to median nerve stimulation were more significant than those in response to ulnar nerve stimulation. There was little correlation between the degree of alterations observed and the clinical state. Latencies of both spinal and cortical potentials were normal following tibial nerve stimulation. The mean latency of cervical MEP and the central conduction time from the thenar eminence were slightly but significantly longer in patients than in controls. Conclusions: The findings support the hypothesis that this disease, which is clinically defined as a focal spinal muscle atrophy of the upper limb, may also involve the sensory system; if traumatic injury caused by stretching plays a role in the pathogenesis, the damage cannot be confined to the anterior horn of the spinal cord.