Defective interhemispheric inhibition in drug-treated focal epilepsies.

BACKGROUND: Focal epilepsies (FEs) arise from a lateralized network, while in generalized epilepsies (GEs) there is a bilateral involvement from the outset. Intuitively, the corpus callosum is the anatomical substrate for interhemispheric spread. OBJECTIVE: We used transcranial magnetic stimulation (TMS) to explore whether there are any physiological differences in the corpus callosum of drug-treated patients with FE and those with genetic GE (GGE), compared to healthy subjects (HS). METHODS: TMS was used to measure the interhemispheric inhibition (IHI) from right-to-left primary motor cortex (M1) and viceversa in 16 patients with FE, 17 patients with GGE and 17 HS. A conditioning stimulus (CS) was given to one M1 10 and 50 ms before a test stimulus delivered to the contralateral M1. Motor evoked potentials (MEPs) were analysed both as a function of the side of stimulation and of the epileptic focus (left-right). RESULTS: In HS, IHI was reproducible with suppression of MEPs at ISIs of 10 and 50 ms. Similar effects occurred in GGE patients. FE patients behaved differently, since IHI was significantly reduced bilaterally. When FE patients were stratified according to the side of their epileptic focus, the long-ISI IHI (=50 ms) appeared to be defective only when the CS was applied over the "focal" hemisphere. CONCLUSIONS: FE patients had a defective inhibitory response of contralateral M1 to inputs travelling from the "focal" hemisphere that was residual to the drug action. Whilst IHI changes would not be crucial for the GGE pathophysiology, they may represent one key factor for the contralateral spread of focal discharges, and seizure generalization.

Overactive visuomotor connections underlie the photoparoxysmal response. A TMS study.

OBJECTIVE: The photoparoxysmal response (PPR) involves rapid spread of epileptic activity from visual to parietal and frontal areas. We used a transcranial magnetic stimulation (TMS) technique to assess the physiologic connections between primary visual (V1) and motor (M1) areas in patients with idiopathic generalized epilepsy (IGE). We hypothesized that in PPR-positive patients, M1 would respond excessively to inputs from V1. METHODS: Eleven photosensitive patients with IGE who had a PPR at the time of the study were compared with 10 similar patients without a PPR, and with 11 healthy subjects of similar age and sex. The connection between V1 and M1 was assessed in resting participants by delivering a conditioning stimulus (CS) over the phosphene hotspot of the visual cortex (intensity 90% phosphene threshold, PT) followed at random interstimulus intervals (ISIs; 15, 18, 21, 24, 27, 30, 35 and 40 msec) by a test stimulus (TS) over the left motor cortex to elicit a motor evoked potential (MEP) of ~1 mV from the right first dorsal interosseous muscle. RESULTS: In healthy subjects, a CS over V1 suppressed M1 at ISIs between 18 and 40 msec. Similar effects occurred in IGE patients without a PPR. This was not true in PPR-positive IGE patients, in whom this type of physiologic inhibition was significantly (p < 0.05) reduced. SIGNIFICANCE: IGE patients with a PPR have an overactive functional response of M1 to inputs traveling from V1. This may represent one core factor for the anterior spread of the PPR itself and for the origin of the abnormal epileptic motor phenomenon, such as myoclonus.

Abnormal motor cortex plasticity in juvenile myoclonic epilepsy.

PURPOSE: Abnormal cortical plasticity has been hypothesized to play a crucial role in the pathogenesis of juvenile myoclonic epilepsy (JME). To study the motor cortical plasticity we used paired associative stimulation (PAS). When a repetitive electrical stimulus to the median nerve is paired with a transcranial magnetic stimulus (TMS) pulse over the controlateral motor cortex with at an interstimulus interval (ISI) of 21.5-25ms, a long term potentiation (LTP)-like synaptic plasticity is induced in the corticospinal system. Aim of this study was to investigate the motor cortex LTP-like synaptic plasticity by means of PAS in patients with JME. METHODS: Twelve adult patients with JME were compared with 13 healthy subjects of similar age and sex. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min. RESULTS: In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude (p<0.001). On the contrary, in patients with JME, the MEP amplitude did not change. CONCLUSION: Defective motor cortex plasticity is likely involved in the pathogenesis of JME.

Impaired visual inhibition in migraine with aura.

OBJECTIVE: The pathophysiology of migraine with or without aura (MA, MO) is still a matter of debate. We thus studied patients with MA and MO by means of paired-pulse flash-visual evoked potentials (paired F-VEPs). This technique, recently revived, analyses the overall excitability of visual system as detected from the cortical occipital signal. METHODS: We enrolled 13 adult patients with MO and 13 with MA. Twenty-two normal subjects of similar age and sex acted as controls. Stimuli were single flashes, intermingled at random to flash pairs at critical interstimulus intervals (ISIs, 16.5-125ms) with closed and open eyes. The "single"(unconditioned) F-VEP was split into a "main complex" (50-200ms after the flash) and a "late response" (200-400ms). As for paired stimulation, the "test" F-VEP emerged from electronic subtraction of the "single" F-VEP to the "paired" F-VEP. Its size was expressed as "test"/"single"F-VEP∗100. RESULTS: As for paired F-VEPs, the "main complex" of the "test" F-VEP in the MA group did not show the size reduction (at ISIs 50-62.5ms) which was typical among the control and MO groups (p⩽0.016) in the "eyes-closed" state. CONCLUSIONS: Paired F-VEPs document a defective neural inhibition in the visual system of patients with MA. SIGNIFICANCE: Paired F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of MA.

Interictal ghrelin levels in adult patients with epilepsy.

PURPOSE: In vitro or in animal models of epilepsy, ghrelin showed a clear anticonvulsant action, whose mechanisms are somewhat obscure. In humans however, a controversial relation exists between ghrelin and epilepsy. Yet most studies investigated just total ghrelin levels, without a proper distinction between acylated (AG) or unacylated ghrelin (UAG). We thus evaluated separately AG and UAG interictal levels in adult patients with epilepsy, and their relation to clinical features. METHOD: Cross-sectional study in a tertiary referral centre. Fifty-six patients were recruited: 19 with idiopathic generalized epilepsy, 18 with cryptogenic focal epilepsy and 19 with symptomatic focal epilepsy. Twenty-six healthy subjects of similar age, sex and body mass index (BMI) acted as controls. AG and UAG levels were measured following an overnight fasting and contrasted to the clinical and biometric features. RESULTS: AG and UAG levels were similar between patients and controls. The AG/UAG ratio was higher in patients, also when weighted for covariates (age, BMI, gender, and drugs). Splitting patients according to their epileptic syndrome, drug-resistance or antiepileptic drug number/type resulted in no significant difference in AG, UAG or their ratio. Yet, AG and UAG levels were positively predicted by disease duration, independently by confounders. CONCLUSION: In adult patients with epilepsy, interictal ghrelin levels did not differ from controls, though the AG/UAG ratio was imbalanced. Interpretation of the latter phenomenon is uncertain. Further, levels of AG and UAG were in direct proportion to disease duration, which may represent a long-term compensatory mechanism, antagonistic to the epileptic process.