Abnormal intracortical facilitation in early-stage Huntington's disease.

OBJECTIVE: It is known from neuropathological and imaging studies that the neuronal degeneration in Huntington's disease (HD) is already quite severe when the first symptoms of the disease become clinically evident. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the neurodegeneration in HD. METHODS: Motor cortex excitability was examined in 12 patients with HD in the early clinical stage of the disease and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, the short-interval paired-pulse intracortical inhibition (SICI) and the paired-pulse intracortical facilitation (ICF) were examined. RESULTS: The early-stage HD patients showed a statistically significant reduction in ICF. The other measures did not differ significantly from the control subjects. CONCLUSIONS: Our findings provide neurophysiological evidence that changes in motor function are present in the early HD. Since ICF is thought to depend upon the activity of intracortical glutamatergic excitatory circuits, the results of our study support the theory that altered NMDA receptor function plays an important role in the pathogenesis of HD. SIGNIFICANCE: These findings may provide clues to the underlying pathophysiology of the disease. A more complete understanding of the changes in motor cortex excitability that occur early in the course of HD will lead to a better definition of the disease process and may allow earlier diagnosis and intervention.

Transcranial magnetic stimulation shows impaired transcallosal inhibition in Marchiafava-Bignami syndrome.

A case of Marchiafava-Bignami (MB) syndrome with selective callosal involvement was evaluated by clinical examination and magnetic resonance imaging (MRI) in the acute phase and 6 months after the onset of symptoms; at the same time, the corticospinally and transcallosally mediated effects elicited by transcranial magnetic stimulation (TMS) were investigated. The first MRI study showed the presence of extensive abnormal signal intensity throughout the entire corpus callosum. After high-dose corticosteroid administration her symptoms rapidly resolved, in parallel with the reversion of MRI changes, except for severe cognitive impairment. Follow-up TMS examination revealed persistent transcallosal inhibition (TI) abnormalities. This report indicates that the measurement of TI during the course of MB syndrome is useful for evaluating functional changes to the corpus callosum, including their evaluation with time and after treatment and for elucidating the pathophysiology of MB syndrome.

Changes in motor cortical excitability in humans following orally administered theophylline.

The effects of theophylline on human corticospinal excitability were studied using transcranial magnetic stimulation (TMS) before and after double-blind oral administration of theophylline or placebo in 20 healthy volunteers. TMS measurements included resting and active motor threshold, silent period, intracortical inhibition (ICI), and intracortical facilitation. F-wave and compound muscle action potential (CMAP) were also measured. Theophylline produces a reduction in ICI, while other parameters of corticospinal excitability remained unaffected. Since ICI is thought to depend on GABAA intracortical inhibitory mechanisms, our data suggest that the increase of human motor cortex excitability is the result of a decrease in GABAergic transmission. Our results further support the hypothesis that theophylline might induce convulsions by inhibiting GABAA receptor binding.