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We conclude that early-performed transcranial magnetic stimulation is a valuable prognostic tool for motor recovery from stroke and that relatively preserved MEP amplitude shortly after stroke is a better prognostic factor than normal central motor conduction time.

If the brain of migraineurs is characterized between attacks by a reduction of mitochondrial phosphorylation potential, riboflavin, which has the potential of increasing mitochondrial energy efficiency, might have prophylactic effects in migraine. In this preliminary open pilot study, 49 patients suffering from migraine (45 without aura, 4 with aura) were treated with 400 mg of riboflavin as a single oral dose for at least 3 months. Twenty-three patients received in addition 75 mg of aspirin. Mean global improvement after therapy was 68.2% and there was no difference between the two groups of patients. With the exception of one patient in the riboflavin plus aspirin group who withdrew because of gastric intolerance, no drug-related side effects were reported. High-dose riboflavin could thus be an effective, low-cost prophylactic treatment of migraine devoid of short-term side effects. A placebo-controlled trial of its efficacy seems worthwhile.

The time course of a decline in inhibition based on TMS after subcortical stroke followed the gain in motor recovery. Increased facilitation in cortical stroke patients is more likely to represent the effect of early cortical circuit disruption and may not play a role in subacute changes in motor function.

OBJECTIVES To conduct a systematic review and analysis of trial data submitted to the US Food and Drug Administration (FDA) to identify possible causes for the failure of pediatric trials of triptans for treatment of migraines. DATA SOURCE The FDA website for drug information and published literature. STUDY SELECTION All pediatric efficacy and pharmacokinetics trial data of drugs used for abortive treatment of migraine submitted to the FDA from January 1, 1999, through December 31, 2011. MAIN OUTCOME MEASURES Patient demographic baseline characteristics, inclusion and exclusion criteria, trial designs, efficacy end points, and pharmacokinetic profiles were analyzed and compared across drug products. RESULTS We analyzed data for sumatriptan succinate nasal spray and zolmitriptan, eletriptan hydrobromide, almotriptan malate, and rizatriptan benzoate tablets. Seven efficacy trials had a randomized, double-blinded, placebo-controlled, parallel-group trial design. In 4 trials, patients were required to have a history of migraine attacks lasting at least 4 hours. High response rates for placebo were observed in all trials, with pain relief at 2 hours ranging from 53% to 57.5%. Nonrandomization of patients with an early placebo response design was used in the rizatriptan trial in 2011. Compared with the rizatriptan trial conducted in 1999, the 2011 rizatriptan trial reduced the placebo response rate by 6% for headache freedom at the 2-hour posttreatment end point owing to study design. The pharmacokinetic profiles between adolescents and adults were statistically similar. CONCLUSIONS High placebo response rates are consistent across all trials and may represent the principal challenge in pediatric trials of drugs for abortive treatment of migraine. Enrichment with selection of subjects with long-lasting migraine attacks is not sufficient to overcome high placebo response rates. Another enrichment strategy, the nonrandomization of patients with an early placebo response, successfully reduces the high placebo response rate for rizatriptan and is a trial design that should be considered for future pediatric trials of abortive migraine therapeutics.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are noninvasive techniques recently used to investigate cortical motor physiology. However, these modalities measure different phenomena, and in studies of human motor control they have given inconsistent results. We have developed a reproducible technique which co-registers TMS and fMRI, using a frameless method. In four normal subjects, the TMS map and fMRI activation were present on the primary motor cortex contralateral to the target hand, with some extension into primary sensory cortex. fMRI activation alone was also present in the medial motor cortex bilaterally and in the sensorimotor cortex ipsilateral to the target hand. This technique allows a more comprehensive evaluation of the physiologic events involved in motor control.

Brain plasticity was investigated in a child with a hemiplegia due to unilateral schizencephaly involving the sensorimotor cortex. This focal lesion led to a dramatic functional reorganization of the undamaged hemisphere, as evidenced by the unusual pattern of fMRI activation during paretic finger movements. The functional relevance of the activation in the undamaged motor cortex was supported by the finding that TMS of this area yielded a response in the paretic hand, indicating that it controls both hands. However, this reorganization was not restricted to the primary motor cortex, but also concerned other structures involved in the control of movements, as shown by the activation of contralesional SMA and thalamus. In contrast, the fMRI activation in the damaged sensorimotor cortex during paretic hand movements appears functionally irrelevant.

The respective contributions of the stroke and undamaged hemispheres to motor recovery after stroke remains controversial. The aim of this article is to evaluate the relationship between location and size of cortical motor areas and outcome after stroke. Twelve controls and 12 stroke patients were studied. Hand cortical motor output areas were determined using transcranial magnetic stimulation. Motor-evoked potentials were recorded simultaneouslyfrom both hands. Functional motor abilities were evaluated using well-validated measures. Surface area, weighted surface area, and center of gravity of motor output areas were calculated. Different patterns of motor output areas to the paretic band were observed; there was no motor output from the stroke hemisphere in patients with poor outcome, contrasting to large motor output area in the stroke hemisphere in patients with good outcome, regardless of infarct size or location. A significant correlation was found between measures of motor outcome in the stroke-affected upper extremity and both the surface area and weight of the central motor output area in the stroke hemisphere. No ipsilateral motor response was obtained after stimulation of either hemisphere. These data support an association between preservation of cortical motor output area to the paretic hand in the stroke hemisphere and good motor outcome.