Pascale Gerard

Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial

Objective: To assess efficacy and safety of trigeminal neurostimulation with a supraorbital transcutaneous stimulator (Cefaly, STX-Med., Herstal, Belgium) in migraine prevention. Methods: This was a double-blinded, randomized, sham-controlled trial conducted at 5 Belgian tertiary headache clinics. After a 1-month run-in, patients with at least 2 migraine attacks/month were randomized 1:1 to verum or sham stimulation, and applied the stimulator daily for 20 minutes during 3 months. Primary outcome measures were change in monthly migraine days and 50% responder rate. Results: Sixty-seven patients were randomized and included in the intention-to-treat analysis. Between run-in and third month of treatment, the mean number of migraine days decreased significantly in the verum (6.94 vs 4.88; p = 0.023), but not in the sham group (6.54 vs 6.22; p = 0.608). The 50% responder rate was significantly greater (p = 0.023) in the verum (38.1%) than in the sham group (12.1%). Monthly migraine attacks (p = 0.044), monthly headache days (p = 0.041), and monthly acute antimigraine drug intake (p = 0.007) were also significantly reduced in the verum but not in the sham group. There were no adverse events in either group. Conclusions: Supraorbital transcutaneous stimulation with the device used in this trial is effective and safe as a preventive therapy for migraine. The therapeutic gain (26%) is within the range of those reported for other preventive drug and nondrug antimigraine treatments. Classification of evidence: This study provides Class III evidence that treatment with a supraorbital transcutaneous stimulator is effective and safe as a preventive therapy for migraine.

Post-stroke reorganization of hand motor area: a 1-year prospective follow-up with focal transcranial magnetic stimulation

OBJECTIVE Focal transcranial magnetic stimulation was used to test prospectively corticospinal excitability changes and reorganization of first dorsal interosseous (FDI) motor cortical representation in 31 patients who experienced a first ischemic stroke in the middle cerebral artery territory. All had severe hand palsy at onset. METHODS Patients were assessed clinically with the Medical Research Council, Rankin, the National Institutes of Health stroke scales and Barthel Index at days 1, 8, 30, 90, 180 and 360 after stroke. The following parameters of FDI motor evoked potential (MEPS) to focal transcranial magnetic stimulation were measured at the same delays: motor threshold, MEP amplitude, excitable cortical area, hot spot and center of gravity of FDI motor maps on affected and unaffected hemispheres. Correlations were sought between clinical and electrophysiological parameters. RESULTS In patients whose affected motor cortex remained excitable at day 1, motor thresholds were not significantly different between sides and were similar to those of controls. Persistence of MEP on the affected side at day 1 was a strong predictor of good recovery. If present at day 1, MEPs recorded in affected FDI were significantly smaller than of the opposite side or in normals and progressively recovered up to day 360. In these patients, area of excitable cortex remained stable throughout the entire study. At day 1, amplitudes of MEPs obtained in unaffected FDI were significantly larger than later. Between days 1 and 360, we observed a significant displacement of center of gravity of motor maps towards more frontal regions on the affected side while no change was noted on the unaffected side. CONCLUSIONS Our data confirm the early prognosis value of transcranial magnetic stimulation in stroke. They indicate that the brain insult induces a transient hyperexcitability of the unaffected motor cortex. The evolution of FDI motor maps along the course of recovery mostly reflect corticospinal excitability changes but might also reveal some degree of brain plasticity. Most modifications observed occurred within 3 months of stroke onset.

Ipsilateral Motor Responses to Focal Transcranial Magnetic Stimulation in Healthy Subjects and Acute-Stroke Patients

Background and Purpose— Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) were compared in healthy subjects and patients with acute stroke. Methods— Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices. If present, MEPs evoked in muscles ipsilateral to TMS were analyzed for latency, amplitude, shape, and center of gravity (ie, preferential coil location to elicit them). In stroke patients, possible relationships between early ipsilateral responses and functional outcome at 6 months were sought. Results— With relaxed or slightly contracting target muscle, maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous (FDI) or biceps of any of 16 normal subjects. In 5 of 8 healthy subjects tested, ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle (in biceps, 6 of 8 subjects) during strong (>50% maximum) contraction of the target muscle. In 15 of 25 stroke patients, ipsilateral MEPs in the unaffected relaxed FDI (in biceps, 6 of 25 stroke patients) were evoked by stimulation of premotor areas of the affected hemisphere. Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere. Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infarcts. Patients harboring these responses had slightly better bimanual dexterity after 6 months. Conclusions— Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins. In the former, they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways, whereas in the latter, early ipsilateral MEPs could originate in hyperexcitable premotor areas.

Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20–35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypo-functioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.

Multiple Clinical and Paraclinical Analyses of Chronic Tension-Type Headache Associated or Unassociated With Disorder of Pericranial Muscles

Thirty-two female patients fulfilling the diagnostic criteria of chronic tension-type headache underwent multiple clinical (severity index before and after biofeedback therapy; anxiety score) and paraclinical (pericranial EMG levels and pressure-pain thresholds, temporalis exteroceptive silent period) assessments. Twenty-three patients (72%) had at least one increased EMG level and/or at least one decreased pain threshold and qualified for the subgroup “associated with disorder of pericranial muscles” (code 2.2.1). Nine patients (28%) were within the normal range for both investigations and would have been classified in the subgroup “unassociated with such disorder” (code 2.2.2). No significant differences were found between these two groups of patients for headache severity, anxiety, response to biofeedback therapy or duration of temporalis second exteroceptive silent period. The various clinical and paraclinical parameters were not significantly correlated to each other. It is therefore suggested that the subdivision of chronic tension-type headache in two subgroups based on pericranial EMG levels and/or pain sensitivity might be artificial. Since both of the latter and temporalis silent periods vary independently, they appear complementary in the study of tension-type headache patients and probably represent peripheral abnormalities, which are induced to varying intensities by a common central nervous system dysfunction.

Emg Activity in Pericranial Muscles During Postural Variation and Mental Activity in Healthy Volunteers and Patients with Chronic Tension Type Headache

SYNOPSIS

Modulation of Temporalis Muscle Exteroceptive Suppression by Limb Stimuli in Normal Man

The effects of noxious and non-noxious limb stimulations on the second exteroceptive suppression of voluntary temporalis muscle activity (ES2) were studied in healthy human volunteers. Duration of temporalis ES2 was measured on averaged rectified responses obtained after stimulating the labial commissure at an intensity of 25 mA. Single peripheral electrical stimuli applied over nerve trunks or over the skin before the labial stimulus decreased ES2 duration. This effect was most pronounced after cutaneous stimuli, especially of the index finger, and it was not observed when the conditioning stimulus was a 10 second, high frequency train. For stimulation at the index finger, temporalis ES2 inhibition progressively increased with intensity from 10 mA to 40 mA; it was maximal for an interstimulus interval between 50 and 140 ms. After naloxone (0.4 mg or 4 mg, i.v.) there was a partial reversal of the index-induced ES2 depression, but this effect was not significant. Immersion of one hand in water heated at 47 degrees C produced a short-lasting ES2 reduction. These results are comparable, though not similar, to the inhibition of the digastric reflex (or jaw opening reflex) observed in animals after limb stimuli and to the depression of the spinal flexion reflex reported in man after heterotopic peripheral stimuli. Although peripheral stimuli were able by themselves to suppress temporalis EMG activity in some subjects, it is likely that they reduce labial-induced ES2 via activation of brainstem structures, such as periaqueductal gray matter or raphe magnus nucleus, which are thought to inhibit the medullary inhibitory interneurons mediating ES2.

Transcutaneous Vagus Nerve Stimulation (tVNS) for headache prophylaxis: initial experience

Neurostimulation is of increasing interest in headache therapy. Invasive neurostimulation methods were found effective in drug-refractory headaches. There is a need for non invasive therapies that could be justified in less disabled patients. Previous case reports suggested that internal Vagus Nerve Stimulation (VNS) might be effective in headache prevention [1-3].

Effects of light deprivation on visual evoked potentials in migraine without aura

BackgroundThe mechanisms underlying the interictal habituation deficit of cortical visual evoked potentials (VEP) in migraine are not well understood. Abnormal long-term functional plasticity of the visual cortex may play a role and it can be assessed experimentally by light deprivation (LD).MethodsWe have compared the effects of LD on VEP in migraine patients without aura between attacks (MO, n = 17) and in healthy volunteers (HV, n = 17). Six sequential blocks of 100 averaged VEP at 3.1 Hz were recorded before and after 1 hour of LD. We measured VEP P100 amplitude of the 1st block of 100 sweeps and its change over 5 sequential blocks of 100 responses.ResultsIn HV, the consequence of LD was a reduction of 1st block VEP amplitude and of the normal habituation pattern. By contrast, in MO patients, the interictal habituation deficit was not significantly modified, although 1st block VEP amplitude, already lower than in HV before LD, further decreased after LD.ConclusionsLight deprivation is thought to decrease both excitatory and subsequent inhibitory processes in visual cortex, which is in line with our findings in healthy volunteers. The VEP results in migraine patients suggest that early excitation was adequately suppressed, but not the inhibitory mechanisms occurring during long term stimulation and habituation. Accordingly, deficient intracortical inhibition is unlikely to be a primary factor in migraine pathophysiology and the habituation deficit.

Cerebral metabolism before and after external trigeminal nerve stimulation in episodic migraine

Background and aim A recent sham-controlled trial showed that external trigeminal nerve stimulation (eTNS) is effective in episodic migraine (MO) prevention. However, its mechanism of action remains unknown. We performed 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to evaluate brain metabolic changes before and after eTNS in episodic migraineurs. Methods Twenty-eight individuals were recruited: 14 with MO and 20 healthy volunteers (HVs). HVs underwent a single FDG-PET, whereas patients were scanned at baseline, directly after a first prolonged session of eTNS (Cefaly®) and after three months of treatment (uncontrolled study). Results The frequency of migraine attacks significantly decreased in compliant patients (N = 10). Baseline FDG-PET revealed a significant hypometabolism in fronto-temporal areas, especially in the orbitofrontal (OFC) and rostral anterior cingulate cortices (rACC) in MO patients. This hypometabolism was reduced after three months of eTNS treatment. Conclusion Our study shows that metabolic activity of OFC and rACC, which are pivotal areas in central pain and behaviour control, is decreased in migraine. This hypometabolism is reduced after three months of eTNS. eTNS might thus exert its beneficial effects via slow neuromodulation of central pain-controlling areas, a mechanism also previously reported in chronic migraine and cluster headache after percutaneous occipital nerve stimulation. However, this finding needs to be confirmed by further studies using a sham condition.