Drug-induced changes in cortical inhibition in medication overuse headache.

in Cephalalgia : An International Journal of Headache (2011), 31(12), 1282-90

BACKGROUND: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy ... [more ▼]

BACKGROUND: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. SUBJECTS AND METHODS: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. RESULTS: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 +/- 14.2 vs. 108.1 +/- 30.1 ms), but similar to that reported in migraineurs (59.9 +/- 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 +/- 46.4 and 103.8 +/- 47.2 ms). CONCLUSIONS: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission. [less ▲]

Migraine preventive drugs differentially affect cortical spreading depression in rat.

in Neurobiology of Disease (2011), 41(2), 430-5

Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the ... [more ▼]

Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of three drugs used in migraine prevention: lamotrigine which is selectively effective on the aura but not on the headache, valproate and riboflavin which have a non-selective effect. Rats received for 4 weeks daily intraperitoneal injections of one of the three drugs. For valproate and riboflavin we used saline as control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment, cortical spreading depressions were elicited for 2h by occipital KCl application. We measured CSD frequency, its propagation between a posterior (parieto-occipital) and an anterior (frontal) electrode, and number of Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37% and 60% at posterior and anterior electrodes. Valproate had no effect on posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity. Riboflavin had no significant effect at neither recording site. Frontal Fos expression was decreased after lamotrigine and valproate, but not after riboflavin. Serum levels of administered drugs were within the range of those usually effective in patients. Our study shows that preventive anti-migraine drugs have differential effects on CSD. Lamotrigine has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin have no effect on the triggering of CSD, although they are effective in migraine without aura. Taken together, these results are compatible with a causal role of CSD in migraine with aura, but not in migraine without aura. [less ▲]

Le laboratoire d’Anatomie : un banc d’essai des nouvelles technologies

in Revue Médicale de Liège (2010), 65(Synthèse 2010), 35-40

STEM CELLS IN THE ADULT RAT SPINAL CORD: PLASTICITY AFTER INJURY AND TREADMILL TRAINING EXERCISE.

in Journal of Neurochemistry (2010), 112(3), 762-772

ABSTRACT Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for ... [more ▼]

ABSTRACT Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for repair strategies. Physical exercise is known to increase ependymal cell proliferation, while improving functional recovery. In this work, we further characterized those endogenous NSCs within the normal and injured adult rat spinal cord and investigated the effects of treadmill training using immunohistochemical and behavioural studies. In uninjured untrained rats, Sox-2, a NSC marker, was detected in all ependymal cells of the central canal, and also scattered throughout the parenchyma of the spinal cord. Within the lesion, Sox-2 expression increased transiently, while the number of nestin-positive ependymal cells increased with a concomitant enhancement of proliferation, as indicated by the mitotic markers Ki67 and BrdU. Exercise, which improved functional recovery and autonomous micturition, maintained nestin expression in both injured and uninjured spinal cords, with a positive correlation between locomotor recovery and the number of nestin-positive cells. [less ▲]

Botulinum toxin for the treatment of headache:a promising path on a “dead end road”?

in Acta Neurologica Belgica (2010), 110

Neurostimulation therapy in intractable headaches.

in Handbook of clinical neurology / edited by P.J. Vinken and G.W. Bruyn (2010), 97

A proportion of chronic headache patients become refractory to medical treatment and severely disabled. In such patients various neurostimulation methods have been proposed, ranging from invasive ... [more ▼]

A proportion of chronic headache patients become refractory to medical treatment and severely disabled. In such patients various neurostimulation methods have been proposed, ranging from invasive procedures such as deep-brain stimulation to minimally invasive ones like occipital nerve stimulation. They have been applied in single cases or small series of patients affected with varying headache disorders: cervicogenic headache, hemicrania continua, posttraumatic headache, chronic migraine, and cluster headache. Although favorable results were reported overall, it is premature to consider neurostimulation as a treatment with established utility in refractory headaches. At present, the most detailed clinical studies have been performed in intractable chronic cluster headache (iCCH) patients, who represent about 1% of all chronic cluster headache (CCH) patients. Various lesional interventions have been attempted in these patients, none with lasting benefits. In recent years, non-destructive neurostimulation methods have raised new hope. Hypothalamic deep-brain stimulation (hDBS) acts rapidly and has lasting efficacy, but is not without risk. Occipital nerve stimulation (ONS) was studied in two trials on a total of 17 iCCH patients. Clinical efficacy was found to be very satisfactory by most patients and by the investigators. Although slightly less efficacious than hDBS, ONS has the advantage of being rather harmless and reversible. At this stage, it should be preferred as first-line invasive therapy for iCCH. Recent case reports mention the efficacy of supraorbital (SNS) and vagal (VNS) nerve stimulation. Whether these neurostimulation methods have a place in the management of iCCH patients remains to be determined. [less ▲]

Headache: spreading from molecules to patients

in Lancet Neurology (2010), 9

NSAIDs in the acute treatment of migraine: A review of clinical and experimental data

in Pharmaceuticals (2010), 3

Reply to the Topical Review entitled "The phenomenon of changes in cortical excitability in migraine is not migraine-specific - A unifying thesis" by Anne Stankewitz and Arne May published on Pain 2009;145:14-7.

in Pain (2010)

Sustained efficacy of occipital nerve stimulation in drug-resistant chronic cluster headache after up to 5 years treatment

in Journal of Headache & Pain (2010), 11(Suppl 1), 15

Background. Drug-resistant chronic cluster headache (drCCH) is a devastating condition for which various invasive procedures have been tempted without any satisfactory effect. Our prospective pilot study ... [more ▼]

Background. Drug-resistant chronic cluster headache (drCCH) is a devastating condition for which various invasive procedures have been tempted without any satisfactory effect. Our prospective pilot study of great occipital nerve stimulation (ONS) in 8 drCCH patients showed encouraging results at 15 months (1). Methods. We recruited 15 patients with drCCH according to the previously published criteria of intractability (2). They were implanted with suboccipital stimulators on the side of their headache. Long-term follow-up was achieved by questionnaires administered during a headache consultation and/or by telephone interviews. Results. One patient had an immediate post operative infection of the material. Mean time with ONS was 28.8 months (range 3-60 months). Nine of the 14 remaining patients were totally pain-free (64%), 2 patients had an improvement in frequency exceeding 90% and one patient a 89% amelioration. Two patients did not respond or described mild improvement. Intensity of residual attacks was not improved by ONS. Four patients (29%) were able to reduce their prophylaxis. Common technical problems were battery depletion (N=8/14, 57%) and material infection (N=3/15, 20%). Recurrent battery replacement (until 2/ year in one patient) is now avoided by the availability of rechargeable batteries. Clinical peculiarities associated with ONS were occurrence of infrequent contralateral attacks (N=5/14, 36%), and/or isolated ispilateral autonomic attacks (N=5/14, 36%). Rapid attack recurrence after stimulator switch off was reported by 7/12 improved patients (58%). Two patients found ONS-related paresthesias unbearable; one had his stimulator removed, the other switched it off though he was objectively ameliorated. Subjectively, nine patients are very satisfied by ONS and one patient moderately satisfied. Conclusions. Our long-term follow-up confirms the efficacy of ONS in drCCH, which remains a safe and well-tolerated technique. The occurrence of contralateral attacks and isolated autonomic attacks in nearly 50% of ONS responders may have therapeutic and pathophysiological implications. [less ▲]