Gilles Géraud

Hypothalamic Activation in Spontaneous Migraine Attacks

Background.— Migraine sufferers experience premonitory symptoms which suggest that primary hypothalamic dysfunction is a likely trigger of the attacks. Neuroendocrine and laboratory data also support this hypothesis. To date, positron emission tomography (PET) scans of migraine sufferers have demonstrated activation of brainstem nuclei, but not of the hypothalamus.

Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions. During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation (weekly frequency of attacks decrease >50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Migraine and Probable Migraine — Results of FRAMIG 3, a French Nationwide Survey Carried out According to the 2004 IHS Classification

The 2004 International Headache Society (IHS) classification of headache disorders introduced the new category of probable migraine defined by the existence of all but one of typical migraine criteria. FRAMIG 3, the first nationwide population-based survey performed in France using the 2004 IHS classification, assessed the prevalence of probable migraine and compared its features and management with those of strict migraine. Of a representative sample of 10 532 adult subjects interviewed, 1179 subjects (11.2%) were diagnosed as having strict migraine and 1066 (10.1%) as having probable migraine. The criterion most frequently missing was typical headache duration (4-72 h) and most subjects with probable headache had shorter average headache duration. Migraine severity and disability, although lower than those noted in subjects with strict migraine, were significant in subjects with probable migraine and quality of life impairment was identical among the two groups of migraine sufferers. Strict and probable migraine, which have similar prevalence and impact on migraine subjects, deserve similar medical and therapeutic management.

Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain

Objective Photophobia is an abnormal sensitivity to light experienced by migraineurs and is perhaps caused by cortical hyperexcitability. In clinical studies, an inter-relation between light perception and trigeminal nociception has been demonstrated in migraineurs but not in controls. The purpose of the study was to verify this interaction by functional imaging. Methods The authors used H2O15 positron emitting tomography (PET) to study the cortical responses of seven migraineurs between attacks and the responses of seven matched control subjects to luminous stimulations at three luminance intensities: 0, 600 and 1800 Cd/m2. All three intensities were both with and without concomitant trigeminal pain stimulation. In order to facilitate habituation, the stimulations were started 30 s before PET acquisitions. Results When no concomitant pain stimulation was applied, luminous stimulations activated the visual cortex bilaterally in migraineurs (specifically in the cuneus, lingual gyrus and posterior cingulate cortex) but not in controls. Concomitant pain stimulation allowed visual cortex activation in control subjects and potentiated its activation in migraineurs. These activations by luminous stimulations were luminance-intensity-dependent in both groups. Concomitant stimulation by pain was associated with activation of the posterior parietal cortex (BA7) in migraineurs and controls. Interpretation The study shows the lack of habituation and/or cortical hyperexcitability to light in migraineurs. Moreover, the activation by light of several visual cortex areas (including the primary visual cortex) was potentiated by trigeminal pain, demonstrating multisensory integration in these areas.

Migraine Headache Recurrence: Relationship to Clinical, Pharmacological, and Pharmacokinetic Properties of Triptans

Background and Objectives.—Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5‐HT1B and 5‐HT1D receptor activities, the pharmacokinetic elimination half‐life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo.

Posterior cerebral hypoperfusion in migraine without aura

In cerebral blood flow studies, migraine aura is characterized by a posterior cortical hypoperfusion. In contrast, only rare and mild changes in brain perfusion have been demonstrated in migraine without aura, suggesting two different haemodynamic patterns in migraine with and without aura. Our aim was to study hypoperfusion with positron emission tomography (PET) as early as possible during spontaneous migraine without aura attacks. We used H2 15O PET to investigate seven patients (six female, one male) with migraine without aura (International Classification of Headache Diseases-II code 1.1) in three situations: during the headache phase, after headache relief following sumatriptan injection, and during an attack-free interval. Statistical analysis was performed with SPM2. Within 4 h after the attack onset, significant relative bilateral posterior cortical hypoperfusion was found and persisted after headache relief following sumatriptan injection. A posterior cortical hypoperfusion demonstrated in migraine without aura could suggest a common pathogenesis in migraine with and without aura. The significance of relative posterior hypoperfusion in migraine without aura is discussed according to the current knowledge of migraine pathogenesis.

Chronic cluster headache: a French clinical descriptive study

Background: Cluster headache (CH) is a relatively rare disease and episodic CH is more frequent than chronic CH. Few studies have described the characteristics of patients with chronic CH. Methods: This was a descriptive study carried out by eight tertiary care specialist headache centres in France participating in the Observatory of Migraine and Headaches (OMH). From 2002 to 2005, OMH collected data from 2074 patients with CH, of whom 316 had chronic CH. From January to June 2005, 113 patients with chronic CH were interviewed using standardised questionnaires during a consultation. Results: The male to female ratio was 4.65:1. Median age was 42 years. The majority of patients were smokers or former smokers (87%). 46% had primary chronic CH (chronic at onset) and 54% secondary chronic CH (evolving from episodic CH). Most patients had unilateral pain during attacks and 7% had sometimes bilateral pain during an attack. 48% reported a persisting painful state between attacks. Symptoms anteceding pain onset (mainly discomfort/diffuse pain, exhaustion, mood disorders) and auras were reported by 55% and 20% of patients, respectively. The functional impact of chronic CH was estimated as severe by 74% of patients, and 75.7% suffered from anxiety, as assessed by the Hospital Anxiety and Depression scale. There was no substantial difference in clinical presentation between primary and secondary CH. Discussion: This study confirms the existence of auras and interictal signs and symptoms in patients with chronic CH, and male sex and smoking as CH risk factors. Primary and secondary chronic CH appear equally prevalent. Male sex does not appear to favour the shift from episodic to chronic CH.

Recognition and Therapeutic Management of Migraine in 2004, in France: Results of FRAMIG 3, a French Nationwide Population-Based Survey

Objective.—To evaluate the proportion of migraineurs who are self‐aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self‐awareness of migraine, and to assess the influence of these factors on migraine attacks.

Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation.

Background: Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. Methods: Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. Results: After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. Conclusions: Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.

Tolerability and Safety of Frovatriptan With Short‐ and Long‐term Use for Treatment of Migraine and in Comparison With Sumatriptan

Objective.—To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine.