Revised guidelines of the French headache society for the diagnosis and management of migraine in adults. Part 3: Non-pharmacological treatment.

The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the third part of the guidelines, which is focused on the non-pharmacological treatment of migraine, including physical exercise, dietary supplements and plants, diets, neuromodulation therapies, acupuncture, behavioral interventions and mindfulness therapy, patent foramen ovale closure and surgical nerve decompression.

Relationships between migraine and epilepsy: Pathophysiological mechanisms and clinical implications.

Migraine and epilepsy are distinct neurological diseases with specific clinical features and underlying pathophysiological mechanisms. However, numerous studies have highlighted the complex and multifaceted relationships between the two conditions. The relationships between headache and epilepsy manifest themselves in different ways. Firstly, the clinical diagnosis of these disorders may be challenging in view of possible overlapping. While post-ictal headache is a frequent condition, ictal epileptic headache is a rare but challenging diagnosis. Both situations raise the question of the pathophysiological mechanism of headache triggered by seizures. Migraine aura and epilepsy can also exhibit overlapping symptoms leading to their misdiagnosis, in particular in the case of visual aura. Secondly, migraine with aura and epilepsy can occur as a co-morbid condition, particularly in familial hemiplegic migraine (FHM). From a pathophysiological perspective, the identification of genetic mutations in FHM has brought significant advances in the understanding of dysfunctions of neuronal networks leading to hyperexcitability. The purpose of this review is to present clinical situations encompassing headache and epilepsy that can be challenging in neurological practice and to discuss the underlying pathophysiological mechanism of such interactions.

Revised guidelines of the French headache society for the diagnosis and management of migraine in adults. Part 2: Pharmacological treatment.

The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the second part of the guidelines, which is focused on the pharmacological treatment of migraine, including both the acute treatment of attacks and the prophylaxis of episodic migraine as well as chronic migraine with and without medication overuse. The specific situations that can be encountered in women with migraine are also discussed, including pregnancy, menstrual migraine, contraception and hormonal replacement therapy.

Revised guidelines of the French Headache Society for the diagnosis and management of migraine in adults. Part 1: Diagnosis and assessment.

The French Headache Society proposes updated French guidelines for the management of migraine. The first part of these recommendations is focused on the diagnosis and assessment of migraine. First, migraine needs to be precisely diagnosed according to the currently validated criteria of the International Classification of Headache Disorders, 3d version (ICHD-3). Migraine-related disability has to be assessed and we suggest to use the 6 questions of the headache impact test (HIT-6). Then, it is important to check for risk factors and comorbidities increasing the risk to develop chronic migraine, especially frequency of headaches, acute medication overuse and presence of depression. We suggest to use a migraine calendar and the Hospital Anxiety and Depression scale (HAD). It is also necessary to evaluate the efficacy and tolerability of current migraine treatments and we suggest to systematically use the self-administered Migraine Treatment Optimization Questionnaire (M-TOQ) for acute migraine treatment. Finally, a treatment strategy and a follow-up plan have to be proposed. Guidelines for pharmacological and non-pharmacological treatments are presented in the second and third part of the recommendations.

Self-perceived attention difficulties are associated with sensory hypersensitivity in migraine.

BACKGROUND: Attention is the process which enables to preferentially select salient or relevant stimuli and to attenuate the response to irrelevant incoming stimuli. Migraine is characterized by both attentional alterations and an abnormal sensory processing to external stimulations. The aim of the study was to investigate potential interactions between self-perceived attentional difficulties and sensory hypersensitivity in migraine patients. METHODS: Forty-six episodic migraineurs without aura and 46 healthy controls filled out questionnaires on self-perceived attention difficulties and self-reported sensitivity to visual, auditory and olfactory stimulations. RESULTS: Compared to controls, migraineurs reported significantly higher levels of attention difficulty and sensory sensitivity. Sensory hypersensitivity correlated significantly with self-perceived attentional difficulties in migraineurs (P=0.002), but not with migraine disability or levels of anxiety or depression. Ictal and interictal sensory sensitivities were significantly correlated in migraineurs within visual (P<0.001), auditory (P<0.001) and olfactory (P=0.001) modalities. CONCLUSION: This study shows for the first time an association between self-reported attentional difficulties and multimodal sensory hypersensitivity. Studies combining behavioral and physiological measures of sensory processing and attention processes are necessary to further understand the peculiar vulnerability of migraineurs to sensory stimuli.

[A causative role of vasodilation in migraine? No]. / La vasodilatation a-t-elle un rôle dans la migraine ? Non.

INTRODUCTION: The hypothesis that migraine pain is caused by vasodilation has been challenged by clinical and experimental evidence. STATE OF ART: The most convincing arguments against the vascular hypothesis come from neuroimaging data. Magnetic resonance imaging studies show that spontaneous migraine attacks are not accompanied by extracranial vasodilation, and by only slight dilation of the intracranial arteries. Pharmacologically-induced migraine attacks also provide further evidence against the role of vasodilation in migraine. Vasodilators such as sildenafil and nitroglycerine trigger attacks without dilation of the middle cerebral artery diameter, whereas VIP (vasoactive intestinal peptide) markedly dilates intra- and extracranial arteries but does not induce migraine attacks. Clinical studies also show a lack of correspondence between the subjective experience of throbbing headache and the arterial pulse. Moreover, many acute anti-migraine agents are not vasoconstrictors. PERSPECTIVES: Further studies are necessary to clarify the mechanisms of migraine headache generation. CONCLUSIONS: Contrary to a longstanding and widespread belief, vasodilatation is neither sufficient nor necessary to cause migraine headache and is probably an epiphenomenon.

Seronegative paraneoplastic cerebellar degeneration: the PNS Euronetwork experience.

BACKGROUND AND PURPOSE: To describe the characteristics of patients presenting a paraneoplastic cerebellar degeneration without classical onconeural antibodies (seronegative PCD). METHODS: Thirty-nine seronegative PCD patients from the Paraneoplastic Neurological Syndrome Euronetwork were retrospectively analyzed and compared with 180 patients with PCD associated with classical onconeural antibodies (seropositive PCD). RESULTS: No patient had anti-CASPR2 or anti-mGluR1 antibodies. No significant difference between the clinical characteristics of seronegative and seropositive PCD patients was observed. Yet the frequency of associated tumors was different. Lymphoma was more frequent in seronegative than in seropositive women (24% vs. 2%, P = 0.002) whilst gynecological cancer were less frequent (38% vs. 74%, P = 0.002). In comparison with seropositive men, seronegative men more frequently had a non-small-cell lung cancer (27% vs. 6%, P = 0.08) or a genitourinary cancer (22% vs. 0%, P = 0.04) but less frequently a small-cell lung cancer (23% vs. 74%, P = 0.002). Seronegative and seropositive PCD patients with similar tumors had a similar overall survival. CONCLUSION: The clinical characteristics of seronegative and seropositive PCD are similar but the spectrum of associated tumors is different. The immunological scenario of seronegative PCD seems to be different from that of limbic encephalitis with only few patients harboring anti-neuropile antibodies.

[Dysautonomic syndrome of the face with Harlequin sign and syndrome: Three new cases and a review of the literature]. / Syndromes dysautonomiques du visage avec signe et syndrome d'Harlequin : étude de trois cas et revue de la littérature.

INTRODUCTION: Harlequin phenomenon is characterized by a strictly unilateral erythrosis of the face with flushing and hyperhydrosis, and controlaterally a pale anhydrotic aspect. This syndrome can occur alone or associated to other dysautonomic phenomena such as Horner syndrome, Adie syndrome or Ross syndrome. PATIENTS AND METHODS: We report three cases: two patients presented a Harlequin sign, associated with Horner syndrome for one and Ross syndrome for the second. The etiologic investigation was normal, allowing recognizing the idiopathic nature of the disorder. For the third patient, Harlequin syndrome was observed in a neoplastic context due to breast cancer, metastatic dissemination, and bone metastases involving the right side of the T2 body. DISCUSSION: We reviewed the literature: 108 cases have been described. This syndrome occurred alone in 48 patients and was associated with other dysautonomic syndromes such as Horner syndrome in 38 patients, Holmes Adie syndrome in six, and Ross syndrome in six; both Ross and Holmes Adie syndrome were associated five cases and associations were not reported in five patients. The pathophysiological mechanisms of this autonomic cranial neuropathy, the possible etiologies, and therapeutic management were discussed. CONCLUSION: Harlequin phenomenon with flushing and unilateral hyperhydrosis is rare, occurring alone or in combination with other autonomic syndromes of the face. Idiopathic in two-thirds of cases, Harlequin phenomenon does not require specific treatment; sympathectomy may be discussed in the severe cases with a significant social impact.

[Neurophysiological evaluation of cortical excitability in migraine: a review of the literature]. / Évaluation électrophysiologique de l'excitabilité corticale dans la migraine.

INTRODUCTION: Neurophysiological studies point to altered cortical neuronal excitability in migraine patients. STATE OF ART: Between attacks, migraine brain seems to be "hyperresponsive" to repetitive stimuli, as suggested by evoked potential studies that show a lack of habituation to sensory stimuli. Transcranial magnetic stimulation suggests an impairment of intracortical inhibitory circuits in migraine, especially in migraine with aura. Controversial results are obtained in migraineurs without aura. Repetitive transcranial magnetic stimulation also shows in migraine with aura a paradoxical enhancement of intracortical facilitation by low frequency stimulation and greater increased facilitatory mechanisms by high-frequency stimulation. Importantly, cortical excitability level fluctuates over time in relation to the migraine cycle. The interictal lack of habituation to sensory stimuli normalizes before and during a migraine attack. Changes of cortical excitability consistent with the theory of cortical spreading depression are also observed during migraine aura with magnetoencephalography. PERSPECTIVES: The exact role of cortical excitability changes in migraine pathophysiology and possibly in chronic migraine is still unknown. Further studies are also necessary to clarify the role of migraine preventive drugs on brain excitability. CONCLUSIONS: In this review, the results of neurophysiological studies conducted in migraine patients will be described and the associated pathophysiological hypotheses will be discussed.

In-patient versus out-patient withdrawal programmes for medication overuse headache: a 2-year randomized trial.

BACKGROUND: Medication-overuse headache (MOH) management usually includes a medication withdrawal. The choice of withdrawal modalities remains a matter of debate. METHODS: We compared the efficacy of in-patient versus out-patient withdrawal programmes in 82 consecutive patients with MOH in an open-label prospective randomized trial. The main outcome measure was the reduction in number of headache days after 2 months and after 2 years. The responders were defined as patients who had reverted to episodic headaches and to an intake of acute treatments for headache less than 10 days per month. RESULTS: Seventy-one patients had a complete drug withdrawal (n = 36 in the out-patient group; n = 35 in the in-patient group). The reduction of headache frequency and subjective improvement did not differ between groups. The long-term responder rate was similar in the out- and in- patient groups (44% and 44%; p = 0.810). The only predictive factor of a bad outcome 2 years after withdrawal was an initial consumption of more than 150 units of acute treatments for headache per month (OR = 3.1; 95% confidence interval 1.1-9.3; p = 0.044). CONCLUSION: Given that we did not observe any difference in efficacy between the in- and out-patient withdrawals, we would recommend out-patient withdrawal in the first instance for patients with uncomplicated MOH.

Brainstem changes in 5-HT1A receptor availability during migraine attack.

BACKGROUND: Among serotonin receptors, 5-HT(1A) receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT(1A) receptors' availability during migraine attacks. METHODS: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [(18)F]MPPF PET tracer, a selective 5-HT(1A) antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. RESULTS: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [(18)F]MPPF binding potential (BP(ND)) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [(18)F]MPPF BP(ND) in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [(18)F]MPPF BP(ND) was observed between headache-free migraineurs and controls. CONCLUSIONS: Our results emphasize the role of 5HT(1A) receptors in the pontine raphe nuclei during the early stage of migraine attacks.

Clinical presentation of immune-mediated cerebellar ataxia.

INTRODUCTION: Accumulation of recent clinical evidence indicates that the immune system plays an important role in some central nervous system diseases usually regarded as degenerative. The most striking example is paraneoplastic cerebellar ataxia (PCA), which is characterized by autoimmune cross-reaction between tumoral and nervous system antigens. STATE OF THE ART: In the past 20 years, several antibodies directed against neuronal and tumoral antigens have been described in association with PCA, leading to the description of different subtypes of PCA based on the associated antibodies, the clinical course and the type of tumor. In some subtypes, cerebellar ataxia occurs in isolation, whereas in others, cerebellar ataxia is a syndrome that occurs in conjunction with extensive nervous system disease. Circulating antibodies have also been described in patients with non-paraneoplastic cerebellar ataxia (N-PCA), suggesting that the immune system may be involved in certain cases of sporadic cerebellar ataxia. PERSPECTIVE: Immune-mediated cerebellar ataxia does not seem to be limited to paraneoplastic neurological syndromes. Further studies are however necessary to understand the exact pathophysiology of these disorders and offer effective treatments. CONCLUSION: In this review, the clinical presentation of the different subtypes of potentially immune-mediated PCA and N-PCA will be described, and the associated tumors will be discussed.

Cerebral imaging and olfactory disorders: a review.

Cerebral imaging and olfactory disorders: a review. Olfactory disorders are often misjudged and rarely given due clinical consideration. Nevertheless, they occur in a wide range of neurological disorders, and their evaluation can help in diagnosis. Whereas psychophysical tests have been used to evaluate olfactory dysfunction in numerous diseases, functional brain imaging using olfactory stimuli is an emergent technique and few studies have been published to date. After a reminder of cerebral imaging and analysis techniques and a rapid description of our actual knowledge of olfactory processes in healthy subjects, the current review focuses on cerebral imaging studies performed on patients with neurological disorders and presenting olfactory dysfunction. Neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, migraine, multiple chemical sensitivity and schizophrenia are examined.

Interictal brain 5-HT1A receptors binding in migraine without aura: a 18F-MPPF-PET study.

In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in migraine patients without aura. Ten female migraine patients and 24 female healthy volunteers underwent magnetic resonance imaging and positron emission tomography using a radioligand antagonist of 5-HT(1A) receptors [4-(2'-methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine ((18)F-MPPF)]. A simplified reference tissue model was used to generate parametric images of 5-HT(1A) receptor binding potential (BP) values. Statistical Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior cortical areas and hippocampi bilaterally in patients compared with controls. Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and raphe nuclei. During the interictal period of migraine patients without aura, the increase of MPPF BP in posterior cortical and limbic areas could reflect an increase in receptor density or a decrease of endogenous serotonin, which could explain their altered cortical excitability.

Olfactory hypersensitivity in migraineurs: a H(2)(15)O-PET study.

Olfactory hypersensitivity (OHS) may occur during migraine attacks and seems to be very specific to this form of headache. OHS is also observed during migraine-free periods and is associated with the presence of odour-triggered attacks. Yet the pathophysiology of OHS remains unknown. The aim of our study was to evaluate olfactory processing in migraineurs with OHS and to investigate whether regional cerebral blood flow (rCBF) associated with olfactory stimulation is modified in these patients compared with controls. Eleven migraineurs with OHS and 12 controls participated in a H(2)(15)O-positron emission tomography study, including three scans in which odours were delivered and three scans where only odourless air was delivered. rCBF during olfactory condition was compared with that for the odourless baseline condition. Between-group analyses were performed using voxel-based and region-of-interest analyses. During both olfactory and non-olfactory conditions, we observed higher rCBF in the left piriform cortex and antero-superior temporal gyrus in migraineurs compared with controls. During odour stimulation, migraineurs also showed significantly higher activation than controls in the left temporal pole and significantly lower activation in the frontal (left inferior as well as left and right middle frontal gyri) and temporo-parietal (left and right angular, and right posterior superior temporal gyri) regions, posterior cingulate gyrus and right locus coeruleus. These results could reflect a particular role of both the piriform cortex and antero-superior temporal gyrus in OHS and odour-triggered migraine. Whether these rCBF changes are the cause or a consequence of odour-triggered migraines and interictal OHS remains unknown. Further comparisons between migraineurs with and without OHS are warranted to address this issue. The abnormal cerebral activation patterns during olfactory stimulation might reflect altered cerebrovascular response to olfactory stimulation due to the migraine disease, or an abnormal top-down regulation process related to OHS.