Migraine Disorders: Schoenen J

Anonymous00401, Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, Göbel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Silberstein SD, Steiner TJ. · Department of Neurology, University of Copenhagen, Glostrup Hospital, Demark. · Cephalalgia. · Pubmed #16686915 No free full text.

Abstract: After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Fernández-de-las-Peñas C, Schoenen J. · Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain. · Curr Opin Neurol. · Pubmed #19300250 No free full text.

Abstract: PURPOSE OF REVIEW: This review discusses current data on nosological boundaries related to diagnosis, pathophysiology and therapeutic strategies in chronic tension-type headache (CTTH). RECENT FINDINGS: Diagnostic criteria of CTTH should be adapted to improve its sensitivity against migraine. It seems that mechanical pain sensitivity is a consequence and not a causative factor of CTTH. Recent evidence is modifying previous knowledge about relationships between muscle tissues and CTTH, suggesting a potential role of muscle trigger points in the genesis of pain. An updated pain model suggests that headache perception can be explained by referred pain from trigger points in the craniocervical muscles, mediated through the spinal cord and the trigeminal nucleus caudalis rather than only tenderness of the muscles themselves. Different therapeutic strategies, pharmacological, physical therapy, psychological and acupuncture, are generally used. The therapeutic efficacy of nonsteroidal anti-inflammatory drugs remains incomplete. The tricyclic antidepressants are the most used first-line therapeutic agents for CTTH. Surprisingly, few controlled studies have been performed and not all of them have found an efficacy superior to placebo. Further, there is insufficient evidence to support/refute the efficacy of physical therapy in CTTH. SUMMARY: Although there is an increasing scientific interest in CTTH, future studies incorporating subgroups of patients who will likely to benefit from a specific treatment (clinical prediction rules) should be conducted.

Fumal A, Gérardy PY, Schoenen J. · Service Uni- versitaire de Neurologie, Unité de Recherches sur les Céphalées, Hôpital de la Citadelle, Liège, Belgique. · Rev Med Liege. · Pubmed #18669199 No free full text.

Abstract: Despite its high prevalence and individual as well as societal burden, migraine remains underdiagnosed and undertreated. In recent years, the options for the management of migraine patients have greatly expanded. A number of drugs belonging to various pharmacological classes and deliverable by several routes are now available both for the acute and the preventive treatments of migraine. Nevertheless, disability and satisfaction remain low in many subjects because treatments are not accessible, not optimized, not effective or simply not tolerated. There is thus still considerable room for better education and for more efficient therapies. In spite of useful internationally accepted guidelines, anti-migraine treatment has to be individually tailored to each patient taking into account the migraine subtype, the ensuing disability, the patient's previous history and present expectations, and the comorbid disorders. In this article we will summarize the phenotypic presentations of migraine and review recommendations for acute and preventive treatment, highlighting recent advances which are relevant for clinical practice in terms of both diagnosis and management.

Coppola G, Pierelli F, Schoenen J. · G.B. Bietti Eye Foundation-IRCCS, Department of Neurophysiology of Vision and Neurophthalmology, Rome, Italy. · Cephalalgia. · Pubmed #18034686 No free full text.

Abstract: Although migraineurs appear in general to be hypersensitive to external stimuli, they maybe also have increased daytime sleepiness and complain of fatigue. Neurophysiological studies between attacks have shown that for a number of different sensory modalities the migrainous brain is characterised by a lack of habituation of evoked responses. Whether this is due to increased cortical hyperexcitability, possibly due to decreased inhibition, or to an abnormal responsivity of the cortex due a decreased preactivation level remains disputed. Studies using transcranial magnetic stimulation in particular have yielded contradictory results. We will review here the available data on cortical excitability obtained with different methodological approaches in patients over the migraine cycle. We will show that these data congruently indicate that the sensory cortices of migraineurs react excessively to repetitive, but not to single, stimuli and that the controversy above hyper- versus hypo-excitability is merely a semantic misunderstanding. Describing the migrainous brain as 'hyperresponsive' would fit most of the available data. Deciphering the precise cellular and molecular underpinnings of this hyperresponsivity remains a challenge for future research. We propose, as a working hypothesis, that a thalamo-cortical dysrhythmia might be the culprit.

Magis D, Bendtsen L, Goadsby PJ, May A, Sánchez del Rio M, Sandór PS, Kaube H, Sandrini G, Schoonman GG, Schoenen J, Anonymous00021. · Headache Research Unit, Department of Neurology, University of Liège, Liège, Belgium. · Cephalalgia. · Pubmed #17970767 No free full text.

Abstract: Neuroimaging methods have been widely used in headache and migraine research. They have provided invaluable information on brain perfusion, metabolism and structure during and outside of migraine attacks, contributing to an improved understanding of the pathophysiology of the disorder. Human models of migraine attacks are indispensable tools in pathophysiological and therapeutic research. This review of neuroimaging methods and the attack-provoking nitroglycerin test is part an initiative by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9) with the objective of critically evaluating neurophysiological tests used in migraine. The first part, presented in a companion paper, is devoted to electrophysiological methods, this second part to neuroimaging methods such as functional magnetic resonance imaging, positron emission tomography and voxel-based morphometry, as well as the nitroglycerin test. For each of these methods, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols.

Magis D, Ambrosini A, Bendtsen L, Ertas M, Kaube H, Schoenen J, Anonymous00020. · Headache Research Unit, Department of Neurology, University of Liège, Liège, Belgium. · Cephalalgia. · Pubmed #17970766 No free full text.

Abstract: Neurophysiological testing has become a valuable tool for investigating brain excitability and nociceptive systems in headache disorders. Previous reviews have suggested that most neurophysiological tests have limited value for headache diagnosis, but a vast potential for exploring the pathophysiology of headaches, the central effects of certain pharmacological treatments and phenotype-genotype correlations. Many protocols, however, lack standardization. This meta-analytical review of neurophysiological methods in migraine was initiated by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9). Most of the neurophysiological approaches that have been used in headache patients are reviewed, i.e. evoked potentials, nociception-specific blink reflex, single-fibre electromyography, neuroimaging methods (functional MRI, PET, and voxel-based morphometry) and the nitroglycerin attack-provoking test. For each of them, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols. The first part is devoted to electrophysiological methods, the second to neuroimaging techniques and the NTG test.

Ambrosini A, Schoenen J. · Headache Clinic, INM Neuromed, IRCCS, Via Atinense 18, I-86077, Pozzilli (IS), Italy. · J Headache Pain. · Pubmed #17164990 No free full text.

Abstract: Migraine is an ictal disorder characterised by a particular vulnerability of patients to sensory overload, both during and outside of the attack. Central nervous system dysfunctions are supposed to play a pivotal role in migraine. Electroneurophysiological methods, which aim to investigate sensory processing, seem thus particularly appropriate to study the pathophysiology of migraine. We have thus reviewed evoked potential studies performed in migraine patients. Although results are in part contradictory, these studies nonetheless demonstrate an interictal dysfunction of sensory cortices, and possibly of subcortical structures, in migraine with and without aura. The predominant abnormality is a deficient habituation of evoked responses to repeated stimuli, probably due to cortical, and possibly widespread neural, "dysexcitability".

Bergerot A, Holland PR, Akerman S, Bartsch T, Ahn AH, MaassenVanDenBrink A, Reuter U, Tassorelli C, Schoenen J, Mitsikostas DD, van den Maagdenberg AM, Goadsby PJ. · Headache Group, Institute of Neurology, and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. · Eur J Neurosci. · Pubmed #17004916 No free full text.

Abstract: Animal models of human disease have been extremely helpful both in advancing the understanding of brain disorders and in developing new therapeutic approaches. Models for studying headache mechanisms, particularly those directed at migraine, have been developed and exploited efficiently in the last decade, leading to better understanding of the potential mechanisms of the disorder and of the action for antimigraine treatments. Model systems employed have focused on the pain-producing cranial structures, the large vessels and dura mater, in order to provide reproducible physiological measures that could be subject to pharmacological exploration. A wide range of methods using both in vivo and in vitro approaches are now employed; these range from manipulation of the mouse genome in order to produce animals with human disease-producing mutations, through sensitive immunohistochemical methods to vascular, neurovascular and electrophysiological studies. No one model system in experimental animals can explain all the features of migraine; however, the systems available have begun to offer ways to dissect migraine's component parts to allow a better understanding of the problem and the development of new treatment strategies.

Schoenen J, Burette P, Materne P. · Unité de Recherches sur les Céphalées, Service de Neurologie, CHR Citadelle, Liège, Belgique. · Rev Med Liege. · Pubmed #16910262 No free full text.

Abstract: Epidemiologic studies have shown a clear comorbidity between migraine with aura and a patent foramen ovale (PFO). Under the age of 55, migraine with aura is a risk factor for ischemic stroke and a proportion of the latter is due to a PFO. It remains to be determined whether PFO is causally related to migraine attacks, or is a fortuitous association due to common genetic factors. Cortical spreading depression which is the underlying mechanism of the migrainous aura, could be favoured by a PFO. Several retrospective and uncontrolled studies suggest that percutaneous closure of a PFO for stroke or decompression illness in divers reduces frequency of migraine attacks with, but also without aura. Multicentric, prospective and controlled trials of this intervention in migraineurs are underway or in preparation. As long as their results are not known, there is no rationale for proposing PFO closure for migraine.

Fumal A, Magis D, Schoenen J. · Services de Neurologie et de Neuroanatomie, Unité de Recherches sur les Céphalées, Université de Liège. · Rev Med Liege. · Pubmed #16789606 No free full text.

Abstract: Medication overuse headache (MOH) insidiously evolves from episodic migraine or tension-type headache because of overconsumption of analgesics, ergotamine or triptans. It affects 1-2% of the general population, but 15-20% of patients attending specialized headache centers. The precise neurobiologic mechanisms underlying this complication of episodic headaches are not well understood. Abnormalities of central monoaminergic systems have been suggested and substance dependence is more frequent in personal and family histories of affected subjects. In a recent FDG-PET study of 16 migraineurs with MOH before and after analgesics withdrawal we found a persistent hypometabolism of the medial orbitofrontal cortex, comparable to the one described after withdrawal in substance abuse. The orbitofrontal cortex plays a pivotal role in drive, decision-making and drug dependence. We postulate that its hypoactivity predisposes certain migraineurs to MOH and to relapse after withdrawal. There is no unique management strategy for these patients, but medication withdrawal is a prerequisite for the effectiveness of preventive treatments and headache improvement.

Schoenen J. · Department of Neurology-Headache Research Unit and Research Center for Cellular and Molecular Neurobiology, University of Liège, Liège, Belgium. · Neurol Sci. · Pubmed #16688634 No free full text.

Abstract: Migraine is a disorder in which central nervous system (CNS) dysfunction might play a pivotal role. As there are no consistent structural disturbances, clinical neurophysiology methods seem particularly suited to study its pathophysiology. This chapter will focus on a review of neurophysiological studies that have provided an insight into migraine pathogenesis. The results are in part contradictory, which may be due to the methodology, patient selection or timing of study. Nonetheless, quantitative electroencephalography and magnetoencephalography recordings during migraine attacks provide strong, though indirect, evidence favouring the occurrence of spreading cortical depression during attacks of migraine with, and possibly without, aura. Evoked cortical potential and nociceptive blink reflex studies demonstrate that lack of habituation during repetitive stimulation is a reproducible CNS dysfunction interictally in both migraine with and without aura. Transcranial magnetic stimulations show excitability changes of the visual cortex. The interictal migrainous CNS dysfunction is likely to play a role in migraine pathogenesis, has a familial character and undergoes periodic modulations with quasi-normalisation just before, during an attack and after treatment with certain prophylactic agents. In addition, neurophysiological methods have revealed subclinical abnormalities of cerebellar function and neuromuscular transmission, which may improve phenotyping of migraineurs for genetic and therapeutic studies.

Fumal A, Schoenen J. · Services de Neurologie et Neuroanatomie, Unité de Recherche sur les Céphalées, ULg. · Rev Med Liege. · Pubmed #15346975 No free full text.

Abstract: Our knowledge about migraine pathogenesis has increased exponentially over the last decade and this greatly due to the advances in genetics. In familial hemiplegic migraine (FHM), the findings of mutations in the CACNA1A gene (19p13), coding for the pore-forming subunit (alpha1A) of neuronal voltage-dependent P/Q-type calcium channels (FHM1), and in the ATP1A2 gene (1q21-23), encoding the alpha2-subunit of the Na+, K+ ATPase ionic pump (FHM2) have focused attention on central nervous system ionic channels and helped to better understand FHM pathophysiology. A dysfunction of these channels modifies neuronal excitability (favouring spreading depression), chemical neurotransmission and, indirectly, neuronal metabolism. These channels may represent targets for novel anti-migraine drugs, which underscores their importance for the frequent forms of migraine (without or with aura). Studies of gene associations, neuromuscular transmission, cerebellar functions, neuronal excitability and metabolism and certain drug effects suggest indeed that ionic channels play a pathogenic role in migraine with aura patients. However, in the majority of patients they are probably not the sole culprit, since most of the frequent forms of migraine seem to have a more complex genetic predisposition based on a number of single nucleotide polymorphisms. The challenge for the next decade is to establish correlations between the geno- and the phenotype of migraine patients which needs more frequent and focused genetic studies and a more precise phenotype, based on clinical as well as on neurophysiologic and metabolic data.

Sandrini G, Friberg L, Jänig W, Jensen R, Russell D, Sanchez del Rìo M, Sand T, Schoenen J, Buchem M, van Dijk JG. · University Centre for Adaptive Disorders and Headache, IRCCS C. Mondino Foundation, Pavia, Italy. · Eur J Neurol. · Pubmed #15061822 No free full text.

Abstract: The use of instrumental examinations in headache patients varies widely. In order to evaluate their usefulness, the most common instrumental procedures were evaluated, on the basis of evidence from the literature, by an EFNS Task Force (TF) on neurophysiological tests and imaging procedures in non-acute headache patients. The conclusions of the TF regarding each technique are expressed in the following guidelines for clinical use. 1 Interictal electroencephalography (EEG) is not routinely indicated in the diagnostic evaluation of headache patients. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic and basilar migraine. 2 Recording of evoked potentials is not recommended for the diagnosis of headache disorders. 3 There is no evidence to justify the recommendation of autonomic tests for the routine clinical examination of headache patients. 4 Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pressure algometry and electromyography (EMG) cannot be recommended as clinical diagnostic tests. 5 In adult and paediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological signs or symptoms, the routine use of neuroimaging is not warranted. In patients with atypical headache patterns, a history of seizures and/or focal neurological signs or symptoms, magnetic resonance imaging (MRI) may be indicated. 6 If attacks can be fully accounted for by the standard headache classification [International Headache Society (IHS)], a positron emission tomography (PET) or single-photon emission computerized tomography (SPECT) and scan will generally be of no further diagnostic value. 7 Nuclear medicine examinations of the cerebral circulation and metabolism can be carried out in subgroups of headache patients for diagnosis and evaluation of complications, when patients experience unusually severe attacks, or when the quality or severity of attacks has changed. 8 Transcranial Doppler examination is not helpful in headache diagnosis. Although many of the examinations described are of little or no value in the clinical setting, most of the tools have a vast potential for further exploring the pathophysiology of headaches and the effects of pharmacological treatment.

Schoenen J, Sándor PS. · Department of Neurology, Headache Research Unit, University of Liège, Belgium. · Lancet Neurol. · Pubmed #15039036 No free full text.

Abstract: Headache syndromes can be associated with focal neurological symptoms or signs. Good knowledge of primary headaches, a detailed history and a thorough clinical examination are prerequisites for their differential diagnosis. The neurological symptoms produced by the migraine aura are the most characteristic and recognisable. However, structural lesions, such as vascular malformations, can produce similar symptoms to migraine with aura, which highlights that paraclinical investigations are necessary in most patients with headache and focal neurological symptoms. In this review, we provide an overview of the differential diagnosis of the most common headache disorders with focal neurological symptoms or signs to refresh the practising neurologist's differential diagnostic knowledge for the clinical situation and to aid the teaching of neurology residents.

Fumal A, Bohotin V, Vandenheede M, Schoenen J. · Departments of Neurology and Neuroanatomy, University of Liège, B-4000 Liège, Belgium. · Acta Neurol Belg. · Pubmed #14626694 No free full text.

Abstract: There is compelling evidence that cortical excitability is modified in migraine patients between attacks. Transcranial magnetic stimulation (TMS) is a non-invasive tool to investigate this abnormality. Repetitive transcranial magnetic stimulation (rTMS) activates the underlying cortex at high, but inhibits it at low stimulation frequencies. This is a review of published results obtained in migraineurs with TMS and rTMS over motor or visual cortices. Prevalence and/or threshold data of phosphenes induced by single pulse TMS of the visual cortex are contradictory, some favouring increased, others decreased interictal excitability. The discrepancies may be due to differences in methodology and poor reliability of phosphene reporting. In a recent rTMS study of the occipital cortex we have found evidence in favour of an interictal decrease of the preactivation excitability level by using amplitude of visual evoked potentials and its habituation during sustained stimulation as indices of cortical excitability. The hypothesis of increased cortical excitability, taken in its strict physiological sense of a decreased response threshold and/or an increased response to a single suprathreshold stimulus, may thus not be any longer tenable. The long lasting effects of rTMS allow in future studies to assess metabolic changes of the cortex and subcortical structures with functional imaging methods and to explore novel therapeutic strategies for migraine.

Ambrosini A, Schoenen J. · Headache Clinic, INM Neuromed, IRCCS, Pozzilli, Isernia, Italy. · Curr Opin Neurol. · Pubmed #12858069 No free full text.

Abstract: PURPOSE OF REVIEW: The pathophysiology of migraine is far from being understood. Electrophysiological methods are useful to investigate peripheral and central mechanisms underlying this disorder. The purpose of this review is to highlight the results of electrophysiological studies published during the last year and to examine their added value to our previous knowledge. RECENT FINDINGS: Studies by visual and auditory evoked potentials and event-related responses suggested that lack of habituation is the principal interictal abnormality of sensory processing in migraineurs. Recently confirmed for somatosensory and laser-evoked cortical potentials and for brainstem responses, it is also responsible for the increased intensity dependence of auditory evoked potentials. This abnormality is possibly caused by a reduced cortical preactivation level due to hypofunctioning subcortico-cortical aminergic pathways. Although studies of cortical excitability by transcranial magnetic stimulation have yielded conflicting results, results obtained using habituation of pattern-reversal visual evoked potentials to explore cortical excitability changes induced by repetitive transcranial magnetic stimulation strongly favour the hypothesis that migraine is characterized by a decreased level of preactivation excitability. With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during the attack, and may even persist interictally. SUMMARY: Scientific publications over the last year confirmed that electrophysiological methods are particularly suited to unravelling some of the pathophysiological mechanisms of migraine. To improve their future contribution, they need to be better standardized and to be correlated with behavioural, metabolic and genetic studies.

Schoenen J, Ambrosini A, Sándor PS, Maertens de Noordhout A. · University Department of Neurology, CHR Citadelle, Blvd du XIIèmede Ligne, 1-B-4000, Liège, Belgium. · Clin Neurophysiol. · Pubmed #12804664 No free full text.

Abstract: Migraine is a disorder in which central nervous sytem dysfunction might play a pivotal role. Electroneurophysiology seems thus particularly suited to study its pathophysiology. We have extensively reviewed evoked potential and transcranial magnetic stimulation studies performed in migraineurs in order to identify their pathophysiologic significance. Publications available to us were completed by a Medline search. Retrieved and personal data were compared with respect to methodology and interpreted according to present knowledge on cortical information processing. Results are in part contradictory which appears to be method-, patient- and disease- related. Nonetheless, both evoked potential and transcranial magnetic stimulation studies demonstrate that the cerebral cortex, and possibly subcortical structures, are dysfunctioning interictally in both migraine with and without aura. These electrophysiologic abnormalities tend to normalise just before and during an attack and some of them seem to have a clear familial and predisposing character. Besides the studies of magnetophosphenes which have yielded contrasting results, chiefly because the method is not sufficiently reliable, most recent electrophysiologic investigations of cortical activities in migraine favour deficient habituation and decreased preactivation cortical excitability as the predominant interictal dysfunctions. We propose that the former is a consequence of the latter and that it could favour both interictal cognitive disturbances as well as a cerebral metabolic disequilibrium that may play a role in migraine pathogenesis. To summarize, electrophysiologic studies demonstrate in migraine between attacks a cortical, and possibly subcortical, dysfunction of which the hallmark is deficient habituation.

Ambrosini A, de Noordhout AM, Sándor PS, Schoenen J. · Headache Clinic, INM Neuromed, IRCCS, Pozzilli (Isernia),Italy. · Cephalalgia. · Pubmed #12699456 No free full text.

Abstract: Electrophysiological methods may help to unravel some of the pathophysiological mechanisms of migraine. Lack of habituation is the principal and most reproducible interictal abnormality in sensory processing in migraineurs. It is found in evoked potential (EP) studies for every stimulation modality including nociceptive stimuli, and it is likely to be responsible for the increased intensity dependence of EP. We have hypothesized that deficient EP habituation in migraine could be due to a reduced preactivation level of sensory cortices because of hypofunctioning subcortico-cortical aminergic pathways. This is not in keeping with simple hyperexcitability of the cortex, which has been suggested by some, but not all, studies of transcranial magnetic stimulation (TMS). A recent study of the effects of repetitive TMS on visual EP strongly supports the hypothesis that migraine is characterized by interictal cortical hypoexcitability. With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during migraine attacks.

Sándor PS, Ambrosini A, Agosti RM, Schoenen J. · Headache and Pain Unit, Neurology Department, University of Zürich, Switzerland. · Headache. · Pubmed #12047339 No free full text.

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Delvaux V, Schoenen J. · University Department of Neurology, University of Liège, Liège, Belgium. · Acta Neurol Belg. · Pubmed #11379275 No free full text.

Abstract: The prophylactic management of recurrent head and facial pains may be challenging because of lack of efficacy and/or bothersome adverse effects of available drug therapies. New generation antiepileptic drugs offer new perspectives in difficult cases. We will review the available published data and present our experience with lamotrigine in various head and facial pains such as migraine, cluster headache, neuropathic trigeminal pain, atypical facial pain, and chronic tension-type headache. Twenty-five patients were enrolled and followed for 18 months. The dose was gradually increased in steps of 25 mg up to the effective dose (mean 250 mg/d). Lamotrigine was most effective in trigeminal neuralgia and dysesthesia, but was of little utility in the other head or facial pains.

Edmeads J, Láinez JM, Brandes JL, Schoenen J, Freitag F. · Department of Medicine, University of Toronto, Ontario, Canada. · Neurology. · Pubmed #11294957 No free full text.

Abstract: Migraine is not always well managed in clinical practice, often being under-diagnosed and under-treated. As a result, many sufferers never consult a physician or lapse from care after physician contact. Although most migraine care is provided by general practitioners, others, including specialists, emergency room physicians, pharmacists, and alternative practitioners, may also be involved. A method of standardizing clinical information about migraine is essential for coordinated, logical, and systematic care. The impact of migraine on the patient is an important clinical parameter but one that is seldom inquired about, perhaps because it exhibits such marked variability among and within individuals. Headache-related disability can be an objective and measurable index of this impact. The Migraine Disability Assessment (MIDAS) Questionnaire is a simple and validated instrument with potential for use in clinical practice, research, and public health. It can improve communication between patients and health-care professionals regarding the impact of migraine which, in turn, allows tailoring of the intensity of treatment to the severity of the illness. Changes in the MIDAS score may serve as an end point in assessing treatment efficacy. In populations, MIDAS scores may indicate the burden of migraine in the community and spark public health initiatives to improve management.

Tfelt-Hansen P, Saxena PR, Dahlöf C, Pascual J, Láinez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ. · Department of Neurology, Glostrup Hospital, Copenhagen, Denmark. The · Brain. · Pubmed #10611116 links to  free full text

Abstract: Ergotamine has been used in clinical practice for the acute treatment of migraine for over 50 years, but there has been little agreement on its place in clinical practice. An expert group from Europe reviewed the pre-clinical and clinical data on ergotamine as it relates to the treatment of migraine. From this review, specific suggestions for the patient groups and appropriate use of ergotamine have been agreed. In essence, ergotamine, from a medical perspective, is the drug of choice in a limited number of migraine sufferers who have infrequent or long duration headaches and are likely to comply with dosing restrictions. For most migraine sufferers requiring a specific anti-migraine treatment, a triptan is generally a better option from both an efficacy and side-effect perspective.

Maertens de Noordhout A, Schoenen J. · University Department of Neurology, Hôpital de la Citadelle, Liège, Belgium. · Electroencephalogr Clin Neurophysiol Suppl. · Pubmed #10590958 No free full text.

This publication has no abstract.

Schoenen J. · Service universitaire de Neurologie, CHR Citadelle. · Rev Med Liege. · Pubmed #10221059 No free full text.

Abstract: This is a review of major new findings in migraine therapy during the last 2-3 years. As for acute treatment, large population studies have underscored both the advantages and the shortcomings of sumatriptan. Its subcutaneous form is by far superior to the other galenic forms, which may not be clearly better than adequately used NSAIDs. If one considers total headache relief at 1 hour (gain over placebo) for second generation oral triptans, elitriptan 80 mg seems superior to the others, but it is probably endowed with more CNS adverse effects; eletriptan 40 mg and rizatriptan 10 mg are slightly superior to sumatriptan 50 mg, zolmitriptan 2.5 mg or naratriptan 2.5 mg. It has been shown, including in humans, that the less hydrophilic triptans can act on central receptors. Efficacity in acute treatment was also demonstrated for an association of lysine acetylsalicylate-metoclopramide, for ibuprofen, for ketoprofen and for intranasal xylocaïne. In migraine prophylaxis a significant breakthrough came from riboflavin 400 mg, which has an outstanding efficacy-side effect profile.

Di Lorenzo C, Pierelli F, Coppola G, Grieco GS, Rengo C, Ciccolella M, Magis D, Bolla M, Casali C, Santorelli FM, Schoenen J. · University Centre for Adaptive Disorders and Headache, University of Rome La Sapienza, Polo Pontino-ICOT, Latina, Italy. · Neurology. · Pubmed #19414726 No free full text.

Abstract: OBJECTIVES: In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA (mtDNA) haplogroups. We focused our attention on haplogroup H, which is known to differ from others in terms of energy metabolism. METHODS: Sixty-four migraineurs completed a 4-month open trial with riboflavin (400 mg QD) and were genotyped blindly for mtDNA haplogroups. RESULTS: Forty patients responded to riboflavin treatment and 24 were nonresponders. The mtDNA haplogroup H was found in 29 subjects (20 migraine without aura, 9 migraine with aura). Riboflavin responders were more numerous in the non-H group (67.5%). Conversely, nonresponders were mostly H (66.7%). The difference between the two groups was significant (chi(2) = 7.07; p = 0.01). The presence of aura had no influence on riboflavin's effectiveness (chi(2) = 0.113; p = 0.74) and was not associated with a particular haplogroup (chi(2) = 0.55; p = 0.46). CONCLUSIONS: In this pharmacogenetic study, riboflavin appears to be more effective in patients with migraine with non-H mitochondrial DNA haplotypes. The underlying mechanisms are unknown, but could be related to the association of haplogroup H with increased activity in complex I, which is a major target for riboflavin. Our results may have ethnic implications, since haplogroup H is chiefly found in the European population.