Migraine Disorders: Sándor PS

Anonymous00234, Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS. · Department of Neurology, University of Münster, Germany. European Federation of NeurologicalSocieties · Eur J Neurol. · Pubmed #16796580 No free full text.

Abstract: Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. To give evidence-based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non-steroidal anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

Straube A, May A, Kropp P, Katsarava Z, Haag G, Lampl C, Sándor PS, Diener HC, Evers S. · Neurologische Klinik, Klinikum Grosshadern der Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 München, Deutschland. · Schmerz. · Pubmed #18483751 No free full text.

Abstract: The criteria of the International Headache Society (IHS) define four different primary headache syndromes with daily chronic headaches: chronic migraine, episodic and chronic tension type headache, hemicrania continua, new daily persisting headache. A further important differential diagnosis is medication overuse headache (previously known as analgesia headache). The German, Austrian, and Swiss headache societies now present the first joint guidelines for therapy of these headache syndromes. The current literature was reviewed and a summary is presented. The therapy recommendations do not only include the scientific evidence but also the practical relevance.

Gantenbein AR, Sándor PS. · Headache and Pain Unit, Neurology Department, University Hospital Zurich, Zurich, Switzerland. · Headache. · Pubmed #16866711 No free full text.

Abstract: We review physical signs and measurements from neurophysiological research, which may be considered biomarkers of migraine. Most studies show that information processing is abnormal in migraineurs. Studies of trigeminal nociception are in line with a central sensitization during the attack. The best documented abnormality is an interictal lack of habituation in migraineurs, with a normalization during the headache state, which has been shown using evoked and event-related potentials. Together with a diminished energy reserve found in MR-spectroscopy studies, these results suggest a possible role of increased energy consumption in attack generation. Importantly, to date, no neurophysiological marker has a high enough sensitivity and specificity to point out the single migraine patient. Therefore, these biomarkers are to be understood as tools for research and are not to be used for diagnostic purposes.

Sándor PS, Afra J. · Headache and Pain Unit, Neurology Department, Frauenklinikstr 26, 8091 Zürich, Switzerland. · Curr Pain Headache Rep. · Pubmed #15907259 No free full text.

Abstract: Nonpharmacologic treatment of migraine is often used by patients and can provide interesting options for physicians. Knowledge about the evidence and its absence is important. Avoidance of trigger factors can help, if individualized. Behavioral approaches, such as relaxation techniques, biofeedback, and cognitive-behavioral therapy, require far more specialist time or technical devices, but are supported by some evidence, which is mostly old. The same is true for hypnosis. A new approach in migraine prevention is aerobic exercise, which is associated with positive side effects. Whether it will take a strong role, similar to the treatment of depression, remains to be seen. There is no convincing evidence for the efficacy of spinal manipulation. Hyperbaric oxygen may be an effective, but rarely practical prophylactic measure. The evidence pertaining to the efficacy of acupuncture is controversial because of methodologic difficulties, but an ongoing large German study may provide valuable evidence in the near future. Nutritional supplements acting on mitochondrial metabolism, such as magnesium, riboflavin, and coenzyme Q10, were shown to be effective in small, randomized, controlled trials. More studies on the different therapeutic interventions are needed, using modern diagnostic standards and state-of-the-art trial methodology.

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.

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.

This publication has no abstract.

Sándor PS, Dydak U, Schoenen J, Kollias SS, Hess K, Boesiger P, Agosti RM. · Neurology Department, University Hospital, Zurich, Switzerland. · Cephalalgia. · Pubmed #15955037 No free full text.

Abstract: Migraine pathophysiology possibly involves deficient mitochondrial energy reserve and diminished cortical habituation. Using functional magnetic resonance spectroscopic imaging (fMRSI), we studied cortical lactate changes during prolonged visual stimulation to search for different pathophysiological mechanisms in clinically distinct subgroups of migraine with aura. Eleven healthy volunteers (HV) and 10 migraine patients were investigated interictally: five with visual aura (MA) and five with visual symptoms and at least one of the following: paraesthesia, paresis or dysphasia (MAplus). Using MRSI (Philips, 1.5 T) (1)H-spectra were repeatedly obtained from a 25 mm-thick slice covering visual and non-visual cortex, with the first and fifth measurements in darkness and the second to fourth with 8-Hz checkerboard stimulation. In MAplus lactate increased only during stimulation, only in visual cortex; in MA resting lactate was high in visual cortex, without further increase during stimulation. This is compatible with an abnormal metabolic strain during stimulation in MAplus, possibly due to dishabituation, and a predominant mitochondrial dysfunction in MA.

Sándor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen J. · Headache and Pain Unit, Neurology Department, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland. · Neurology. · Pubmed #15728298 No free full text.

Abstract: Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 x 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

Sándor PS, Afra J, Proietti Cecchini AP, Albert A, Schoenen J. · Department of Neurology, CHR Citadelle, University of Liège, Belgium. · Funct Neurol. · Pubmed #11200803 No free full text.

Abstract: Migraine patients show impaired cortical information processing between attacks with deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. VEP-habituation and IDAP were studied in 40 migraine patients, i.e. pairs of 20 parents and their children. We developed a novel approach based on Monte Carlo statistics to selectively assess vertical familial influences. Both groups, parents and children, were characterized by abnormal VEP-habituation and IDAP. However, similarity between related pairs was far more pronounced than similarity between unrelated pairs. Assessed with a novel statistical approach, familial influences proved to be highly significant in determining cortical information processing in migraineurs, thus supporting the important role of genetic factors.

Andrée C, Vaillant M, Rott C, Katsarava Z, Sándor PS. · Centre d'Etudes en Santé, Centre de Recherche Public, Santé, Luxembourg, Luxembourg. · J Headache Pain. · Pubmed #18712275 No free full text.

Abstract: We developed a 77-item self-reporting questionnaire to assess the burden of migraine (BURMIG), including headache characteristics, migraine associated disability, comorbidities, management, and the consequences on the patients' lives. We translated BURMIG into four languages (French, Portuguese, German and English) and tested it in 130 headache patients (20 pain clinic, 17 primary care and 93 general public) in Luxembourg. We performed a linguistic and a face-content validation and tested the questionnaire for its comprehensiveness, internal consistency and for its retest-reliability at an interval of 1 month (completion rates were 79.6 and 76.4%, for test and retest, respectively). Retest-reliability for the different parts of the questionnaire varied between 0.6 and 1.0 (Kappa coefficient), with an intracorrelation coefficient of 0.7-1.0. The internal consistency was between 0.74 and 0.91 (Cronbach's alpha). The questionnaire BURMIG is suitable to evaluate the burden of migraine and can be used in English, German, French and Portuguese.

Ambrosini A, Sándor PS, De Pasqua V, Pierelli F, Schoenen J. · Headache Clinic, IRCCS INM Neuromed, via Atinense 18, 86077 Pozzilli, Isernia, Italy. · J Headache Pain. · Pubmed #18250962 links to  free full text

Abstract: In previous studies, we described subclinical abnormalities of neuromuscular transmission and cerebellar functions in migraineurs. The aim of this study was to search if these two functions are correlated in the same patient. Thirteen migraineurs [five without aura (MO) and eight with aura (MA)] underwent both stimulation-SFEMG and 3D-movement analysis. Single fiber EMG (SFEMG) results were expressed as the "mean value of consecutive differences" (mean MCD). Precision of arm-reaching movements (measured with an infrared optoelectronic tracking system) was expressed as the average deviation in the horizontal plane. Median values of mean MCD and mean horizontal deviation were not different between MO and MA. However, in MA, but not in MO, both variables were positively correlated. Thus, we conclude that neuromuscular transmission and cerebellar functions are correlated in the same patient when affected by migraine with aura. We suggest that this correlation might be due to a common molecular abnormality.

Gaul C, Sándor PS, Galli U, Palla S, Ettlin DA. · Clinic for Masticatory Disorders and Complete Dentures, Centre for Dental and Oral Medicine and Cranio-Maxillofacial Surgery, University of Zurich, Zurich, Switzerland. · Cephalalgia. · Pubmed #17645761 No free full text.

This publication has no abstract.

Schoonman GG, Sándor PS, Agosti RM, Siccoli M, Bärtsch P, Ferrari MD, Baumgartner RW. · Department of Neurology, Leiden University Medical Centre, the Netherlands. · Cephalalgia. · Pubmed #16776696 No free full text.

Abstract: Migraine prevalence is increased in high-altitude populations and symptoms of acute mountain sickness mimic migraine symptoms. Here we tested whether normobaric hypoxia may trigger migraine attacks. As positive control we used nitrolgycerin (NTG), which has been shown to induce migraine attacks in up to 80% of migraineurs. Sixteen patients (12 females, mean age 28.9 +/- 7.2 years) suffering from migraine with (n = 8) and without aura (n = 8) underwent three different provocations (normobaric hypoxia, NTG and placebo) in a randomized, cross-over, double dummy design. Each provocation was performed on a separate day. The primary outcome measure was the proportion of patients developing a migraine attack according to the criteria of the International Headache Society within 8 h after provocation onset. Fourteen patients completed all three provocations. Migraine was provoked in six (42%) patients by hypoxia, in three (21%) by NTG and in two (14%) by placebo. The differences among groups were not significant (P = 0.197). The median time to attacks was 5 h. In conclusion, the (remarkably) low response rate to NTG is surprising in view of previous data. Further studies are required to establish fully the potency of hypoxia in triggering migraine attacks.

Sándor PS, Morath GP, Hess K, Kaube H, Agosti RM, Regard M. · Headache & Pain Unit, Neurology Department, University Hospital Zurich, Zurich, Switzerland. · Cephalalgia. · Pubmed #16472345 No free full text.

This publication has no abstract.

Thomas E, Sándor PS, Ambrosini A, Schoenen J. · Research Center for Cellular and Molecular Neurobiology, University of Liège, Belgium. · Cephalalgia. · Pubmed #11993613 No free full text.

Abstract: Migraine patients show abnormalities of cerebral electrophysiology that manifest themselves mainly during the attack interval. Cortical-evoked potentials of migraineurs fail to habituate to repetitive presentations of visual stimuli, and the amplitude of components of their auditory cortical-evoked potentials have a higher dependence on the stimulus intensities than in healthy subjects. A computer model of a neural hetwork has been developed that is able to reproduce both these neurophysiological dysfunctions. It predicts a positive correlation between the magnitudes of both these dysfunctions. The model also offers an explanation of why mutations in the same ion channel gene with opposite consequences on channel function, e.g. P/Q Ca2+ channels in migraine, may lead to similar electrophysiological abnormalities.

Sándor PS, Mascia A, Seidel L, de Pasqua V, Schoenen J. · Neurology Department, University Hospitals of Zurich, Switzerland. · Ann Neurol. · Pubmed #11357959 No free full text.

Abstract: Mutations in the CACNA1A gene can cause familial hemiplegic migraine (FHM) and/or cerebellar ataxia CACNA1A codes for the alpha1 subunit of P/Q-Ca2+ channels and is highly expressed in the cerebellum. Using a pointing paradigm and infrared optoelectronic tracking system, we found subclinical hypermetria and other subtle cerebellar signs in the common forms of migraine. These were more pronounced in migraine with than without aura. Whether this reflects involvement of Ca2+ channel genes in the common types of migraine needs to be investigated by genetic analyses.

Judit A, Sándor PS, Schoenen J. · Department of Neurology, Semmelweis University of Medicine, Budapest, Hungary. · Cephalalgia. · Pubmed #11167900 No free full text.

Abstract: Between attacks, migraine with (MO) or without aura (MA) patients show deficient habituation of pattern-reversal visual evoked potentials (PR-VEP) and a strong intensity dependence of auditory evoked cortical potentials (IDAP). Clinical observations of migraine prodromes and previously published electrophysiological studies suggest that cortical information processing may vary in close temporal relationship to the attack. We studied PR-VEP and IDAP just before (11 MO pts), during (23 MO, 3 MA), 1 day following (27 MO, 1 MA) and 2 days following (14 MO) a migraine attack. The results were compared with a large group of MO patients recorded at a distance of at least 3 days from an attack (n = 66 for IDAP; n = 39 for VEP). Patients recorded the day before the attack had on average an habituation of -13.6+/-20.5% (mean +/- SD) between the 5th and 1st block of 100 averaged VEP responses and a flat (0.38+/-1.06 microV/10 dB) amplitude-stimulus intensity function (ASF) slope of the auditory evoked cortical potential. Both values were significantly different from those obtained in the attack interval (P=0.003; P=0.020). During the attack, VEP habituation was less pronounced (-0.17+/-26.2%) and ASF slopes remained flat (0.32+/-1.44 microV/10 dB; P=0.002 compared to interval). During the 2 days following the attack, VEP habituation was replaced by potentiation (+0.09+/-29.1% the 1st day; 19.5+/-45.7% the 2nd day) and ASF slopes increased markedly (0.87+/-1.39 and 1.14+/-1.12 microV/10 dB). The normalization of evoked cortical responses just before and during the attack, might reflect an increase in the cortical preactivation level due to enhanced activity in raphe-cortical serotonergic pathways.

Afra J, Proietti Cecchini A, Sándor PS, Schoenen J. · Department of Neurology Semmelweis University of Medicine, Budapest, Hungary. · Clin Neurophysiol. · Pubmed #10825720 No free full text.

Abstract: OBJECTIVE: As both habituation of pattern reversal visual evoked potentials (PR-VEP) (Schoenen J, Wang W, Albert A, Delwaide PJ. Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks. Eur J Neurol 1995;2:115-122) and intensity dependence of auditory evoked cortical potentials (IDAP) (Wang W, Timsit-Berthier M, Schoenen J. Intensity dependence of auditory evoked potentials in migraine: an indication of cortical potentiation and low serotonergic neurotransmission? Neurology 1996;46:1404-1409) were found abnormal in migraine between attacks, we have searched for intraindividual correlations between both tests in 59 migraine patients (22 with aura [MA], 37 without aura [MO]) and in 23 healthy volunteers (HV). METHODS: Amplitude change of the PR-VEP N1-P1 was measured between the 1st and 5th block of 50 sequential averagings during continuous stimulation at 3.1 Hz. IDAP was computed from N1-P2 amplitudes of 100 averagings during stimulations at 40, 50, 60 and 70 dB SL. Amplitude-stimulus intensity function (ASF) slopes and amplitude changes between 40 and 70 dB were calculated. MO and MA differed from HV in PR-VEP amplitude change (P=0.007) and IDAP slope (P = 0.0004). RESULTS: There was no significant correlation between VEP amplitude changes and IDAP slopes, nor between the latter two and attack frequency or disease duration. A negative correlation was found between the amplitude of the first block of averaged responses and potentiation of VEP in all subject groups (P = 0.03) as well as between the amplitude of the auditory evoked potential, at 40 dB, and the percentage of amplitude increase between 40 and 70 dB in MO (P = 0.004) and MA (P = 0.007). ASF slopes and 40 dB amplitudes were significantly correlated only in the MA group (P = 0.002). These results confirm the interictal deficit of habituation in cortical processing of repetitive visual and auditory information in migraine. Since there is no intraindividual correlation between the cortical responses to these sensory modalities they are complementary tools for the study of migraine and may help to identify subgroups of patients with distinct pathophysiological mechanisms. CONCLUSIONS: The strong negative correlation between the initial amplitude of evoked potentials and their amplitude increase during subsequent averaging confirms that the response potentiation in migraine is likely to be due to a reduced preactivation level of sensory cortices.

Sándor PS, Afra J, Ambrosini A, Schoenen J. · Neurology Department, CHR Citadelle, University of Liège, Belgium. · Headache. · Pubmed #10759900 No free full text.

Abstract: OBJECTIVE: To investigate the influence of different pharmacological treatments on the intensity dependence of auditory evoked cortical potentials in migraineurs. BACKGROUND: Between attacks, patients with migraine show abnormalities in cortical information processing and decreased brain mitochondrial energy reserve. Both are most probably relevant for migraine pathogenesis, and they could be differentially modified by prophylactic drug therapy. Design.-The intensity dependence of the auditory evoked cortical potentials is, on average, increased in migraine. We have studied this intensity dependence in 26 patients before and after a 4-month period of prophylaxis with beta-blockers (n = 11, all migraine without aura; metoprolol or bisoprolol) or riboflavin (n = 15, migraine without aura: 13, migraine with aura: 2). Recordings were performed at least 3 days before or after an attack. RESULTS: After the treatment with beta-blockers, the intensity dependence of the auditory evoked cortical potentials was significantly decreased (before: 1.66+/-1.02 microV/10 dB; after: 0.79+/-1.06 microV/10 dB, P=.02). The decrease in intensity dependence was correlated significantly with clinical improvement (r = .69, P = .02). There was no change in intensity dependence after riboflavin treatment (before: 1.80+/-0.81 microV/10 dB; after: 1.56+/-0.83 microV/10 dB, P = .39), although the majority of patients showed improvement. CONCLUSIONS: These results confirm that beta-blockers and riboflavin act on two distinct pathophysiological mechanisms. Combining both treatments might enhance their efficacy without increasing central nervous system side effects.

Schoenen J, Sándor PS. · No affiliation provided · Cephalalgia. · Pubmed #10526679 No free full text.

This publication has no abstract.

Sándor PS, Afra J, Proietti-Cecchini A, Albert A, Schoenen J. · Neurology Department, University of Zurich, Switzerland. · Neuroreport. · Pubmed #10363931 No free full text.

Abstract: Cortical information processing in migraine patients is impaired between attacks, showing deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. We investigated VEP habituation and IDAP in 20 pairs of migraineurs made up of parents and their children. Using a Monte-Carlo statistical method, we selectively assessed vertical familial influences. VEP habituation and IDAP were abnormal in both parents and children. However, similarity was far more pronounced between related pairs than between unrelated pairs. Familial influences are highly significant in determinants of cortical information processing in migraineurs, hence supporting the important role of genetic factors.

Gaul C, Sándor PS, Ettlin DA. · No affiliation provided · Cephalalgia. · Pubmed #18254900 No free full text.

This publication has no abstract.