Peter S. Sándor

EFNS guideline on the drug treatment of migraine – revised report of an EFNS task force

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.

Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial

Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 × 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.

Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance

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.

Habituation of visual and intensity dependence of auditory evoked cortical potentials tends to normalize just before and during the migraine attack.

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.

Electrophysiological studies in migraine: a comprehensive review of their interest and limitations.

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.

Subclinical cerebellar impairment in the common types of migraine: A three-dimensional analysis of reaching movements

Mutations in the CACNA1A gene can cause familial hemiplegic migraine (FHM) and/or cerebellar ataxia. CACNA1A codes for the α1 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.

Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior.

BACKGROUND There is ample evidence that a subgroup of Parkinsons disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. Using a pharmacogenetic approach, we investigated how variation in this gene modulates the impact of dopaminergic stimulation on gambling behavior in healthy subjects. METHODS We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration. RESULTS Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individuals DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation. CONCLUSIONS These findings demonstrate that genetic variation in the DRD4 gene determines an individuals gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinsons disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.

Hypoxia-Induced Acute Mountain Sickness is Associated with Intracellular Cerebral Edema: A 3 T Magnetic Resonance Imaging Study

Acute mountain sickness is common among not acclimatized persons ascending to high altitude; the underlying mechanism is unknown, but may be related to cerebral edema. Nine healthy male students were studied before and after 6-h exposure to isobaric hypoxia. Subjects inhaled room air enriched with N2 to obtain arterial O2 saturation values of 75 to 80%. Acute mountain sickness was assessed with the environmental symptom questionnaire, and cerebral edema with 3 T magnetic resonance imaging in 18 regions of interest in the cerebral white matter. The main outcome measures were development of intra- and extracellular cerebral white matter edema assessed by visual inspection and quantitative analysis of apparent diffusion coefficients derived from diffusion-weighted imaging, and B0 signal intensities derived from T2-weighted imaging. Seven of nine subjects developed acute mountain sickness. Mean apparent diffusion coefficient increased 2.12% (baseline, 0.80±0.09; 6 h hypoxia, 0.81 ± 0.09; P = 0.034), and mean B0 signal intensity increased 4.56% (baseline, 432.1 ±98.2; 6 h hypoxia, 450.7 ± 102.5; P < 0.001). Visual inspection of magnetic resonance images failed to reveal cerebral edema. Cerebral acute mountain sickness scores showed a negative correlation with relative changes of apparent diffusion coefficients (r = 0.83, P = 0.006); there was no correlation with relative changes of B0 signal intensities. In conclusion, isobaric hypoxia is associated with mild extracellular (vasogenic) cerebral edema irrespective of the presence of acute mountain sickness in most subjects, and severe acute mountain sickness with additional mild intracellular (cytotoxic) cerebral edema.

Reduced gating of middle-latency auditory evoked potentials (P50) in migraine patients: another indication of abnormal sensory processing?

Habituation of cortical evoked responses to repetitive stimuli is reduced in migraine between attacks. To explore another aspect of information processing, we measured auditory sensory gating. The amplitude of the P50 response to the second of two homologous stimuli was significantly less reduced in migraineurs than in healthy volunteers. This lack of auditory sensory gating may be due to a hypofunction of monoaminergic subcortico-cortical pathways, which is also supposed to cause the interictal deficit of cortical habituation to repetitive stimuli.

Facial pain: clinical differential diagnosis

Differential diagnosis of pain in the face as the presenting complaint can be difficult. We propose an approach based on history and neurological examination, which allows a working diagnosis to be made at the bedside, including aetiological hypotheses, leading to a choice of investigations. Neuralgias are characterised by stabs of short lasting, lancinating pain, and, although neuralgias are often primary, imaging may be needed to exclude symptomatic forms. Facial pain with cranial nerve symptoms and signs is almost exclusively of secondary origin and requires urgent examination. Facial pain with focal autonomic signs is mostly primary and belongs to the group of the idiopathic trigeminal autonomic cephalalgias, but can occasionally be secondary. Pure facial pain is most often due to sinusitis and the chewing apparatus, but also a multitude of other causes. The pain can also be idiopathic. Imaging as well as non-neurological specialist assessment is often necessary in these cases.