Anna Ambrosini

Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study.

&NA; Oral steroids can interrupt bouts of cluster headache (CH) attacks, but recurrence is frequent and may lead to steroid‐dependency. Suboccipital steroid injection may be an effective ‘single shot’ alternative, but no placebo‐controlled trial is available. The aim of our study was to assess in a double‐blind placebo‐controlled trial the preventative effect on CH attacks of an ipsilateral steroid injection in the region of the greater occipital nerve. Sixteen episodic (ECH) and seven chronic (CCH) CH outpatients were included. ECH patients were in a new bout since no more than 1 week. After a one‐week run‐in period, patients were allocated by randomization to the placebo or verum arms and received on the side of attacks a suboccipital injection of a mixture of long‐ and rapid‐acting betamethasone (n=13; Verum‐group) or physiological saline (n=10; Plac‐group). Acute treatment was allowed at any time, additional preventative therapy if attacks persisted after 1 week. Three investigators performed the injections, while four others, blinded to group allocation, followed the patients. Follow‐up visits were after 1 and 4 weeks, whereafter patients were followed routinely. Eleven Verum‐group patients (3 CCH) (85%) became attack‐free in the first week after the injection compared to none in the Plac‐group (P=0.0001). Among them eight remained attack‐free for 4 weeks (P=0.0026). Remission lasted between 4 and 26 months in five patients. A single suboccipital steroid injection completely suppresses attacks in more than 80% of CH patients. This effect is maintained for at least 4 weeks in the majority of them.

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.

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.

Prophylactic Treatment of Migraine With β‐Blockers and Riboflavin: Differential Effects on the Intensity Dependence of Auditory Evoked Cortical Potentials

Objective.– To investigate the influence of different pharmacological treatments on the intensity dependence of auditory evoked cortical potentials in migraineurs.

Familial basilar migraine associated with a new mutation in the ATP1A2 gene

Basilar migraine (BM), familial hemiplegic migraine (FHM), and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by motor symptoms, which are absent in BM. Mutations in CACNA1A and ATP1A2 have been found in FHM. The authors detected a novel mutation in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and FHM may be allelic disorders.

The electrophysiology of migraine

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.

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brains electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes.

Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20–35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypo-functioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.

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.

Neuromuscular transmission in migraine A single-fiber EMG study in clinical subgroups

Objective: To search for impairment of neuromuscular transmission by single-fiber electromyography (SFEMG) in patients with common forms of migraine. Background: P/Q Ca2+ channels are genetically abnormal in most cases of familial hemiplegic migraine (International Headache Society [IHS] code 1.2.3) and may be involved in other types of migraine. Besides in the brain, these channels are found in motor nerve endings, where they control stimulation-induced acetylcholine release. If they are functionally abnormal, the neuromuscular transmission might be impaired. Methods: Sixty-two migraineurs (18 without aura, IHS code 1.1; 19 with typical aura, IHS code 1.2.1; 10 with prolonged aura, IHS code 1.2.2; 15 with and without aura) and 16 healthy control subjects underwent stimulation SFEMG. Results were expressed as the mean value of consecutive differences (MCD) and percentage of single-fiber abnormalities (abnormal jitter or impulse blocking). Results: Average MCD was comparable in control subjects and migraineurs (17.1 ± 2.6 versus 17.5 ± 4.7 μsec). By contrast, single-fiber abnormalities were found in 17 patients but in none of the control subjects (p = 0.036). Most of these patients had unilateral sensorimotor symptoms and/or aphasia and/or loss of balance during the aura. SFEMG abnormalities were significantly correlated with the occurrence of these clinical features and with a diagnosis of migraine with prolonged aura. Conclusions: Stimulation SFEMG shows mild abnormalities of neuromuscular transmission in a subgroup of migraineurs with aura, characterized by clinical features frequently found in human P/Q Ca2+ channelopathies. These abnormalities might thus be due to genetically modified P/Q Ca2+ channels.