Epileptic auras: phenomenology and neurophysiology

This review discusses the phenomenology, neurophysiology, and localization of epileptic auras with particular emphasis on how auras can manifest as part of an epileptic network. Epileptic auras, as the first clinical symptom of a seizure, may lead us to infer the site of seizure onset. At the same time, auras can also be a result of activation or alteration in an epileptic network. They can be highly specific or ill‐defined in symptomatology. They occur as a result of limited seizure activation, allowing access of the neural signal to the conscious brain. An understanding of epileptic auras offers a window into understanding fundamental brain functions, and helps the clinician at the bedside to make appropriate diagnostic and therapeutic choices.     

Familial migraine with and without aura: clinical characteristics and co-occurrence

Migraine with aura (MwA) and migraine without aura (MwoA) are the two common forms of migraine. Many migraine patients suffer from both kinds of attacks. In a questionnaire-based study using the current International Headache Society (IHS) criteria we determined the clinical characteristics and occurrence of MwA + MwoA in 1000 migraine patients belonging to 210 Finnish migraine families. Nine hundred and six patients were able to indicate whether they suffered from MwA (but not MwoA), migraine aura without headache (migraine equivalent) (but not MwA) or MwA and MwoA. Of these patients, 3.2% had experienced MwoA, 11.1% MwA, 40.6% MwA + MwoA, 23.5% MwoA and 20.3% MwA-like symptoms not meeting the IHS criteria. The high prevalence of MwA attacks in the families studied supports the belief that aura has a strong hereditary component. The MwA + MwoA patients had significantly more severe attacks, more typical headache and more prodromal symptoms than the MwA and MwoA subjects. Therefore, it is possible that there is a continuum with pure MwA at the neural and pure MwoA at the headache end of the spectrum, and MwA + MwoA lying in between the two. The MwA + MwoA patients would thus be liable to both types of migraine, making their attacks more characteristic and more severe. This would also explain why the co-occurrence of MwA and MwoA is more common in the clinic compared with population based epidemiological studies. These findings have consequences for future research on liability genes for migraine.     

Validation of a migraine-specific questionnaire for use in family studies

The availability of valid migraine-specific questionnaires is important when large numbers of migraine patients have to be analysed. The Finnish Migraine-Specific Questionnaire has been validated in two stages. In the first, a clinical diagnosis of migraine was reached, using International Headache Society criteria, in 100 consecutive patients. Migraine was then diagnosed independently on the basis of responses to the Finnish Migraine-Specific Questionnaire. In the second stage, responses to 100 questionnaires returned consecutively in a family study in progress were analysed, and respondents were contacted by telephone for interview and diagnosis of migraine. Contact proved impossible in six cases. The sensitivity of the questionnaire for migraine was 0.99 (167 out of 168; validation stages 1 and 2 combined) and specificity was 0.96 (25 out of 26 cases; validation stage 2). It also proved possible to differentiate between migraine with and without aura on the basis of responses to the Finnish Migraine-Specific Questionnaire: chance-corrected agreement (Cohen's kappa) was 0.804 in relation to diagnoses reached on the basis of responses to the Finnish Migraine-Specific Questionnaire and clinically was 0.858 in relation to diagnoses reached on the basis of responses to the Finnish Migraine-Specific Questionnaire combined with the results of the telephone interviews. A value for Cohen's kappa > 0.75 indicates good agreement. Therefore, use of the Finnish Migraine-Specific Questionnaire in research into migraine genetics is justified.     

Clinical characteristics of migraine concordant monozygotic twin pairs

OBJECTIVES: The aim of the study was to search for clinical differences between migraine with and without aura. MATERIALS AND METHODS: From a population-based Finnish Twin Cohort we studied 51 migraine concordant monozygotic twin pairs. RESULTS: There were 20 pairs concordant for migraine with aura, 6 pairs concordant for migraine without aura and 12 "mixed" pairs. In the remaining 13 pairs the aura of at least 1 twin could not be classified. All 20 migraine with aura pairs were concordant for visual aura and 19 for moderate or severe headache while all 6 pairs with migraine without aura were concordant for headache duration of 4 to 24 h, moderate or severe headache and nausea. The 12 "mixed" pairs had more often unilateral and pulsating headache compared to both the migraine with or without aura pairs. Overall individual migraine with aura twins had more photophobia (P = 0.032) and the migraine without aura twins more nausea (P = 0.025). CONCLUSIONS: The difference between migraine with and without aura is not explained entirely by genetical factors: 12 genetically identical twin pairs were discordant for the aura. The headache phase in migraine with and without aura is very similar, but not identical. Probably there are several and different liability loci for the migraine aura and the migraine headache. The distribution of these several loci along with acquired factors will decide whether the phenotype is migraine with or without aura.     

The genetics of migraine

Clinical, pathophysiological and genetic studies indicate that migraine without aura (MO) and migraine with aura (MA) are distinct entities. Compared with the general population, first degree relatives of probands with MO have a two-fold increased risk of MO. The mode of inheritance is most likely multifactorial inheritance without generational difference, but genetic heterogeneity can not be excluded. Compared with the general population, first degree relatives of probands with MA have a four-fold increased risk of MA. The mode of inheritance is most likely multifactorial inheritance without generational differences. Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of MA. A gene for FHM maps to chromosome 19. Some families with FHM do not link to this locus, indicating genetic heterogeneity of FHM. The gene for FHM is soon to be cloned. Loci for the more common types of migraine MO; and MA will problably be identified in the near future.     

应用对比经颅多普勒技术评价偏头痛和卵圆孔未闭的关系

目的：观察门诊有先兆偏头痛（MA），无先兆偏头痛（M0）患者和无头痛人群中卵圆孔未闭（PFO）的发生率，以及产生中或大分流PFO的发生率。方法：经受试者同意后，随机抽取我院神经内科门诊从2006年3月至2007年3月就诊的MA患者38例（男14例，女24例），MO患者44例（男15例，女29例），无头痛对照24例（男10例，女14例）。以肘前静脉注射手振生理盐水作为造影剂，并结合Valsaval动作，行经颅多普勒（TCD）监测，诊断PFO并对分流量进行分级。结果：MA组与对照组比，具有PFO者占42％，高于对照组的20％；其中中分流或大分流者高于对照组，差异有统计学意义。MO组具有PFO者也高于对照组，但差异无统计学意义。结论：MA患者比无头痛人群存在较多的PFO，其巾出现中分流或大分流的显著增多。     

Temporal–occipital glioblastoma presenting with Alice in Wonderland Syndrome in a patient with a long-time history of migraine without aura

ABSTRACT

Alice in Wonderland Syndrome (AIWS) is a rare perceptual disorder characterized by an erroneous perception of the body or the surrounding space. AIWS may be caused by different pathologies, ranging from infections to migraine. We present the case of a 54-year-old man, with a long-time history of migraine without aura, diagnosed with AIWS due to a glioblastoma located in the left temporal–occipital junction. To date, this is the first case of AIWS caused by glioblastoma. This case suggests that to exclude aura-mimic phenomena, a careful diagnostic workup should always be performed even in patients with a long-time history of migraine.     

Increased risk of migraine with typical aura in probands with familial hemiplegic migraine and their relatives

We investigated the occurrence of migraine without aura (MO) and migraine with typical aura (MA) amongst probands with familial hemiplegic migraine (FHM) and their first degree relatives in order to evaluate the relations between these syndromes. A total of 44 FHM probands and 240 first degree relatives were identified in the Danish population. The pattern of familial aggregation was assessed by population relative risk (PRR) calculations. Amongst FHM probands the PRR of MO was 1.5 (95% CI: 0.8-2.2), whereas the PRR of MA was 7.1 (95% CI: 5.0-9.2). Thus, compared with the general population, FHM probands had no increased risk of MO but a significantly increased risk of MA. A similar pattern was seen amongst their first degree relatives, who had no increased risk of MO, whereas the risk of MA was significantly increased; 7.6 times in FHM-affected first degree relatives and 2.4-times in non-FHM-affected first degree relatives. These results are contrary to a sharing of genetic mechanisms between FHM and MO. Furthermore, they suggest that the genetic abnormality causing FHM may also cause attacks with the symptomatology of MA.     

Evidence for an altered dopamine-hydroxylase activity in migraine and tension-type headache

Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis.     

The localizing value of epileptic auras: pitfalls in semiology and involved networks

A more complete understanding of the epileptic aura represents an important challenge for localizing the epileptogenic zone and understanding brain networks. This review re‐visits the localizing value of the epileptic aura, focusing on clinical pitfalls in epileptogenic zone detection and the importance of defining functional connectivity. We review the role of network node activation or alteration and its relationship to hub activation.     

Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis

Background: Many studies investigated the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and migraine, with controversial results. Thus, we performed a meta-analysis to better evaluate the correlation of this polymorphism and migraine. Methods: We retrieved studies published up to September 2014 about the ACE gene polymorphism and migraine from electronic database. Pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated to examine the strength of association between the ACE I/D polymorphism and migraine, using random-effects models. Results: We identified 14 separate studies, in which 7334 migraineurs and 22 990 healthy controls were eligible for the meta-analysis. The results showed no relationship between the ACE I/D polymorphism and any migraine. Stratification revealed a protective effect in the Turkish population against migraine with aura for the II genotype model (II vs. DD: pooled OR = 0.366, 95% CI = 0.137–0.980; II vs. DI + DD: pooled OR = 0.370, 95% CI = 0.145–0.945). Similar results were obtained for Turkish people with migraine without aura (II vs. DD: pooled OR = 0.386; 95% CI = 0.166–0.900; II vs. DI + DD: pooled OR = 0.347; 95% CI = 0.156–0.773). Conclusions: The data suggest that the ACE II genotype could exert a protective effect against migraine with aura and without aura at least in the Turkish population.     

Simple partial seizures with hemisensory phenomena and dysgeusia: an insular pattern

Insular seizures are rarely described, in part owing to the complex anatomy of this brain region. We present a patient with simple partial seizures, recorded intracranially, originating in the right insula and characterized by dysgeusia and contralateral somatosensory phenomena. This rare clinical pattern seems to be characteristic of the insula and may be undetectable with surface EEG.     

Cephalic aura after frontal lobe resection

A cephalic aura is a common sensory aura typically seen in frontal lobe epilepsy. The generation mechanism of cephalic aura is not fully understood. It is hypothesized that to generate a cephalic aura extensive cortical areas need to be excited. We report a patient who started to have cephalic aura after right frontal lobe resection. Magnetoencephalography (MEG) showed interictal spike and ictal change during cephalic aura, both of which were distributed in the right frontal region, and the latter involved much more widespread areas than the former on MEG sensors. The peculiar seizure onset pattern may indicate that surgical modification of the epileptic network was related to the appearance of cephalic aura. We hypothesize that generation of cephalic aura may be associated with more extensive cortical involvement of epileptic activity than that of interictal activity, in at least a subset of cases.     

Is the genetic liability in multifactorial disorders higher in concordant than discordant monozygotic twin pairs? A population‐based family twin study of migraine without aura

Migraine without aura (MO) is a multifactorial disorder. Expression of a disorder with multifactorial inheritance depends on the genetic liability and on environmental factors. A high liability is reflected by a high frequency of affected relatives. We have previously shown that monozygotic (MZ) twin pairs have a significant higher concordance of MO than dizygotic twin pairs. The incomplete concordance among MZ twin pairs may be due to a lower genetic liability among discordant than concordant MZ twin pairs. The present study analysed the genetic liability in MZ twin pairs concordant and discordant for MO by the population-relative risk of MO among parents and siblings. The twin pairs were from the population-based Danish Twin Register. First-degree relatives of 29 concordant and 34 discordant MZ twin pairs were blindly telephone interviewed by a physician. The participation rate of the eligible first-degree relatives was 96%. The population-relative risk of MO among parents and siblings was 2.73 (2.39-3.06) in concordant and 2.37 (2.03-2.71) in discordant MZ twin pairs. The relative risk of MO was significantly higher in female first-degree relatives of concordant than of discordant MZ male and female twin pairs. An opposite effect was observed in male first-degree relatives, although this was not significant for male first-degree relatives of female MZ twin pairs. The present study found no statistically significant difference in genetic liability to MO among concordant and discordant MZ twin pairs. However, a difference in genetic liability among MZ and DZ twin pairs is anticipated to be small. Thus, it may be possible to show the effect in a larger study population or by investigating a more frequent trait than MO.     

Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot study

Termine C, Trotti R, Ondei P, Gamba G, Montani N, Gamba A, De Simone M, Marni E, Balottin U. Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot study.
Acta Neurol Scand: 2010: 122: 91–96.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To investigate the prevalence of mitral valve prolapse (MVP) and abnormalities of haemostasis in children and adolescents with migraine with aura (MA) compared with peers affected by other idiopathic headaches. Materials and methods – We recruited 20 MA patients (10 men and 10 women; age range 8–17 years) and 20 sex‐ and age‐matched subjects with other idiopathic headaches. Both groups underwent colour Doppler transthoracic echocardiography to detect MVP and the following laboratory work‐up: plasma prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, protein C, protein S, homocysteine, lupus anticoagulant, von Willebrand factor (vWF) ristocetin cofactor activity, immunoglobulins (Ig) G and M anticardiolipin antibodies (aCL). Factor V Leiden, factor II and methylenetetrahydrofolate reductase were investigated (we did not test the entire genes, but screened for specific point mutations). Results – The prevalence of MVP was significantly higher in the MA subjects than in the patients affected by other idiopathic headaches (40% vs 10%; P < 0.05). Moreover, the MA patients showed a higher rate of above‐normal IgM aCL titres (45% vs 10%; P < 0.05). Finally, in the group of patients with MVP we found a higher prevalence of aCL in those with MA compared with those affected by other idiopathic headaches. Conclusions – A proportion, at least, of the MA patients showed a more complex phenotype characterized by MVP and/or positive aCL titres. The pathogenetic role of these associations is obscure and larger studies are needed to confirm the usefulness of echocardiographic and laboratory investigations in this area and to identify possible new treatment approaches that might be explored in this group of MA patients.     

No effect of eletriptan administration during the aura phase of migraine

Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in > 50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase.