Vestibular migraine pathophysiology: insights from structural and functional neuroimaging

Vestibular migraine (VM) has been increasingly recognized as a frequent cause of episodic vertigo, affecting up to 1 % of the general population, with female preponderance. Recently, both the Bárány Society and the Migraine Classification Subcommittee of the International Headache Society have proposed original diagnostic criteria for VM, which have been included in the recent edition of the ICHD-3 beta version. VM diagnosis implies that vestibular symptoms are present during a migraine attack, with or without headache, in the absence of objectively demonstrated interictal vestibulopathy. Nevertheless, despite a growing body of literature, there is still an ongoing debate regarding whether VM origin is principally central or peripheral. However, during the past few years, the extensive application of advanced MRI techniques has contributed to significantly improve the understanding VM pathophysiology. Functional and structural abnormalities have been detected in brain areas involved in multisensory vestibular control and central vestibular processing in patients with VM. In this brief review, we will focus on these recent neuroimaging findings.     

Migraine vestibulaire : critères diagnostiques. Document consensuel de la Société Bárány et de la Société internationale des céphalées

This paper presents diagnostic criteria for vestibular migraine, jointly formulated by the Committee for Classification of Vestibular Disorders of the Bárány Society and the Migraine Classification Subcommittee of the International Headache Society (IHS). The classification includes vestibular migraine and probable vestibular migraine. Vestibular migraine will appear in an appendix of the third edition of the International Classification of Headache Disorders (ICHD) as a first step for new entities, in accordance with the usual IHS procedures. Probable vestibular migraine may be included in a later version of the ICHD, when further evidence has been accumulated. The diagnosis of vestibular migraine is based on recurrent vestibular symptoms, a history of migraine, a temporal association between vestibular symptoms and migraine symptoms and exclusion of other causes of vestibular symptoms. Symptoms that qualify for a diagnosis of vestibular migraine include various types of vertigo as well as head motion-induced dizziness with nausea. Symptoms must be of moderate or severe intensity. Duration of acute episodes is limited to a window of between 5 minutes and 72 hours.     

Increased frequency of migraine in narcoleptic patients

We explored the relationship between narcolepsy and different types of headaches. We interviewed 68 patients with idiopathic narcolepsy for the presence of headache symptoms based on the criteria of the International Headache Society (IHS). Eighty-one percent of the patients reported headaches that warranted an IHS headache diagnosis. Fifty-four percent of the patients (64% women, 35% men) had migraine with all IHS criteria fulfilled.     

The interrelations of migraine, vertigo, and migrainous vertigo

OBJECTIVE: To assess the prevalence of migrainous vertigo in patients with migraine and in patients with vertigo according to explicit diagnostic criteria that are presented for discussion. METHODS: The authors prospectively evaluated 200 consecutive patients from a dizziness clinic and 200 patients from a migraine clinic for migrainous vertigo based on the following criteria: 1) recurrent vestibular symptoms (rotatory/positional vertigo, other illusory self or object motion, head motion intolerance); 2) migraine according to the criteria of the International Headache Society (IHS); 3) at least one of the following migrainous symptoms during at least two vertiginous attacks: migrainous headache, photophobia, phonophobia, visual or other auras; and 4) other causes ruled out by appropriate investigations. In addition, the authors compared the prevalence of migraine according to the IHS criteria in the dizziness clinic group with a sex- and age-matched control group of 200 orthopedic patients. RESULTS: The prevalence of migraine according to the IHS criteria was higher in the dizziness clinic group (38%) compared with the age- and sex-matched control group (24%, p < 0.01). The prevalence of migrainous vertigo was 7% in the dizziness clinic group, and 9% in the migraine clinic group. In 15 of 33 patients with migrainous vertigo, vertigo was regularly associated with migrainous headache. In 16 patients, vertigo occurred both with and without headache, and in two patients headache and vertigo never occurred together. The duration of attacks varied from minutes to days. CONCLUSION: These results substantiate the epidemiologic association between migraine and vertigo and indicate that migrainous vertigo affects a significant proportion of patients both in dizziness and headache clinics.     

Epidemiology of vertigo,migraine and vestibular migraine

Both migraine and vertigo are common in the general population with lifetime prevalences of about 16 % for migraine and 7 % for vertigo. Therefore, a concurrence of the two conditions can be expected in about 1.1 % of the general population by chance alone. However, recent epidemiological evidence suggests that the actual comorbidity is higher, namely 3.2 %. This can be explained by the fact that several dizziness and vertigo syndromes occur more frequently in migraineurs than in controls including benign paroxysmal positional vertigo, Meniere’s disease, motion sickness, cerebellar disorders and anxiety syndromes which may present with dizziness. In addition, there is increasing recognition of a syndrome called vestibular migraine (VM), which is vertigo directly caused by migraine. VM affects more than 1 % of the general population, about 10 % of patients in dizziness clinics and at least 9 % of patients in migraine clinics. Clinically, VM presents with attacks of spontaneous or positional vertigo lasting seconds to days. Migrainous accompaniments such as headache, phonophobia, photophobia or auras are common but not mandatory. Cochlear symptoms may be associated but are mostly mild and non-progressive. During acute attacks one may find central spontaneous or positional nystagmus and, less commonly, unilateral vestibular hypofunction. In the symptom-free interval, vestibular testing adds little to the diagnosis as findings are mostly minor and non-specific. In the absence of controlled studies, treatment of VM is adopted from the migraine sphere comprising avoidance of triggers, stress management as well as pharmacotherapy for acute attacks and prophylaxis.     

Lack of migraine in headaches of familial dysautonomia patients

Familial Dysautonomia (FD) is an autosomal recessive genetic disease where autonomic and sensory functions are defective affecting many body systems including the vascular. Plasma level of the neurotransmitter Calcitonin Gene Related Peptide (CGRP) is decreased in FD patients. This compound has been implicated to take part in the pathogenesis of migraine. We aimed to evaluate the symptoms of headaches in FD patients and to test the hypothesis that these patients will have a low incidence of migrainous headache. Sixty-five FD patients were evaluated by a medical headache questionnaire. Mean age was 23.73 + 10.82 years (mean 21 years) and there were 37 males (57 %).Thirty-eight patients (58.5 %) described having episodic headache conforming to criteria of tension headache, and in 17 of those 38 (44.7 %) headache were dependent on changes in blood pressure, except from one patient who had complaints that matched diagnosis of acephalic migraine. None of the patients had symptoms compatible with migraine or cluster headache. Results show that the headache is a very common complaint in FD, there is lack of migraine symptoms in this group. This might be attributed to defective sensory innervation and deficiency of CGRP. FD could be regarded as a human model for CGRP deficiency when studying the pathogenesis of migraine.     

Psychopathology and headache

Headache patients seen in headache clinics, apart from pain and physical symptoms, commonly present psychological problems of anxio-depressive nature, and in some cases traits of a pathological personnality. It is thus worthwhile to review the present state of knowledge about the comorbidity of psychiatric disorders and migraine, tension type headache, chronic daily headache and transformed migraines. Migraine sufferers in particular have been investigated more thoroughly than patients with other types of headache. Several studies have been conducted on migraine sufferers in the general population diagnosed using well-defined criteria ("International Headache Society" and "American Psychiatric Association"). There is a consensus that migraine sufferers have a higher risk of anxio-depressive disorders than the general population. Some authors also found a higher risk of substance (alcohol, drugs) abuse in migraine sufferers, which is consistent with the abuse of pain-killers commonly noted in patients seen in headache clinics. The patients seen in such clinics are, therefore, not representative of the general population. The coexistence of anxiety and/or depression and analgesic abuse in headache patients has been little explored from an epidemiological point of view. The nature of the link between the two types of disorder remains unknown: cause and effect, common etiological factor. However, it is apparent that the anxio-depressive disorder and analgesic abuse worsens the prognosis of the headache condition and that the treatment of headache in the general sense needs to take account of the underlying psychiatric morbidity rather than be restricted to treatment of the headache per se.     

Health services utilization of patients with vertigo in primary care: a retrospective cohort study

Vertigo and dizziness count among the most frequent symptoms in outpatient practices. Although most vestibular disorders are manageable, they are often under- and misdiagnosed in primary care. This may result in prolonged absence from work, increased resource use and, potentially, in chronification. Reliable information on health services utilization of patients with vertigo in primary care is scarce. Retrospective cohort study in patients referred to a tertiary care balance clinic. Included patients had a confirmed diagnosis of benign paroxysmal positional vertigo (BPPV), Menière’s disease (MD), vestibular paroxysmia (VP), bilateral vestibulopathy (BVP), vestibular migraine (VM), or psychogenic vertigo (PSY). All previous diagnostic and therapeutic measures prior to the first visit to the clinic were recorded. 2,374 patients were included (19.7 % BPPV, 12.7 % MD, 5.8 % VP, 7.2 % BVP, 14.1 % VM, 40.6 % PSY), 61.3 % with more than two consultations. Most frequent diagnostic measures were magnetic resonance imaging (MRI, 76.2 %, 71 % in BPPV) and electrocardiography (53.5 %). Most frequent therapies were medication (61.0 %) and physical therapy (41.3 %). 37.3 % had received homoeopathic medication (39 % in BPPV), and 25.9 % were treated with betahistine (20 % in BPPV). Patients had undergone on average 3.2 (median 3.0, maximum 6) diagnostic measures, had received 1.8 (median 2.0, maximum 8) therapies and 1.8 (median 1.0, maximum 17) different drugs. Diagnostic subgroups differed significantly regarding number of diagnostic measures, therapies and drugs. The results emphasize the need for establishing systematic training to improve oto-neurological skills in primary care services not specialized on the treatment of dizzy patients.     

Migraine and Ménière's disease: is there a link?

BACKGROUND: A possible link between Ménière's disease (MD) and migraine was originally suggested by Prosper Ménière. Subsequent studies of the prevalence of migraine in MD produced conflicting results. OBJECTIVE: To determine the lifetime prevalence of migraine in patients with MD compared to sex- and age-matched controls. METHODS: The authors studied 78 patients (40 women, 38 men; age range 29 to 81 years) with idiopathic unilateral or bilateral MD according to the criteria of the American Academy of Otolaryngology. Diagnosis of migraine with and without aura was made via telephone interviews according to the criteria of the International Headache Society. Additional information was obtained concerning the concurrence of vertigo and migrainous symptoms during Ménière attacks. The authors interviewed sex- and age-matched orthopedic patients (n = 78) as controls. RESULTS: The lifetime prevalence of migraine with and without aura was higher in the MD group (56%) compared to controls (25%; p < 0.001). Forty-five percent of the patients with MD always experienced at least one migrainous symptom (migrainous headache, photophobia, aura symptoms) with Ménière attacks. CONCLUSIONS: The lifetime prevalence of migraine is increased in patients with MD when strict diagnostic criteria for both conditions are applied. The frequent occurrence of migrainous symptoms during Ménière attacks suggests a pathophysiologic link between the two diseases. Alternatively, because migraine itself is a frequent cause of audio-vestibular symptoms, current diagnostic criteria may not differentiate between MD and migrainous vertigo.     

Clinical progress in headache]

In Western communities, 15 to 20% of the general population experiences migraine headaches. In Japan, 3 to 9% of the population experience migraine headaches. Quality of life in headache patients is impaired. The International Headache Society (IHS) published the new headache classification in 1988. Chronic daily headache (CDH) is a common problem in headache clinics. Recently, the problems in classifying CDH have been discussed. CDH is not easily classified within the IHS criteria. For migraine attacks, triptans are effective. The genetic analysis in migraine is progressing. Point mutations in the P/Q-type Ca2+ channel alpha 1 subunit gene in familial hemiplegic migraine and in Notch 3 gene in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), have been identified. Although CADASIL patients in Europe often show migraine headache, migraine attacks are less common in Japanese CADASIL patients.     

Efficacy of Ginkgolide B in the prophylaxis of migraine with aura

In a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll^®), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 ± 2.2 in the run-in period, to 2.0 ± 1.9 during TI and to 1.2 ± 1.6 during TII; Anova for repeated measures: P < 0.0001). There was also a statistically significant decrease in the average MA duration, which was 40.4 ± 19.4 min during run-in, 28.2 ± 19.9 during TI, and 17.6 ± 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll^® administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second.

     

Cerebrovascular reactivity during the Valsalva maneuver in migraine, tension-type headache and medication overuse headache

The aim of this study was to investigate, by means of transcranial Doppler ultrasound (TCD), cerebrovascular reactivity during the Valsalva maneuver (VM) during the headache-free interval in patients with migraine (M), migraine plus tension-type headache (M+TTH), and migraine plus medication overuse headache (M+MOH). A total of 114 patients (n=60 M, n=38 M+TTH, n=16 M+MOH) and n=60 controls were investigated; diagnoses were made according to the International Headache Society criteria. All subjects underwent TCD monitoring and, simultaneously, non-invasive assessment of arterial blood pressure and end-tidal CO2. Two indices were determined: the cerebrovascular Valsalva ratio (CVR) was calculated as the maximum end-diastolic flow velocity acceleration during the late straining phase of the VM [cm/s2] and the centroperipheral Valsalva ratio (CPVR) was defined as the quotient of CVR to the concomitant arterial blood pressure acceleration [cm/mmHg x s]. The dynamic cerebrovascular autoregulatory response to the VM, measured as CVR, was increased in patients with M and M+TTH compared to age-matched healthy subjects. By contrast, CPVR (i.e. the quotient of the cerebrovascular to the peripheral autonomic response), was increased in M patients compared to healthy subjects and all other headache conditions tested. Cerebrovascular autoregulatory response during the VM was increased in M patients compared to age-matched normal healthy subjects, indicating a disturbed autonomic control of cerebral vasoreactivity. The CPVR seems to be a sensitive parameter for distinguishing between M patients and M+TTH or M+MOH patients.     

Intracranial pressure in unresponsive chronic migraine

To assess the prevalence and possible pathogenetic involvement of raised intracranial pressure in patients presenting with unresponsive chronic migraine (CM), we evaluated the intracranial opening pressure (OP) and clinical outcome of a single cerebrospinal fluid withdrawal by lumbar puncture in 44 consecutive patients diagnosed with unresponsive chronic/transformed migraine and evidence of sinus stenosis at magnetic resonance venography. The large majority of patients complained of daily or near-daily headache. Thirty-eight (86.4 %) had an OP >200 mmH₂O. Lumbar puncture-induced normalization of intracranial pressure resulted in prompt remission of chronic pain in 34/44 patients (77.3 %); and an episodic pattern of headache was maintained for 2, 3 and 4 months in 24 (54.6 %), 20 (45.4 %) and 17 (38.6 %) patients, respectively. The medians of overall headache days/month and of disabling headache days/month significantly decreased (p < 0.0001) at each follow-up versus baseline. Despite the absence of papilledema, 31/44 (70.5 %) patients fulfilled the ICHD-II criteria for “Headache attributed to Intracranial Hypertension”. Our findings indicate that most patients diagnosed with unresponsive CM in specialized headache clinics may present an increased intracranial pressure involved in the progression and refractoriness of pain. Moreover, a single lumbar puncture with cerebrospinal fluid withdrawal results in sustained remission of chronic pain in many cases. Prospective controlled studies are needed before this procedure can be translated into clinical practice. Nonetheless, we suggest that intracranial hypertension without papilledema should be considered in all patients with almost daily migraine pain, with evidence of sinus stenosis, and unresponsive to medical treatment referred to specialized headache clinics.     

Migraine and isolated recurrent vertigo of unknown cause

Chronic recurrent attacks of vertigo, not associated with any auditory or neurological symptoms, are a common reason for referral to our neurotology clinic. Even after an extensive neurotological evaluation, some cases remain undiagnosed. We prospectively evaluated 72 consecutive patients who presented to the clinic with isolated recurrent vertigo of unknown cause. All patients underwent diagnostic evaluation to exclude identifiable causes of isolated recurrent vertigo. We compared the prevalence of migraine, according to the International Headache Society (IHS) criteria, in the isolated recurrent vertigo group, with a sex- and age-matched control group of orthopedic patients. The prevalence of migraine according to IHS criteria was higher in the isolated recurrent vertigo group (61.1%) than in the control group (10%; p < 0.01). Only 16.7% of patients had an abnormal vestibular function test. The most common abnormal finding was a unilateral vestibular weakness to caloric stimulation. Our results suggest that migraine should be considered in the differential diagnosis of isolated recurrent vertigo of unknown cause.     

Instrumental investigations and migraine diagnosis

Migraine diagnosis is based on clinical parameters. Before reaching a correct diagnosis, patients usually consult a large number of specialists and perform unhelpful exams. This represents a significant problem for an optimization of healthy resources. Our aim in this study was to evaluate the relationship between time interval from symptoms’ onset to a correct diagnosis and number and type of clinical and instrumental investigations. We considered 180 consecutive patients referred to our Headache Center who obtained the first diagnosis of migraine without aura. Most patients were referred to our center by general practitioners (80%). Previously, about half of patients consulted a specialist not involved in migraine management. In 68% of cases, patients performed radiological and/or laboratory exams. Time from symptom onset to a correct diagnosis of migraine was less than 1 year in only 16.7% of the cases. In 83.3% of patients, the time delay overcame 1 year. In 53.3%, it reached 5 or more years. The time interval to obtain a correct diagnosis significantly influenced the number of specialists consulted and the number of radiological and laboratory investigations performed. Our findings confirm the presence of problems in migraine management. In particular, expensive and unnecessary visits and exams are very often prescribed. This inappropriate procedure could be easily counteracted by a correct application of diagnostic criteria for migraine.

     

Migraine and isolated recurrent vertigo of unknown cause

Abstract

Chronic recurrent attacks of vertigo, not associated with any auditory or neurological symptoms, are a common reason for referral to our neurotology clinic. Even after an extensive neurotological evaluation, some cases remain undiagnosed. We prospectively evaluated 72 consecutive patients who presented to the clinic with isolated recurrent vertigo of unknown cause. All patients underwent diagnostic evaluation to exclude identifiable causes of isolated recurrent vertigo. We compared the prevalence of migraine, according to the International Headache Society (IHS) criteria, in the isolated recurrent vertigo group, with a sex- and age-matched control group of orthopedic patients. The prevalence of migraine according to IHS criteria was higher in the isolated recurrent vertigo group (61.1%) than in the control group (10%; p< 0.01). Only 16.7% of patients had an abnormal vestibular function test. The most common abnormal finding was a unilateral vestibular weakness to caloric stimulation. Our results suggest that migraine should be considered in the differential diagnosis of isolated recurrent vertigo of unknown cause.     

Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label,add-on,controlled trial

Despite the huge health and economic burden of migraine headache, few medications have been approved for its prophylactic treatment, most of which can potentially induce serious adverse effects. Coenzyme Q10 (CoQ10) is a supplement and has shown preliminary benefits in migraine prophylaxis. We aimed to assess this effect in an adult population. This is an open-label, parallel, add-on, match-controlled trial. Eighty patients diagnosed with migraine headache based on International Headache Society criteria were allocated to receiving only their current preventive drugs or their current preventive drugs plus 100 mg CoQ10 daily, matching for their baseline characteristics, and were assessed for frequency and severity of attacks, and ≥50 % reduction in attack frequency per month. Thirty-six and 37 patients were analyzed in CoQ10 and control groups, respectively. Number of attacks per month dropped significantly in the CoQ10 group (mean decrease: 1.6 vs. 0.5 among CoQ10 and control groups, respectively, p < 0.001). A significant reduction was also evident in the severity of headaches (mean decrease: 2.3 vs. 0.6 among CoQ10 and control groups, respectively, p < 0.001). For ≥50 % reduction in the frequency of attacks per month, the number needed to treat was calculated as 1.6. No side effects for CoQ10 were observed. This study suggests that CoQ10 might reduce the frequency of headaches, and may also make them shorter in duration, and less severe, with a favorable safety profile.     

Episodic vertigo related to migraine (90 cases): vestibular migraine?

A retrospective study was conducted on 90 patients with episodic vertigo that could be related to migraine as the most probable pathomechanism. Since the majority of the patients did not fulfill the criteria of the International Headache Society (IHS) for basilar migraine, the diagnosis was substantiated by disease course, medical efficacy in treating (ergotamines) and preventing (metoprolol, flunarizine) attacks, ocular motor abnormalities in the symptom-free interval, and careful exclusion of the most relevant differential diagnoses, such as transient ischemic attacks, Menière’s disease, and vestibular paroxysmia. The following clinical features were elaborated. The initial manifestation could occur at any time throughout life, with a peak in the fourth decade in men and a “plateau” between the third and fifth decades in women. The duration of rotational (78%) and/or to-and-fro vertigo (38%) could last from a few seconds to several hours or, less frequently, even days; duration of a few minutes or of several hours was most frequent. Monosymptomatic audiovestibular attacks (78%) occurred as vertigo associated with auditory symptoms in only 16%. Vertigo was not associated with headache in 32% of the patients. In the symptom-free interval 66% of the patients showed mild central ocular motor signs such as vertical (48%) and/or horizontal (22%) saccadic pursuit, gaze-evoked nystagmus (27%), moderate positional nystagmus (11%), and spontaneous nystagmus (11%). Combinations with other forms of migraine were found in 52%. Thus, migraine is a relevant differential diagnosis for episodic vertigo. According to the criteria of the IHS, only 7.8% of these patients would be diagnosed as having basilar migraine. However, to ensure that at least those presenting with monosymptomatic episodic vertigo (78% in our study) receive effective treatment, we propose the use of the more appropriate term “vestibular migraine.” Received: 22 September 1998 Received in revised form: 3 March 1999 Accepted: 16 March 1999     

Migralepsy: A call for a revision of the definition

Migralepsy is an ill-defined nosologic entity, with only a few cases described in the literature. In the 2004 International Classification for Headache Disorders (ICHD-II), the International Headache Society proposed that the following diagnostic criteria should be met: (1) migraine fulfilling criteria for 1.2 Migraine with aura (MA) and (2) a seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within 1 h after a migraine aura. Herein, by presenting a case with symptoms suggestive of migralepsy and by reviewing all previous cases described in the literature, we discuss the challenges of differentiating this condition from epileptic seizures, as well as the inaccuracy of the current ICHD-II definition.