Ménière’s disease (MD) (alone)
Vestibular migraine (VM) (alone)
Idiopathic intracranial hypertension
Vertebrobasilar insufficiency (VBI)
Benign recurrent vertigo (BRV)
Benign paroxysmal positional vertigo (BPPV) (vertigo lasting seconds)
Cerebellopontine angle (CPA) tumor
Multiple sclerosis (MS)
Episodic ataxia type 2 (EA2) syndrome
Autoimmune inner ear disease (AIED)
Benign paroxysmal vertigo (BPV) of childhood (children)
Juvenile migraine (children)
Enlarged vestibular aqueduct (EVA) (children)
Cranial nerve eight vascular compression
Chiari type I malformation
6.4.1 Basilar Migraine
Patients with basilar migraine make up only a small fraction of all migraine sufferers and there are formal International Headache Society (IHS) criteria for diagnosis . Patients are typically younger women who have an occipital headache that is preceded by less than 1 h of aura. The aura can include typical visual auras, visual field defects, vertigo, dysarthria, diplopia, tinnitus, hearing loss, ataxia, bilateral paresthesias, mental status changes, or bilateral limb weakness. The reason basilar migraine can occasionally be confused with MDVM is that MDVM can include symptoms of migraine headache, vertigo, tinnitus, and, rarely, a transient low-frequency sensorineural hearing loss (SNHL) [16, 17].
6.4.2 Idiopathic Intracranial Hypertension
Idiopathic intracranial hypertension has gone by many previous names such as benign intracranial hypertension and pseudotumor cerebri. It typically presents in women aged 20–40 years with an elevated body mass index (BMI) ≥25 kg/m2. Holocephalic headache without migrainous features and low-tone SNHL and vertigo have been reported, explaining why idiopathic intracranial hypertension is included in the differential for MDVM. Up to 25 % of untreated patients can develop vision loss or blindness. Other symptoms include pulsatile tinnitus, nausea, vomiting, nonspecific dizziness, imbalance, and visual flashes of light (scotomas). Patients do not have focal neurologic deficits or mental status changes. An MRI with a partial or completely empty sella turcica is suggestive of elevated intracranial pressure, but the diagnosis requires that the modified Dandy criteria be met, including: symptoms of increased intracranial pressure, non-focal neurologic exam with the exception of abducens palsy, normal mental status, normal imaging studies (not including empty sella on MRI), lumbar puncture opening pressures of greater than 250 mm H2O without cytological or chemical abnormality, and no other explanation for raised intracranial pressure . Although many physicians rely heavily on the presence or absence of ocular papilledema as a diagnostic screening, it is absent in 5–10 % of confirmed cases .
6.4.3 Vertebrobasilar Insufficiency
Vertebrobasilar insufficiency (VBI) is an intracranial posterior circulation transient ischemic attack (TIA), which, if left untreated, can lead to posterior cerebral infarction (anterior inferior cerebellar artery (AICA) or posterior inferior cerebellar artery (PICA) infarct). Most patients are over the age of 60 years and also have atherosclerotic risk factors such as smoking, high cholesterol, and hypertension. Multiple spontaneous bouts of vertigo can occur that usually last less than 20 min but can be longer. Clusters of attacks have been reported. Many times vertigo is brought on by neck extension; however, this is not always necessary. Around 19 % of patients present with vertigo without associated symptoms such as diplopia, visual loss, visual field deficit, dysarthria, dysphagia, mental status changes, or extremity weakness or clumsiness. Finally, headaches occur in 14 % of patients, explaining its inclusion in the differential diagnosis of MDVM. If isolated and repetitive vertigo has occurred for over 6 months without additional symptoms appearing, then VBI is unlikely to be the diagnosis [17, 20]. VBI diagnosis is usually confirmed with MRI/MRA or CT angiogram.
6.4.4 Benign Recurrent Vertigo
Benign recurrent vertigo (BRV) is a diagnosis given to patients with recurrent spontaneous vertigo that demonstrates overlapping features with vestibular migraine, Ménière’s disease, or MDVM; however BRV patients do not meet formal diagnostic criteria for any of these conditions. This is usually due to a lack of documented audiometric hearing loss or consistent timing between vertigo spells and migrainous symptoms. BRV has suffered from a lack of consistent nomenclature (chronic vestibulopathy, recurrent vestibulopathy, vestibular Ménière’s disease) and diagnostic validity. However, the stricter the vestibular migraine and Ménière’s disease criteria get, the more patients will default into this category. A few studies have shown that most of these patient’s symptoms will spontaneously resolve and do not evolve into Ménière’s disease [21, 22]. Similarly, most of these patients have migraine symptoms, such as photophobia, or strong family histories of migraine and, thus, from a practical clinical standpoint should be treated similar to vestibular migraine .
6.5 Hypotheses Concerning Comorbidity
6.5.1 Endolymphatic Hydrops
In 1938, Hallpike and Cairns performed an autopsy study and established the histopathologic description of endolymphatic hydrops (EH) in temporal bones of patients with Ménière’s disease . In a more recent meta-analysis, 541 temporal bone specimens with EH were analyzed and 276 (51 %) of these were found to have clinical Ménière’s disease by varying criteria. When applying the more strict diagnostic criteria set forth by the 1995 American Academy of Otolaryngology (AAO) Committee on Hearing and Equilibrium Ménière’s disease criteria, 98.8 % (163/165) of Ménière’s disease patients had EH, otherwise defined as certain Ménière’s disease. Of the 276 patients diagnosed with Ménière’s disease by varying criteria, 111 (40 %) of them did not meet the 1995 AAO criteria. Of these, 106/111 (95 %) had EH despite not having Ménière’s disease. The authors postulated that many of the EH patients not meeting the 1995 AAO Ménière’s disease criteria had fluctuating or progressive hearing loss without vertigo or had vertigo without documented hearing loss [4, 24]. A major problem with the authors’ assertion is that the clinical descriptions of vertigo from Ménière’s disease and vestibular migraine are often indistinguishable. None of the patients in the temporal bone meta-analysis were evaluated with vestibular migraine clinical criteria, and while not all of these patients had vestibular migraine, epidemiology statistics would suggest that at least some of them did. Consequently, it is possible that some percentage of vestibular migraine patients have EH. Temporal bone studies utilizing vestibular migraine diagnostic criteria are needed.
If vestibular migraine patients demonstrate EH, it is unknown if the presence or absence of EH is a predictor of later development of Ménière’s disease in addition to the vestibular migraine. Many vestibular migraine patients have isolated otologic symptoms such as tinnitus or aural fullness, which do not seem to predict Ménière’s disease development. Although controversial, a few have mild fluctuating SNHL while maintaining good speech discrimination scores. Could EH be a possible explanation for this? A natural question follows: does EH develop from repetitive ischemic episodes from vestibular migraine, and is Ménière’s disease just a more advanced disease presentation given the greater degree of hearing loss, the often permanent hearing loss, and the frequent vestibular hypofunction? Conversely, do vestibular migraine and EH occur independently due to another mechanism such as a channelopathy that leads to Ménière’s disease? Why do many vestibular migraine patients who may or may not have EH not develop Ménière’s disease? These and many other unproven hypotheses and unanswered questions will hopefully be answered or refuted with future research.
Transient changes in inner ear perfusion could cause vertigo in migraine patients, and repetitive vascular ischemia could lead to permanent cochleovestibular damage and symptoms seen in Ménière’s disease [11, 14]. It is unknown if the proposed decline in perfusion is from vasospasm of cochlear arteries (intralabyrinthine artery) or arterioles in a manner similar to the rare phenomenon of retinal artery vasospasm and retinal migraine . Another hypothesis is that EH can create increased resistance to blood flow and change autoregulation of microvasculature within the cochlea and labyrinth .
Foster et al. present logical, but as yet, unproven hypotheses for the physiology of Ménière’s disease and its interrelatedness to migraine. They postulated that preexisting EH is necessary but not sufficient to cause Ménière’s disease; however, they did not explain why EH develops. The patients must also have a heightened risk for intracerebral and intra-aural ischemia caused by such diseases as migraine, otosyphilis, and neuroborreliosis. Finally, the symptoms seen in Ménière’s disease are from inner ear tissues that are differentially sensitive to inner ear ischemia, particularly the apical stria vascularis in the cochlea. They hypothesized that any disease process that can cause decreased intracerebral arterial pressure, increased venous outflow resistance, or chronically raised intracerebral CSF pressure can provide heightened ischemia risk. They state that EH is not caused by ischemia and vascular risk factors do not result from EH, i.e., EH and vascular risk factors are related by chance . Unfortunately, this is not consistent with epidemiologic data where migraine and Ménière’s disease are not chance co-occurrences.
Since there is evidence that episodic ataxia syndromes and hemiplegic migraine result from channelopathies, many authors have recently hypothesized that Ménière’s disease and vestibular migraine may result from a similar pathogenesis. Ménière’s disease and vestibular migraine might be caused by a defective ion channel selectively expressed in neuronal and inner ear tissues. This would cause cortical spreading depression in migraine and toxic increases of perilymphatic potassium in the inner ear in Ménière’s disease . Further supporting this hypothesis is the observation that most potassium and calcium channelopathies produce adult-onset, paroxysmal symptoms, which are patterns consistent with vestibular migraine and Ménière’s disease . However, actual genetic, histologic, or pathophysiologic evidence for this hypothesis is currently lacking.
6.5.4 Central Mechanisms of Migraine Dizziness and Sterile Inflammation of the Inner Ear
Central mechanisms of vertigo play a major role in vestibular migraine pathophysiology. The vestibular nuclei receive serotonin-mediated input from the dorsal raphe nucleus and noradrenergic input from the locus ceruleus, which are both areas of the brain heavily involved in migraine physiology and, possibly, vertigo generation . The understanding of interconnections between different central migraine and pain pathways and central vestibular circuits is increasingly expanding and complex. These central migraine and vestibular pathways may also interact with the peripheral end organ, the inner ear. In addition to triggering spreading cortical depression, the trigeminovascular system is definitively implicated in the development of migraine pain and has been found to innervate the vasculature of the inner ear . The trigeminovascular reflex has been shown to cause sterile inflammation of the dura mater and the perivascular tissue of the basilar and anterior inferior cerebellar artery in animal models. Recent studies have shown a similar plasma/protein extravasation from the spiral modiolar artery and its arterioles. Koo et al. have shown neurogenic plasma extravasation by activation of the trigeminovascular reflex into the apical spiral ganglion, the modiolus, and the inner ear segments of the vestibular nerves in mice. Similarly, trigeminal sensory afferent fibers are found in very high density within the stria vascularis and, when stimulated, release neuropeptides such as calcitonin gene-related peptide, substance P, and neurokinin A. These neuropeptides induce a vasodilatory response and protein extravasation into the stria vascularis and endolymph . Additionally, neuropeptide release has an excitatory effect on the baseline neural activity of the inner ear [13, 31]. Although not conclusive, this sterile inner ear inflammation might be partly regulated by the main serotonin receptor targets of the triptans (5-HT 1A, 1B, 1D, 1F) which have been documented in the spiral ganglion and vestibular ganglion cells . Koo et al. also hypothesized that this sterile inflammation may cause an osmotic load that could interfere with the potassium recycling mechanism of the inner ear. They did not study the potential ischemic changes, loss of hair cells or stria cells, or development of possible EH after repetitive sterile inflammatory insults . While yet unproven, this hypothesis is very attractive as a potential explanation of auditory symptoms with vestibular migraine and possibly the development of EH or Ménière’s disease in the human patient.
6.6 Overlap in Clinical Presentation and Testing
A primary difficulty in diagnosing and categorizing Ménière’s disease and vestibular migraine is that some physicians have not adopted the Bárány classification of vestibular symptoms that are at the core of Ménière’s disease and vestibular migraine definition . Furthermore, there is yet no universal agreement as to which vertigo descriptions should be included in “typical” Ménière’s disease and vestibular migraine dizziness attacks. An example of such, Sargent used the Bárány definition of internal vertigo which is described as a “sense of self-motion when no motion is occurring, or the sensation of distorted self-motion during an otherwise normal head movement” when describing Ménière’s disease vertigo . This definition did not include external vertigo, which is “a false sensation that the visual surround is spinning or flowing” which most physicians would also include . Another problem with the definitions when applied to Ménière’s disease and vestibular migraine is that certain descriptions of internal or external vertigo do not likely belong in Ménière’s disease or vestibular migraine disease classification. An example of such includes this description of internal vertigo: “there is a spinning inside of my head; or it feels as if my brain is turning within my skull.” This sensation of internal vertigo is more likely described with conversion disorder and does not fall into most clinician’s definition of Ménière’s disease or vestibular migraine-like vertigo. Lastly, physicians have the problem that the patient may not be able to reliably discriminate these subtleties and relay them accurately. It is the author’s experience that many cannot.
Increasing recognition of vestibular migraine criteria such as the Neuhauser criteria or the most recent Bárány and IHS society definition can only help to better categorize these patients for prognosis and treatment trials [33, 34]. However, there are some issues with these criteria when it comes to treating everyday Ménière’s disease, vestibular migraine, and MDVM patients. The regular temporal pattern of migraine headache and vestibular symptoms is absent in 30–50 % of reported vestibular migraine patients, and up to 30 % of patients eventually diagnosed with vestibular migraine will initially present without headache [12, 35]. Alternatively, vestibular migraine criteria have increasingly demanded this temporal relationship with the exclusion of greater numbers of patients. As mentioned, this will likely be helpful in studying the natural course of vestibular migraine and treatment effects by ensuring a greater purity in vestibular migraine patient inclusion. However, in the clinical arena, this has left an increasing number of patients without a diagnosis or at least an attempt at empirical treatment for vestibular migraine. Hopefully, the increasing exclusion of these patients will lead to the discovery of a new diagnostic phenotype rather than including them in “waste basket” diagnoses such as BRV or shifting them to other vertigo diagnoses that equally do not fit such as Ménière’s disease or BPPV.
Another major clinical challenge is that there is currently no history, physical exam, vestibular test, or imaging finding that is pathognomonic for Ménière’s disease alone, vestibular migraine alone, or MDVM . This may be from a limitation in the current classification systems and limitations in current testing capabilities and technology, or it may be that these two entities are not distinguishable and are slightly different phenotypic presentations of an underlying unifying pathophysiology. More research is necessary to clarify the definitions in the future. Clearly certain historical points build evidentiary support for vestibular migraine, Ménière’s disease, or MDVM, but significant exceptions always exist for the clinician. For example, classic Ménière’s disease symptoms of subjective fluctuating or progressive hearing loss, tinnitus, and aural fullness occur in vestibular migraine patients 36, 55, and 51 % of the time, respectively. Conversely, vestibular migraine symptoms of headache, photophobia episodes, and aura occur in 81, 40, and 22 % of Ménière’s disease sufferers who do not meet formal vestibular migraine criteria . As a common practice, vestibular testing is frequently used to rule Ménière’s disease “in or out,” but this is not really possible since many Ménière’s disease patients have normal vestibular testing results, especially early in the disease process. Additionally, vestibular migraine patients have abnormalities in VNG, rotary chair, VEMP, and ECoG in up to 15–35 % of patients [3, 12, 14, 36, 37]. Newer tests such as ocular VEMP (oVEMP) and intratympanic gadolinium-enhanced MRI scans hold some promise for help in distinguishing vestibular migraine and Ménière’s disease. However, early reports are also showing overlaps in abnormalities in Ménière’s disease and vestibular migraine patients. Zuniga et al. were unable to find any cVEMP or oVEMP test that could distinguish between Ménière’s disease and vestibular migraine . Additionally, 19 consecutive definite and probable vestibular migraine patients without Ménière’s disease or hearing loss were scanned with intratympanic gadolinium-enhanced MRI technique, and 4 (19 %) were found to have endolymphatic hydrops . Currently, the 1995 AAO Ménière’s disease guidelines should be used to diagnose Ménière’s disease, and the Bárány society criteria should be used for vestibular migraine [4, 32]. If the patient meets the criteria for both, then the diagnosis of MDVM should be made. Objective SNHL criteria for low-tone PTA per the 1995 AAO Ménière’s disease guidelines are the most specific criteria for Ménière’s disease diagnosis. Future Ménière’s disease criterion revisions might consider adding speech discrimination score requirements to the audiologic requirements. Finally, a history of moderate or severe headache and photophobia during vertigo spells was the most specific diagnostic history point for vestibular migraine diagnosis .