Dysmodulation of audiovestibular sensory input in vestibular migraine

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Dysmodulation of audiovestibular sensory input in
vestibular migraine

• Dr Louisa Murdin
• Academic Clinical Fellow
• UCL Ear Institute London
• BAAP Hallpike Symposium 18.2.11

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Migraine a disorder of sensory dysmodulation?
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Abormalities occur across the modalities
Allodynia scores versus sound aversion thresholds
(SATs) during acute attacks.
Ashkenazi A et al. J Neurol Neurosurg Psychiatry
2010811256-1260
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A neural mechanism for exacerbation of headache
by light Nature Neuroscience Noseda et al 13,
239245 (2010)
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How can studying the audiovestibular system
illuminate this further?
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Otoacoustic emission suppression assesses the
auditory efferent system
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Vestibular evoked myogenic potentials assess the
sacculocollic reflex pathway
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Hypotheses
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Where?

• prospective
• controlled
• observational
• tertiary level Neurology specialist hospital
• Neuro-otology clinics
• institutional ethics committee approval

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Who?

• Patients
• age 18-60
• definite vestibular migraine (Neuhauser 2001)
• Excluded any otological or neurological disease,
  noise exposure, systemic medical disease,
  conductive hearing loss, abnormal tympanograms
• Controls
• no headaches with migrainous features
• age and sex matching to patients

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Otoacoustic emission suppression protocol

• Otodynamics ILO88
• confirm presence of TEOAE using non-uniform click
  at 85 dB SPL
• Stimulus is uniform click at 603 dB SPL
• The noise is
• Contralateral
• White noise
• 40 dB SL
• 600 sweeps (60x10 autorepeat takes, alternating
  with and without contralateral noise)
• noise rejection set at 48dB SPL
• Normal value gt1.0dB each ear

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VEMP protocol

• Prerequisites
• Normal otoscopy and tympanometry
• No conductive hearing loss
• Stimulus
• 500 Hz tone burst
• max 125 dB SPL
• Repetition rate 4.7/s
• 200 sweeps
• 2-4-2 ms rise-plateau-fall
• monaural stimulation via headphone
• Recording
• Ipsilateral
• EMG activation 60-80 µV
• visual biofeedback technique

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Cases Controls
n 38 31
age / yrs 36.2 9.2 36.110.0
female 82 61
Duration of symptoms /yrs range 0-41 mean 12 -
Aura 13 -
Auditory symptoms 17 (52) -
Migraine prophylactics 17 (52) -
Phonophobic 29 (88) -
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OAE Results

• all controls had recordable TEOAEs and
  suppression
• one case had absent TEOAEs bilaterally
• 5 cases had OAE amplitude too small to record
  suppression

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Do cases have low suppression?
Yes!
Suppression total lt2.0 dB Suppression total gt2.0 dB n in each group
Cases 11 (33) 22 (67) 33
Controls 3 (10) 28 (90) 31
2.0 dB derived from published departmental data
Chi squared test, p0.022
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Binary logistic regression analysis
Regression coefficient Odds ratio estimate (95 CI) sig
Low total suppression -1.540 0.214 (0.053-0.863) p0.03
Sex 0.506 4.659 (0.626-4.396) p0.30
Age -0.013 0.987 (0.944-1.033) p0.57
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Does phonophobia relate to suppression?
No
Phonophobia
No phonophobia
Number of participants
Total suppression / dB
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Is there a characteristic feature of the low
suppression group?

• Regression analysis shows no relationship with
• disease duration
• age
• gender
• medication
• ENG abnormalities

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Where is the processing deficit causing
suppression abnormality?
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OAE suppression results summary

• A higher than expected proportion of subjects
  with vestibular migraine have low total OAE
  suppression.
• This is in keeping with the concept of sensory
  dymodulation in an as yet unidentified subgroup
  of patients.

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VEMP recordings
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Patients Controls
Abnormal VEMP 17/35 (49) 6/30 (20) p0.016 ?2
VEMP absence 5/35 4 unilateral 1 bilateral 0/30 p0.057 Fisher
Latency 3/35 prolonged unilaterally 2/35 with high asymmetry 1/30 prolonged unilaterally p0.2
Threshold 1/35 low threshold unilaterally 0/30 p1
Amplitude 5/29 high asymmetry 4/30 high asymmetry p0.73
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Binary logistic regression analysis

• Age, sex, medication, phonophobia not significant
  factors
• For all VEMP abnormalities
• OR estimate 3.8 (95 CI 1.2 to 11.5) p0.07
• for absence in at least one ear
• OR estimate 7.3 (95CI 0.8 62.8) plt0.05

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Why are the VEMPs absent?
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VEMP absence is reported in

• multiple sclerosis
• benign paroxysmal vertigo of childhood
• brainstem strokes
• dizzy patients
• HTLV with cervical myelopathy
• Menieres disease
• sudden SNHL with vertigo
• in 33 papers, 2 reported absence in normals

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The significance of absence

• The usual reasons for failing to record robust
  responses are inadequate tonic activation of the
  SCM muscles, confusion about the intensity of
  clicks required, or the presence of conductive
  hearing loss responses can be obtained in nearly
  all normal individuals less than 65 years old...

Colebatch 2001
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Is it technical?

• inadequate tonic activation?
• But we measure it and maintain it using feedback
• inadequate stimulus?
• But we use 125dBSPL
• conductive hearing loss?
• But this was excluded by audiometry
• age?
• But all participants under 60

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Is it normal variation?

• VEMP thresholds and latencies, but not
  amplitudes, are highly repeatable.

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Is it reporting bias?

• Subjective component to absence and presence
• Repeatability
• Blinded assessment by independent reporter

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Is it statistical?

• Although VEMPS were recorded in all controls, the
  p value for persistently absent VEMPs is around
  0.05
• BUT other groups do not publish reports of high
  levels of VEMP absence in normals

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Is it misdiagnosis?

• Vestibular migraine is a clinical diagnosis
• Neuhausers definition is being refined

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Is it a synergistic pathology?

• For example
• Vestibular neuritis
• Menieres disease

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Is it a pathological feature of vestibular
migraine?

• absence is not a feature suggestive of
  disinhibition
• there are other papers which have and have not
  reported this finding

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VEMP Summary

• Heterogeneous VEMP abnormalities, especially
  absence of response, are seen more frequently
  than expected in cases of vestibular migraine

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Do the VEMP and OAE abnormalities correlate?
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Do OAE suppression measures or VEMP recording
values change during an attack?
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Does suppression change during an attack?
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Do VEMP recordings change during an attack?
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Audiovestibular sensory dysmodulation?
Study ID number OAE ictal-interictal comparison VEMP ictal-interictal comparison
MRD17 abnormally large shift in Ts right ear showed large increase in latency
MRD3 normal left ear showed large reduction in latency
MRD19 abnormally large shift in Ts no recordings made
MRD5 no recordings made normal
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Conclusions

• Abnormalities of VEMP and OAE suppression are not
  uncommon in cases of VM
• These abnormalities appear to have some dynamic
  qualities
• there is some evidence from this study in support
  of audiovestibular sensory dysmodulation in
  migraine

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Thank you
Acknowledgements Presanna Premachandra and
Rosalyn Davies

• louisa_at_murdin.com

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Evidence form genetics
RG Lafreniere, MZ Cader and JF Poulin et al., A
dominant-negative mutation in the TRESK potassium
channel is linked to familial migraine with aura,
Nat Med 16 (2010), pp. 11571160.
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What are otoacoustic emissions?

• low amplitude sounds
• a by-product of the way sound is processed by the
  inner ear
• a measure of cochlear outer hair cell function

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Discussion

• OAE suppression is lost in migraineurs in one
  study
• Bolay 2008
• migraine in general or vestibular migraine in
  particular?

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Anatomical location?
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Does suppression relate to phonophobia?
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Participants

• 35 patients
• definite migrainous vertigo (Neuhauser 2001)
• under 60 years old
• 74 female
• mean age 37 yrs (SD 11)
• migraine duration 0-47 yrs (mean 15)
• aura 37 (20 basilar)
• auditory symptoms 51
• phonophobia 71
• migraine prophylaxis 49

• 30 healthy controls
• 70 female
• mean age 38 yrs (SD 9)

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Brainstem
Cochlea TEOAE
SOC
Cochlear nuclei
Inferior vestibular nerve
Ipsilateral noise to saccule
Contra lateral noise to cochlea
SCM VEMP
Vestibular nuclei
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MVST
S
L
M
MLF
D
IVN
SCM
SCM
Saccule
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Evidence from genetics
V Anttila, H Stefansson and M Kallela et al.,
Genome-wide association study of migraine
implicates a common susceptibility variant on
8q22.1, Nat Genet 42 (2010), pp. 869873
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Evidence from genetics
V Anttila, H Stefansson and M Kallela et al.,
Genome-wide association study of migraine
implicates a common susceptibility variant on
8q22.1, Nat Genet 42 (2010), pp. 869873
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Suppression 7.1- 3.8 3.3 dB
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• Study of 20 basilar migraine patients
• abnormalities of presence, latency or threshold
  in 10 (50)
• Abnormalities resolved in 9/10 with 3 months
  flunarizine 10mg

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OAE suppression is abnormal in

• William syndrome Attias 2009
• cerebello-pontine tumours Ferguson 2001
• multiple sclerosis Coelho 2007
• noise exposure Veuillet 2001

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OAE suppression was clear in both groups
Mean 3.95 SD 1.90
Mean 3.53 SD 2.57
Number of participants
Total suppression/dB controls
Total suppression / dB cases
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Do variations in VEMPS correlate with clinical
state?
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MVST
S
cVEMP assesses the sacculo-collic reflex
L
M
MLF
D
IVN
SCM
SCM
Saccule
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Noise OFF
Click stimulus in TEOAEq recording out
x
Noise ON
Click stimulus in TEOAEn recording out
Suppression TEOAEq - TEOAEn