Dysmodulation of audiovestibular sensory input in vestibular migraine

1. Dysmodulation of audiovestibular sensory input in vestibular migraine Dr Louisa Murdin Academic Clinical Fellow UCL Ear Institute London BAAP Hallpike Symposium 18.2.11

3. Migraine: a disorder of sensory dysmodulation?

4. Abormalities occur across the modalities Allodynia scores versus sound aversion thresholds (SATs) during acute attacks. Ashkenazi A et al. J Neurol Neurosurg Psychiatry 2010;81:1256-1260

5. A neural mechanism for exacerbation of headache by light Nature Neuroscience Noseda et al 13, 239–245 (2010)

6. How can studying the audiovestibular system illuminate this further?

7. Brainstem Cochlea Cochlear nerve Cochlear nuclei Contra- lateral input Inferior vestibular nerve SOC Vestibule Vestibular nuclei muscle

8. Brainstem Cochlea Cochlear nerve Cochlear nuclei Contra- lateral input Inferior vestibular nerve SOC Vestibule Vestibular nuclei muscle

9. Brainstem Cochlea Cochlear nerve Cochlear nuclei Contra- lateral input Inferior vestibular nerve SOC Vestibule Vestibular nuclei muscle Otoacoustic emission suppression assesses the auditory efferent system

10. Brainstem Cochlea Cochlear nerve Cochlear nuclei Contra- lateral input Inferior vestibular nerve SOC Vestibule Vestibular nuclei muscle Vestibular evoked myogenic potentials assess the sacculocollic reflex pathway

11. Hypotheses

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

13. 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

14. Otoacoustic emission suppression: protocol • Otodynamics ILO88 • confirm presence of TEOAE using non-uniform click at 85 dB SPL • Stimulus is uniform click at 60±3 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 >1.0dB each ear

15. 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

17. 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

18. Do cases have low suppression? Yes! 2.0 dB derived from published departmental data Chi squared test, p=0.022

19. Binary logistic regression analysis

20. Does phonophobia relate to suppression? No Phonophobia No phonophobia Number of participants Total suppression / dB

21. Is there a characteristic feature of the low suppression group? • Regression analysis shows no relationship with: • disease duration • age • gender • medication • ENG abnormalities

22. Where is the processing deficit causing suppression abnormality?

23. Brainstem Cochlea Cochlear nerve Cochlear nuclei Contra- lateral input Inferior vestibular nerve SOC Vestibule Vestibular nuclei muscle

24. 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.

25. Controls n=30 Cases n=35 n=30 present both ears n=28 present both ears n=4 absent one ear n=3 absent bilaterally First session persistent absence one ear n=2 present both ears n=1 persistent absence one ear n=2 declined repeat testing n=1 persistent absence both ears n=1 Second session VEMP recordings

27. 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); p=0.07 • for absence in at least one ear • OR estimate 7.3 (95%CI 0.8 – 62.8); p<0.05

28. Why are the VEMPs absent?

29. VEMP absence is reported in… • multiple sclerosis • benign paroxysmal vertigo of childhood • brainstem strokes • dizzy patients • HTLV with cervical myelopathy • Meniere’s disease • sudden SNHL with vertigo • in 33 papers, 2 reported absence in normals

30. The significance of absence “The usual reasons for failing to record robust responses are inadequate tonic activation of the SCM muscles, confusion about the intensityof 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

31. 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

32. Is it normal variation? • VEMP thresholds and latencies, but not amplitudes, are highly repeatable.

33. Is it reporting bias? • Subjective component to absence and presence • Repeatability • Blinded assessment by independent reporter

34. 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

35. Is it misdiagnosis? • Vestibular migraine is a clinical diagnosis • Neuhauser’s definition is being refined

36. Is it a synergistic pathology? • For example • Vestibular neuritis • Meniere’s disease

37. absence is not a feature suggestive of disinhibition there are other papers which have and have not reported this finding Is it a pathological feature of vestibular migraine?

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

39. Do the VEMP and OAE abnormalities correlate?

40. Do OAE suppression measures or VEMP recording values change during an attack?

41. Does suppression change during an attack?

42. Do VEMP recordings change during an attack? normal range of ±1.3 ms

43. Audiovestibular sensory dysmodulation?

44. 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

45. Thank you louisa@murdin.com Acknowledgements: Presanna Premachandra and Rosalyn Davies

46. 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 Med16 (2010), pp. 1157–1160.

47. 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

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

49. Anatomical location?

50. Does suppression relate to phonophobia?