1. Lund University Hospital
Mènière
Vad är på gång?
Mikael Karlberg MD, PhD
Oto-rhino-laryngology, Head & Neck Surgery
Lund University Hospital
Sweden

2. New criteria for diagnosing Menière´s disease 2015!
Prosper Meniere 1861
New criteria for diagnosing
Menière´s disease 2015!
Lopez-Escamez JA et al. J Vestib Res 2015;25:1-7
Definite Menière´s disease
2 or more spontaneous episodes of vertigo lasting 20 minutes – 12 hours
Documented low-medium frequency sensorineural hearing loss
Fluctuating aural symptoms (hearing, tinnitus, fullness) in the affected ear
Not better explained by another vestibular diagnosis
Probable Menière´s disease
2 or more episodes of vertigo or dizziness lasting 20 minutes – 24 hours

3. All with definite
Meniere´s disease
have endolymphatic hydrops!!
But all with endolymphatic
hydrops do not have
Meniere´s disease!!

4. Prevalence VERY uncommon in children! About 0.5 % (finnish data)
Most common between years (1,5 %)

5. Eye doctor?
Piece of cake!
Can see the organ!
Measure pressure!

6. How do we make a diagnosis of Meniere?
History
Get a ”typical” audiogram (low-frequency loss)
Rule out ”other diseases” = MRI
(Vestibular testing: ipsi-lesional vestibular damage)

7. Diagnostic problems Migraine variants? Meniere without hearing loss?
60% of Meniere mono-symptomatic at start!

8. Robert Barany
Nobel laureate medicine and physiology 1914

9. “old faithful”
Non-physiologic test
Low frequency
Slow acceleration

10. Caloric test and Meniere
60 % of Meniere mono-symptomatic at start!
1 – 20 years latency until next symptom!
Recurrent vertigo attacks: 0 audiologic symptoms:
Significant canal paresis: probably Meniere
in ear with canal paresis

11. Caloric test and Meniere
Recurrent vertigo attacks: 0 audiologic symptoms:
Significant directional preponderance: probably Meniere
but in what ear?

12. Caloric test and Meniere
Significant canal paresis (>25%) BUT
normal video head impulse test (vHIT):
Probably Meniere

13. Normal ampulla
Hydrops in ampulla
Rizvi 1986

14. Caloric test
Head impulse test

15. Caloric test and Meniere
Recurrent vertigo attacks: 0 audiologic symptoms:
Normal caloric test: probably migraine

16. Animals: experimental endolymphatic hydrops
(chronic vasopressin treatment or
obstructing the endolymphatic duct)
results in hearing loss but no vertigo attacks!

17. ”Multi-factorial”? Many different causes give the same result?
Genetics! (no genes found so far)
Too much endolymph produced?
Disturbed resorption of endolymph?
(”stop” in endolymphatic duct)
loose otoconias?
Disturbed pressure regulation?
Stress? Hormones? Inflammation?

18. I believe that in Meniere´s disease:
-there is overpressure in the endolymphatic space
(or underpressure in the perilymphatic space!)
-when the overpressure suddenly releases there is
a Meniere attack
-over time there is a permanent lesion of auditory and
vestibular hair cells with permanent hearing loss (and
no more vertigo attacks)
Earlier and more active
treatment might save
hearing!?

19. Betaserc / Serc (betahistin)
Mechanism of action?? ”increased cochlear blood flow”
Är på god väg att godkännas i Sverige (Medical Need)
No good studies
(one on-going: 24mg x 3 vs 48mg x 3 vs placebo x 3
Academic study, not sponsored)
0 effect???
24-48 mg x 3 for bilateral Meniere
No effect on hearing loss

20. Possible mechanisms of endolymphatic hydrops
perilymph
endolymph +
1. Increased endolymphatic volume

21. Possible mechanisms of endolymphatic hydrops
perilymph -
endolymph +
2. Decreased perilymphatic pressure

22. “Typical” case of decreased perilymphatic pressure?
Woman 42 years
Headache, fluctuating left-sided tinnitus, fullness and hearing loss
Attacks of vertigo and nausea > 20 minutes
Headache disappears when she lies down = “orthostatic headache”
Fluctuating left-sided, low-frequency sensorineural hearing loss

24. CT brain normal
MRI with gadolinium: pachymeningeal enhancement and “sagging brain”

25. ”Idiopathic intracranial hypotension”
pachymeningeal contrast enhancement
”Idiopathic intracranial hypotension”
Spontaneous spinal CSF leakage

26. No spontaneous remission
After 1 month epidural autologous 20 ml “blood patch” at L2-3,
repeated after 3 days
1 day after last blood patch headache disappears
Audio-vestibular symptoms gradually disappear during one month
MRI and audiometry normal 2 months later

28. - CSF + 2. Decreased perilymphatic pressure
endolymph +
2. Decreased perilymphatic pressure
due to decreased CSF pressure / volume

29. perilymph -
endolymph +
middle ear
3. Decreased perilymphatic pressure
due to low middle ear pressure?

30. Montandon et al ORL 1988
28 Meniere patients referred for surgery (shunt or VNx)
TMD in LA
Follow-up at months (mean 30 months)
23 patients (82%) total remission or improved
20 (71%) AAO score 0 total remission
1 (4%) AAO score much improved
2 (7%) AAO score improved
2 (7%) AAO score no change
3 (11%) AAO score >120 worse

31. Latanoprost (Xalatan®)
Latanoprost (Xalatan®) used for glaucoma treatment worldwide
Prostaglandin F2α analogue
Reduces the intraocular pressure by enhancing the drainage of fluid from the eye

32. Previous study design Randomized Double-blind Cross-over
Placebo controlled
Active drug or placebo
Day: 1, 2 and 3
Study variables monitored
Day 1, 5, 15 and 29
Wash out
2 months

33. Tinnitus loudness

34. Speech discrimination

35. Vertigo attacks
Placebo
Placebo
Placebo

36. A clear trend of improvement
Better speech
discrimination
Less tinnitus

37. On-going multi-center clinical study ”proof-of-concept” study
Lund Kristianstad
Karlskrona Linköping
Göteborg Stockholm
Karlstad Örebro
Västerås Uppsala
Falun Luleå (Sunderbyn)

38. Clinical study protocol1 2 3
Months
Placebo: 3 injections
20 patients
Latanoprost ester, 0.005%: 3 injections
40 patients
Placebo: 1 injection
10 patients
Latanoprost ester, 0.005%: 1 injection
30 patients

39. Clinical study protocol
Primary endpoint:
Speech discrimination in noise; Change from baseline to day 14
Secondary endpoints:
PTA (Pure Tone Average) in lower frequency interval (125, 250 and 500 Hz)
PTA in higher frequencey interval (500, 1,000, 2,000 and 3,000 Hz)
Subjective Hearing (Likert scale)
Subjective Tinnitus (Likert scale)
Subjective Dizziness (Likert scale)
Number of vertigo attacks > 20 mins
Right now? 87 of 100 patients included!

40. See endolymphatic hydrops on MRI!!!
Gadolinium diluted 1:8 with NaCl
Injected into middle ear
Patient lies 30 min
24 hours later MRI (3T, 3D-FLAIR)
Alternatively i.v. gadolinium normal dose - MR 4 hours later

41. Normal gadolinium enhancement (of perilyphatic space)
intratymp. gadolinium
Normal gadolinium enhancement
(of perilyphatic space)
Severe hydrops
(black = non-enhanced expanded
endolymphatic space)

42. i.v. gad cochlear hydrops Naganawa S et al 2013
Magn Reson Med Sci 2013
i.v. gad
cochlear
hydrops

43. i.v. gad
vestibular
hydrops

44. Significant relation between grade of hydrops on MRI and hearing loss!
TMV 250, 500, 1000 Hz
TMV 500, 1000, 2000, 3000 Hz
Significant relation between grade of hydrops on MRI
and hearing loss!
(no relation between ECoG, VEMP, calorics)
Gϋrkow R et al Eur Arch Otorhinolaryngol 2011

45. Acute unilateral low-frequency hearing loss: 25 patients
23 (92%) endolymphatic hydrops on MRI
(40% also on the normal ear!)
Shimono M et al Otol Neurotol 2013
Hydrops in a majority of patients with ”vestibular” Meniere
and”cochlear” Meniere
Kato M et al Acta Otolaryngol 2013
Effect of Betaserc? No decrease in hydrops on MRI
after 3-7 months treatment with 16 mg x 3
Gϋrkow R et al Eur Arch Otorhinolaryngol 2013
No effect on hydrops after gentamicin
Fiorino F et al Otol Neurotol 2012
A patient with ”typical” Meniere: MR – hydrops
Spontaneous remission: MR after 1 år – 0 hydrops
Nakashima et al EAONO2014

46. A 7 T MRI-machine is now in place in Lund!
Better resolution of inner ear structures?
”certain” Meniere diagnosis in living patients?