Download Meniere for AHRF 2015-05-25a.pptx [Read

American Hearing Research FoundaFon EducaFonal Series July 25, 2015 Ménière’s disease Diagnosis and medical therapy Marcello Cherchi, MD PhD Assistant Professor of Neurology Northwestern University Feinberg School of Medicine Disclosures •  My fellowship in otoneurology (2007 – 2009) was partly funded by a Georgia Birtman grant through the American Hearing Research FoundaFon. •  My research was partly NIH funded through the NaFonal InsFtute on Deafness and Other CommunicaFon Disorders (NRSA 1F32DC009154–
01A2). •  I have a US patent pending for an algorithm pertaining to eye movement analysis. •  I have no financial conflicts of interest to declare. ObjecFves • 
• 
• 
• 
Ménière and his clinical descripFon Epidemiology What is Ménère’s disease? Medical therapy Who was Ménière? •  Prosper Ménière was born in Angers, France, in 1799. •  He became the chief physician at the Ins$tut Na$onal de Jeunes Sourdes in Paris, where he focused his work on diseases of the ear. •  In 1861 he published two papers regarding the disease that now bears his name. •  He died in Paris in 1862. •  Méniere, Prosper (1861). Sur une forme de surdité grave dépendant d’une lésion de l’oreille interne. Bulle$n de l’Adadémie Impériale de médecine, 26, 241. •  Ménière, Prosper (1961). Maladies de l’oreille interne offrant des symptoms de la congesFon cerebral apoplecFforme. Gaz Med de Paris, 16:88. Resume of Ménière’s note 1.  An auditory organ, otherwise perfectly healthy, may suddenly become the site of a funcFonal disturbance consisFng of variable tones, conFnuous or intermicent, and these noises are soon accompanied by a greater or lesser diminuFon of hearing. 2.  These funcFonal disturbances take place in the internal ear, can cause symptoms [previously] imputed to the brain, such as verFgo, lightheadedness, uncertainty of gait, spins and drops, also accompanied by nausea, vomiFng and fainFng. 3.  These events, which are intermicent, are soon followed by progressive hearing loss, and ogen hearing is completely abolished. 4.  This all leads one to believe that the main lesion of these episodes localizes to the semicircular canals. Méniere, Prosper (1861). Sur une forme de surdité grave dépendant d’une lésion de l’oreille interne. Bulle$n de l’Adadémie Impériale de médecine, 26, 241. Resume of Ménière’s note •  Ménière listed these cardinal features: –  Episodic verFgo –  Episodic or chronic Fnnitus –  Episodic worsening of hearing, with an overall trajectory of decline (even in between episodes) •  He explicitly arFculated a relaFonship between the symptoms “imputed to the brain” (verFgo, impaired gait, nausea, vomiFng, fainFng) and the aural symptoms (Fnnitus and hearing loss), which is what led him to hypothesize that the disease “resides” in the ear. This idea was novel at the Fme. Current criteria for Ménière’s disease
•  Ménière’s original descripFon has basically been carried forward even to the current criteria arFculated by the American Academy of Otolaryngology in 1995, which requires that there be: –  Recurrent, spontaneous episodes of verFgo –  Hearing loss (in at least one ear) –  Aural fullness, or Fnnitus, or both, on the same side as the hearing loss. Commicee on Hearing and Equilibrium guidelines for the diagnosis and evaluaFon of therapy in Meniere's disease. American Academy of Otolaryngology-­‐Head and Neck FoundaFon, Inc. (1995). Otolaryngol Head Neck Surg, 113(3), 181-­‐185. Epidemiology of Ménière’s disease: How common is it? •  There is controversy regarding how common Ménière’s is. The variability in the literature is probably partly due to differing methods of data collecFon, and partly due to variability in the stringency of diagnosFc criteria across studies. •  There is also some evidence for geographic variability. •  Wladislavosky-­‐Wasserman and colleagues (1984), reporFng on paFents seen at Mayo Clinic over a 30-­‐year period, report a prevalence of 218.2 and an annual incidence of 15.3 per 100,000. In other words: –  About 0.2% of the populaFon (1 in 500 people) at any given Fme has Ménière’s disease (prevalence). –  Every year about 0.015% of the populaFon (1 in 6,536 people) newly develops Ménière’s disease (incidence). Wladislavosky-­‐Waserman, P., Facer, G. W., Mokri, B., & Kurland, L. T. (1984). Meniere's disease: a 30-­‐year epidemiologic and clinical study in Rochester, Mn, 1951-­‐1980. Laryngoscope, 94(8), 1098-­‐1102. Epidemiology of Ménière’s disease: Age histogram Helsinki Havia, M., & Kentala, E. (2004). Progression of symptoms of dizziness in Meniere's disease. Arch Otolaryngol Head Neck Surg, 130(4), 431-­‐435. Chicago hcp://www.dizziness-­‐and-­‐balance.com/
disorders/menieres/menieres.html What is Ménière’s disease? •  The short answer is that we don’t know. •  Even though we have some histologic evidence of what an inner ear affected by Ménière’s disease looks like, we really do not know what the underlying pathobiology is. What is Ménière’s disease? “EndolymphaFc hydrops” •  Early autopsy studies reported that paFents with Ménière’s consistently had a dilated inner ear structure, which is called “hydrops.” Normal labyrinth EndolymphaFc hydrops hcp://www.dizziness-­‐and-­‐balance.com/disorders/menieres/menieres.html What is Ménière’s disease? “EndolymphaFc hydrops” •  High resoluFon MRI can someFmes demonstrate hydrops, but this is not currently in wide use for diagnosing Ménière’s. Normal labyrinth www.dirjournal.org/text.php3?id=127 EndolymphaFc hydrops Gurkov, R., Berman, A., Dietrich, O., Flatz, W., Jerin, C., Krause, E., Ertl-­‐Wagner, B. (2015). MR volumetric assessment of endolymphaFc hydrops. Eur Radiol, 25(2), 585-­‐595. What is Ménière’s disease? “EndolymphaFc hydrops” •  Rauch and colleagues (1989) reported that of 13 paFents who in life had been confidently diagnosed with Ménière’s disease, at autopsy all 13 had “hydrops.” •  However, autopsies of the general populaFon report that up to 6% of individuals (30 out of 500) have “hydrops,” whereas only around 0.2% of people (1 out of 500) have Ménière’s disease — a difference greater than one order of magnitude. •  Consequently, the state of “hydrops” is thought to be necessary but not sufficient for Ménière’s disease. In other words, something else (in addiFon to hydrops) must go wrong in order for Ménière’s disease to manifest clinically — but exactly what that “something else” is, is unknown. Rauch, S. D., Merchant, S. N., & Thedinger, B. A. (1989). Meniere's syndrome and endolymphaFc hydrops. Double-­‐blind temporal bone study. Ann Otol Rhinol Laryngol, 98(11), 873-­‐883. “EndolymphaFc hydrops” •  A variety of eFologies have been proposed, including: –  GeneFc –  Immunological disorders •  Autoimmune •  Allergic –  InfecFous •  Viral •  Bacterial –  “Hydraulic” •  Over-­‐producFon of endolymphaFc fluid •  Under-­‐absorpFon of endolymphaFc fluid (e.g., obstrucFon of vesFbular and cochlear aqueducts) •  FluctuaFons of intracranial pressure •  But none of these has been well-­‐supported by convincing data. GeneFc? •  Of individuals affected by Ménière’s disease, 7 — 15% of them report having a relaFve with the disease (Eppsteiner 2011). •  Although such numbers seem greater than what is likely by chance, remember that family members share more than just their genes; they also share environments and exposures. •  A broad range of genes have been proposed as candidates, including those that encode various HLAs (human leukocyte anFgens), potassium channels, sodium channels and others. Eppsteiner, R. W., & Smith, R. J. (2011). GeneFc disorders of the vesFbular system. Curr Opin Otolaryngol Head Neck Surg, 19(5), 397-­‐402. Allergic? •  Although allergies and Ménière’s disease have frequently been noted to be comorbid (Banks 2012), there is licle evidence that allergies cause Ménière’s disease (Weinreich 2014). •  Nevertheless, some researchers advocate allergy treatment (Derebery 2010), at least in paFents who otherwise have a clear history of allergies (e.g., to foods or environmental factors). •  Banks, C., McGinness, S., Harvey, R., & Sacks, R. (2012). Is allergy related to Meniere's disease? Curr Allergy Asthma Rep, 12(3), 255-­‐260. •  Derebery, M. J., & Berliner, K. I. (2010). Allergy and its relaFon to Meniere's disease. Otolaryngol Clin North Am, 43(5), 1047-­‐1058. •  Weinreich, H. M., & Agrawal, Y. (2014). The link between allergy and Meniere's disease. Curr Opin Otolaryngol Head Neck Surg, 22(3), 227-­‐230. Autoimmune? •  Although some paFents with Ménière’s disease also have autoimmune diseases, the link between the two is uncertain (Greco 2012). Greco, A., Gallo, A., Fusconi, M., Marinelli, C., Macri, G. F., & de VincenFis, M. (2012). Meniere's disease might be an autoimmune condiFon? Autoimmun Rev, 11(10), 731-­‐738. InfecFous? •  Although DNA to herpes viruses has been reported in the vesFbular ganglion in paFents with Ménière’s disease, this finding does not appear to be higher than in the general populaFon, so a causal link has been firmly established. Gartner, M., Bossart, W., & Linder, T. (2008). Herpes virus and Meniere's disease. ORL J Otorhinolaryngol Relat Spec, 70(1), 28-­‐31. “Hydraulic”? •  If hydrops is due to excess fluid (endolymph) accumulaFon in the inner ear, then there must be either excess fluid producFon, or insufficient fluid resorpFon, or both. •  Histopathological studies of the labyrinth in Ménière’s disease show a variety of findings, including changes in the cells lining the endolymphaFc duct (Michaels 2009), raising the quesFon of whether alteraFon in the funcFons of these cells may contribute to the “fluid imbalance” of the labyrinth. Michaels, L., Soucek, S., & Linthicum, F. (2009). The intravesFbular source of the vesFbular aqueduct: Its structure and pathology in Meniere's disease. Acta Otolaryngol, 129(6), 592-­‐601. Ménière’s disease, natural history •  Although Ménière’s disease is not common, it is rare enough that it is difficult to establish what the “natural history” of the disease is — in other words, how the disease progresses over Fme if untreated. •  Specific quesFons include: –  Does Ménière’s disease “burn out”? –  How likely is Ménière’s to involve the “other ear”? –  What happens with the dizziness? Does Ménière’s disease “burn out”? •  For many years clinicians endorsed the view that Ménière’s disease eventually “burns out.” •  More recent research (Havia et al 2004) suggests that this is probably not true. Havia, M., & Kentala, E. (2004). Progression of symptoms of dizziness in Meniere's disease. Arch Otolaryngol Head Neck Surg, 130(4), 431-­‐435. Bilaterality •  Most cases of Ménière’s disease begin unilaterally. •  Stahle and colleagues followed a cohort of 167 paFents, and found that only 3 (1.7%) presented with bilateral ear symptoms from the outset. •  Of the cases that begin unilaterally, there is controversy regarding what proporFon of cases progresses to bilateral involvement. The cited figures are generally in the range of one-­‐third to one-­‐half of cases. –  The longitudinal study by Wladislavosky-­‐Wasserman and colleagues reported 34% of paFents eventually developed bilateral involvement. –  Havia and colleagues reported that of their paFents who were followed for at least 20 years, 43% developed bilateral ear symptoms. –  Stahle and colleagues reported that of the 34 paFents who were followed for at least 20 years, 47% developed bilateral ear symptoms. •  Havia, M., & Kentala, E. (2004). Progression of symptoms of dizziness in Meniere's disease. Arch Otolaryngol Head Neck Surg, 130(4), 431-­‐435. Wladislavosky-­‐Waserman, P., Facer, G. W., Mokri, B., & Kurland, L. T. (1984). •  Stahle, J., Friberg, U., & Svedberg, A. (1991). Long-­‐term progression of Meniere's disease. Acta Otolaryngol Suppl, 485, 78-­‐83. •  Wladislavosky-­‐Waserman, P., Facer, G. W., Mokri, B., & Kurland, L. T. (1984). Meniere's disease: a 30-­‐year epidemiologic and clinical study in Rochester, Mn, 1951-­‐1980. Laryngoscope, 94(8), 1098-­‐1102. Otolithic crises of Tumarkin •  Some paFents, generally at more advanced stages of Ménière’s disease, begin experiencing abrupt “drop acacks” without any prodrome of aural symptoms. •  These acacks are someFmes referred to as “otolithic crises of Tumarkin” (ager the first invesFgator to describe them in 1936). •  PaFents who have reached this stage of symptoms generally can no longer control the verFginous symptoms with medical therapy, and must move on to more invasive procedures for management. Tumarkin, A. (1936). The Otolithic Catastrophe: A New Syndrome. Br Med J, 2(3942), 175-­‐177. Management •  Medical treatment of Ménière’s disease consists of –  TreaFng individual acacks (acute management) –  Trying to reduce the frequency of acacks (prophylacFc management) Management: Acute •  Acute management of episodes can involve –  MedicaFons for dizziness. These are vesFbular suppressants, such as meclizine and lorazepam. –  MedicaFons for nausea and vomiFng. These can include ondansetron, prochlorperazine, metoclopramide, trimethobenzamide •  Most paFents will first try to treat the dizziness, because if they are successful, then nausea/vomiFng do not develop. •  For paFents who develop nausea/vomiFng quickly (and who don’t have an opportunity to ingest medicaFons easily), some of the medicaFons are available in “orally disintegraFng tablet” formulaFons, and others are available as suppositories. Management: Prophylaxis Dietary sodium restricFon •  A common iniFal “therapy” is restricFon of total daily dietary sodium intake to 2000 mg. Management: Prophylaxis DiureFcs •  If dietary sodium restricFon fails, a typical first-­‐line medicaFon is a diureFc, such as hydrochlorothiazide/
triamterene (marketed as Dyazide® and Maxzide®). Results of studies on this have been mixed. •  For instance, van Deelen and colleagues (1986) reported that hydrochlorothiazide/triamterene reduced the frequency of acacks. •  In contrast, a meta-­‐analysis by Thirlwall and colleagues (2006) found insufficient evidence of efficacy for diureFcs in management of Ménière’s. •  van Deelen, G. W., & Huizing, E. H. (1986). Use of a diureFc (Dyazide) in the treatment of Meniere's disease. A double-­‐blind cross-­‐over placebo-­‐controlled study. ORL J Otorhinolaryngol Relat Spec, 48(5), 287-­‐292. •  Thirlwall, A. S., & Kundu, S. (2006). DiureFcs for Meniere's disease or syndrome. Cochrane Database Syst Rev(3), CD003599. Management: Prophylaxis Calcium channel blockers •  There is modest evidence that calcium channel blockers (such as flunarizine, nimodipine or verapamil), or drugs whose acFons modulate both calcium channels and histamine channels (such as cinnarizine), offer benefit. •  Djelilovic-­‐Vranic, J., Alajbegovic, A., Tiric-­‐Campara, M., Volic, A., Sarajlic, Z., Osmanagic, E., . . . Beslagic, O. (2012). BetahisFne or Cinnarizine for treatment of Meniere's disease. Med Arch, 66(6), 396-­‐398. •  Fraysse, B., Bebear, J. P., Dubreuil, C., Berges, C., & Dauman, R. (1991). BetahisFne dihydrochloride versus flunarizine. A double-­‐blind study on recurrent verFgo with or without cochlear syndrome typical of Meniere's disease. Acta Otolaryngol Suppl, 490, 1-­‐10. •  Lassen, L. F., Hirsch, B. E., & Kamerer, D. B. (1996). Use of nimodipine in the medical treatment of Meniere's disease: clinical experience. Am J Otol, 17(4), 577-­‐580. Management: Prophylaxis BetahisFne •  BetahisFne (marketed in Canada and Europe under the proprietary name Serc) is widely used as a medical therapy for Ménière’s. •  This drug is not currently FDA approved in the US, but is sFll available through compounding pharmacies. •  Animal experiments suggest that some of betahisFne’s catabolites (aminoethylpyridine and hydroxyethylpyridine) promote blood flow in the cochlea (Bertlich et al 2014). Even if this is also true in humans, it is unclear why this would help Ménière’s disease. •  A meta-­‐analysis by James and colleagues (2001) concluded that there is insufficient evidence for efficacy of betahisFne in treatment of Ménière’s disease. •  Bertlich, M., Ihler, F., Sharaf, K., Weiss, B. G., Strupp, M., & Canis, M. (2014). BetahisFne metabolites, Aminoethylpyridine, and Hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo. Int J Audiol, 53(10), 753-­‐759. •  James, A. L., & Burton, M. J. (2001). BetahisFne for Meniere's disease or syndrome. Cochrane Database Syst Rev(1), CD001873. References • 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Commicee on Hearing and Equilibrium guidelines for the diagnosis and evaluaFon of therapy in Meniere's disease. American Academy of Otolaryngology-­‐Head and Neck FoundaFon, Inc. (1995). Otolaryngol Head Neck Surg, 113(3), 181-­‐185. Eppsteiner, R. W., & Smith, R. J. (2011). GeneFc disorders of the vesFbular system. Curr Opin Otolaryngol Head Neck Surg, 19(5), 397-­‐402. Havia, M., & Kentala, E. (2004). Progression of symptoms of dizziness in Meniere's disease. Arch Otolaryngol Head Neck Surg, 130(4), 431-­‐435. James, A. L., & Burton, M. J. (2001). BetahisFne for Meniere's disease or syndrome. Cochrane Database Syst Rev(1), CD001873. Méniere, Prosper (1861). Sur une forme de surdité grave dépendant d’une lésion de l’oreille interne. Bulle$n de l’Adadémie Impériale de médecine, 26, 241. Rauch, S. D., Merchant, S. N., & Thedinger, B. A. (1989). Meniere's syndrome and endolymphaFc hydrops. Double-­‐blind temporal bone study. Ann Otol Rhinol Laryngol, 98(11), 873-­‐883. Stahle, J., Friberg, U., & Svedberg, A. (1991). Long-­‐term progression of Meniere's disease. Acta Otolaryngol Suppl, 485, 78-­‐83. Thirlwall, A. S., & Kundu, S. (2006). DiureFcs for Meniere's disease or syndrome. Cochrane Database Syst Rev(3), CD003599. Tumarkin, A. (1936). The Otolithic Catastrophe: A New Syndrome. Br Med J, 2(3942), 175-­‐177. van Deelen, G. W., & Huizing, E. H. (1986). Use of a diureFc (Dyazide) in the treatment of Meniere's disease. A double-­‐blind cross-­‐over placebo-­‐controlled study. ORL J Otorhinolaryngol Relat Spec, 48(5), 287-­‐292. Wladislavosky-­‐Waserman, P., Facer, G. W., Mokri, B., & Kurland, L. T. (1984). Meniere's disease: a 30-­‐year epidemiologic and clinical study in Rochester, Mn, 1951-­‐1980. Laryngoscope, 94(8), 1098-­‐1102. Thank you! QuesFons? Marcello Cherchi, MD PhD Chicago Dizziness & Hearing 645 N. Michigan Ave., Suite 410 Chicago, IL 60611 Tel: 312-­‐274-­‐0197 Fax: 312-­‐376-­‐8707 Web: hcp://www.dizzy-­‐doc.com/