Meniere's Disease

Meniere's disease results from multifactorial inheritance, endolymphatic malabsorption and, subsequently, hydrops. Clinical and laboratory evidence supports this concept. Cases in patients with Meniere's symptom-complex with a likely or known cause have been found in studies of temporal bones that correlate clinical and pathologic findings. These cases are thought to have been subsequent to infections, chronic otitis media (both active and inactive), inflammation (eg, following viral labyrinthitis), trauma, otosclerosis, syphilis, allergy, leukemia, and autoimmune disease [Paparella et al, 1991].

Endolymph is primarily produced in the stria vascularis [Paparella et al, 1984]. The planum semilunatum and dark vestibular cells also contribute to production of endolymph. Slowly, endolymph is absorbed in the endolymphatic duct and sac—a biologically active transporting structure where absorption occurs primarily and, to a lesser degree, secretion [Paparella et al, 1984]. The evidence strongly suggests that both longitudinal flow (slow process) and radial flow (rapid) occur. Hydrostatic and osmotic pressure gradients are also operational.

Malabsorption of endolymph in the endolymphatic duct or sac is the fundamental problem in Meniere's disease [Paparella, 1991]. Development of dysfunctional outflow is a slow process that takes many years to develop. The inciting event in all forms of Meniere's disease may have occurred years earlier and, thus, onset is delayed. When the endolymphatic duct is mechanically obstructed, as in the case of a fracture following head trauma, endolymphatic hydrops develops faster [Paparella et al, 1983] (Figure 1).

Figure 1: Profound endolymphatic hydrops in all turns of the cochlea.

Endolymphatic malabsorption over a long period of time is most likely related to developmental abnormality of the endolymphatic duct and sac in association with a displaced lateral sinus. It has been found that unimpeded venous drainage of the vestibular system through the paravestibular canaliculi vein is an important aspect of homeostasis of fluids of the inner ear. Abnormalities of the vasculature may contribute to the quantity of endolymphatic hydrops.

Genetic anomalies

Genetic Meniere's disease has been found in up to 20% of patients who indicated (in a questionnaire) a positive family history [Paparella, 1985]. Hereditary factors play a significant role in approximately 10% to 50% of cases [Arweiler, et al.,1995;Koyama et al.,1993]. Morrison [1995] found an autosomal dominant pattern with 60% penetrance in 41 families with more than one member with Meniere's disease. That study found that the genetic pattern of Meniere's disease shows anticipation, which means that in each successive generation with the disease, an earlier age of onset and more severe symptoms are found.

A few studies have attempted to better delineate the genetic basis of Meniere's disease. Koyama and colleagues [1993] studied histocompatibility antigens (HLA) in association with Meniere's disease in 20 Japanese patients with no apparent family history and compared their findings with those for a group of controls. Higher frequencies were found for HLA-DR, DQ, and DP in patients with Meniere's disease compared with controls. Also, a 70% incidence in groups with the DR2 subtype was found compared with an incidence of 17.8% in controls. Koyama and coworkers  [1993]  suggested that HLA-DR2 was (in particular, DRB1*1602 and Cw4 were) related genetic factors that may be involved in susceptibility to the pathogenesis of Meniere's disease. A German study of 48 patients (including five with a positive family history) was conducted by Arweiler and colleagues [1995].  They found a 90% incidence of HLA-A2 in patients with a family history and a 75% incidence in those without a familial pattern. One gene related to symptoms like those of Meniere's disease has been identified [deKok et al, 1999]. Linkage studies have been done in a Belgian and two large Dutch families with progressive sensorineural hearing loss associated with vestibular dysfunction. The disease locus was localized to the DFNA9 locus on chromosome 14. Mutation analysis revealed a mis-sense mutation of the COCH gene. In all three families, the same mis-sense mutation was found, changing Pro to Ser (P51S). The P51S mutation also has been found in four Dutch families [deKok et al, 1999] with symptoms similar to those of Meniere's disease. The family studies suggest that the genetic basis of Meniere's disease is complex and that probably more than one gene is involved. Genetic predisposition combined with other factors may contribute to the development of Meniere's disease.

Pathophysiology

Explanations of the attacks of Meniere's disease have been made on both physical and chemical grounds. Rupture of Reissner's membrane has been described as a cause for all attacks of Meniere's disease [Schuknecht, 1968], but histologic review of cases of human temporal bones with Meniere's disease has shown that approximately two thirds of patients have no evidence of rupture [Sperling et al., 1993]. The disturbance in balance of ions between production and resorption of endolymph is the primary etiologic factor in creating hydrops and its symptoms [Vosteen et al., 1986].

Medical management

Medical therapy of Meniere's disease is geared toward the differential diagnosis and toward supportive therapy for the physical manifestations of the disease and for the psychological sequelae of the disease such as mild-to-moderate situational depression and even chronic depression.  Episodic intractable vertigo that comes with or without warning can be quite disabling, both physically and psychologically, to those who are afflicted with it. Many times, patients with Meniere's disease are in the prime of their lives (in their fourth and fifth decades) and are productive members of society. When afflicted, they feel a significant loss of self-control and loss of ability to take care of themselves and their families. This significant physical and psychological insult may lead to situational depression that when not treated adequately can lead to chronic depression.

Environmental and food allergies remain the most common form of autoimmune disease in the general population, at an incidence of 20% to 25%. Avoidance of caffeinated products, chocolate, and alcohol significantly reduces symptoms of Meniere's in many patients. This may be related to a variation of food allergy that may not be easy to diagnose. Many patients report significant exacerbation of their vertigo and tinnitus after consumption of a bar of concentrated chocolate or other foods.

The endolymphatic sac and duct appear to be the center of immune reactivity in the apparatus of the inner ear. The characteristics of the endolymphatic sac predispose it to increased deposition of circulating immune complexes. These characteristics include fenestrated capillary vessels [Leone et. al., 1984] and a relative hyperosmotic state in the endolymphatic sac compared with the serum [Stergers et al., 1984].   Dornhoffer and co-workers [1993] demonstrated accumulation of IgG in 40% of the samples of endolymphatic sacs taken during endolymphatic shunt surgery for Meniere's disease. 

Changes in lifestyle and diet

All patients with symptoms of Meniere's are encouraged to follow a strict diet low in salt (less than 1500 mg of sodium per day) and completely abstinent from all caffeinated products. Furthermore, patients are encouraged to cease all consumption of alcohol and tobacco.  A large percentage of patients also report significant exacerbation of dizziness after consuming large quantities of chocolate, so we empirically advise patients to avoid indulgence in chocolate as well.

Steroid therapy

There is a significant amount of clinical and animal evidence that in most patients there is a strong association of immune-mediated phenomena and Meniere's disease [Suzuki et al.,1997; Yoshino et al., 1996] . All patients who present with acute episodes of Meniere's disease are treated with intramuscular steroids followed by oral steroids. For acute attacks, methylprednisolone acetate (Depomedrol), 60 to 80 mg, is given intramuscularly followed by a high dose of prednisone at 1 mg/kg given on a daily basis for ten days before slowly tapering the dosage over the next ten days. Patients are re-evaluated in two weeks' time with a repeat audiogram, and the symptoms are assessed. If patients show significant improvement, they will be kept on a lower dose of prednisone every other day at 10 to 20 mg, and a significant workup of the autoimmune problem in the inner ear will be undertaken at that time for steroid-sensitive and steroid-responsive patients.

For patients who present with chronic Meniere's disease, our (authors’) clinic usually prefers to start the patient on oral prednisone at the same dosage of 1 mg/kg given daily for ten days and tapered, with the same follow-up audiogram and evaluation done.

Intratympanic Steroids:

There have been several studies examining the effectiveness of intra-tympanic use of steroids in patients with Meniere’s.  Currently, there is no standard dose, duration, or concentration used.  Overall, the results have been minimally encouraging.  Therefore, we do not recommend this as a potential treatment for these patients at this time.

Diuretics

All patients with Meniere's disease are given a trial of diuretics. Treatment is continued for at least three prior to a declaring the treatment a success or failure.

Supportive and psychologic therapy

It is imperative to provide patients with adequate counseling and a support group for patients with Meniere's. Furthermore, patients should be questioned about sleep patterns, libido, and other signs of depression. For patients who have depressive symptoms, full psychiatric/psychologic consultation is highly recommended.

ELSE: Endolymphatic Sac Enhancement

Everyone favors using medical treatment first.  No medical treatment will cure the anomalies or the disease-process itself when and if it becomes progressive or intractable and incapacitating. At this point, clinicians can then choose from two categories of surgery: either destructive or conservative. Once something is destroyed, it cannot be replaced. In conservative endolymphatic sac surgeries, the purpose is to preserve and, if possible, to enhance function.

Endolymphatic sac enhancement has stood the test of time for 77 years since the original description by Portmann in 1927 ^[57].  It was not until the early 1960s that House [1962] described and popularized the modern endolymphatic sac surgery (the “shunt” procedure).  Many articles appear throughout the literature describing the efficacy of endolymphatic sac surgery.  As a result, it is the most commonly performed operation for Meniere's disease [Paparella, 1994].

Selection of patients

The indications for endolymphatic sac surgery are found in patients who have developed progressive or intractable Meniere's disease.  Despite prolonged medical treatment these patients have a downhill course in vestibular symptoms and function, cochlear function, or both. In these circumstances endolymphatic sac enhancement surgery constitutes a conservative surgical option.

Another indication for sac enhancement surgery is rapidly progressive Meniere's disease. Successful surgical treatment of the endolymphatic sac for Meniere's disease requires that the labyrinth be in a state of temporary threshold shift, involving both the vestibular and cochlear labyrinth. When permanent damage or permanent threshold shift develops, it is unlikely that sac surgery can remedy completely destroyed sensory cells and/or neurons, although many such patients benefit. The average duration of disease prior to performance of sac enhancement surgery is approximately six years [Paparella and Sajjadi, 1994].

Complications

The major complication encountered is the up-to-2% incidence of deafness or profound hearing loss, usually developing within the first few postoperative weeks or months.  Such profound hearing loss does not appear to be related to intraoperative entrance into the labyrinth but is more likely due to acute inflammatory reaction with formation of exuberant scar tissue. Other major complications include intraoperative bleeding, particularly from the lateral sinus, or drainage of spinal fluid. Bleeding from the lateral sinus is packed with dry pieces of Gelfoam, and the patient’s head is elevated. If there is drainage of spinal fluid, the mastoid is packed with dry pieces of Gelfoam.

Rarely, there may be postoperative infection of the wound, but in our practice, any early sign of this is treated aggressively with antibiotics and local care before infection can spread into the labyrinth or incite formation of scar tissue.

Other Procedures:

Vestibular Nerve Section

Vestibular nerve section should be considered if medical management, techniques to perfuse the inner ear, and endolymphatic sac enhancement fail to alleviate symptoms in a patient with normal or near normal hearing. 

Chemical labyrinthectomy

Schuknecht [1957] first modified the method of delivery of chemical ablation and perfused the middle ear with streptomycin for treatment of unilateral Meniere's disease. All his patients had resolution of their vertigo, but five of eight suffered complete hearing loss.  Gentamicin is now used, due to its perceived preferential vestibular toxicity.  Intratympanic gentamicin is thought to be a relatively safe, effective treatment for unilateral Meniere's disease. Several studies, however, have shown this not to be the case [Hoffer et al., 2001; Keene et al., 1982; Tran Ba Huy and Deffrennes, 1988;Wanamaker 1998]. Investigators are still struggling to find the elusive balance of method, administration, dose, schedule, and end-point of therapy in order to preserve cochlear function.

Physical labyrinthectomy

The transmastoid labyrinthectomy has been accepted as the “gold standard” of surgical techniques for complete removal of all neuroepithelial elements of the ear that may be causing disabling disequilibrium. In the appropriate surgical candidate, excellent control rates of 97% to 100% are reported [Benecke et al.,1986; Kemink et al., 1989; Langman and Lindeman, 1998]. Surgical labyrinthectomy is reserved for persistent or recurrent symptoms attributable to a single ear with severe-to-profound hearing loss. Usefulness of the ear, whatever the standard (50 to 75 dB speech recognition threshold or discrimination scores of 50% to 20%), is an individualized process best assessed by the patient and surgeon while weighing the risks and benefits of the procedure. Disadvantages of surgical labyrinthectomy include total hearing loss, risk of injury to the facial nerve, potential leaks of cerebrospinal fluid, and possible prolonged central compensation. 

References

Paparella MM. The cause (multifactorial inheritance) and pathogenesis (endolymphatic malabsorption) of Meniere's disease and its symptoms. Acta Otolaryngol (Stockh) 1985;99:445-51.  

Paparella MM, daCosta SS, Fox R, et al. Meniere's disease and other labyrinthine diseases. Philadelphia: WB Saunders; 1991. p. 1689-714.

Paparella MM. Pathogenesis of Meniere's disease and Meniere's syndrome. Acta Otolaryngol (Stockh) 1984;(Suppl 485)10.  

Paparella MM. Pathogenesis and pathophysiology of Meniere's disease. Acta Otolaryngol (Stockh) 1991;(Suppl 485)26.  

Paparella MM, Mancini F. Trauma and Meniere's syndrome. Laryngoscope 1983;93:1004-12.  

Arweiler DJ, Jahnke K, Grosse-Wilde H. Meniere disease as an autosomal dominant hereditary disease. Laryngsorhinootologie 1995;74(8):512-5.  

Koyama S, Mitsuishi Y, Bibee K, et al. HLA associations with Meniere's disease. Acta Otolaryngol (Stockh) 1993;113(5):575-8.  

Morrison AW. Anticipation in Meniere's disease. J Laryngol Otol 1995;109(6):499-502.  

deKok Y, Bom SJH, Brunt TM, et al. A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects. Hum Mol Genet 1999;8:361-6.  

Schuknecht HF. Correlation of pathology with symptoms of Meniere's disease. Otolaryngol Clin N Am 1968;1:433.  

Sperling NM, Paparella MM, Yoon TH, Zelterman D. Symptomatic versus asymptomatic endolymphatic hydrops: a histopathologic comparison. Laryngoscope 1993;103:277-85.  

Vosteen KH, Morgenstern C. Biochemical aspects of inner ear pathophysiology. In: PfaltzCR, editors. Controversial aspects of Meniere's disease New York: Georg Thieme; 1986.

Dornhoffer JL, Warner M, Arenberg IJ. Immunoperoxidase study of the endolymphatic sac in Meniere's disease. Laryngoscope 1993;103:1027-34.  

Leone CA, Feghali JG, Linthicum Jr. FH. Endolymphatic sac: possible role in autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol 1984;93:208-9.  

Stergers O, Ferray E, Amiel C. Inter- and intra-compartmental osmotic gradients within the rat cochlea. Am J Physiol 1984;247:F602-6.  

Paparella M, Sajjadi H. Endolymphatic sac enhancement. Otolaryngol Clin N Am 1994;27(2):381.  

Suzuki M, Krug MS, Cheng KC, et al. Antibodies against inner ear proteins in the sera of patients with inner ear disease. J Otorhinolaryngol Rel Spec 1997;59:10-7.  

Yoshino Y, Ohashi T, Urushibata T, et al. Antibodies to type II collagen and immune complexes in Meniere's disease. Acta Otolaryngol (Stockh) 1996;(Suppl 522)79-85.

House WF. Subarachnoid shunt for drainage of endolymphatic hydrops. Laryngoscope 1962;72:713-29.  

Paparella MM. Endolymphatic sac procedures. In: BrackmannD, SheltonC, ArriagaMA, editors. Otologic surgery Philadelphia: W.B. Saunders; 1994. p. 460-73.

Schuknecht HF. Ablation therapy in the management of Meniere's disease. Acta Otolaruyngol (Stockh) 1957;132:1-42.  

Hoffer ME, Allen K, Kopke RD, et al. Transtympanic versus sustained-release administration of gentamicin: kinetics, morphology, and function. Laryngoscope 2001;111:1343-57.  

Keene M, Hawke M, Barber HO, et al. Histopathological findings in a clinical gentamicin ototoxicity. Arch Otolaryngol 1982;108:65-70.  

Tran Ba Huy P, Deffrennes D. Aminoglycosides ototoxicity: influence of dosage regimen on drug uptake and correleation between membrane binding and some clinical features. Acta Otolaryngol 1988;105:511-5.  

Wanamaker HH, Gruenwald L, Damm KJ. Dose-related vestibular and cochlear effects of transtympanic gentamicin. Am J Otol 1998;19:170-9.  

Benecke JE, Tubergen LB, Miyamoto RT. Transmastoid labyrinthectomy. Am J Otol 1986;7:41-3.  

Kemink JL, Telian SA, Graham MD, et al. Transmastoid labyrinthectomy: reliable surgical management of vertigo. Otolaryngol Head Neck Surg 1989;101(1):5-10.

Langman AW, Lindeman RC. Surgical labyrinthectomy in the older patient. Otolaryngol Head Neck Surg 1998;118(6):739-42.