Ear Center: Meniere's Disease

ABOUT
Vertigo  |   Hearing Loss  |   Tinnitus  |   Pathophysiology  |   Natural History  |   Diagnosis  

TESTING FOR
Hearing   |   Balance  |   Nerve  |   Cochlea  |  Brain Imaging   |   Blood 

MEDICAL TREATMENT
Medications  |   Methotrexate  |   Vestibular Rehabilitation

SURGICAL TREATMENT  
Sac Decompression
  |    Nerve Section  |   Labyrinthectomy  |   Middle Ear Perfusion   |  References

Meniere's Disease: The Problem

Meniere's disease is a disorder of the inner ear. The symptoms of this condition include recurrent episodes of spinning-around dizziness or vertigo, fluctuating hearing loss, tinnitus (noise in the ear, often likened to listening to a conch sea shell), and sensations of ear fullness and/or pressure. Often, Meniere's spells are unpredictable.

The exact cause of Meniere's disease is not known. Spells may be due to ischemia (decrease or lack of blood flow) within inner ear tisues.

Meniere's Disease is thought to be triggered by immune reactions, metabolic disturbances within the inner ear, inner ear infections or trauma, possible allergic conditions, and other injures to the inner ear.

A new theory by Carol Foster, M.D. of the University of Colorad,o is that Meniere's Disease is caused by ischemia or lack of blood flow to inner ear tissue. Dr. Foster has proposed that increase fluid pressure within the cochlea (endolymphatic hydrops) causes a decrease in blood flow to cochlear and vestibular tissues. Her theory is compatible with the clinical presentation of Meniere's Disease. However, we do not know what causes the increase in fluid pressure within the cochlea (increased production of inner ear fluid, decreased reabsorption of the fluid, or a combination of both).

Classically, Meniere's disease begins in one ear at around age 50. In 30-50% of patients, it may eventually involve both ears. There is no physical pain associated with Meniere's Disease. However, there is considerable emotional pain when the disease is difficult to control, and the spells are unpredictable.

Rarely, Meniere's Disease is genetic. It may be expressed in multiple family members such as brothers and sisters. The genetics of Meniere's Disease is not well understood at this time. Genetic studies are being performed at The University of Iowa, Iowa City, IA as well as several other leading research centers.

Vertigo (Rotational Spinning)

The disease is characterized by sudden, often unpredictable, spells of rotational dizziness called "vertigo" that is usually the most bothersome symptom along with hearing loss. Episodes of true vertigo classically last from 20 minutes to 24 hours, occur unpredictably, and are usually accompanied by nausea, vomiting, intense sweating, inability to walk, and general incapacitation.

Hearing Loss

Hearing loss is generally most pronounced in the lower frequencies and is accompanied by a distinct sensation of pressure, fullness or a stopped-up feeling in the ear. Initially, hearing levels may fluctuate and then return almost to normal. However, as the disease becomes more advanced, hearing levels may remain permanently and severely impaired. Hearing loss may effect one or both ears. Typically, one ear will lose hearing and then the other ear will begin to lose hearing months or years later. Again, the hearing loss may be due to patchy areas of ischemic tissue within the inner ear secondary to a lack of adequate blood flow.

Tinnitus (Ear Noises)

Sea shell-like roaring, ringing or bell-like noises in the ear (tinnitus) can be extremely distracting and bothersome. Tinnitus tends to worsen during the acute episodes of vertigo and then subside. It may never quite disappear even after the acute spell is over. Other symptoms may include:

  • a feeling of constant fullness in or around the ear
  • a sensation of distortion of sounds even when hearing levels are not impaired
  • an increased sensitivity to loud sounds
  • drop attacks without loss of consciousness (Falling Spells of Tumarkin)

Pathophysiology

The clinical symptoms of Meniere's disease are thought to be caused by an increase in the fluid pressure within the delicate membranes of the inner ear. The medical name for this condition is "endolymphatic hydrops".

The classic theory is that during a Meniere's spell, the delicate membranes within the inner ear (cochlea) rupture. The mixing of inner ear fluids results in a sudden electrical discharge within the cochlea due to fluids with different electrolyte concentrations mixing together. The spell continues until the fragile membranes heal, and the body recovers its equilibrium.

However, not all cases of Meniere's Disease demonstrate the "membrane rupture" findings. It is possible that some, if not many, cases are due to a decrease in blood flow to the inner ear when the inner ear hydrostatic pressure prevents normal blood flow from reaching inner ear tissues. Meniere's Disease may be due to vessel inflammation (vasculitis), aging and narrowing of blood vessels, and additional unrecognized factors such as problems with calcium channel metabolism, etc.

Unfortunately, the sudden disruption of the normal inner ear tissues leads to injury of the tiny hair cells that are responsible for hearing and balance. Injury of these cells causes permanent loss of hearing and unsteadiness associated with Meniere's disease. Symptoms are thought to be worsened by:

  • stressful situations and fatigue
  • excessive alcohol use
  • increase in dietary salt (sodium) intake
  • caffeine
  • smoking
  • food sensitivities (possibly)
  • increasing barometric pressure (low altitudes)
  • toxic exposure to chemicals (such as chlordane), fungal toxins, and carbon monoxide (possibly)

Natural History

In some patients, Meniere's disease is only intermittently bothersome and takes an overall mild course. Such patients experience ear fullness, tinnitus, and fluctuations in hearing, but no vertigo (cochlear Meniere's Disease).

Periods of increased symptoms, which are unpredictable and occur without warning, may be followed by long periods of improvement or even complete remission. However in some patients, the disease takes a much more serious course and is associated with frequent, disabling attacks of vertigo with nausea and vomiting, progressive loss of hearing, and constant roaring tinnitus. It is not possible to predict who will have a mild form of the disease and who will be severely affected. Some patients experience on fluctuations in hearing and tinnitus without having vertigo (Cochlear Meniere's Disease).  Some patients that have vertigo, tinnitus, and fullness without vertigo have a condition called "atypical migraine variant" and do not have Meniere's Disease.

Currently, there are no blood, x-ray, or scan tests available that can
be used to specifically diagnose Meniere's disease.

Some blood tests are available to help rule out autoimmune inner ear disease that may simulate Meniere's Disease. The diagnosis is based on a combination of:

  • the patient's history over time
  • symptoms during spells
  • hearing and balance testing
  • negative MRI/MRA brain scan results
  • clinical behavior over time

Diagnosis of Meniere's Disease

The history and quality of symptoms are very important in making the diagnosis of Meniere's disease. Vertigo, hearing loss, and tinnitus may not always be present at the same time. The pattern of symptoms may prompt additional evaluations such as for idiopathic sudden sensorineural hearing loss, atypical migraine variant disease, auto-immune inner ear disease, and superior semi-circular canal dehiscence syndrome.

On physical examination, the eardrums and neurological exam are usually normal, especially between the acute episodes of dizziness. During acute attacks, the eyes may exhibit a rapid beating motion called "nystagmus". The eyes may be observed to be beating rapidly from side to side. The fast beating component generally goes toward the side opposite the affected ear. During an episode of nystagmus, the patient will often feel as if either the room is spinning around or that he or she is spinning, and the room is remaining still. Walking is difficult or impossible until the spell subsides. Nausea and vomiting can be severe.

Hearing Testing (Audiometry)

Special tests are necessary in order to help make a diagnosis. Basic hearing testing called an "audiogram" is essential to assess and document hearing levels. Audiograms are often repeated to see if hearing levels are fluctuating. Audiograms are usually abnormal in Meniere's disease. Early in the disease process, low frequency hearing loss is a common finding. Usually, hearing will decrease in only one ear. If the disease becomes bilateral, hearing loss may develop in the other ear over months to years. Moderate to severe hearing loss may occur in one or both ears.

Balance Testing (Electronystagmography & VEMP)

Evaluation of the inner ear balance system and its connections to the central nervous system are done by a test called "electronystagmography" (ENG). Eye motions related to the inner ear are measured by placing the head in various positions and by placing cold water in the ear canals. The affected ear will often show a balance weakness and decrease levels of function compared to the unaffected ear. If both ears are involved, both inner ear balance systems may show decreased activity. Balance tests are usually abnormal in Meniere's disease with one or both ears demonstrating decreased inner ear function.

A new test, vestibular evoked myopotentials, VEMP, are now being used to test patients who are suspected of having Meniere's Disease. VEMPs test otolith function and are measured on muscles. Classically, two muscles are used: (1) the sternocleidomastoid muscle (cervical VEMP or cVEMP) and (2) the inferior rectus muscle of the eye (ocular VEMP or oVEMP). Distension of the saccule of the inner ear in Meniere's Disease is what is being indirectly measured and porvides diagnostic potential.

Nerve Pathway Testing

The hearing nerve and hearing pathways within the brain can be measured by a special computerized test called an "Auditory Brainstem Response Test" or ABR. This test is also referred to in the medical literature as a BSER, BEAR, etc. Using headphones in a quiet room, rapid clicks of sound are placed in the ear canal. The clicks are heard by the ear and nerve impulses travel from the inner ear to the brain. The electrical impulses create brain waves that can be measured from the skin and analyzed by a computer. Interpretation of the brain wave patterns can help diagnose alterations in function of the hearing pathways within the ear and brain. Abnormalities can be seen with tumors of the hearing or balance nerves, multiple sclerosis, and other conditions that affect the nerve pathways. Usually, this study is normal in Meniere's disease.

Inner Ear or Cochlear Testing

Several tests of inner ear function are available. One test called "Otoacoustic Emissions" or OAE is performed to evaluate the health of tiny inner ear hair cells (the outer hair cells). OAE's are performed by placing a small sound probe with a delicate microphone in the ear canal. Sounds are presented to the ear and faint inner ear echoes are analyzed. This test takes only a few minutes to perform and is usually abnormal in the affected ear(s) in Meniere's disease.

A second test called "Electrocochleography" or ECOG is used to assess the electrical activity within the inner ear. Sounds are placed in the ear canal and measurements are made of the electrical activity generated by the conversion of sound energy to electrical energy in the inner ear. There are characteristic electrical abnormalities in endolymphatic hydrops.

Brain Imaging (MRI, MRA, CT Angiography)

An image of the brain and hearing/balance nerves can be made by performing a brain scan called a "Magnetic Resonance Imaging" (MRI) Scan. This study enables visualization of the structures of the inner ear and brain in order to rule out tumors, strokes, multiple sclerosis, hydrocephalus, congenital anomalies, and other abnormalities which can cause dizziness and imbalance. Unlike the other studies mentioned above, this study is performed at either a hospital or special MRI imaging center, rather than in a doctor's office.

MRI scanning uses strong magnets and radio waves, rather than x-rays, to image the brain. Because strong magnets are used, MRI scans cannot be done if the patient has any metal materials in his/her body such as cardiac pacemakers, metal wires, screws or plates, metal fragments from injuries, or cochlear implants, just to name a few. If metal materials are present, a CAT scan, rather than an MRI scan, can be performed.

In order to be useful, the MRI must be performed using a special contrast substance called "gadolinium". Gadolinium is not radioactive and does not contain any iodine dyes. During an MRI scan, gadolinium is routinely injected into a large arm vein after initial images are made. Gadolinium helps to uncover small, easily overlooked problems that may exist. Fortunately, MRI brain scans are usually normal in Meniere's disease.

Other imaging tests such as "Magnetic Resonance Angiography" or "CT Angiography" may also be ordered by your surgeon.These are non-invasive tests like the MRI but use intravenous contrast and different software to make the images. They are also performed at a hospital or out-patient imaging center.

High resolution CT scans may be performed to rule out superior semi-circular dehiscence syndrome (SSCDS). In SSCDS, there is an erosion of the normal bone that covers the top of the superior semi-circular canal.

Blood Testing

Measurements of hemoglobin, blood sugar (glucose), cholesterol, immune system status, liver, kidney, thyroid function testing, and testing for infectious diseases such as syphilis, lyme disease, and infectious mononucleosis may be among the studies needed to rule out other conditions that may cause symptoms similar to those found in Meniere's disease. Testing for food or environmental allergies may also be warranted. These tests are normal in Meniere's disease.

There is no single study that diagnoses Meniere's disease with absolute certainty. Ultimately, the patient and a skilled ear specialist must evaluate the history, physical examinations, entire clinical picture, and test results together in order to arrive at a diagnosis. If symptoms are not classic or the patient has had just one spell, it may take some time in order to arrive at a clear diagnosis. Occasionally, hair or blood samples are sent for toxicology screening if the possibility of exposure warrants the testing.

Medical Treatment of Meniere's Disease

Medical treatment is directed towards decreasing the frequency of attacks, stabilizing the hearing, and managing the episodes of vertigo when they occur. Medical management can lead to symptom control in approximately 85% of patients. Lifestyle changes are crucial to the Meniere's disease sufferer:

  • Avoidance of tobacco products, alcohol, caffeine
  • Avoidance of excessive sodium (sodium ion or Na+ as well as actual salt ( NaCL))

can be of great benefit. Sodium intake should be restricted to 1,800 mg. per day. Also, care should be taken to realize that the crucial element is sodium ion (Na+) itself, not sodium chloride.

Sodium chloride (NaCL) tastes salty whereas sodium ion (Na+) does not taste salty.

Many foods contain large amounts of sodium ion alone and not sodium chloride. Regular exercise, adequate rest, and control of other medical problems may be helpful as well. If food or respiratory allergies play a role, the environment should be modified accordingly. Flare-ups of Meniere's disease may be triggered by stress, so stress reduction, when possible, is important. Some patients derive benefit from biofeedback, relaxation techniques, or psychiatric intervention, if indicated. Avoidance of toxic substances such as pesticides (chlordane), carbon monoxide, and fungal toxins are also important.

Medications

Medication(s) may be prescribed to reduce the severity of symptoms and possibly to decrease the frequency of Meniere's spells. Diuretics (water pills) may act on the inner ear to help remove excess fluid. Anti-vertigo medications (meclizine or Antivert® ) or tranquilizers (Valium® or Xanax®) can provide temporary relief but may be sedating or habit-forming. Steroids, such as prednisone, can help reduce the severity of acute attacks but have significant side effects if taken for prolonged lengths of time. Medications such as Glycerol USP, Diamox®, or Neptazane® are recommended by some physicians. Occasionally, vasodilators or vitamins are helpful, but their results are less predictable; they are rarely indicated. Many of the medications used to treat Meniere's disease only treat the symptoms and cannot "cure" the condition.

Low Dose Oral Methotrexate

A recent treatment for patients with Meniere's Disease that is effecting both ears (Bilateral Meniere's Disease) is the administration of oral methotrexate in low, weekly doses. Methotrexate in high doses is used to treat various types of cancer. In much lower doses, it is commonly used to treat rheumatoid arthritis. For specific patients who have bilateral Meniere's Disease of probable immune-mediated origin (they have responded to steroid medication with a decrease in vertigo and an increase in hearing), methotrexate treatment may be considered. Treatment is begun at 7.5 mg./week and progressively increased to 12.5 mg, 15 mg, and possibly 20 mg./week. Such treatment is done in conjunction with a local rheumatologist-immunologist. Baseline laboratory studies and periodic blood tests are necessary in order to monitor potential toxicity. The most common side effect of methotrexate therapy is nausea. Methotrexate treatment is often combined with every other day steroid treatment of 10mg of prednisone.

Vestibular Rehabilitation

Vestibular (balance) rehabilitation programs may be useful in helping to adjust to the loss of balance function that is often seen in more advanced cases of Meniere's disease.

Surgical Treatment

Endolymphatic Sac Decompression (ELSD)

Endolymphatic sac decompression is a surgical procedure performed to treat intractable Meniere's disease. In this transmastoid surgical procedure, an incision is made behind the ear, and the mastoid bone is entered. A small sac called the "endolymphatic sac" is located and either decompressed or opened, theoretically permitting drainage of excessive inner ear fluid into the mastoid. (In our technique, we do not place a shunt tube from the endolymphatic sac into the subarachnoid space.) The procedure is usually performed for unilateral Meniere's Disease but may be performed on both ears during separate procedures, if indicated. The procedure usually requires an overnight stay in an outpatient surgery center and is of relatively low risk. Approximately, 8 out of 10 patients (80%) receive benefit from endolymphatic sac surgery.

Vestibular Nerve Section (VNS)

Other surgical procedures are available to treat Meniere's disease but must be tailored to the patient's individual needs and circumstances. One procedure involves cutting the balance nerves (Vestibular Nerve Section) which is a neurosurgical procedure. VNS was popular in the 1980's and 1990's and was the gold standard. However, it has been found to have limitations such as not completely resolving the vertigo and sometimes leading to additional hearing loss.

Labyrinthectomy

A second surgical option includes removal/mechanical destruction of the balance system (Transmastoid Labyrinthectomy). Transmastoid labyrinthectomy is the current "gold standard" procedure and is very effective. However, the procedure results in obligatory destruction of any remaining hearing. Transmastoid labyrinthectomy is very effective. It is usually performed when useful hearing has already been lost. A patient may have a cochlear implant after having a transmastoid labyrinthectomy. Labyrinthectomy is seldom performed but can be a very effective treatment in certain circumstances.

Middle Ear Perfusion: A New Treatment Option

For most patients with Meniere's Disease, a combination of lifestyle changes and medication leads to significant improvement. However, some individuals will continue to have disabling symptoms in spite of comprehensive medical therapy. Fortunately, new treatments have been developed that may offer relief from severe episodes of vertigo.

In the last few years, a minimally invasive procedure has been developed that can lead to a significant relief of vertigo with less surgical risk. This procedure involves the use of a carbon dioxide laser, small fiberoptic telescopes, and placement of steroids or ototoxic medication through a very small opening made in the eardrum. The procedure is call "Laser Assisted Tympanotomy with Middle Ear Perfusion" or "LAT" for short.

The success of Middle Ear Perfusion with dexamethasone (a steroid medication) or gentamicin (a common antibiotic) is based on known properties of these drugs:

Dexamethasone (a steroid)

Dexamethasone is a potent anti-inflammatory steroid. When placed in the inner ear in patients with Meniere's disease, small doses of dexamethasone have been found, in some centers, to lead to a reduction in the immune-mediated response in the endolymphatic sac and related structures. This can result in stabilization of hearing and balance problems.

Gentamicin (an antibiotic)

Gentamicin is a common antibiotic that has been used for many years to treat serious bacterial infections intravenously. As a side effect, it was noted to reduce balance (vestibular) response. Treating the inner ear with very small, strategically-placed doses of gentamicin takes advantage of this effect by inactivating the sensory cells that cause episodes of vertigo.

Both of these medications can be toxic when the large doses are given orally or intravenously. When used in smaller doses, both medications readily pass through the round window membrane, a membrane that divides the middle ear from the inner ear. Thus, much smaller, non-toxic doses of these medications may be used to treat the symptoms of Meniere's disease.

Middle ear perfusion treatment of the inner ear with these medications has been performed at both academic and clinical medical centers in the United States. The operative technique has become more standardized, and middle ear perfusion has become an effective method for treating Meniere's Disease that has not responded to medical therapy. In contrast to some of the older, less predictable operations, middle ear perfusion can be safely performed under local anesthesia as an outpatient.

The Procedure

The success of Middle Ear Perfusion has been aided by advances in carbon dioxide lasers, fiberoptic endoscopic technology, and high definition video imaging. In an outpatient surgical center setting using intravenous sedation, a local anesthetic is used to numb the ear canal and the eardrum. Once the eardrum is numb, a carbon dioxide laser beam focused through a microscope is used to perform a Laser Assisted Tympanostomy (LAT) - an extremely small, bloodless opening in the eardrum approximately 2-3 mm. wide over the area of the round window. (The opening in the eardrum usually heals spontaneously in about 4-6 weeks). A fiberoptic examination of the middle ear and round window area is then performed using delicate 1.7 mm Middle Ear Endoscopes (lighted fiberoptic tubes) attached to a miniature television camera. The round window is located and any scar tissue, adhesions, or obstructions that may be present are carefully removed. Medication, such as dexamethasone or gentamicin, placed on a small amount of surgical gel (Gelfoam) can then be precisely placed over the round window membrane where it will slowly perfuse into the inner ear.  The middle ear is filled with the same medication. An ear tube is placed in the laser opening to permit subsequent doses of medication to be administered in the office setting.

Patent Round Window Niche - medication placed in the middle ear can reach the inner ear

md_laser_tympanostomy md_left_rwn md_left_rwn_gelfoam md_left_paparella_tube
1. Left Eardrum: CO2 laser tympanostomy 2. Left Middle Ear: Round window niche 3. Left Middle Ear: Round window niche packed with Gelfoam containing medication. 4. Left Eardrum: Paparella Type I tube to aid in delivering additional doses of medication to the middle ear.

 

Obstructed Round Window Niche: medication placed in the middle ear would not reach the inner ear without removal of the mucosa obstructing the round window niche

R_RWN_obstructed R_RWN_opened R_RWN_gelfoam R_Paparella_Tube
1. Right Middle Ear: Round window niche completely obstructed by mucosa. 2. Right Middle Ear: Mucosa removed from round window niche, exposing the round window membrane. 3.Right Middle Ear: Round window niche packed with Gelfoam containing medication. 4. Right Eardrum: Paparella Type I tube to aid in delivering additional doses of medication to the middle ear.

 

Dexamethasone seems to be most effective in patients with early Meniere's disease who have tinnitus, fluctuating hearing loss, and dizzy spells. Gentamicin is best at relieving intractable vertigo in patients with more advanced Meniere's disease. Neither medication is expected to reverse permanent hearing loss that has already occurred. Middle Ear Perfusion is 80% - 90% effective at relieving the symptoms of vertigo and balance disturbance. Dexamethasone seems to work nearly as well in earlier Meniere's disease for preserving hearing and reducing tinnitus. Gentamicin is used in patients who already have irreversible hearing loss; it usually does not lead to any improvement in hearing. About 30 percent of patients treated with gentamicin experience additional temporary or permanent decrease in hearing. Often, several doses of the medications are necessary to affect a lasting outcome.

In a recent LAT study by Silverstein, et.al. published in May 1999, gentamicin 26.7 mg/ml. was used initially to treat the inner ears of 32 patients. Three study groups were evaluated, each receiving a different number of doses of gentamicin. Overall study results showed control of vertigo in 75%, improvement in tinnitus in 48%, improvement in ear fullness in 62%, and hearing preservation in 90% of patients.

Conclusion

Middle Ear Perfusion is a promising treatment for Meniere's disease that does not respond to medical therapy. It is performed on an outpatient basis and appears to be safe, is much less invasive than older surgical techniques, and will hopefully benefit many patients who have either failed conservative medical management or who require a more active approach to their condition.

With proper evaluation and treatment, Meniere's Disease is usually able to be controlled. Treatment needs to be customized for each individual.

References

  1. Driscoll CL, Kasperbauer JL, Facer GW et al. Low-dose intratympanic gentamicin and the treatment of Meniere's disease. Laryngoscope, 107: 83 - 89, 1997. (Mayo Clinic)
  2. Shea JJ, Ge X. Dexamethasone perfusion of the labyrinth plus intravenous dexamethasone for Meniere's disease. Otolaryngologic Clinics of North America 29: 353 - 358, 1996. (Shea Clinic, Memphis, TN)
  3. Rauch SD, Oas JG. Intratympanic gentamicin for treatment of intractable Meniere's disease. Laryngoscope 107: 49 - 55, 1997. (Harvard Medical School)
  4. Hirsch BE, Kamerer DB. Intratympanic gentamicin therapy for Meniere's disease. American Journal of Otology 18: 44 - 51, 1997. (University of Pittsburgh)
  5. Rosenberg SI. Endoscopic otologic surgery. Otolaryngologic Clinics of North America 29: 291 - 300. (Ear Research Foundation, Sarasota, FL)
  6. Murofushi T, Halmagyi GM. Intratympanic gentamicin in Meniere's Disease: Results of Therapy. Am J Otology, 18: 52-57, 1997.
  7. Silverstein H, Isaacson JE, Olds MJ, et.al.: Dexamethasone inner ear perfusion for the treatment of Meniere's Disease: a prospective, randomized, double-blind, crossover trial. Am J Otology, 19:196-201, 1998. (Ear Research Foundation, Sarasota, FL)
  8. Wanamaker HH, Gruenwald L, Damm KJ, et.al.: Dose-related vestibular and cochlear effects of transtympanic gentamicin. Am J Otology, 19:170-179, 1998.
  9. Harner SG, Kasperbauer JL, Facer GW, et.al.: Transtympanic gentamicin for Meniere's syndrome. Laryngoscope, 108, 1446-1449, 1998. (Mayo Clinic)
  10. Atlas JT, Parnes LS: Intratympanic gentamicin titration therapy for intractable Meniere's Disease. Am J Otology, 20:357-363, 1999. (London Health Sciences Center, London, England)
  11. Eklund S, Pyykko I, Aalto H, et.al.: Effect of intratympanic gentamicin on hearing and tinnitus in Meniere's disease. Am J Otology, 20:350-356, 1999. (Karolinska Hospital, Stockholm, Sweden)
  12. Silverstein H, Arruda J, Rosenberg SI: Direct round window membrane application of gentamicin in the treatment of Meniere's disease. Otolaryngol Head & Neck Surg, 120(5), 649-655, 1999. (Ear Research Foundation, Sarasota, FL)
  13. Minor LB: Intratympanic gentamicin for control of vertigo in Meniere's disease: vestibular signs that specify completion of therapy. Am J Otology, 20:209-219, 1999. (Johns Hopkins).
  14. Adamonis J, Stanton SG, Cashman MZ, et.al.: Electrocochleography and gentamicin therapy for Meniere's Disease: a preliminary report. Am J Otology, 21:534-542, 2000. (University of Toronto)
  15. Kilpatrick JK, Sismanis A, Spencer RF, Wise CM: Low-dose oral methotrexate management of patients with bilateral Meniere's disease. Ear, Nose & Throat J, 79(2), 82-92, 2000. (Medical College of Virginia)
  16. Blakley BW: Update of intratympanic gentamicin for Meniere's Disease. Laryngoscope, 110, 236-240, 2000. (University of Manitoba)
  17. Marzo SJ, Leonetti JP: Intratympanic gentamicin therapy for persistent vertigo after endolymphatic sac surgery. Otolaryngol Head & Neck Surg, 126(1), 31-33, 2002.
  18. Gacek RR, Gacek MR: The three faces of vestibular ganglionitis. Annal ORL, 111(2), 103-114, 2002.
  19. Hargunani CA, Kempton JB, et.al. Intratympanic injection of dexamethasone: time course of inner ear distribution and conversion to its active form. Otol Neurotol, 27 (June): 5554-5569, 2006.
  20. Smith WK, Sandooram D, Prinsley PR. Intratympanic gentamicin treatment in Meniere's Disease: patients' experiences and outcomes. J Laryngol Otol, 120 (September), 730-735, 2006.
  21. Haynes DS, O"Malley M, Cohen S, Watford K, labadie RF. Intratympanic dexamethasone for sudden sensorineural hearing loss after failure of system treatment. Laryngoscope, 117(1) January, 3-15, 2007.
  22. Klockars T, Kentala E. Inheritance of Meniere's Disease in the Finnish Population. Arch Oto HNS, 133(1) (January), 73-77, 2007.
  23. Nakashima T, Naganawa S, Sugiura M, Teranishi M, Sone M, Hayashi H, Nakata S, Katayama N, Ishida IM. Visualization of endolymphatic hydrops in patients with Meniere's Disease. Laryngoscope 2007;117(3):415-419.
  24. Boleas-Aguirre MS, Lin FR, et al. Longitudinal results with intratympanic dexamethasone in the treatment of Meniere's disease. Otol Neurotol, 2008;29 (January), 33-38.
  25. Salt AN, Gill RM. Dependence of hearing changes on the dose of intratympanically applied gentamicin: a meta-analysis using mathematical simulations of clinical drug delivery protocols. Laryngoscope, 118(October), 2008, 1793-1800.
  26. Silverstein H, Farrugia M, Van Ess M. Dexamethasone inner ear perfusion for subclinical endolymphatic hydrops. Ear, Nose & Throat Journal, 88(2), 2009, 778-785.
  27. Nguyen KD, Minor LB, Della Santina CC, Carey JP. Time course of repeated intratympanic gentamicin for Meniere's Disease. Laryngoscope, 119, 2009, 792-798.
  28. Teggi R, Zagato L, Carpini SD, Messaggio E, Casamassima N, Lanzani C, Manunta P, Bussi M. Endogenous Ouabain in Meniere's Disease, Otol Neurotol, 31(1), 2010, 153-156.
  29. Silverstein H, Wazen J, Van Ess MJ, Daugherty J, Alameda YA. Intratympanic gentamicin treatment of patients with Meniere's disease with normal hearing. Oto HNS, 142(4), April, 2010, 570-575
  30. Arslan N, Oguz H, et.al. Combined intratympanic and systemic use of steroids for idiopathic sudden sensorineural hearing loss. Otol Neurotol 2011;January 8 epub ahead of print.
  31. Manrique-Huarte R, Guillen-Grima F, Perez-Fernandez N. Treatment of Meniere's Disease with "On-Demand" intratympanic gentamicin injections. Otol Neurotol 2011;32:461-465.
  32. Ng D, Fouladvand M, Lalwani AK. Skew deviation after intratympanic gentamiciin therapy. Laryngoscope 2011;121 (March):492-494
  33. Bird PA, Murray DP, Zhang M, Begg EJ. Intratympanic versus intravenous delivery of dexamethasone and dexamethasone sodium phosphate to cochlear perilymph. Otol Neurotol 2011;32:933-936.
  34. H-P W, Y-F Chou, etal. Intratympanic steroid injections as a salvage treatment for sudden sensorineural hearing loss: a randomized, double-blind, placebo-controlled study. Otol Neurotol 2011;32(July):774-779.
  35. Phillips JS, Westerberg B. Intratympanic steroids for Meniere's disease or syndrome. Cochrane database of systemic reviews (Online) 2011, 7 (July 6), p. CD008514, epub ahead of print.
  36. Di Berardino F, Cesarani A. Gluten sensitivity in Meniere's Disease. Laryngoscope 2012;122 (March):700-702
  37. Sandhu JS, Low R, et al. Altered frequency dynamics of cervical and ocular vestibular evoked myogenic potentials in patients with Meniere's Disease. Otol Neurotol 2012; 33(Apr):444-449.
  38. Casani AP, Piaggi P, et al. Intratympanic treatment of intractable unilateral Meniere's Disease: Gentamicin or Dexamethasone? A randomized controlled trial. Otolaryngol Head Neck Surg 2012;146(Mar):430-437.
  39. Lambert PR, Nguyen S. et al. A randomized, double-blind, placebo-controlled clinical study to assess safety and clinical activity of OTO-104 given as a single intratympanic injection in patients with unilateral Meniere's disease. Otol Neurotol 2012;33 (September):1257-1265.
  40. Gabra N, Saliba I. The effect of intratympanic methyl prednisolone and gentamicin injection on Meniere's Disease. Otolaryngol HN Surg 2013:148 (April):642-647.
  41. Paradis J, Hu A, Parnes LS. Endolymphatic sac surgery versus intratympanic gentamicin for the treatment of intractable Meniere's Disease: a retrospective review with survey. Otol Neurotol 2013; July 10:epub ahead of print.
  42. Foster CA, Breeze RE. Endolymphatic hydrops in Meniere's Disease: cause, consequence, or epiphenomenon. Otol Neurotol 2013;34:1210-1214.

Updated March 9, 2014