The

Ear, Nose and Throat Institute

of

Johannesburg

_________________________________

A New Look

at

Meni�re Syndrome

H. Hamersma

M.B., Ch.B. (Pretoria), M.D. (Amsterdam)

Neuro-otologist

Florida Park, Gauteng,

South Africa.

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The Ear, Nose and Throat Institute of Johannesburg is a non-profit organisation founded by Ear, Nose and throat specialists. The Institute aims at developing the science, research and teaching of otorhinolaryngology and related areas, supplementary to other institutions in Southern Africa. Publications by its members express the opinions of the authors and do not indicate official policy of the Institute.

The main incentive for medical research is to find solutions to our patients' suffering.. Basic research in the laboratory is one cornerstone of scientific progress, but countless success stories originated from the astute observations made by clinicians when they carefully listened to, and examined their patients thoroughly. The symptoms, signs, clinical course and interpretation of a patient's condition remain vital to the practice of medicine.

It is with great pride that otologists recall the events of January 8th, 1861, when Prosper Meni�re brought a syndrome of episodic cochleo-vestibulopathy to the attention of his colleagues. This was done shortly before his death, and one wonders what would have happened had he postponed his presentation just a little bit, as all of us are inclined to do.

At the time of Meni�re's presentation it was thought that dizziness (the hallucination of movement of either the patient or the surroundings) was caused by intracranial disease, and that nausea was caused by abdominal conditions. Meni�re had previously worked with Flourens, the Parisian anatomist and physiologist, who experimented with pigeons. In 1842 Flourens had published about violent rotational movements, which followed on sectioning of the semicircular canals or the cerebellum. The seed for Meni�re's thoughts on the inner ear must have been planted when, in 1837, Meni�re observed a girl with severe imbalance:

An anecdotal story often told is that Meni�re, while travelling in an open tram, saw a severely unbalanced woman on the sidewalk. People were laughing at her because they regarded her as being drunk. However, Meni�re observed that her falling tendency was towards one side and concluded that she may be ill. He got off the tram, went to the girl and immediately saw that she was very pale and totally off balance (did he possibly observe nystagmus?). He had her admitted to a hospital, where she died. Today we are sure that she probably suffered from acute leukaemia with a hemorrhagic infiltrate in her inner ear.

After thus having been alerted to the inner ear as a cause of vertigo, deafness and vomiting, Meni�re took an active interest in a number of patients suffering from a strange symptom complex (syndrome), which reminded him of the experiments of Flourens. Meni�re became totally convinced that the inner ear was the cause of the syndrome, and eventually, with trepidation, reported his findings at the Acad�mie imp�riale de m�dicine de Paris, and asked his colleagues whether any of them had seen similar cases:

The presentation was followed by a lively discussion, and he had patients referred to him. Within one year Politzer in Vienna (Austria) and Voltolini in Breslau (Poland) reported similar observations. Voltolini was the first scientist to start using the term Morbus Meni�re (Meni�re's disease). Thirteen months after his presentation Meni�re died from pneumonia.

What a pity that not all the colleagues in France took note of the syndrome, because then Van Gogh, the painter, would not have been regarded as psychotic, but as suffering from episodic cochleo-vestibulopathy, i.e. Meni�re syndrome.

Other famous people who suffered from this condition were:

The syndrome complex, which Meni�re described, is currently known as Classic Meni�re's, and presents no problems with diagnosis. However, in the majority of the classical Meni�re cases the first couple of attacks of vertigo are not accompanied by any auditory symptoms, which confuses the doctors who deal with the patient in the acute stage. It is now known that this can be the vestibular form of Meni�re syndrome. To confuse the issue even more, in a small percentage of classical Meni�re's cases the first attacks can have only auditory symptoms without any vertigo, and this is then called Cochlear Meni�re's. By and large, the majority of cases with these forms eventually convert into classic Meni�re's, but there is definitely a small percentage who do not change, thereby causing problems with final diagnosis and treatment.

A very important aspect of the disease is the fact that, after one single attack, or after a few attacks over some months, the condition can go into remission, either for many years or even permanently. Not only does this present problems as far as the etiology is concerned, but also leads to erroneous conclusions about the efficacy of treatments.

Etiology of Meni�re Syndrome

The custom of calling Meni�re syndrome an idiopathic episodic cochleo-vestibulopathy is now in the process of being abandoned. Very often patients present with symptoms other than the eighth nerve being involved, e.g. the trigeminal, as well as spinal nerves, i.e. Cervical 2-3.

The virus hypothesis for an etiology is gaining support, as well as the viral induced autoimmune response of the inner ear. Based upon these new developments, the author and Dr Kedar Adour from San Francisco are proposing the following classification of Meni�re Syndrome:

EPISODIC VERTIGO

a. Episodic Vestibulopathy -

b. Episodic Cochleo-Vestibulopathy (Classic form of

Meni�re Syndrome) -

Recurrent attacks of vertigo plus ear symptoms which last from 5 minutes to 48 hours (previously called classic Meni�re's disease) -

1. Caused by replication of the HSV-1 virus, i.e. PGE = polyganglionitis episodica;

3. Autoimmune inner ear disease, and

4. Cogan's disease.

The Viral and Autoimmune Etiology

In 1952 Furstenberg noted, "When vertigo dominates the clinical picture but is associated with a burning sensation in the pharynx, numbness on one side of the face and ear, or a typical tic doloreux, it is impossible to reconcile these findings with an isolated lesion in the inner ear."

Lempert et al (1952) concluded that, "Meni�re's disease is a chronic Herpetic Neuritis of the vestibular labyrinth of either toxic or trophic origin."

In 1980 Adour et al from the Cranial Nerve Research Unit of the Kaiser Permanente in San Francisco, found sensory disturbances in other cranial nerves as well as in the upper cervical nerves in patients suffering from acute attacks of Meni�re's disease. They supported the hypothesis that acute attacks may be an acute exacerbation of a viral cranial polyganglionitis, and concluded that the commonly accepted hypothesis of endolymphatic hydrops only develops as a sequel to the cranial polyganglionitis, while the fluctuating low tone hearing loss early in the disease may be due to hypaesthesia of the cochlear nerve during the attacks. The hyperacusis occurring during attacks as well as in late stages of the disease can be explained on the basis that the inhibitory fibers of the cochlear nerve are affected, i.e. loudness intolerance (phonophobia) occurs.

In 1997 Arnold and Niedermeyer discovered Herpes Simplex (HSV) in the perilymph of patients with Meni�re syndrome.

In 1997, during a visit to South Africa, the author and Dr Adour found herpetic eruptions on the skin of the face as well as in the throat of patients during acute episodes of Meni�re's syndrome. Also, in about one third of patients, earache and pain around and inside the ear, occurred during acute attacks of Meni�re syndrome.

In 1998 Pyykk� et al (Stockholm) reported circulating autoimmune antibodies. They concluded a viral infection breaks the labyrinthine barrier and triggers an autoimmune-like reaction. The herpes group of viruses are primary candidates.

Regarding Herpes Simplex 1 virus infection of the cornea, Biswell (1998) stated that 'the antigenic particles of the viruses remain in the cornea long after live virus infection has passed, sensitised lymphocytes attack cells with virus particles attached, with resultant cell wall lysis and necrosis. Infiltration and edema ensues. This is an Antigen-Antibody-Complement (AAC) mediated immune complex reaction which may be equally important in the suspected pathophysiology'. Therefore, what happens in the inner ear in Meni�re syndrome may very well be regarded as

Antigen-Antibody-Complement (AAC)

Immune Complex Disease

Pathophysiology of Herpes Simplex Reactivation

Approximately 80% of humans carry the herpes simplex virus (HSV-1) in the ganglia of cranial and spinal nerves, and are known carriers of the virus. During the acute primary herpetic infection the virus enters the ganglion, where it resides in a latent stage until it is reactivated and causes a ganglionitis. Once the virus gets into the ganglion, it resides in the ganglion in a latent stage until it is reactivated and causes a ganglionitis. The virus then migrates down the nerve to cause mucocutaneous vesicles, and up the nerve to cause a localised meningo-encephalitis at the brainstem. When the virus leaves the neural cell membrane, it takes on a coat of neurolipoprotein, and deposits it in the perineural compartment. This neurolipoprotein causes an immune mediated reaction, which causes demyelinization 8 - 10 days after the disease process has taken place. Therefore when mucocutaneous vesicles appear, this is the lip of the volcano, i.e. this superficial sign indicates what is going on inside the ganglion. Depending on which nerve the virus is reactivated in, signs and symptoms develop which have been described as various disease entities, e.g., Bell's palsy, Meni�re's disease, etc.. Herpes simplex is the big masquerader. It causes the inflammatory ganglionitis, which then causes a viral induced immunological (not an autoimmine) response.

The cranial ganglions contain bipolar sensory cells, and in the cranial nerves there is a relationship with motor and inhibitory fibres, which is unique. In the cranial nerves the motor and inhibitory fibres pass through the ganglion and any disease affecting the sensory nuclei will also affect the motor and inhibitory fibres. Unlike the motor fibres in the peripheral systems (which are separated from the sensory ganglion), the motor fibres of the cranial nerves traverse the ganglion. So, any process, which takes place inside the ganglion, is going to affect the motor nerve fibres, and indirectly the motor nerve cells - they become involved as innocent bystanders. Any sensory system has an inhibitory system, and those inhibitory fibres must traverse the ganglion. When such an inhibitory system is affected a hyperactive state occurs - see the section on individual nerves.

Clinical Syndromes of Cranial Polyganglionitis

The conditions ascribed to Herpes Simplex - 1 are Bell's palsy, Meni�re syndrome (classic as well as the vestibular and cochlear forms), vestibular neuritis, viral cochleitis, viral labyrinthitis, idiopathic sudden sensorineural hearing loss, carotidynia, blocked ear without detectable abnormality, some cases of otalgia and pain in the throat, hypersensitive scalp, dysphonia, tempero-mandibular joint syndrome (also called Costen syndrome), and globus syndrome. A very well known Polyganglionitis condition due to Varicella zoster virus is Ramsay Hunt syndrome (herpes zoster acustico-facialis).

Trigeminal nerve (Cr V)

Sensory branches: The pain is due to inflammation of the nerve roots. Hypesthesia or numbness is due to decreased function of the nerve endings. When inhibition is decreased a hypersensitivity to touch takes place. A new term of 'somatophobia' is proposed for intolerance to touch (Adour et al).

Motor branches: When the masseter and pterygoid muscles are unilaterally affected, the jaw shifts to the paralyzed side and there is a clicking of the jaw joint. Along with the shift there is a stuffy or 'blocked ear' due to paralysis of the branches to the M. tensor veli palatini, which opens the eustachian tube, and the branches to the M. tensor tympani, which moves the ear drum. This results in an acute temperomandibular joint dysfunction previously called 'Costen syndrome'. So, if a patient complains of a stuffy ear and the examination shows no abnormality or hearing loss, check the other branches of the trigeminal nerve as well as other cranial nerves for involvement.

Facial Nerve (Cr VII)

Motor branches: The facial muscles, stapedius, buccinator, platysma, stylohyoid and digastric muscles are supplied.

Secretomotor fibres: The salivary, lacrimal and nasal glands are supplied.

Special sensory fibres provide taste to the anterior two thirds of the tongue (chorda tympani nerve).

There are no somatic sensory fibres in the facial nerve trunk, therefore Hunt's zone of anaesthesia of the auricle or Hitselberger's sign of anaesthesia of the posterior aspect of the external ear canal does not exist.

In Bell's palsy the paralysis of the muscles is due to the seventh nerve motor fibres being affected, the numbness and pain in the cheek is due to trigeminal nerve involvement, the post auricular pain is due to the 2nd Cervical nerve involvement, the taste disturbance (dysgeusia) is due to the chorda tympani cell bodies in the geniculate ganglion being involved.

The hyperacusis, which is better called dysacousis or phonophobia, is not related to an absent stapedial reflex but is a function of the cochlear division of the 8th Cranial nerve (see later).

Vestibulo-cochlear Nerve (Cr. VIII)

Every sensory nerve has an inhibitory system and in the cochlear nerve the inhibitory fibres, possibly in the olivo-cochlear bundle, are affected as they pass through the ganglion. Loss of cochlear inhibition causes loudness intolerance (phonophobia), a common complaint of patients with classic Meni�re syndrome.

Vertigo can occur alone and is then called vestibular neuritis (when the attack lasts longer than a few days), or vestibular Meni�re's if it last for hours to 2 days only.

Acute hearing loss, which occurs alone and lasts longer than hours to 2 days, is called idiopathic sensorineural hearing loss or viral cochleitis.

Vertigo plus hearing loss, which lasts for many days, and occurring once only, is called labyrinthitis, and if it is episodic it is presently called Meni�re's disease or endolymphatic hydrops. However, the virus causes the disease initially (hearing and balance affected but returning to normal after an episode), and the endolymphatic hydrops (chronic stage) is an end stage of the diseased hearing and balance organs.

Rather than individual diseases with individual pathophysiology, the above diseases are a spectrum of the same process, i.e., viral inflammation, probably caused by herpes simplex reactivation.

Glossopharyngeal Nerve (Cr IX)

Somatic sensory branches supply the pharynx, tonsils and middle ear. For the complaint of pain on swallowing with no detected abnormality, check the nasopharynx for inflammation. For the complaint of a 'lump in the throat' check the posterior pharyngeal wall for a loss of sensation. The clue to the finding lies in the phenomenon that a patient always complains of a lump in the throat after the throat has been sprayed with surface anaesthetic. Therefore, the 'globus syndrome' of a lump in the throat is a true neuritis and not a hysterical condition.

Vagus Nerve (Cr X)

Inflammation of the tenth cranial nerve can lead to pain in the throat, ear and carotid artery. Carotidynia (moderate to severe pain with palpation of the carotid artery) is probably due to loss of inhibition to the nerve endings surrounding the carotid sheath. These patients often have a paresis or paralysis of the superior laryngeal nerve (the nerve most often paralysed in the body). The loss of sensation allows mucus and saliva to enter the larynx and a cough results because the swallowing reflex is not initiated in time. The superior laryngeal nerve also stretches the vocal cord, and when affected the patient complains of a change in the voice and cannot sing a high note. On examination the larynx is rotated to the affected side and the vocal cord is shorter. Let the patient put out the tongue and sing a high note - the palate will move asymmetrically.

Cervical Nerves

Pain behind the ear and hypaesthesia in this area is due to involvement of Cervical nerves 2 and 3. This is a common phenomenon with Bell's (Antoni's) palsy and can also occur with acute vestibulo-cochlear symptoms, e.g., Meni�re syndrome. Somatophobia of the scalp can occur. Patients complain of pain on touching the hair or skin of the scalp.

CONCLUSION

The concept of more than the eighth cranial nerve being involved during an attack of Meni�re syndrome/disease is a revolutionary concept. The author has taken this concept into account during the assessment of patients over a period of three years, of which more than 200 suffered from Meni�re syndrome. The concept has serious merit, and one is alerted to this when one actively enquires from the patients about the various symptoms mentioned above, and also look for herpetic eruptions. When one finds that one third of patients complain of pain during an acute attack of vertigo, it makes one sit up and think.

Just as Meni�re was alerted to the inner ear being the cause of vertigo, we must also remain alert to the clinical symptoms and signs which may be right in front of us if we only look for it and pay attention.

A good anecdotal pointer is the experience, which alerted Dr Adour to the polyganglionitis concept in Bell's palsy. Dr Adour saw a patient with an acute Bell's palsy and the man told him that his face was numb. Dr Adour replied that he knew the face was numb because it could not move. To this the patient replied: "Doctor, you are not listening to me. What I mean by numb is a numbness like one gets from an injection by a dentist." At this point Dr Adour became alert and examined the patient carefully - and found an area of hypesthesia of the cheek due to involvement of the trigeminal nerve. That was the day when he started examining the Bell's palsy patients more thoroughly and confirmed the observations of Antonio of 1918, i.e. that the "idiopathic" facial palsy (Bell's palsy) was due to a cranial polyganglionitis, probably caused by Herpes Simplex - I. These findings have subsequently been proved by numerous laboratory examinations of the nerves.

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References

1. Adour KK: "Cranial polyneuritis and Bell's Palsy".

Arch Otolaryngol 102; 262-264, 1976

2. Adour KK, Byl FM, Hilsinger R I & Wilcox RD:

"Meni�re's Disease as a Form of Cranial Polyganglionitis"

Laryngoscope 90: 392-398, 1980.

3. Arnold W, Niedermeyer HP: "Herpes simplex virus antibodies in the

perilymph of patients with Meni�re's disease.

Arch Otolaryngol 123: 53-56, 1997.

4. Hamersma H: "Polyganglionitis Episodica (PGE). A new concept for viral

UPDATE June 1997, pages 135-137.

5. Pyykk� I, et al: "Meni�re's disease: An autoimmune mediated disease

caused by viral infection?"

Presentation at the Collegium Otorhinolaryngologicum Amicitiae Sacrum,

Copenhagen, 1998,

and at the

American Academy of Otolaryngology, Head and Neck Surgery, 1998.

6. Hamersma H: "Meni�re Syndrome. 1999 Update."

The Ear Nose and Throat Institute of Johannesburg, 1999.

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Address:

Dr H Hamersma,

Secretary,

The Ear Nose and Throat Institute of Johannesburg.

P O Box 5973,

Weltevreden Park,

1715,

South Africa.

Tel: 27-11-472-3517

Fax 27-11-472-3519

e-mail: [email protected]