Timothy C. Hain, MD Marcello Cherchi M.D. Ph.D., Page last modified: May 1, 2017
Familial amyloidosis is an uncommon cause of damage to the inner ear. Amyloid is a name for a group of abnormal proteins that are deposited in the body. Thus amyloid is a somewhat generic term. The heart and the kidney are the most commonly affected organs. There are more than 30 different types of amyloidosis each due to a specific protein malfolding. Some are genetic while some are acquired. An excellent article about amyloidosis in general is found in Wikipedia.
The three most common forms of amyloidosis are AL, AA and ATTR. AL is the main form of amyloidosis in the western Hemisphere. The L in AL means light chain. Here the amyloid is derived from plasma cells, often due to light chains.
AA amyloidosis largely occurs in persons with long term inflammatory disorders. Serum amyloid protein (SAA) is produced during inflammation.
The ATTR type of amyloidosis is a hereditory type of amyloidosis. This type is sometimes associated with progressive deafness. (Mascalchi et al, 1999), as well as weakness and numbness, cardiomyopathy, and enlarged tongues (Meng et al, 2015).
There are also other types of hereditory amyloidosis.
The "Muckle-Wells" syndrome is a rare autosomal dominant type of amyloidosis where there is hypothyroidism, amyloid goitre, cervical lymphadenopathy, adn facial rash (Biswas and Stafford, 2010). There is often sensorineural defness in the Mucle-Wells syndrome. (Dalgi et al, 2007; Hass et al, 2004). Some of these patients have urticaria. Treatment with Anakinra has been reported to be successful in one case.
The Finnish type of familial amyloidosis also have progressive cranial neuropathies, such as hearing loss and facial weakness. (Hornigold et al, 2006)
While persons with amyloidosis do not generally get brain disturbances, they can develop neuropathies. This is the mechanism through which amyloid can affect the inner ear. When unilateral, these are called "amyloidomas" (Meir et al, 2005), basically meaning that there is a tumor like deposit of amyloid. Some of these patients have demyelinating polyneuropathies, which may provide another explanation (Shimizu et al, 2006).
At Chicago Dizziness and Hearing, amyloidosis is not at all a common association with vestibular or cochlear disease, but on the other hand, without a clear method of linking together amyloid and the inner ear, these cases may simply be part of the large "idiopathic" group of patients with hearing loss or vestibular nerve problems.
Amyloidosis is diagnosed through a biopsy.
Concerning amyloid in the inner ear, generally a biopsy is not possible. The diagnosis here is usually based on having known amyloidosis and an inner ear disorder, not better explained by another process.
We would expect that amyloidosis of the inner ear should present as a neuropathy --possibly an auditory neuropathy or a vestibular neuropathy. We would also expect that slowly progressive symptoms might suggest bilateral disease, and rapid onset symptoms might suggest a unilateral damage, difficult to distinguish from the combination of another disorder (such as sudden hearing loss, or vestibular neuritis), and amyloidosis.
A man in his mid 30's, with TTR type amyloidosis, and orthostatic hypotension presented with vertigo.
cVEMP testing revealed a small response on the right, and no response on the left.
VHIT testing revealed a low-normal response on the right, and severe loss on the left.
Rotatory chair testing was very abnormal due to a low gain-TC product (normal is 11.5, his was about 4), and numerous signs suggesting a left sided vestibular loss.
Overall, the picture is of a unilateral vestibular loss, which might also be due to vestibular neuritis.
We have encountered a few cases of patients with monoclonal spikes in their SPEP, and bilateral vestibular loss. It is possible that these patients have amyloid induced inner ear disease.
Like many neurological diseases, this is somewhat of a "locking the barn door after the cows are out" situation. The amyloid is deposited in the tissue, and it is somewhat unrealistic to think that it can be made to dissolve. The production of amyloid might be slowed down. Chemotherapy and steroids are used.Organ transplantation can replace the affected organ. Liver transplants are very helpful for the ATTR type of amyloidosis.
Prognosis is generally poor, although it depends on the type of amyloid. The ATTR type has a better prognosis.
The situation with amyloidosis is that we really do not know how many people with hearing or vestibular deficits also have amylodosis. As the prevalence of amyloidosis is very high in the very old, we could be missing a very large numer of cases. A gigantic amount of basic work needs to be done. The start should be to separate out hearing/vestibular deficits into those from hair-cell damage (i.e. inner ear disease), or nerve damage (i.e. damage to the 8th nerve).
Differentiating nerve and end-organ failure in the inner ear is possible, but rarely done. In theory, ABR testing can detect nerve damage due to demylenating neuropathy -- because of slowing. Again in theory, galvanic testing should be able to differentiate nerve damage (no response) from hair cell disease (response). It also seems possible that latencies of vestibular tests such as the numerous variants of VEMP testing might be sensitive to demyelination.