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 TTR. 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.
Familial amyloidosis is an uncommon cause of damage to the inner ear. The TTR type of amyloidosis is a hereditary 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). Deafness is not universal to all TTR amyloid patients, and presumably depends on the locus of the mutation.
There are also other types of hereditary amyloidosis.
The "Muckle-Wells" syndrome is a rare autosomal dominant type of amyloidosis where there is hypothyroidism, amyloid goiter, cervical lymphadenopathy, and facial rash (Biswas and Stafford, 2010). There is often sensorineural deafness in the Muckle-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 probably 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). Some types of light-chain monoclonal proteins can damage nerves as well (and are associated with amyloid).
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 generally 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. In other words, there is no method (while the person is alive) to definitively establish that amyloid has damaged the inner ear.
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, which might be difficult to distinguish from the combination of another disorder (such as sudden hearing loss, or vestibular neuritis), and amyloidosis.
Following from the discussion above, lacking an autopsy, all "cases" are really just associations between amyloidosis and a hearing or vestibular problem. Nothing is proven. They could have amyloidosis AND something else causing their hearing/vestibular problem.
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.
Case 2: Unknown type Amyloidosis.
This patient in h is 70's presented with "constant dizziness unless he was still". He had been dizzy for 5 years, and been seen by several other doctors. Brain MRI was almost normal, with some patchy white matter lesions in the occipital areas. Hearing was reduced, but consistent with noise exposure in his occupation.
This "5-6" pattern is nonspecific, and shows there is imbalance in difficult conditions.
This rotatory chair test is abnormal due to decreased gain and increased phase, and suggests a vestibular disorder.
He had a normal Tilt table test, but he had orthostatic hypotension at bedisde exam.
This VHIT test documents bilateral reduction of VOR, suggesting a bilateral vestibular neuronopathy.
This patient started falling, and deteriorated. He developed dementia, was bedridden, and died.
What can we learn from this case ? Well, the combination of orthostatic hypotension and bilateral weakness is rare, and perhaps this is a clue that suggests amyloid. In theory this might be the combination of a vestibular neuropathy with a small fiber neuropathy (impairing blood pressure control).
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 TTR 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 amyloidosis. As the prevalence of amyloidosis is very high in the very old, we could be missing a very large number 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 demyelinating 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..
We thank the wife of patient described in Case 2 for informing us about her husbands ultimate diagnosis.