Endolymphatic Sac: Hearing Loss in VHL

• Testing hearing, checking for possible ELST
• Research Study Seeking People with ELST

Endolymphatic sac tumors (ELSTs) are extremely rare in the general population. While some of the aspects of von Hippel-Lindau disease (VHL) were reported as early as 1884, ELSTs were not described until a century later. While there had been a few isolated cases reported of people with VHL having invasive tumors of the temporal bone₂, until now there was no definite linkage between VHL and ELST (see Figure 1).

Figure 1: Endolymphatic sac. The endolymphatic duct (11) runs from the inner ear to the posterior surgace of the petrous bone and ends beneath the dura at the boundary of the brain as a flattened expansion, the endolymphatic sac (12).   Illustration by Gerhard Spitzer, as published in Color Atlas and Textbook of Human Anatomy, 3:319, by W. Kahle, H. Leonhardt, and W. Platzer (Georg Thieme Publishers, Stuttgart, 1978).  Reproduced with the permission of the publisher.

A new study¹ from the National Institutes of Health reports that hearing loss and ELST are frequently associated with VHL and should be considered when screening individuals at risk for VHL and when monitoring patients with an established diagnosis of VHL. Many patients with VHL have hearing loss even when an ELST is not visible on an MRI. It could be that there is an ELST which is too small to be seen on the MRI, or there may be other causes of hearing loss, we just don’t know yet. Audiologic³ evaluation and MRI should allow early detection and help to limit or avoid hearing loss in people with VHL.

In 1993, Lois Erickson and other volunteers on the VHL Family Alliance hotline noticed that a number of people with VHL were reporting hearing issues ranging from ringing in the ears and Menière’s disease⁴ to severe hearing loss. About the same time, researchers at the National Institutes of Health had noticed that several of their patients with VHL had invasive tumors of the temporal bone and endolymphatic sac.

To determine if hearing issues and ELSTs are a component of VHL, a research team at the U.S. National Institutes of Health (NIH) under Dr. Thomas Manski undertook to look back at the records of 374 people whose brain MRIs were on file at NIH, 121 of whom have VHL. Thus in this MRI grouping were 253 MRIs of people screened but not diagnosed with VHL.

Medical records were reviewed and telephone interviews conducted to detect history of hearing loss, tinnitus, or vertigo. The results of that study showed that there was a relationship between VHL and some degree of hearing disturbance. 33 people with evidence of ELST on their MRI (10 of these 33 people), or with persistent or recurring symptoms of hearing loss (32 of them), tinnitus (23), or vertigo (11) were asked to return for further radiologic and audiologic evaluation. The 30 people who accepted underwent MRI and CT focused on the petrous⁵ bones. In addition, the team reviewed the findings from four VHL patients with ELSTs referred to the Armed Forces Institute of Pathology (AFIP) and analyzed the 13 prior case reports of tumors in the petrous bone of patients with VHL. This grouping, which has some overlap with the MRI group, consisted of 37 people specifically selected for ELST or hearing issues.

For the hearing issues group, MRI was performed on the internal auditory canal and the petrous bones. These people also underwent complete audiologic (hearing) and otolaryngologic (ear, nose and throat) evaluations. Audiologic assessment included psychoacoustic⁶ measurements of pure tone and speech stimuli, studies of middle ear integrity, and electrophysiologic studies of cochlear and auditory brainstem function. VHL gene analysis was also performed for some of these patients.

The next 66 patients seen at the VHL clinic were also evaluated in this same way, with complete audiologic and radiologic examination for hearing issues and ELST. This group was a relatively random selection of people with VHL, with perhaps some greater percentage of people with hearing issues, since the VHL Family Alliance was actively referring to NIH people with hearing issues.

In the MRI grouping, 13 of the 374 patients had petrous bone lesions consistent with ELSTs visible on MRIs. Two people had bilateral lesions. Thus MRI revealed 15 ELSTs in 13 (11%) of the 121 patients with VHL, but no ELSTs in the 253 patients without VHL.  (See Figure 2.) These 13 patients experienced hearing loss (13), tinnitus (12), and a variety of symptoms of dysequilibrium (8). Only one person had some loss of muscle power in the facial muscles. Of those with some hearing loss, the loss occurred between the ages of 12 and 50 years (average = 22) and had been there for 3 to 31 years (average=15.3 years). In 8 (62%) of these people, hearing loss was their first symptom of VHL. Five people (38%) reported a sudden complete loss of hearing on the side with the tumor. The four patients with complete hearing loss on one side and invasive temporal bone tumors larger than 2 cm. underwent removal of these tumors. Each was definitely identified as an ELST.

Figure 2. Of 374 MRIs reviewed at the National Institutes of Health, 15 ELSTs were found in 13 people. While 11% of the 121 patients with VHL had ELSTs, no ELST were found in the patients who did not have VHL.

Audiologic testing revealed that hearing for pure tones was abnormal in all ears with ELSTs identified on MRI. Ten affected ears demonstrated absent or profoundly decreased pure tone hearing, 2 had mild to moderately handicapping pure tone deficits, and 3 showed pure tone sensitivity changes that were not yet handicapping. Acoustic reflex studies were abnormal in 11 of the 15 ears.

VHL genotype information was available for 10 of the ELST patients from 9 different families. Affected patients belonged to VHL type 1 and type 2 families. In 7 of the 10 patients, there were 4 large deletions and 2 mutations ending at a stop codon. Thus in this small sample, distribution of types of VHL was broad, with a large proportion of mutations predicted to truncate the VHL protein. At this time, genetic screening will not permit identification of VHL patients who are particularly susceptible to development of an ELST.

In the clinic group, forty-three (65%) of the 66 patients from the VHL clinic, without additional screening criteria, had abnormalities in pure tone testing,⁷ including 11 patients (17%) with handicapping or profound hearing loss; 23 (54%) of the 43 patients had some degree of hearing loss in both ears. Among the 49 patients from the clinic with proven VHL, 32 (65%) had pure tone abnormalities and 3 (6%) had ELSTs evident on MRI (2 of whom had bilateral MRI-visible ELSTs).

Their results indicate that hearing loss, often bilateral, is frequently associated with VHL and that many patients with VHL and hearing loss have ELSTs. The results suggest that, left untreated, most ELSTs will eventually cause hearing loss which can progress to total deafness. People with ELSTs most commonly complain of hearing loss, frequently accompanied by tinnitus and a variety of vestibular symptoms (nystagmus, vertigo, or a tendency to fall). When progressive growth occurs, these tumors may impinge on adjacent neural structures, may cause the facial nerves to lose tension or sensation, and may even (very rarely) cause paralysis of the vocal cords.

The findings of this team indicate that the prevalence of hearing loss (65%) and ELSTs (at least 6%, higher if hearing loss is the result of hidden ELST in patients with normal MRI) is at least as high as the occurrence of other more commonly understood manifestations of VHL. We cannot say that hearing issues are always caused by ELST (only 3 of 49 patients with VHL had MRI evidence of ELST), but current evidence suggests that fewer than 10% of adults in the general population in this age range have detectable hearing loss. Moreover, in 62% (8 of 13) of patients in the study, hearing loss was the first symptomatic manifestation of VHL. Since ELSTs are rare in the general population, and as their association with VHL implies a common genetic origin, patients with an ELST should receive a screening evaluation for VHL.

The very long interval between the onset of symptoms and the diagnosis of ELST is probably due to the fact that good imaging technology is quite recent, and ELSTs are small. They have commonly been mistaken for hemangioblastomas, metastatic renal cell carcinomas, cholesteatomas, or ectopic choroid plexus papillomas. Even with modern MRI techniques, most patients are diagnosed only after significant or total hearing loss leads to modern audiologic evaluation.

In 8 of the people studied, the symptoms came on slowly and progressed slowly over a number of years, potentially permitting early diagnosis and treatment to preserve functional hearing in the affected ear.

The ideal treatment of ELSTs should eliminate the tumor while preserving hearing. It appears as if curative therapy for ELSTs requires complete surgical excision, as partial resection, with or without postoperative radiation therapy, is associated with a high incidence of tumor recurrence. Early identification of small ELSTs, before complete hearing loss has occurred, should improve the likelihood of preserving hearing after the removal of the tumor. Only 5 ELSTs (3 patients) associated with some preservation of hearing in the affected ear have received surgery. In all 5 ears the preoperative level of hearing was preserved after surgery. Although results in these patients indicate that it should be possible, too few ELSTs have been removed before severe hearing loss has occurred to establish whether hearing preservation can be achieved regularly with total tumor resection. Treatment plans must also consider that these tumors usually grow slowly. To justify early surgery, probability of cure must heavily outweigh risk of hearing loss associated with the surgery itself. This is especially true in people with bilateral ELST who are deaf in one ear and are found to have a small ELST involving the hearing ear.

Hearing loss and ELST should be considered part of the VHL syndrome. When screening individuals at risk for VHL and monitoring known VHL patients, a detailed audiologic examination should be included. Although results of audiologic evaluation were consistently abnormal in patients with radiographic evidence of ELST, the abnormal hearing test results were nonspecific, and no pattern or combination of findings was clearly diagnostic of an ELST. Audiologic examination and MRI should be repeated on a regular basis if symptoms of hearing loss, tinnitus, vertigo, or imbalance appear. Since we are still learning about the natural course of these tumors, the interval for repeating these studies remains to be established. Enhanced awareness of the association between VHL and hearing loss and ELSTs by patients and physicians and use of the diagnostic evaluations described here should allow early detection of ELSTs and hearing loss and may enhance management and prevention of hearing loss in VHL.

1. "Endolymphatic Sac Tumors," by Manski et al, Journal of the American Medical Association, 277:18, May 14, 1997.

2. The temporal bone is near the temple. The hard bone you can feel behind your ear is the temporal bone.

3. Audiologic evaluation: testing and measurement of the hearing.

4. Menière’s disease: a disorder causing extreme dizziness and vertigo. While its exact causes are unknown, it is thought to be a symptom of subtle changes in the pressure in the endolymphatic sac.

5. The petrous bone is the hard (stone-like) portion of the temporal bone which projects inside the skull and houses the inner ear.

6. Psychoacoustic testing is where the person whose hearing is being studied is listening and responding, as opposed to other audiologic studies which measure electro- or neuro-physiological functions of certain parts of the auditory system without the subject responding in any way.

7. These people have pure tone threshholds poorer than 20 dB, which was less than criteria for normal.

As printed in the VHL Family Forum, June 1997

Note1:

Testing hearing, checking for possible ELST

Studies of pure tone and speech threshholds, biomechanical evaluation of the middle ear (tympanometry and acoustic reflex studies), auditory brainstem responses, and otoacoustic emissions accomplished in the context of a detailed audiologic individual and family history

For people with symptoms, neuro-imaging techniques may be added, especially MRI of the petrous bones (with special attention to the region of the external aperture of the vestibular aqueduct).

Note 2:

Research Study Seeking People with ELST

The National Institues of Health has defined a research protocol to investigate the natural history of ELST hearing loss with VHL, and surgical treatment of ELST to conserve hearing. This study will be directed by Dr. Edward H. Oldfield and Dr. Daniel Choo.

If you would like to apply for admission into the protocol, please contact Dr. Oldfield’s office at 301-496-5728.

As published in the VHL Family Forum  5:2, June 1997. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.