BASIC AND CLINICAL ASPECTS OF VERTIGO AND DIZZINESS

Causative Factors, Epidemiology, andFollow-up of Bilateral Vestibulopathy

Vera Carina Zingler, Eva Weintz, Klaus Jahn, Doreen Huppert,Christian Cnyrim, Thomas Brandt, and Michael Strupp

Department of Neurology, Ludwig-Maximilians University, Munich, Germany

Bilateral vestibulopathy (BV) is characterized by impaired or lost function of both pe-ripheral labyrinths or of the eighth nerves. In a review of 255 patients (mean age ± SD,62 ± 16 years) with BV diagnosed in the authors’ dizziness unit between 1988 and 2005,62% of the patients were male. Previous vertigo attacks had occurred in 36%, indicat-ing a sequential manifestation. The definite cause of BV was determined in 24% andthe probable cause in 25%. The most common causes were ototoxic aminoglycosides(13%), Meniere’s disease (7%), and meningitis (5%). Strikingly, 25% exhibited cerebellarsigns. Cerebellar dysfunction was associated with peripheral polyneuropathy in 32%compared with 18% in BV patients without cerebellar signs. In a follow-up study on82 BV-patients (mean age at the time of diagnosis 56.3 ± 17.6 years), the frequencyand degree of recovery or worsening of vestibular function over time were determined.The patients were reexamined 51 ± 6 months after the first examination. Electronys-tagmography with bithermal caloric irrigation was analyzed by measurement of themean peak slow-phase velocity (SPV) of the induced nystagmus. Statistical analysis ofthe mean peak SPV revealed a nonsignificant worsening over time (initial mean peakSPV 3.0 ± 3.5◦/s vs. 2.1 ± 2.8◦/s). Only patients with BV due to meningitis exhibited anincreasing, but nonsignificant SPV (1.0 ± 1.4◦/s vs. 1.9 ± 1.6◦/s). Forty-three percent ofpatients subjectively rated the course of their disease as stable, 28% as worsened, and29% as improved.

Key words: bilateral vestibulopathy; prognosis; follow-up

Bilateral vestibulopathy (BV) is characterizedby impaired or lost function of both peripherallabyrinths or of the eighth nerves. The cause ofBV varies and includes ototoxic drugs, menin-gitis, and inner-ear autoimmune and degenera-tive disorders;1,2 however, it remains unclear ina considerable percentage of patients. In theirreport on a series of 53 patients with BV, Rinneand colleagues.1 concluded that the probablecause of BV could be defined in approximately80% of the patients. This contradicts our expe-rience that the proportion of idiopathic BV is

Address for correspondence: Vera Carina Zingler, M.D., Departmentof Neurology, Ludwig-Maximilians University, Klinikum Grosshadern,Marchioninistraße 15, D-81377 Munich, Germany. vzingler@med.uni-muenchen.de

considerably higher. There is also little agree-ment about the course of the disease, especiallyrecovery. A few small case series have reportedcontradictory recovery rates.2–5

The aim of this study6 was to evaluate (1)the relationship between definite, probable, andunknown etiology; (2) the course of manifesta-tion of the disease; (3) associated clinical signs,symptoms, and diseases; and (4) epidemiologi-cal parameters.

We therefore retrospectively analyzed thehistories, clinical presentations, and causesof 255 cases of BV seen in our dizzinessunit (1988–2005). All patients had undergonea standardized, complete neuro-ophthalmolog-ical and neuro-otological work-up, electronys-tagmography (with caloric irrigation), and cra-nial MRI or CT.

Basic and Clinical Aspects of Vertigo and Dizziness: Ann. N.Y. Acad. Sci. 1164: 505–508 (2009).doi: 10.1111/j.1749-6632.2009.03765.x C© 2009 New York Academy of Sciences.

505

506 Annals of the New York Academy of Sciences

TABLE 1. Patients with a Definite or Probable Bilateral Vestibulopathya

Definite cause Probable cause∑

Etiology N % N % N %

Antibiotics 27 11 5 2 32 13

Meniere’s disease 4 2 13 5 17 7

Meningitis/encephalitis/cerebellitis 12 5 1 0 13 5

Two different causes 1 0 11 4 12 5

SCA 6/EA II/MSA 0 0 9 4 9 4

Systemic autoimmune disease 2 1 6 3 8 3

Deficit of vitamin B12/folic acid 3 1 1 0 4 2

Creutzfeldt-Jakob disease 3 1 0 0 3 1

Cogan’s syndrome 3 1 0 0 3 1

Positive family history for inner ear diseases 0 0 3 1 3 1

Miscellaneous 7 3 14 5 21 8

an = 125, 49% of total.Note: Frequency of each etiology is given as percentage of all included patients (n = 255).Abbreviations: SCA = spinocerebellar ataxia; EA = episodic ataxia; MSA = multiple system atrophy.

The results of this study6 are as follows. Themean age of the patients was 61.9 ± 15.9 years(range 12–98 years) at the time of assessmentof diagnosis. The majority were male (62%,n = 157). Diagnosis of BV was made at all ages,but most were made between 61 and 70 yearsof age, and the frequency increased in theelderly.

Episodes of vertigo or dizziness preceded themanifestation of BV in 36% of the patients(n = 91); they were said to have a “sequen-

tial course.” BV developed simultaneously, mostoften slowly progressively in 64% of all patients(n = 164), as indicated by a patient history ofprogressive unsteadiness of gait and oscillopsia.The neurological examination revealed gait un-steadiness in 99% of patients (n = 253) at thetime that BV was diagnosed. Oscillopsia dur-ing head and body movements was reportedspontaneously by 112 of all patients (n = 44%of total).

Overall the definite cause of BV was definedin 24% and the probable cause in 25% of all in-cluded patients (49% of total; n = 125). Table 1gives an overview of the different causes of BV.The most frequent cause (13% of total) wasadverse effects of aminoglycosides. The secondlargest group (7% of total) consisted of patientswith Meniere’s disease, and the third largest

group (5% of total) were patients who had suf-fered from meningoencephalitis.

Cranial imaging studies were performed inthe majority of the BV patients (n = 210 MRI;n = 4 CT). The following abnormalities werefound: cerebellar atrophy (n = 10), other cere-bellar lesions (e.g., cerebellar infarction, n = 6),bilateral acoustic neuroma (n = 1), Cogan’s syn-drome (n = 1), and supra- or infratentorial vas-cular lesions (n = 36).

Twenty-five percent of all patients with BV(n = 65) were also diagnosed to have a cere-bellar syndrome. The MRI of 10 patientsrevealed a cerebellar atrophy. Cerebellar dys-function was associated with a peripheralpolyneuropathy in 32% of these patients, thusmore often than in the BV patients without anycerebellar signs (18%).

In a follow-up study7 we reexamined 82 pa-tients with BV of different etiologies (59 males,23 females; mean age ± SD at the time of diag-nosis 56.3 ± 17.6 years) 51 ± 36 months afterthe first examination. The main goal of this sec-ond study was to determine the frequency anddegree of recovery or worsening of vestibularfunction over time.

All patients underwent a neuro-ophthalmological and neuro-otological exami-nation and electronystagmography (ENG) with

Zingler et al.: Bilateral Vestibulopathy 507

caloric irrigation and measurement of themean peak slow-phase velocity (SPV). TheENG of three patients could not be evaluateddue to technical reasons; thus, the followingstatistical analyses are based on the remaining79 patients.

Patients subjectively evaluated the course oftheir disease by comparing the change of im-balance and gait unsteadiness and the changesof their health-related quality of life.

The results of this study7 were as follows. Theinitial ENG showed no significant differencesin responses to caloric irrigation with respect tosubgroups of etiologies or time course of mani-festation (either sequentially or slowly progres-sively). In general, the mean peak SPV aftercaloric irrigation tended to decrease at follow-up, but not significantly. This was true for thetotal study population as well as for patientswith different time courses of manifestation ofBV (Fig. 1A) and etiologies (Fig. 1B). The meanpeak SPV of the patients with BV due to onlymeningitis slightly increased at the follow-upinvestigation (n = 7).

Single analysis of all patients showed thata substantial improvement of caloric responses≥5◦/s occurred in two patients on both sides(idiopathic n = 1; Sjogren’s syndrome n = 1)and in eight patients on one side (idiopathicn = 6; meningitis n = 1; Meniere’s diseasen = 1). The patient with Sjogren’s syndromehad received immunosuppressive treatmentwith cortisone and azathioprine. The statisti-cal analysis of vestibular outcome as regardsage, gender, and complete versus incompleteBV also revealed no significant differences.

Oscillopsia during head and body move-ments was reported by 56% of all patients atthe first examination, and by 53% at follow-up.Gait unsteadiness was reported by all patientsat both examinations.

Most of the patients (43%) considered thecourse of their disease stable. The rest esti-mated their clinical condition to have eitherworsened or improved by similar percentages(29%, respectively, 28%). The majority of pa-tients (42%) stated that BV caused a slight im-

Figure 1. (A) Response to caloric irrigation in theinitial and follow-up ENG (mean peak slow-phase ve-locity (SPV) ± SD) in the patients with sequential andslowly progressive BV, and (B) for subgroups withBV of various etiologies. Gray column: first exami-nation; white column: follow-up examination (misc =miscellaneous; antibodies = pathological inner earantibodies).

pairment of their health-related quality of life(24% moderate and 18% severe impairment).Only a minority of patients (16%) felt that BVhad not impaired their quality of life. Thirteenpercent of the patients had noticed a develop-ment of impaired spatial navigation.

Conclusion

The cause of BV remains unclear in abouthalf of all patients despite intensive exami-nations. A large subgroup of these patientshave associated cerebellar dysfunction andperipheral polyneuropathy. This suggests a new

508 Annals of the New York Academy of Sciences

syndrome that may be caused by neurodegen-erative or autoimmune processes. More than80% of patients with BV do not improve. Thus,the prognosis of BV is less favorable than as-sumed. This emphasizes the need for intensivevestibular rehabilitation to reduce the burdenof the disease.

Conflicts of Interest

The authors declare no conflicts of interest.

References

1. Rinne, T. et al. 1998. Bilateral loss of vestibular func-tion: clinical findings in 53 patients. J. Neurol. 245:314–321.

2. Vibert, D. et al. 1995. Bilateral idiopathic loss of pe-ripheral vestibular function with normal hearing. Acta

Otolaryngol. 115: 611–615.3. Baloh, R.W. et al. 2001. Age-related changes in vestibu-

lar function: a longitudinal study. Ann. N. Y. Acad. Sci.

942: 210–219.4. Deutschlander, A. et al. 2005. Immunosuppres-

sive treatment in bilateral vestibulopathy with in-ner ear antibodies. Acta Otolaryngol. 125: 848–851.

5. Frese, K.A. et al. 2003. Der beidseitige Vestibularisaus-fall. HNO 51: 221–225.

6. Zingler, V.C. et al. 2007. Causative factors and epi-demiology of bilateral vestibulopathy in 255 patients.Ann. Neurol. 61: 524–532.

7. Zingler, V.C. et al. 2008. Follow-up of vestibular func-tion in bilateral vestibulopathy. J. Neurol. Neurosurg. Psy-

chiatry 79: 284–288.