J. Thomsen

Results of Translabyrinthine Removal of 300 Acoustic Neuromas Related to Tumour Size

The results from the Danish model of acoustic neuroma surgery are presented. In the period from 1976 to 1985, 300 patients with acoustic neuromas were operated upon using the translabyrinthine procedure. There were one small intrameatal tumour; 96 medium-sized tumours with an extrameatal diameter up to 25 mm; 85 large tumours, measuring 26-40 mm, and 118 very large tumours with a diameter exceeding 40 mm. The mortality rate was 2%, and CSF leak occurred in 11%, persisting for more than 2 weeks in 5% of the patients in whom the fistula had to be closed operatively. Facial nerve function was completely normal in 66%, slightly reduced in 17%, moderately reduced in 8% and abolished in 9%. The facial nerve was anatomically preserved in 95% of the patients. Reconstruction of the facial nerve, most often an XII-VII anastomosis, was performed in only 6% of the patients. Cerebellar symptoms, occurring in 45% preoperatively, were demonstrated in only 7% postoperatively. We find that a standardization of the measurement of tumor size and of the assessment of sequelae changes is urgently needed.

Placebo effect in surgery for Meniere's disease: three-year follow-up.

In 1981 we published the results of a double-blind, placebo-controlled study in which the efficacy of a regular endolymphatic sac mastoid shunt was compared with a purely placebo operation (mastoidectomy) in controlling the symptoms of 30 patients with typical Menieres disease. Minor differences could be demonstrated between the shunt and the sham operation, but the greatest difference was between the preoperative and postoperative scores, and both groups improved significantly. It was concluded that the impact of the various endolymphatic sac shunts on the symptoms of patients with Menieres disease is nonspecific, and that the 70% improvement in both groups was most likely caused by a placebo effect. At the time of the presentation, the results were based on a 1-year follow-up of all patients. As of January 1982 the patients had been followed for a minimum of 3 years. The 3-year results are the same as our results from the first year: no significant difference could be found between the two groups.

MÉNIÈRE'S DISEASE: ENDOLYMPHATIC SAC DECOMPRESSION COMPARED WITH SHAM (PLACEBO) DECOMPRESSION

The placebo effect in surgery for Ménières disease was investigated in a double-blind, controlled surgery by comparing the effect of a regular endolymphatic shunt with the effect of a purely placebo operation (regular mastoidectomy). Thirty patients with typical Ménières disease participated in the study. They were selected for surgery because of unsuccessful medical treatment and were chosen randomly for each treatment group. The patients filled in daily dizziness questionnaires for 3 months before and 12 months after surgery, registering nausea, vomiting, vertigo, tinnitus, hearing impairment, and pressure in the ears. The patients were operated on in two university ENT departments. Those operated on in one department were controlled each month at the other department, and vice versa. At the termination of the trial, the investigators as well as the patients gave their overall opinion of the efficacy of the operation. Minor differences could be demonstrated between the active and the placebo group, but the greatest difference in symptoms was found when comparing pre- and postoperative scores, in which both groups improved significantly.

Is preservation of hearing in acoustic neuroma worthwhile

In a series of 300 translabyrinthine removals of acoustic neuromas, comprising almost all tumours operated on in Denmark during a period of 10 years, the preoperative hearing in the tumour ear and in the contralateral ear was analysed in 72 patients with tumours smaller than 2 cm in extrameatal diameter. These patients constitute likely candidates for a hearing preserving operation via the suboccipital approach. In the tumour ear in 4 patients there was a pure-tone average (PTA) of 0-20 dB and a discrimination score (DS) of 81-100%. Applying this criterion to the whole series, 1% of the patients would be candidates for a hearing preserving procedure. Changing the criterion to a PTA of 0-40 dB and a DS of 61-100%, the number of candidates would increase to 8 patients (3%), and with a PTA of 0-50 dB and a DS of 51-100% 14 candidates (5%) would have been found. In all of these patients, contralateral hearing was normal (SRT 0-20 dB, DS 95-100%). Since preservation of hearing would be achieved in only half of those subjected to suboccipital removal and since the hearing retained in patients with successful operations is generally poorer than the preoperative level, the number of patients obtaining serviceable hearing is so modest that preservation of hearing cannot be considered an argument in favour of suboccipital tumour removal. It should be borne in mind that contralateral hearing is normal in these patients and that, according to most reports, the mortality rate is higher and paralysis of the facial nerve more frequent with the suboccipital approach than with the translabyrinthine procedure.

Antigenicity and Protein Content of Perilymph in Acoustic Neuroma Patients

11 acoustic neuroma patients, exhibiting cell-mediated immunity in vitro against acoustic neuroma extract, were tested for cell-mediated immunity in vitro against perilymph samples from other acoustic neuroma patients. 14 of 21 perilymph samples were antigenic. None of three healthy persons reacted against antigenic perilymph samples. The perilymph antigenicity was reproducible and negatively correlated to the perilymph sample volume. Differences in sample volume could not be ascribed to admixture of endolymph, cerebrospinal fluid, plasma or blood. The perilymph protein concentration varied from 31 to 54 g/l. Gel electrophoresis of perilymph proteins revealed less staining in the alpha-region compared to plasma proteins and a distinct band in the pre-gamma region absent in plasma. Tau-transferrin was not detected in any of 13 samples. The findings support that the cell-mediated immune response against acoustic neuroma extract may be mediated through release of antigen(s) to the perilymph.

Implications of DNA Characterization of Human Acoustic Neuromas

Based on in vitro detection of cell-mediated immunity against human acoustic neuroma extract, a malignant potential of acoustic neuromas could be surmised, as malignant DNA patterns have been demonstrated in benign pituitary tumours. Flow-cytofluorometric characterization of the DNA content in 10 human acoustic neuromas, however, only revealed diploid cell lines and normal distributions of cells in different cell cycle phases. All acoustic neuromas were histopathology benign. The percentage of cells in S-phase (range: 1.8-8.3%, median: 3.6%) reflected a slow growth rate correlated neither to age, size of tumour, nor length of case history at time of surgery. These findings may in part be due to the analytical variation in the determinations of the S-phases. The investigation has not offered any explanation for the observed cell-mediated immunity against acoustic neuromas, and confirms that acoustic neuromas are benign tuours.

Diagnostic Strategies in Search for Acoustic Neuromas: Findings in 300 Acoustic Neuroma Patients

The diagnostic findings in 300 patients with acoustic neuromas are reported. Because of a centralized treatment of acoustic neuromas, we have a uniform work-up of all the patients, which enables us to make a non-selected comparison of the diagnostic efficiency of the various tests. Diagnostic dilemmas in patients with normal hearing, anakusis, normal auditory brainstem recordings, normal vestibular function and normal tomography of the internal acoustic meatus are discussed. In patients with hearing better than 80 dB, a normal ABR, the presence of recruitment and a normal caloric reaction can exclude the presence of a tumour, making tomography superfluous. In patients with poor hearing, the need for tomography is imperative. We perform CT if two procedures among the following produce tumour-positive results: ABR, recruitment tests, caloric test, and tomography. Those who have only one tumour-positive finding at the screening are re-examined after one year. If, even with contrast enhancement, CT proves negative, we continue to perform air CT. Only then do we know for sure whether the patient has a tumour or not. An advantage with using many tests for the same physiological function is that they complement each other, though, on the other hand this often adds to the confusion. With fewer tests, the confusion is reduced, but the requirements regarding technical quality must be very stringent. ABR, the Metz recruitment test and tomography are purely objective, while the caloric test is subjective on the part of the investigator. The Hallpike procedure, however, has stood the test of time in separating pathologic from normal.

Specific cellular immunity in acoustic neuroma patients.

An indirect leukocyte migration agarose technique to detect cell-mediated immunity was modified to obtain a specific assay for release of human leukocyte migration inhibitory factor. Acoustic neuroma patients exhibited a significant cellular immune response against acoustic neuroma extract (P < .01) as well as perilymph from acoustic neuroma patients (P < .01) when compared to healthy control persons. All 19 patients tested reacted to acoustic neuroma extract. Seven of 21 perilymph samples did not elicit migration inhibition. Crossover determination of antigenicity of two negative and four positive perilymph samples against three patients revealed highly reproducible results, uncorrelated to perilymph concentration of potassium and protein. Flow cytofluorometry did not reveal malignant DNA patterns in 10 acoustic neuromas examined. Immunofluorescence studies did not reveal autoantibodies against acoustic neuromas in sera from 11 patients. The responsible antigen(s), the mechanism of Immunization, and the diagnostic implications remain to be determined.

Inherited Congenital Bilateral Atresia of the External Auditory Canal, Congenital Bilateral Vertical Talus and Increased Interocular Distance

Six out of twenty descendants of a reportedly affected grandfather have congenital bilateral symmetrical and isolated subtotal atresia of the external auditory canal. Four of the six affected descendants have bilateral foot anomalies--two affected cousins having congenital vertical talus. All of the three affected boys in the third generation have increased interocular distance. Short fifth fingers, bilateral single transverse palmar creases, pyloric stenosis and congenital exotropia were found infrequently and are considered coincidental features. Apart from the atresia, oto-rhinolaryngologic examination, mental function, dermatoglyphics, IgA, kidney function and heart function of the affected descendants were all normal. The karyotype of four affected descendants examined was normal. An autosomal dominant inheritance with variable expressivity is suggested.

PATIENT-SPECIFIC CELL-MEDIATED IMMUNITY AGAINST HUMAN ACOUSTIC NEUROMA EXTRACT

Lymphocytes from 8 patients with acoustic neuromas and 8 healthy control persons were exposed to acoustic neuroma extract. Indirect leukocyte migration agarose technique was applied for detection of leukocyte migration inhibition (LMI). The standard technique was additionally modified using a specific assay for release of human leukocyte migration inhibitory factor (LIF). Both the standard technique and the LIF-specific assay revealed a significant LMI exerted by lymphocytes from patients, as compared with control persons. The LIF-specific assay demonstrates that the LMI is an expression of cell-mediated immunity due to release of LIF. The immune reaction is raised against an unknown antigen in acoustic neuroma extract. Further studies must determine whether the immune reaction is specific for acoustic neuroma patients vis-a-vis patients with other tumours, especially other neuromas.