Ulla Friberg

The Natural Course of Meniere's Disease

A retrospective study of 161 Meniere patients followed up for 9 years or more is presented. The development with respect to hearing, caloric response, vertigo and ability to work was analysed. The main functional loss was found to take place early in the course of the disease. There was an increase in bilaterality with time.

Long-term progression of Meniére's disease.

A retrospective study of 161 Meniére patients followed up for 9 years or more is presented. The development with respect to hearing, caloric response, vertigo and ability to work was analysed. The main functional loss was found to take place early in the course of the disease. There was an increase in bilaterality with time. Spontaneous relief in vertigo over the years has been noticed.

Human endolymphatic sac: morphologic evidence of immunologic function

The ultrastructure of ten normal human endolymphatic sacs (ES), fixed immediately after death and obtained at autopsy, was observed by transmission electron microscopy. The roles of the epithelium, subepithelial space, vasculature, and ES leukocytes were morphologically studied to evaluate possible immunologic functions of the human ES. In addition, five intraosseous ES biopsies from patients undergoing translabyrinthine acoustic neuroma resection were studied using the immunoperoxidase technique to identify specific leukocyte subpopulations. Evidence of phagocytic activity included the presence of phagocytic epithelial cells, monocytes, macrophages, and polymorphonuclear leukocytes. Immune surveillance was suggested by intraepithelial and subepithelial T-lymphocytes, numerous fenestrated blood vessels, and the presence of a homogeneously staining substance within the lumina of ES epithelial tubules. No B-lymphocytes were found. The findings support the existence of a local immune system of the normal human inner ear.

The endolymphatic sac in a mouse mutant with cochleo-saccular degeneration: Electrophysiological and ultrastructural correlations

The response of the endolymphatic sac to a disturbance in endolymph homeostasis was investigated by examining the sac in a mouse mutant, viable dominant spotting, which is known to exhibit primary strial dysfunction and cochleo-saccular degeneration. The function of the vascular stria was assessed by measuring the endocochlear potential and the sacs were then studied by light and transmission electron microscopy. The endolymphatic sac was found to be morphologically abnormal in these mutants, the main abnormality being the presence of granular epithelial cells, which showed clear histological signs of secretory activity. A stainable precipitate, believed to be secreted by the granular cells, was observed in the lumen of the endolymphatic sac in the mutants. The findings strengthen the view that the sac is involved in the regulation of endolymph volume and pressure.

Fourth branchial pouch sinus with recurrent deep cervical abscesses successfully treated with trichloroacetic acid cauterization.

A previously healthy 13-year-old girl presented with a left-sided deep cervical abscess. A CT scan demonstrated an abscess in the lower neck, anterior to the common carotid artery. Treatment with i.v. antibiotics and incision drainage resolved the condition. A recurrence of the abscess 7 months later was trea ted identi cally. Further in vesti ga tions with MRI showed a 2-3-mm wide, 10-mm long structure in the lateral aspect of the left thyroid lobe. A barium radiograph depicted a narrow, 20-mm long fistula originating from the left pharynx. At endoscopy a 2-3-mm wide opening was found at the left pyri form sinus apex. This, together with the radiological findings, verified the diagnosis of a 4th branchial pouch sinus. The recurrence of the abscess may have been due 10 contamination by infectious pharyngeal secretions. Although radical surgical excision is traditionally recommended for this condition a non-invasive treatment, namely chemocauterization with 40% trichloroacetic acid (TCA), was chosen in this case. Three cauterizations were needed to close the pyriform sinus opening. To date (Month 14) there has been no recurrence of the cervical abscesses. TCA chemocauterization seems to be a safe first-line treatment for patients with a pyriform sinus fistula.A previously healthy 13-year-old girl presented with a left-sided deep cervical abscess. A CT scan demonstrated an abscess in the lower neck, anterior to the common carotid artery. Treatment with i.v. antibiotics and incision drainage resolved the condition. A recurrence of the abscess 7 months later was trea ted identi cally. Further in vesti ga tions with MRI showed a 2-3-mm wide, 10-mm long structure in the lateral aspect of the left thyroid lobe. A barium radiograph depicted a narrow, 20-mm long fistula originating from the left pharynx. At endoscopy a 2-3-mm wide opening was found at the left pyri form sinus apex. This, together with the radiological findings, verified the diagnosis of a 4th branchial pouch sinus. The recurrence of the abscess may have been due 10 contamination by infectious pharyngeal secretions. Although radical surgical excision is traditionally recommended for this condition a non-invasive treatment, namely chemocauterization with 40% trichloroacetic acid (TCA), was chosen in this case. Three cauterizations were needed to close the pyriform sinus opening. To date (Month 14) there has been no recurrence of the cervical abscesses. TCA chemocauterization seems to be a safe first-line treatment for patients with a pyriform sinus fistula.

A Meniere's disease gene linked to chromosome 12p12.3.

Menieres disease (MD) is characterized by spontaneous attacks of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The majority of patients with MD appear sporadic but 5%–13% of the cases have a family history for the disease. The cause of both the sporadic and inherited forms of MD remains unclear despite a number of candidate genes defined from their association with hearing loss. We have performed a genome wide linkage scan on a large Swedish family segregating MD in five generations. Five candidate regions with a lod score of >1 were identified. Two additional families with autosomal dominant MD were analyzed for linkage to these regions and a cumulative Zmax of 3.46 was obtained for a single region on chromosome 12p. In two of the three families, a shared haplotype was found to extend over 1.7 Mb which suggests a common ancestral origin. Within this region, a single recombination event restricts the candidate region to 463 kb.

Familial Ménière's disease in five generations.

Objective: Clinical characterization of a Swedish family followed for five generations. Several members of each generation had Ménières disease (MD). Possible modes of genetic transmission were assessed. Study Design: Retrospective family survey. Setting: University hospital. Tertiary referral center. Patients: Members of a large family in which several members in each generation were affected by MD. Interventions: Hearing levels were assessed, and the patients were asked to complete a questionnaire regarding age at onset, hearing loss, tinnitus, aural fullness, vertigo, and if MD was unilateral or bilateral. Glycerol tests were performed in a few cases. For deceased relatives, information was obtained from patient charts and interviews with relatives. Genetic studies with linkage analysis was performed for the loci DFNA 1, DFNA6/14, DFNA9, and DFNA15. Results: One member of Generation I and, according to patient charts, two members of Generation II could have suffered from MD. In Generations III to V, 9 of 25 members developed inner ear dysfunction. Six of these individuals developed MD that was strictly in accordance with American Academy of Otolaryngology and Head and Neck Surgery, 1995 guidelines criteria, whereas three individuals had unilateral or bilateral hearing impairment, one in combination with benign paroxysmal positioning vertigo, which could represent an incomplete expression of the disease. The mean age at disease onset was 64.5 years in Generation III, 43 years in Generation IV, and 25 years in Generation V. In the genetic studies, none of the regions investigated showed linkage to the disease gene with a significant calculated log of odds ratio (LOD) score above three. Conclusion: The pattern of inheritance suggested that familial MD was autosomal dominant and exhibited incomplete expression of inner ear symptoms in some affected members. The decreasing age at onset of disease with succeeding generations could indicate anticipation. None of the hitherto-known DFNA loci, which has phenotypes bearing some resemblance to MD, had haplotypes in common with this large family affected by MD.

“Endolymphatic Sacitis” in a Case of Active Meniere's Disease An Ultrastructural Histopathologic Investigation

An ultrastructural analysis of an entire intraosseous endolymphatic sac (ES) from a patient with active, well-documented Menieres disease was performed for the first time. The results were compared with those obtained from ES biopsy material from patients with acoustic neuromas. The ES was small in size and showed signs of focal inflammation with intraepithelial invasion by mononuclear cells. At these places the normal fine structure, including the vascular anatomy, was altered. The possible relationship between these changes and Menieres disease is discussed.

The Lateral Intercellular Spaces in the Endolymphatic Sac. A Pathway for Fluid Transport

The lateral intercellular spaces (LIS) in the epithelium of the endolymphatic sac in different mammals were studied using light and transmission electron microscopy. The reason for the study was that widened LIS are known to occur in fluid transporting epithelia, where they may reflect transepithelial flux of water and solutes. Increased knowledge about LIS may lead to further insight into the mechanisms of endolymph resorption in the endolymphatic sac. The effects of various fixatives, fixation methods and osmolality, and also of surgical labyrinthectomy, on the ultrastructure of LIS were investigated. Widened LIS regularly occurred in the mammalian endolymphatic sac and seem to reflect an in vivo condition. It is thought that LIS may form a pathway for transepithelial water flow in the endolymphatic sac. A hypothetical model of the function of LIS during transepithelial fluid movement in the sac is presented.

Vascular Occlusion in the Endolymphatic Sac in Meniere's Disease

In 2 patients with severe Menieres disease (MD), there was histologic evidence of occlusion of the vein of the vestibular aqueduct (VVA). This finding coincided with total or partial occlusion of numerous small vessels around the endolymphatic sac (ES), flattening of epithelium, extensive perisaccular fibrosis, and signs of new bone formation. Ultrastructural analysis of the occluding material showed foci with dense connective tissue, calcification, lipid deposits, and layers of basement membrane, sometimes concentrically arranged. The exact nature of the occluding material was unknown. In another 2 MD patients, the VVA was not visualized, and the ES vessels showed no signs of occlusion. Seven controls with acoustic schwannoma or meningioma had normal vasculature. The presence of vascular impairment in the ES in MD patients indicated that altered hemodynamics may contribute to the pathogenesis of endolymphatic hydrops and MD.