ro-16-0154 and Tinnitus

Tinnitus affects nearly 50 million people in the United States, with a minority demonstrating marked functional impairment. Alterations of gamma aminobutyric acid (GABA) neuronal function and benzodiazepine receptor (BZR) function in particular have been implicated in the pathophysiology of severe, chronic tinnitus. The purpose of our study was to evaluate the distribution of BZR in the brain using 123I-iomazenil single-photon emission computed tomography (SPECT) imaging in patients with severe, intractable central tinnitus. Six patients with severe intractable tinnitus received a bolus and constant infusion of 123I-iomazenil intravenously over 7 hours with SPECT and magnetic resonance imaging of the brain. After magnetic resonance imaging coregistration, standardized regions of interest were placed over the cerebellar, frontal (control), superior temporal, hippocampal, and thalamic regions bilaterally on (SPECT) images. Venous blood samples were drawn at specified intervals to determine equilibrium distribution volumes (V3') for each of the regions. Variation in V3' values in homotypic regions were calculated using a Wilcoxon signed rank test. Twelve normal control subjects were compared to the study subjects using statistical parametric mapping. Comparison of homotypic brain regions showed statistically significant asymmetry in the V3' data in the superior temporal cortex (p = .03 for both). No statistically significant difference was noted in any of the other regions studied. Comparison of the group of study subjects to healthy controls revealed an insignificant trend toward reduction in BZR density in the frontal lobes bilaterally (p = .000) and a reduction in the cerebellum (p = .045). Current understanding suggests GABA receptors and the temporal lobe system as the final common pathway. This pilot study suggests possible alterations on 123I-iomazenil SPECT imaging and the need for larger studies.

Topics: Adult; Aged; Brain; Brain Mapping; Case-Control Studies; Female; Flumazenil; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Receptors, GABA-A; Tinnitus; Tomography, Emission-Computed, Single-Photon

As regards the symptom of a predominantly central tinnitus of the severe, disabling type, it has been hypothesized that a deficiency in the benzodiazepine receptor exists in the medial temporal lobe system of brain and is directly related to affect impairments including anxiety, stress, depression, and fear. This hypothesis has been investigated with single-photon emission computed tomography using the benzodiazepine radioligand 123I Iomazenil. Visual analysis revealed preliminary results of diminished benzodiazepine-binding sites in the medial temporal cortex of all patients with severe tinnitus (N = 6), a finding that is consistent with the hypothesis implicating GABAergic mechanisms in the pathophysiology of the disorder. An abnormal gamma-aminobutyric acid--A benzodiazepine receptor density may be an objective neurochemical measure of the severity of a central-type tinnitus and a rationale for treatment. Clinical correlation with the history, clinical course of the patient, and stress questionnaire are presented.

Topics: Adult; Aged; Brain; Female; Flumazenil; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Receptors, GABA-A; Surveys and Questionnaires; Tinnitus; Tomography, Emission-Computed, Single-Photon