Benzodiazepine receptor distribution in severe intractable 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.

[1]  J. Seibyl,et al.  Quantitation of benzodiazepine receptor binding with PET [11C]iomazenil and SPECT [123I]iomazenil: preliminary results of a direct comparison in healthy human subjects , 1999, Psychiatry Research: Neuroimaging.

[2]  J. Seibyl,et al.  Benzodiazepine receptor deficiency and tinnitus. , 2000, The international tinnitus journal.

[3]  J. Seibyl,et al.  SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil: kinetic and equilibrium paradigms. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  E. Sybirska,et al.  Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates. , 1992, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[5]  M Laruelle,et al.  Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil. , 1998, The American journal of psychiatry.

[6]  Shulman,et al.  A Final Common Pathway for Tinnitus - Implications for Treatment. , 1996, The international tinnitus journal.

[7]  S. Zoghbi,et al.  Evaluation of ultrafiltration for the free-fraction determination of single photon emission computed tomography (SPECT) radiotracers: beta-CIT, IBF, and iomazenil. , 1994, Journal of pharmaceutical sciences.

[8]  A. Shulman Tinnitus: Diagnosis/Treatment , 1991 .

[9]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[10]  S. Woods,et al.  Changes of benzodiazepine receptors during chronic benzodiazepine administration in humans. , 1999, European journal of pharmacology.

[11]  Shulman,et al.  Medical Significance of Tinnitus. , 1997, The international tinnitus journal.

[12]  O. Inoue,et al.  No age-related changes in human benzodiazepine receptor binding measured by PET with [11C]Ro 15-4513 , 1993, Neuroscience Letters.

[13]  E. Sybirska,et al.  [123I]Iomazenil spect imaging demonstrates significant benzodiazepine receptor reserve in human and nonhuman primate brain , 1993, Neuropharmacology.

[14]  M Schwaiger,et al.  Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: a PET study with [18F]deoxyglucose. , 1996, ORL; journal for oto-rhino-laryngology and its related specialties.

[15]  S. Zoghbi,et al.  Formation of 1-[123I]iodobutane in labeling [123I]iomazenil by iododestannylation: implications for the reaction mechanism. , 1994, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[16]  A. Shulman,et al.  Neuroprotective Drug Therapy: A Medical and Pharmacological Treatment for Tinnitus Control. , 1997, The international tinnitus journal.

[17]  A. Vighetto,et al.  A selective imaging of tinnitus. , 1999, Neuroreport.

[18]  John Seibyl,et al.  No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia , 1999, Neuropsychopharmacology.

[19]  S. Southwick,et al.  Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. , 2000, The American journal of psychiatry.

[20]  Shulman A Final Common Pathway for Tinnitus - The Medial Temporal Lobe System. , 1995, The international tinnitus journal.

[21]  Abel,et al.  SPECT Imaging of Brain and Tinnitus-Neurotologic/Neurologic Implications. , 1995, The international tinnitus journal.

[22]  R. Lechtenberg,et al.  Benzodiazepines in the treatment of tinnitus , 1984, The Journal of Laryngology & Otology.

[23]  P. Thorne,et al.  The use of intravenous lignocaine in the diagnosis and treatment of tinnitus , 1978, The Journal of Laryngology & Otology.

[24]  R. C. Collins,et al.  Selective vulnerability of the brain: new insights into the pathophysiology of stroke. , 1989, Annals of internal medicine.

[25]  J. Krystal,et al.  [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia , 1999, Psychiatry Research: Neuroimaging.

[26]  Albert Gjedde,et al.  Positron emission tomography of cortical centers of tinnitus , 1999, Hearing Research.