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Author: admin | 24.04.2014 | Category: Tinnitus Causes And Treatments

During the examination of patients who complain of vertigo or who have equilibrium disorders, often identifying the etiology of the disorders is difficult.
Spontaneous nystagmus of peripheral origin is wellknown to have little influence on the eye-tracking pattern (ETP) [1].
The results obtained on a normal subject are shown in Figure 1 and are typical of the findings of the 17 normal subjects tested.
During 3 years prior to his first visit, a 32-year-old male patient had monthly attacks of rotatory vertigo without cochlear sign. During a period of 2 months, a 52-year-old female patient presented with a rotatory vertigo with alternating, fluctuating glove-and-stocking paresthesia, tremor, hoarseness, dysphagia, and motor weakness of the lower extremities. A 33-year-old female patient had severe rotatory vertigo with laryngeal paralysis, hoarseness, seesaw nystagmus, crossed sensory disturbance, and Homer's sign, but no cochlear sign.
The method described in this report-three patterns of ENG recording-is presented as a basis for diagnosis.
Obviously, normal subjects and patients with vestibular peripheral disorders exhibit no oculomotor disorders.
This work was presented as a memorial lecture for Jan Parmentier at the Twenty-Seventh Meeting of the Neurootological and Equilibriometric Society in Bad Kissingen, Germany, March 23-26, 2000. The Heart of the Matter: What Does America Really Know about Coronary Artery Disease Treatments? How to cite this article Daftary A, Shulman A, Strashun AM, Gottschalk C, Zoghbi SS, Seibyl JP. Tinnitus affects nearly 50 million people in the United States, with a minority demonstrating marked functional impairment. Tinnitus is defined as a sensory disorder of auditory perception reflecting an aberrant auditory signal produced by interference in the excitatory-inhibitory processes involved in neurotransmission [1]. Although some have speculated regarding the pathophysiological mechanisms associated with severe centraltype tinnitus, little is definitively understood.
123I-iomazenil is a partial inverse agonist of the benzodiazepine receptor (BZR) and has been used in a number of studies evaluating the role of gamma aminobutyric acid (GABA) mechanisms in neuropsychiatry disorders [6-10]. The study was performed in accordance with the protocols approved by the institutional review board at the Yale University School of Medicine.
Three venous blood samples were collected at 240, 300, and 360 minutes (means ± SD: 264 ± 25 minutes, 324 ± 2 1 minutes, and 369 ± 1 5 minutes, respectively) after starting the infusion of iomazenil, and blood samples were analyzed as previously described [14].
The primary imaging outcome measures of this study were (1) the homotypic ratio of count density for the a priori selected brain regions, (2) the regional equilibrium distribution volume determined by the ratio of activity in brain region divided by the concentration of parent compound, and (3) statistical parametric analysis of tinnitus patients compared with age-and gendermatched controls. This study was an intrasubject analysis in which assessment of the asymmetry in distribution of BZR in homotypic brain regions was performed.
The concentration of the free fraction of iomazenil in plasma was calculated at three different time points as described (except in one patient, owing to technical reasons). As regards asymmetry of radiotracer distribution in homotypic brain regions, V3' data from the regions already described were analyzed using a Wilcoxon signed rank test.
Statistical analysis of volume-of-interest activity in homotypic regions showed statistically significant asymmetry in BZR density (expressed as V3' ) in the superior temporal cortical region. Comparison of cases and controls showed a significant decrease in counts in the frontal lobes (p = .000) and an insignificant decrease in the cerebellum.
This study evaluated patients with severe intractable tinnitus using a bolus and constant infusion of 123I-iomazenil SPECT brain imaging.
In the first part, we analyzed asymmetry in V3' values in each region of interest (volume of interest), findings that would enable us to identify visually detectable difference, which may assist in interpretation of these scans in the future and act as a direct measure of receptor distribution.
The results of the voxel-based SPM analysis also suggest changes in BZR distribution in the frontal lobes and, to a lesser extent, in the cerebellum. Conclusions based on these data should be tempered by several issues in the study design; these include a relatively small number of patients studied, potential confound of age on BZR in the healthy control population, and effect of drug treatment on the imaging. Multiple studies show that short-term administration of benzodiazepines produces mild to no change that reverses rapidly on cessation of therapy [6,27].
Some studies have shown alteration in cerebral metabolism with the presence and absence of symptoms [21]. Finally, imaging measures of alteration in the density of BZR binding may well represent an epiphenomenon associated with tinnitus rather than the primary pathophysiological process. This preliminary study of BZR distribution in a cohort experiencing severe, chronic tinnitus supports temporal, frontal lobe, and cerebellar involvement in the disorder. This work was generously supported by the Martha Entenmann Tinnitus Research Center, Inc., Brooklyn, NY.
The finding of Endolymphatic Hydrops has driven many clinicians to focus on that pathological sign and establish "Hydrops Centered theories and treatments". Some of the clinicians are are using a different terminology, based on the finding of "Hydrops" and call it: Idiopathic Endolymphatic Hydrops. Meniere's disease treatment should be given to patients that underwent a comprehensive evaluation of their auditory and vestibular systems by a specialist. The treatment program in this clinic based on clinical studies started in 1981 as a co-production between the Israeli Defence Forces (IDF) and The "Hadassah" university Hospital (Jeruzalem). The typical course of meniere's disease is attacks of vertigo and tinnitus that come together.
When the vertigo is the dominant symptom – the patient is almost paralyzed and cannot move by himself. Many times it takes years to know that a patient who started with tinnitus – continued with vertigo and hearing loss. Viral infection was suspected very frequently, and theories of autoimmune disease or allergy may be considered as a cause or precipitating factors.
On the basis of the 4 symptoms: tinnitus, vertigo, hearing loss and plugged ear, the clinician has to rule out the possibility of other medical conditions.
A comprehensive Otto-neurological assessment should be performed in order to rule out tumors, blood vessels abnormality or "canal paresis" in one or more of the semi-circular canals. The clinician should check the list of medications that the patient takes for other medical conditions. Men and women have the same probability of suffering from the disease, typical age range: 20–50 years. Caloric Eye-Tracking Pattern Test: Visual Suppression and the Possibility of Simplified Differential Diagnosis Between Peripheral and Central Vertigo. To attempt to determine the etiology in these cases, we devised a new method: the caloric eye-tracking pattern test. In contrast, spontaneous nystagmus of central origin has an influence on the ETP, for instance, as the congenital nystagmus is superimposed on the ETP [1-4].
However, he had hand tremor, diplopia, motor weakness, and "glove-and-stocking" paresthesia during these attacks.
In normal subjects, pattern A is normal, and caloric nystagmus has little influence on the ETP. 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 definition of tinnitus is constantly being refined as a result of the integration of information from otolaryngology, psychiatry, neurology, and nuclear medicine.
Current hypotheses implicate excitatory amino acid-induced neuroexcitotoxicity and abnormal epileptiform activity [2-5]; hence, antiseizure drugs have been used in the treatment of tinnitus. Using a method of bolus plus constant infusion to establish equilibrium-binding kinetics in the brain allows the performance of accurate quantitative analyses of the density of BZR binding sites in the cortex. Patients were recruited from the Martha Entenmann Tinnitus Research Center-Health Sciences Center, Brooklyn, State University of New York and Forest Hills, NY.
Of these patients, two had bilateral tinnitus in the ears, two in the head only, and two in both the head and the ears. Sterility was confirmed by lack of growth in fluid thioglycolate at 35? and soybean-casein digest at 25? for 2 weeks. We chose these intervals on the basis of previous studies indicating that plasma levels of iomazenil reach steady state by these times [15].


All patient and control images were processed as described (see the section, "Image Analysis") and then imported into a commercial image analysis program (MedX, vol.
The results of paired two-tailed comparison of homotypic brain regions with raw counts and V3' levels are described in Table 3. The cerebellum, hippocampus, and thalamic regions did not show any significant asymmetry in receptor density (see Table 3).
Cross-sectional appearance of most significant voxels in the two clusters (A, frontal ; E, cerebellar) demonstrating decreased receptor density in subjects with tinnitus. We also compared the SPECT scans of these patients with scans of historically normal control subjects. The first was a study of region (volume) of interest in which we collected data from brain regions that have been implicated in tinnitus [1,19-22] followed by a voxelbased SPM analysis that would not be biased by our previous concerns about specific area involvement in tinnitus.
We found that the asymmetries identified in the superior temporal region with V3' data matched with our informal visual estimation of asymmetry.
The frontal lobe showed the least asymmetry; for the volume-ofinterest assessment, however, this analysis does not account for the symmetrical relative reduction in frontal lobe receptor concentration.
Owing to the low number of healthy control iomazenil SPECT scans, we were unable to age- and gender-match our controls exactly to the cases.
We cannot, however, exclude that these changes may be in part secondary to reduced affinity of BZR to 123I-iomazenil or to changes in receptor distribution from long-term treatment of the condition with benzodiazepines. What is useful to know, however, is that at the time of the study, all these patients were suffering from tinnitus and that their symptoms had been refractory to treatment. This study, however, should prove to be an effective method on which to base future work and improve our understanding of tinnitus, of its pathophysiology, and of monitoring treatment. This study is the first time that quantification of BZR has been performed on patients with severe, chronic, intractable tinnitus, and it should form a framework for some of the larger studies that could bring to bear an improved description of the natural history of the symptoms and improve treatments.
Institute for Neurodegenerative Disorders, New Haven, CT; and5National Institutes of Mental Health, Bethesda, MD. Proper management of the Biological Clock may contribute to the relive of some of the symptoms. Sometimes the vertigo and the tinnitus are co-dominant, in other cases the symptoms are separated by long time intervals. When the tinnitus comes in attacks – the patient may suffer from hearing loss after every attack. Such atypical patients, prevents a good monitoring of the relevant factors at the beginning of their disease. Audiograms (Hearing test), Imaging (CT, MRI), ENG or Posturography (see: Glossary) may help. In normal subjects and in patients with peripheral disorders, as is well-known, caloric nystagmus has little influence on the eye-tracking pattern.
In normal subjects and in patients with peripheral disorders, even if vestibular asymmetry is revealed by the caloric test, only a slight influence is evoked on the ETP [5]. The cases of central disorders were limited to those patients whose ETP before caloric stimulation was normal or borderline. The results from the normal subjects, as shown in Figure 2, illustrate the well-known fact that nystagmus of peripheral origin has little influence on the ETP. Pattern A is normal , but in patterns Band C it is seen that the caloric nystagmus is superimposed on both the quick and slow phases. On the caloric eye-tracking pattern test, pattern A is normal but, in patterns Band C, it is seen that the caloric nystagmus is superimposed. Therefore, even if vestibular asymmetry is revealed by the caloric test, the superimposed nystagmus is not remarkable. Results of electronystagmography in man: The value of optokinetic, vestibular, and spontaneous nystagmus for neurologic diagnosis and research. 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.
Tinnitus has been attributed to peripheral abnormality in the function of the vestibulocochlear apparatus, to cranial nerve dysfunction, or to central nervous system causes. The therapeutic effect of benzodiazepines in treating tinnitus was studied initially by Melding et al.
An intrasubject study comparing nC-iomazenil positron emission tomography (PET) and 123I-iomazenil single-photon emission tomography (SPECT) in healthy subjects demonstrated excellent comparability of these tracers for in vivo assessment of BZR binding [11].
SPECT images were coregistered to the respective magnetic resonance images using Statistical Parametric Mapping (SPM96) [18].
The variability of V3' data in each volume of interest, when compared to the opposite side, was calculated using the Wilcoxon signed rank test. To the best of our knowledge, this is the first time BZR imaging studies have been performed on patients with severe, chronic central tinnitus.
This brought up an interesting question: Were age- and gender-matching of controls actually necessary in iomazenil studies? Neuroprotective drug therapy: A medical and pharmacological treatment for tinnitus control. Changes of benzodiazepine receptors during chronic benzodiazepine administration in humans. Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I] Iomazenil. Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. Quantitation of benzodiazepine receptor binding with PET [11C] Iomazenil and SPECT [123I] Iomazenil: Preliminary results of a direct comparison in healthy human subjects. Formation of 1-[123I] Iodobutane in labeling [123I] Iomazenil by iododestannylation: Implications for the reaction mechanism. Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I] Iomazenil in human and non-human primates. SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil: Kinetic and equilibrium paradigms.
Evaluation of ultrafiltration for the free-fraction determination of single photon emission computed tomography (SPECT) radiotracers: beta-CIT, IBF, and iomazenil. Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus a PET study with [18F] deoxyglucose. No age-related changes in human benzodiazepine receptor binding measured by PET with [11C] Ro 15-4513.
In contrast, in patients with central vestibular disorders, caloric nystagmus evoked abnormalities in the eye-tracking pattern, either superimposed or as saccades, despite the fact that the eye-tracking pattern before caloric stimulation was normal.
In patients with central disorders, however, caloric nystagmus evoked abnormalities on the ETP, either superimposed or as saccades, despite the fact that the ETP before caloric stimulation was normal.
The eye movement (upper traces of patterns B and C) is affected only slightly by the caloric nystagmus; we can say that this is a case of borderline recording. These results are obviously quite different from those illustrated for normal subjects and for patients with vestibular peripheral disorders. On the CETP test, pattern A is normal, but patterns Band C demonstrate superimposed caloric nystagmus (Fig.
At that time, neither seesaw nystagmus nor neurological signs were evident, but she complained of slight dizziness. In patterns Band C, however, it is obvious that the caloric nystagmus is superimposed on the eyetracking pattern, although its amplitude is very small.
In contrast, in central vestibular disorders, 121 of 128 patients exhibited abnormalities on the ETP. In some cases of central disorders, if the disorder of the oculomotor system is slight, the ETP is normal. Zur Beurteilung ihrer diagnostischen Bedeutung und Begrenzung bei GleichgewichtsstCirung mit und ohne Schwindel, in Riicksicht auf die gegenwiirtige Lage. 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.


According to the American Tinnitus Association, approximately 50 million people are affected with tinnitus in the United States.
The purpose of our study was to apply these techniques to evaluate cortical BZR using 123I-iomazenil SPECT imaging in patients with severe, central-type tinnitus as compared with healthy age-matched controls. Patients were excluded from the study for (1) pregnancy, (2) neurological or axis I psychiatric illness, (3) significant medical disease, (4) intake of medications known to affect GABA or BZR in 2 weeks before radiopharmaceutical administration, and (5) alcohol or psychotropic drug use within 2 weeks before the SPECT study. All patients received potassium iodide (0.6 g SSKI solution) in the 24-hour period before the scan. An operational method for a standardized region-ofinterest strategy was developed by consensus of two experienced research nuclear medicine physicians, and regions of interest were placed. The V3' value for the radiotracer in each region of interest was calculated using the free fraction of the parent. The findings of this study do not correlate with the current understanding of tinnitus, which indicates a possible seat of pathology in the temporal lobes [1,19,23,24]. In 16 healthy volunteers aged 21-78 years and studied with 11C-RO-4513 PET, no significant change with age was seen in 10 brain regions studied [26].
Between the attacks of vertigo, the patient may experience episodes of Dizziness for few seconds or Imbalance. However, these patients do not complain of tinnitus; their audiological examination and caloric test results are normal. These results suggest to us the possible differential diagnosis of both peripheral and central disorders. Pursuit eye movements were recorded with the aid of electronystagmography (ENG), which results in a sinusoidal curve tracing for the horizontal component. Concerning the eye velocity (lower traces of patterns B and C), the change of speed is slight, as the figure shows. Pattern A is normal, but patterns Band C demonstrate the caloric nystagmus superimposed on both the quick and slow phases. One question that arises is whether the amplitude of the calorically induced nystagmus has an influence on the ETP. However, once the vestibular asymmetry is shown by the caloric test, the caloric nystagmus is superimposed clearly on the ETP. 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.
Twelve control subjects were selected from a database of healthy controls with no lifetime psychiatric diagnosis and no clinically significant medical or neurological history, including tinnitus, on the basis of physical examination and laboratory studies. The mean bolus-to-infusion ratios were comparable to those from our previous studies, where they were shown to be optimal in achieving steady state of parent compound and unchanging time-activity curves in cortex [15].
The a priori hypothesis in this preliminary investigation was that chronic tinnitus would show abnormalities in the cerebellum, hippocampus, temporal lobes, and thalamic nuclei [19]. At an earlier stage of this project, we noted a trend showing decreased receptor density in the right cerebellum [25]; however, since then, we have reanalyzed data with closer age matching and also using newer image-processing techniques.
Also, correlation between 123I-iomazenil SPECT and 11C-iomazenil PET studies has been good [11]; however, in both these studies, only a bolus injection of the tracer was performed, which does not necessarily produce equilibrium binding offered by the bolus and constant infusion method used in our study.
We can conclude that the visual suppression to vestibular nystagmus is evoked more strongly by pursuing a moving visual stimulus than by gazing at a stationary target. These results are obviously fairly different from those illustrated for normal subjects and for patients with vestibular peripheral disorders.
In patterns Band C, however, obviously the caloric nystagmus is superimposed on the ETP, although its amplitude is very small (Fig.
As the amplitude of caloric nystagmus is small in patients with peripheral vestibular disorders, it may not be superimposed on the ETP.
Venous blood samples were drawn at specified intervals to determine equilibrium distribution volumes (V3') for each of the regions. This procedure was repeated for each patient, and correction to the time of injection was performed. Imaging was started on average within 345 ± 19 minutes and 363 ± 3 8 minutes after bolus radiotracer administration, respectively, for cases and controls. The study group (n = 6) was compared to the control group (n = 12) using a two-sample t-test for areas of relative increase or decrease in radiotracer accumulation. These results are interesting, not only from the physiological viewpoint but from the clinical viewpoint.
Moreover, no disorders of the central nervous system are disclosed either in their medical histories or in their neurological examination results. During the evoked caloric nystagmus, we administered the eye-tracking test, and the ETP was recorded for 20 seconds beginning 50 seconds after the start of the ice-water injection.
Figure 3 shows the results obtained in a case of left-sided Meniere's disease, which is representative of this group.
Conversely, in central vestibular disorders, because caloric nystagmus has a large amplitude, it may be superimposed on the ETP. In conclusion, we can say that the visual suppression to the vestibular nystagmus is evoked more strongly by pursuing a moving visual stimulus than by gazing at a stationary target. Variation in V3' values in homotypic regions were calculated using a Wilcoxon signed rank test. The extent threshold (k), below which clusters were rejected, was 125 voxels, which corresponds to the approximate resolution of SPECT imaging in tissue, which is 1 mm3.
We cannot diagnose their conditions with confidence, for instance, as vertebral basilar artery insufficiencies. The CETPs are normal, just as they are for the normal subjects (as illustrated in Figure 2).
The records that were obtained from a patient with Wallenberg's syndrome would seem to answer this question. Moreover, this CETP test seems to afford the possibility of a simplified differential diagnosis between peripheral and central disorders and the ability to judge the results of treatment over time. Twelve normal control subjects were compared to the study subjects using statistical parametric mapping. Control subject images were acquired by three serial 18-minute scans that were summed before being used in image analysis. The results in each case were presented as three patterns of ENG recording: pattern A obtained before caloric stimulation, pattern B obtained during caloric testing of the right ear, and pattern C obtained during caloric testing of the left ear.
The eye-tracking pattern is recorded for 20 seconds, beginning 50 seconds after the start of the icewater injection.
Comparison of homotypic brain regions showed statistically significant asymmetry in the V3' data in the superior temporal cortex (p = .03 for both). We call the pattern while the caloric nystagmus is evoked the caloric eye-tracking pattern. The results demonstrated that 121 of 128 cases had obvious superimposed nystagmus or saccades. In patterns Band C, however, obviously the caloric nystagmus is superimposed on the ETP, although its amplitude is very small.
The middle part of the eyetracking pattern is deleted and indicated by the breaks in the curves.
All tinnitus patients underwent MRI and coregistration with SPECT scans (as described later) for directing region-of-interest placement. 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.



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