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18.03.2015
In daily clinical practice, it is seen that elderly patients complain most frequently of dizziness, tinnitus, and hearing loss. With an increase in the elderly population, the pattern of diseases changes, and the age factor has to be considered in diagnosis and treatment. In daily clinical practice, the elderly patients seen complain most frequently of dizziness, tinnitus, and hearing loss. In comparison to younger people, what is first noticeable about elderly people is that they have a good deal of body fat and a markedly low level of intracellular water. Listed in Table 2 are the diseases involving vertigo, which we often encounter in daily clinical practice, specifically among elderly patients. The extension, flexion, or stenosis of a vertebral artery, cervical spondylosis, and cervical torsion due to the abnormality of cervical soft tissue induce rotary vertigo and sometimes a transient disturbance of consciousness. For oral drug treatment, it is important to use such agents as clonazepam, imipramine hydrochloride, and thyrotropin-releasing hormone. The diagnosis of a predominantly central, severe, and disabling tinnitus in the patients in our study was established by completion of a medical audiological tinnitus patient protocol (MATPP) [5,6], which identified positive central cochleovestibular test findings and abnormalities in brain perfusion as identified on brain SPECT both at baseline and after acetazolamide (Diamox). Significant for tinnitus are reports of involvement of GABA with physiological processes, including network synchronization and theta and gamma rhythms in brain, both considered to be associated with cognitive functions [S, 15]. Gabapentin is a selected agonist for the GABAA receptor, and baclofen is a selective agonist for the GABAB receptor. This preliminary report of RTT-GABA for attempted TC presents the method of patient selection, the establishment of a titration schedule for both initial and long-term gabapentin and clonazepam therapy, and a discussion of the neuropharmacological issues involved for patients with diagnosed severe, disabling, predominantly central tinnitus. Patients suffering from severe, disabling, predominantly central type tinnitus with a duration equal to or greater than I year were selected for RTT-GABA. A trial of medication either alone or in combination with instrumentation was the initial therapy for attempting TC.
Intake outcome questionnaires were completed by each tinnitus patient both prior to the initial consultation and at the time of each follow-up visit. Outcome questionnaires were completed by each patient for intensity, annoyance, handicap, depression, and stress. In general, the dosage for each medication was differentiated on the basis of the sensory and affective components of the tinnitus symptom.
The medication titration schedules for both gabapentin and clonazepam followed the pharmacological principle of using the lowest dose of each preparation to achieve the maximal desired effect and "to do no harm." The dosage of each was increased or decreased on the basis of reported unit change of the TII and TAI, respectively. Our dosage titration schedule for gabapentin was based on the reported tinnitus intensity response to one tablet (100 mg) of gabapentin (Neurontin). All patients were asked to begin taking clonazepam (Klonopin), 0.25 mg, at bedtime for the tinnitus affective component. SupplemenTAI clonazepam therapy (0.25 mg) was recommended if the TII or the TAI was at a unit level of at least 5 for more than 1 hour. Brain SPECT, both at baseline and after acetazolamide administration, is recommended between 6 months and 1 year in an attempt to monitor the efficacy of RTT, to adjust dosage, and to improve the accuracy of the tinnitus diagnosis. Complications to the prescribed medication, which may be expected, were explained to the patient. The parameters of tinnitus identification as regards quality, location, and masking curve were established for each patient. The results of TC with RTT-GABA are reported for 30 patients, divided into two groups and all suffering from severe, disabling, predominantly central type tinnitus treated over the period October 1996-December 2000. The outcome questionnaires for TII and TAI reported at this time showed a 90% unit reduction average for TII and TAI in group II (19 of 21; Fig.
A statistical analysis of TC, based on TII and TAI score of a unit change of 2, was completed (Table 2). Significant reduction in the associated complaint of vertigo was reported by 10 patients, and cognitive function improvement was reported by 4 patients. The duration of tinnitus relief in group II patients ranged from 4-6 weeks to 3 or more years (Table 3). Sequential brain SPECT, both at baseline and after acetazolamide administration, with radioisotope 99TcHMPAO was completed for 10 of 19 group II patients.
All patients were cautioned to observe and report complaints highlighted by headache, nausea, vertigo, increased hearing loss, tinnitus, ear blockage (occurring alone or in combination), excitability, interference in cognitive function, blurring of vision, or possible seizure. The criteria established for success for TC after RTT-GABA are clinically interpreted to be significant on the basis of reported results at this time. Outcome questionnaires based on the TII and TAI identified and demonstrated the individuality of the tinnitus symptom by the distribution of unit change in visual analog scales and by the significant relief reported by unit changes of less than 2 (see Fig. We completed the statistical analysis of groups I and II for unit change in TII and TAI on the basis of a goal of less than 2, 2, or greater than 2 (see Table 2).
Whether the statistically significant result for annoyance on the TAI scale is the underlying basis for the TC reported by patients with RTT must be considered (see Table 2).
The BZ receptor and its relationship to GABAA are significant in the transition of the sensory to the affective components of tinnitus. At this time, in answer to the foregoing questions, we considered as most significant the reports of TC cited by a significant number of tinnitus patients (19 of 21; 90%).
The interesting questions raised by our initial study with the BZ radioligand 123I-iomazenil are considered to be reinforced by the results of this study [1]. This report supports RTT-GABA as one additional method to be considered in the attempt at TC of a predominantly central type tinnitus. RTT-GABA has resulted in significant long-term maintenance relief in patients suffering from severe, predominantly dentral tinnitus (19 of 21; 90%).
Meniere’s disease is a chronic disorder of the inner ear involving sensorineural hearing loss, severe vertigo and tinnitus. Meniere’s disease appears to involve overproduction or decreased absorption of endolymph, with resultant degeneration of vestibular and cochlear hair cells. Recurrent attacks result in progressive sensorineural hearing loss (especially low tones), usually unilateral in nature. Goal of treatment may include recommendations for changes in lifestyle and habits or surgical treatment. Psychological evaluation may be indicated if patient is anxious, uncertain, fearful or depressed.
Tranquilizers and antihistamines such as meclizine (Antivert) to control vertigo and to suppress the vestibular system; antiemetics for nausea and vomiting.
Impaired adjustment related to disability requiring change in lifestyle because of unpredictability of vertigo.
Risk for fluid volume imbalance and deficit related to increased fluid output, altered intake, and medications. Anxiety related to threat of, or change in, health status and disabling effects of vertigo. Ineffective coping related to personal vulnerability and unmet expectations stemming from vertigo. Discuss medications that may be prescribed to prevent attacks or self-administration of appropriate medications during an attack, which may include anticholinergics, vasodilation, antihsitamines, and possibly, diuretics or nicotinic acid.
A labyrinthectomy is the most radical procedure and involves resection of the vestibular nerve or total removal of the labyrinth performed by the transcanal route, which results in deafness in that eat. Another very common cause of vertigo that worsens with a change in position is dehydration.
In the ear, nose, and throat field also, we are required to consider changes in organs and diseases associated with age and corresponding treatment approaches. In other words, elderly people are always at risk of dehydration and are liable to enter a shock state.
Even if they have the same disorder as is seen in younger people, they are less likely to manifest typical symptoms.
Hypotension produces rotary vertigo in patients, as it does paroxysmal positional vertigo (PPY).
Hyperlipidemia, ischemic heart disease, and diabetes mellitus require special attention in the elderly, as does orthostatic hypotension.


Cerebellar infarction, particularly in the bilateral or median portion, often produces vertigo (Fig. The rare onset of this disease after the retirement age of between 60 and 65 years has to do with the decline of internal ear function with aging. Recall the familiar scene in which Robert Kennedy lay in the hotel lobby waiting for an ambulance immediately after he had been shot [4]. Of course, treatment should be provided on a case-by-case basis, but what is essential is to improve blood circulation. GABAA - Benzodiazepine-Chloride Receptor-Targeted Therapy for Tinnitus Control: Preliminary Report.
Thirty tinnitus patients completed a medical audiological tinnitus patient protocol and brain magnetic resonance imaging and single-photon emission computed tomography of brain. Impairment of GABAergic function has been implicated in neuropsychiatric disorders of epilepsy and anx iety [16].
High levels of the GABAB protein molecular structure have a demonstrated similarity to the metabotropic glutamate receptors (CmGluRs) and GABAB (1) [13]. Examination of the CNS, including brain SPECT and brain and internal auditory canal MRI with gadolinium, was recommended if the severe disabling tinnitus symptom was unchanged after an initial trial of combined instrumentation and medication. Interval follow-up visits were determined by patients' clinical course and by their report of the degree of TC, which was individual and varied from biweekly to every 6 months. Gabapentin was prescribed for the sensory component, and clonazepam was prescribed for the affective component. We recommended a duration of therapy of at least 4- 6 weeks and that therapy be continued with a maintenance dose to be determined for each medication so as to maintain an acceptable level of TC individualized for each patient.
The toTAI supplemenTAI c10nazepam dose was not to exceed two additional 0.25-mg tablets in a 24-hour period, these tablets to be taken no sooner than 4 hours apart. Psychiatric therapy attempts to treat with anxiolytic or antidepressant medication the affective component, highlighted by anxiety or depression (or both). They include (for gabapentin) drowsiness or nausea, visual disturbance, vertigo, headache, or interference in cognition and memory. The number of patients who experienced tinnitus relief of a unit reduction of 2 or more on the TII and TAI scales but considered the tinnitus relief to be nonsignificant was 3 of 19 (15.7%). In group I, transient vertigo was reported by three patients, and drowsiness was reported by four patients. Such an analysis suggests that a statistically significant value for achieving TC can be expected on the basis of a unit reduction for annoyance of equal to or greater than 2 and a possible similar result for intensity.
The brain SPECT confirmation findings of subjective TC in 10 patients may not be a primary reflection of tinnitus but may be an epiphenomenon reflecting stress and its clinical manifestations of anxiety, depression, and the like.
The clinical results reported at this time for TC with RTT-GABA are considered additional clinical support for the hypothesis of a GABAergic mechanism involvement in the pathophysiology of some clinical types of tinnitus, one clinical manifestation of which may be a BZ deficiency [1]. This is hypothesized in the concept of the final common pathway for all clinical types of tinnitus and the stress diathesis model for tinnitus [19, 20]. They provide objective evidence that supports the subjective reduction in tinnitus as reported by the patient for TC. Additionally, the response to RTT-GABAA supports the concept of the final common pathway for all clinical types of tinnitus and the stress diathesis model of tinnitus. Sequential brain SPECT studies support the clinical impression of a BZ deficiency syndrome. Biala, MD, for preparation of the graphics and the Martha Entenmann Tinnitus Research Center, Inc., for support of this educational and research activity.
The treatment is designed to eliminate vertigo or to stop the progression of or stabilizes the disease.
Two common causes of vertigo are labrynthitis (inner ear infection) or a condition called Meniere's disease. Against this background, we review vertigo in elderly patients briefly and consider the key points of its treatment. Using this as backdrop, we review vertigo in elderly patients briefly and consider the key points of its treatment. The dorsal root in the elderly is also degenerated, which ex-plains such diverse complaints as dizziness, tinnitus, ringing in the head, headache, neck and shoulder stiffness, and lumbago. Special effort should be made to differentiate between not only benign PPY but pseudobenign PPY and malignant PPY. Atrial fibrillation, among others, can be one of the major causes for cardiogenic embolism [3].
The leftward conjugated deviation of the eyes and right facial palsy were due to a pontine lesion. The three keys are to facilitate blood circulation, prevent thrombosis, and improve blood rheology.
Preliminary investigation with single-photon emission computed tomography (SPECT) of the brain with the radionucleopharmaceutical 99Tc-HMPAO has demonstrated perfusion asymmetries in multiple regions of interest in the brain, highlighted by the cortex of the medial temporal lobe system (MTLS) [3]. Synaptic inhibition in the mammalian brain results largely from binding of the small-amino acid GABA to its receptors [S].
GABAB (1) heterodimerizes with GABAB (2) to form a functional G protein-coupled receptor (GPCR). The tinnitus diagnosis for the clinical type of tinnitus was established by completion of a MATPP [5,6, IS]. The brain MRI was not repeated prior to RTT if patients reported a brain MRI to be normal within 6 months of consultation. A visual analog scale scoring 0-7, wherein 0 equals absence of tinnitus and 7 equals the worst tinnitus that the patient may experience, were completed for both tinnitus intensity (tinnitus intensity index [TII]) and annoyance (tinnitus annoyance index [TAI]). We explained to each patient that neither medication is specific for attempting to provide TC for a predominantly central type tinnitus. Such treatment should be continued in an attempt to establish or maintain a stable personality. For c1onazepam, they include drowsiness, headache, vertigo, interference in cognition, agitation, and memory loss. In group II, 19 of21 (70%) completed the trial period and established a maintenance dose of both medications for TC.
Sequential brain SPECT studies, both at baseline and after acetazolamide administration, were obtained in 10 of 19 patients, all of whom revealed improvement highlighted by increased perfusion in the MTLS.
The patient-estimated percent improvement from the start of receptor-targeted therapy was 36.8%. Correlation with outcome questionnaires for TII and TAI was positive in all patients (10 of 10).
It provides an estimate of the proportions of patients who will show a tendency for TC involving both intensity and annoyance.
The symptom of tinnitus, particularly a predominantly central type, may be a clinical manifestation of a BZ deficiency syndrome with associated complaints, highlighted by interference in memory, speech expression, and cognitive function. The role of BZ, particularly with respect to the GABAA receptor and modulation of the GABAA BZ receptor by cortisol (especially under stress), is considered significant in the clinical course of patients affected by severe disabling tinnitus [1].
Further, the brain SPECT alterations in perfusion, particularly in the MTLS, provide a monitoring system for the sensory-affect transformation in tinnitus patients and an objective measure of the severity of some clinical types and subtypes of tinnitus. Neuroprotective drug therapy: A medical and pharmacological treatment for tinnitus control. Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABA-a function.
Subtypes of gamma-amino butyric acid A receptors: Classification on the basis of subunit structure and receptor function. Vertigo often causes nausea and vomiting, so it may be hard to distinguish inner ear problems from dehydration. In comparison to younger people, what is first noticeable about elderly people is that they have a lot of fat in the body and a markedly low level of intracellular water.
However, these complaints cannot be dismissed simply as an "unidentified syndrome." One or another organic disorder always is behind these complaints.


Because they are more or less conscious of death in daily life, they have a strong sensation of fear and thus visit with a variety of complaints.
This tendency is particularly conspicuous among women, and their typical complaints include headache, vertigo, shoulder stiffness, palpitation, tinnitus, and lumbago (Table 1).
When this vertigo is induced and associated with PPY symptoms, it is important to differentiate between benign and malignant forms (Fig. As compensation declines with aging, one usually becomes slower with age to recover from the same degree of disorder. This therapy should be continued for 10 consecutive days, followed by cessation for a subsequent 10 days. Brain SPECT with 123I-iomazenil, an iodine containing a radionucleopharmaceutical specific for attachment to the BZ-binding sites in the GABA receptor, demonstrated diminished binding sites in multiple regions of interest in the brain, highlighted by the cortex of the MTLS, consistent with the hypothesis implicating GABAergic mechanisms in the pathophysiology of the tinnitus disorder [1; JP Seibyl, personal communication, 2001].
Food and Drug Administration for indications other than tinnitus and is not considered specific for the symptom of tinnitus.
Approximately 17% of the synapses in the mammalian cerebral cortex have been estimated to be GABAergic [9]. Clinically, pharmacological application of such SUbtypes is suggested to be of therapeutic value in treating epilepsy, pain, and drug addiction.
The tinnitus evaluation included an electrodiagnostic cochleovestibular test battery that identified clinical cochleoves tibular correlates for tinnitus.
Additional outcome questionnaires included the tinnitus handicap inventory, the Zung depression score, and the stress questionnaire. If TC was not achieved when combined with gabapentin, patients were instructed to add a supplemenTAI dose of clonazepam. All patients in this report were considered stable by their psychiatrist and had received prior medication other than RTT GABA with no reported TC. The parameter of tinnitus identification for quality for those in group II (19 of 21) included tone (5 patients), noise (8), and tone-noise (8). The overall patient estimated subjective improvement for TC from the start of RTT was 36.8%. The null hypothesis that this proportion is as low as 50% can be rejected (p =.0002, exact test) [J Weedon, personal communication, 2001].
In group II, significantly, improvement in cognitive function was reported by 4 patients, and 10 patients cited reduction of vertigo. TC was focused primarily on intensity and annoyance, both of which demonstrated fluctuation with overall reduction (see Fig.
The complexity of the structural heterogeneity of the GABAA receptor and its specificity for both pharmacological and pharmacokinetic activity and the site of action suggest the complexity involved in underlying mechanisms of tinnitus production and in attempts at TC.
This study provides clinical support for the role of the GABAA receptor as a biochemical marker for tinnitus. The ear sends a message to the brain that the victim is moving, while the eyes send a different message. In other words, elderly people are always at risk of dehydration and liable to enter a shock state. Therefore, when we examine elderly patients, we need to pay special attention to various factors [1]. Because of brain atrophy with aging, they are less likely to present, for example, symptoms of increased intracranial pressure even if they have a brain tumor.
Indeed, the eyes are the windows of the mind, they are more eloquent than lips, and they are a window for diagnosis. All patients in this report had been under the care of a psychiatrist for anxiety or depression (or both).
Impairment of GABAmediated inhibition has been considered to lead to convulsions [17], a finding that provides clinical support for the concept of tinnitogenesis, an epileptiform auditory phenomenon. No patient declined therapy because of a reported increase in intensity or annoyance (or both) after RTT, as reflected and recorded on the TII and TAI. Location included right ear (3 patients), left ear (2), both ears (8), head and both ears (5), and head (1). A Wilcoxon signed rank test of the null hypothesis that the median change score is zero was rejected at the 0.0001 level. Also, drowsiness was reported by three patients; however, it was not sufficiently significant to interfere with continuation of RTT.
Is the finding of perfusion improvement highlighted by the MTLS an epiphenomenon, reflecting improvement in anxiety or depression associated with severe disabling tinnitus? Untreated, inner ear problems can lead to a loss of hearing and dehydration can lead to shock.
The dorsal root in the elderly is also degenerated, and this explains such diverse complaints as dizziness, tinnitus, ringing in the head, headache, neck and shoulder stiffness, and lumbago. When such patients have cerebral infarction, in particular, they experience a dizziness that is unexpectedly transient; thus, it requires careful attention. Cerebellar or pontine hemorrhage causes severe rotary vertigo, nausea and vomiting, tinnitus, and headache. The elements of the GABAA receptor are GABA and the attachments of the BZ and steroid molecules. Its structural heterogeneity includes 5 types and 16 subtypes and is controlled or modulated by at least 20 genes [14]. Brain SPECT, both at baseline and after acetazolamide administration, revealed abnormal perfusion asymmetries of both hypoperfusion and hyperperfusion in multiple regions of interest highlighted by the cortex of the MTLS.
For both scales (TII and TAI), a Wilcoxon signed rank test of the null hypothesis that the median change score is zero was rejected at the 0.0001 level [J Weedon, Academic Science Computing Center of the State University of New York, personal communication, 2001].
It also points the way to a neuropharmacological treatment method for severe, disabling, predominantly central type tinnitus. However, these complaints cannot be dismissed simply as "an unidentified syndrome." Behind these complaints is invariably one or another organic disorder. By contrast, cerebral hemorrhage causes nonrotary vertigo and is sel-dom associated with tinnitus. In many cases, it progresses slowly after repeat transient ischemic attack and improves between episodes. Kennedy, Robert Kennedy's fatal bullet penetrated through the right mastoid to the right cerebellar hemisphere. The degree or extent of attachment determines chloride flux, which controls the degree of inhibition [10]. This structural heterogeneity is reflected in specificity of both pharmacokinetic and pharmacological actions and in site specificity.
Additional manifestations of TC were seen in reported changes in quality and in location of the tinnitus. Is this treatment another method directed to factors that have been identified to influence the clinical course of tinnitus (e.g., stress)?
Subarachnoid hemorrhage, which occurs from various causes, produces headache, vomiting, and dizziness. Location included head (1 patient), right ear (1), left ear (1), both ears (2), and head and ear (4).
Three patients reported a change from a high to a lower frequency; four patients reported a location change from head to ears.
Sequential brain single-photon emission computed tomography in 10 patients revealed objective evidence of increased brain perfusion. Patients with a predominantly central type tinnitus experience significant tinnitus control with medication directed to the γ-aminobutyric acid-benzodiazepine-chloride receptor.
GABA activates two qualitatively different inhibitory mechanisms through GABAA and GABAB receptors [12].



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