Autonomic Related Vertigo

Transcription

1 The Laryngoscope Lippincott Williams & Wilkins, Inc The American Laryn ological, Rhinological and Otological lociety, Inc. Autonomic Related Vertigo Dennis G. Pappas, Jr., MD Objectives: To demonstrate clinical evidence that vestibular symptomatology can occur in relation to autonomic dysfunction. Characterization of clinical findings and treatment response would then allow autonomic related vertigo to be differentiated from other vertiginous conditions that present in a like manner. Study Desigm This was a retrospective review of 113 patients that described symptoms consistent with spontaneous, rotational vertigo and autonomic dysfunction. Methods: Vestibular, otologic, and autonomic symptoms are presented along with the results of audiologic, orthostatic, and autonomic testing. Medical management included fluid loading, dietary changes, exercise, and patient education. Treatment results were analyzed according to the effectiveness in control of vestibular and otologic symptoms. Results were compared with a control group that demonstrated a similar vestibular and otologic presentation without autonomic symptomatology. Renults: All patients described spontaneous, rotational vertigo, with complete or substantial vertigo control obtained in 93 (85%) of 110 patients. Postural vertigo and distinct lightheadedness were also documented in 53% and 97% of cases, respectively. Vertigo failed to improve or worsened with prior treatment of low sodium diet or diuretic in 53 (91%) of 58 cases. Vertigo improvement was subsequently achieved in 48 (86%) of 56 cases with an autonomic treatment regimen. Long-term vertigo control was obtained in 56 (88%) of64 patients followed for at least 18 months. Tinnitus was reported in 97 (86%) patients, aural fullness in 93 (82%) patients, and subjective hearing loss (HL) in 46 (41%) of 111 cases. Bilateral tinnitus and aural fullness occurred in 65% and 63%, respectively. Tinnitus improved with treatment in 56 (67%) of 84 patients, whereas aural fullness improved in 59 (74%) of 80 patients. Autonomic symptoms included palpitations in 103 (91%) patients, chronic fatigue in 102 (SocTO) patients, cold extremities in 91 (81%) patients, and previous fainting in 72 (64%) patients. A history of mitral valve prolapse was documented in 51 (45%) of cases and demonstrated with echocardiogram in 68 From Pappas Ear Clinic, Birmingham, Alabama, USA. Editor s Note: This Manuscript was accepted for publication May 9, Send Correspondence to Dr. Dennis Pappas. Pappas Ear Clinic, th Avenue South, Birmingham, AL U.S.A. pappas.ear@att.net Laryngoscope 1 13: October (93%) of the 73 patients tested. Audiologic testing was normal in 104 (95%) of 109 patients, and electrocochleography was abnormal in 42 (40%) of 105 patients. Orthostatic blood pressure and heart rate testing met the criteria for orthostatic hypotension in 16 (16%) of 104 patients. Autonomic testing was obtained in 34 cases, with orthostatic intolerance demonstrated in 33 (97%) patients and orthostatic hypotension demonstrated in 13 (38%) patients. Overall, orthostatic hypotension was documented through combined testing results in 23 (21%) of 107 patients. Vertigo was reproduced during autonomic testing in 17 (77%) of 22 patients, and otologic symptoms were reproduce in 9 (47%) of 19 patients. Comparison of the study population with a control group without autonomic symptoms revealed statistically significant differences in orthostatic testing and treatment results. There was no statistical difference noted in findings between patients of this study that demonstrated or failed to demonstrate orthostatic hypotension. Conclusions: There is a subgroup of patients with spontaneous vertigo who also demonstrate symptoms and findings consistent with poor autonomic regulation. These patients report vertigo improvement with a treatment strategy that aims to improve autonomic dysfunction through expansion of effective circulating volume. Clinical findings and treatment results of this study suggest an underlying autonomic influence in the production of vertigo and otologic symptoms. Words: Autonomic dysfunction, vertigo, orthostatic intolerance, orthostatic hypotension. Laryngoscope, ,2003 INTRODUCTION Otolaryngologists treat hundreds, if not thousands, of vertiginous patients a year. The differential diagnosis of conditions that can produce the hallucination of motion, or vertigo, is vast. The site and mechanism of vestibular dysfunction is well understood in some of these conditions but hypothetical in others, As an example, peripheral pathology associated with endolymphatic hydrops has been demonstrated, but the actual etiology of Meniere s disease is unknown. Autoimmune inner ear disease also remains a poorly understood process where the immune system is suspected of inducing peripheral injury to the inner ear, Limited pathologic study has demonstrated a diffuse degeneration of all neural elements in the inner

2 ear rather than a localized vasculitis.' Metabolic disorders such as diabetes, uremia, and hypothyroidism are suspected of producing vertigo, but both the site of injury and mechanism are unknown. Although many conceptual causes of vertigo are accepted and established in the literature, it seems likely that there are other mechanisms of vestibular dysfunction that have not been well described. Vertigo associated with autonomic dysfunction, orthostatic hypotension (OH), or mitral valve prolapse WVP) may represent one of several forms of dizziness experienced by a dysautonomic individual. Diagnosis and treatment becomes more confused by the multisystem and multisymptom nature of such disorders. As a result, these individuals are often misdiagnosed as having hypoglycemia, chronic fatigue syndrome, neurocardiogenic syncope, or mislabeled as being "neurotic." The adrenergic and parasympathetic subdivisions of the autonomic nervous system act in constant dynamic balance with one another. Disruption of this balance can result in a hyperadrenergic, hypervagal, or mixed state. Excessive adrenergic tone may result in elevated blood pressure (BP), heart rate (HR), or exaggerated responses to stimuli that generate an adrenergic response, such as standing from a seated position. A hypervagal state can be manifested in a lower BP, lower HR, or an inordinate lowering of both, with circumstances that provoke vagal discharge. Most patients with autonomic dysfunction probably have a mixture of both components, resulting in faulty regulation. Because the autonomic nervous system innervates the cardiovascular system, the exocrine glands, and the peripheral involuntary muscles, autonomic dysfunction can produce an extensive variety of symptoms including dizziness, palpitations, anxiety, headache, fatigue, gastrointestinal upset, and synco~e.~-~ Although autonomic dizziness is generally considered lightheadedness, vertigo in association with autonomic dysfunction is becoming more frequently LOW et a1.,6 in 1995, documented vertigo as a symptom of OH in 37% of cases and nausea in 18% of cases. Although lightheadedness or presyncope are believed to occur as a result of an acute decrease in cerebral blood flow, the mechanism of vertigo onset is poorly understood. AKMSAND OBJECTIVES The autonomic and vestibular systems are physiologically related. As an example, nausea, pallor, and sweating are sympathetic sequelae common to vertigo attacks, demonstrating an afferent vestibular influence on the sympathetic nervous system. At the same time, definitive evidence of an efferent autonomic influence on the vestibular system has remained elusive. The purpose of this retrospective study is to demonstrate clinical evidence that vestibular symptomatology can occur in relation to autonomic dysfunction. To characterize this condition, discerning factors are sought, such as clinical evaluation results and treatment response to conventional vestibular therapy. This would allow autonomic related vertigo to be differentiated from other vertiginous conditions that present in a like manner. This topic is particularly challenging because the study and comprehension of autonomic dysfunction re- mains within its infancy. At the same time, many vestibular disorders are defined as idiopathic in nature. In addition, autonomic dizziness is typically considered to be exclusively lightheadedness. This misconception could be likened to the belief that Meniere's patients experience only rotational vertigo and never describe additional forms of dizziness such as disequilibrium or unsteadiness. Thus, this study's strongest challenge may involve overcoming such stereotypes through objective and statistical data. PATIENTS AND METHODS As described by the American Academy of Otolaryngology- Head and Neck Surgery (AAO-HNS) Committee on Hearing and Equilibrium in 1995, dizziness was considered vertigo within this study when the patient described a sensation of motion when no motion was occurring relative to the earth's gravity." All patients were questioned carefully in this regard to differentiate one form of dizziness from another. Patients were considered to have autonomic related vertigo when vertigo was accompanied by a history or clinical findings consistent with autonomic dysfunction. Specifically, patients were included in this study if spontaneous, episodic, rotational vertigo was associated with two or more of the following conditions: 1. Review of systems was suggestive of autonomic dysfunction when at least 5 of the following symptoms were described: palpitations, chronic fatigue, sleeping disorders, cold extremities, frequent headaches, anxiety attacks, gastrointestinal symptoms, medication intolerance, or fainting independent of the current description of vertigo. 2. A systolic BP mm Hg or OH was demonstrated on clinical examination. OH was diagnosed on standing from the supine position when systolic BP decreased at least 20 mm Hg, diastolic BP decreased at least 10 mm Hg, or HR increased at least 20 beats per minute (bpm). 3. A history of MVP or dysautonomia was reported. The diagnosis of MVP required record of echocardiogram confirmation. The diagnosis of dysautonomia required documentation or prior treatment by a specialist such as a cardiologist. 4. An additional history of lightheadedness or postural vertigo were described, distinct from spontaneous, rotational vertigo episodes. Patients were excluded from the study when otoneurologic examination, audiologic findings, or any additional tests were consistent with well-defined otologic or neurologic disorders such as benign paroxysmal positional vertigo, vestibular neuronitis, acoustic neuroma, chronic ear disease, vertebrobasilar insuficiency, multiple sclerosis, or post concussive syndrome. Care was taken to exclude patients with known coronary disease as well. Patients with definite Meniere's disease, as defined in the 1995 guidelines by the AAO-HNS were also excluded from the study." The records of 113 patients with clinical history and findings consistent with both vestibular and autonomic dysfunction were reviewed. Telephone interviews were obtained when needed. Cases were accumulated over a 10-year period at a referral center for otologic and neurotologic disorders. Patients underwent otologic evaluation, including physical examination, pure tone and speech audiometry, and orthostatic BP and HR testing. Because the same AAO-HNS guidelines omitted electronystagmogram (ENG) from the criteria for the diagnosis and evaluation of Meniere's disease, ENG was not routinely performed on this patient population." Extratympanic electroco- Laryngoscope 11 3: October

3 chleography (ECoG) was routinely performed when objective audiologic findings were lacking. ECoG recordings were obtained on a commercially available auditory evoked potential system. A summating potential: action potential greater than or equal to 0.50 was considered a positive study, reported as unilateral or bilateral. Orthostatic testing was performed in the clinic setting. BP was recorded by standard dtechniques. The patient was placed in the supine position, and BP and HR were obtained after 5 minutes to establish resting control values. The patient was then asked to stand. BP and HR were then measured on standing and every 30 seconds thereafter for 3 minutes. The patient was then asked to resume the supine position. Again, BP and HR were measured immediately and every 30 seconds for 3 minutes. Autonomic and cardiologic evaluation were obtained when possible. Patients were asked to avoid vasoactive medications for several days before testing. Cardiologic evaluation typically included electrocardiogram (EKG), echocardiogram, and exercise testing. EKG was performed by the standard 12 lead method and interpreted by a cardiologist, as were all cardiac and autonomic studies. Exercise testing was performed using a tread mill while HR and BP responses were monitored. Exercise testing was considered abnormal when responses were blunted or excessive compared with control value ranges. With the exception of MVP, patients with an abnormal echocardiogram were excluded from the study. Formal autonomic evaluation consisted of a battery of tests used as the standard autonomic testing protom1 in a clinical cardiology laboratory. Testing results were graded by a cardiologist specializing in autonomic dysfunction. This testing battery consisted of tilt table, Valsalva maneuver, deep breathing, hand grip, and echo stress testing. Patients were asked to express any symptoms experienced during any phase of testing. For tilt table testing, each participant was placed supine on the tilt table for a 10 minute rest period. Then resting BP and HR were measured. The table was then tilted to a near upright (80" from the horizontal) position while BP and HR were immediately measured, followed by repeat measurements every 30 seconds for 3 minutes. After 3 minutes of tilt, the patient was then tilted back to the horizontal position. Again, BP and HR were immediately recorded in the recumbent position, followed by repeat measurements every 30 seconds for another 3 minutes. HR measurements were then calculated as the percentage change with respect to control HR. The percent changes in HR were then plotted on a graph against the testing time interval. The graph's coordinates and curve pattern were then compared with a mean pattern established by 23 normal control subjects (Fig. 1).In cases where OH was strongly suspected or previously confrmed. the tilt period was extended to 45 minutes in an attempt to better delineate the autonomic dysfunction. Orthostatic intolerance was diagnosed when there was a pattern of deviation fmm normal standards or control test results or when presyncope or syncope were encountered during testing. Orthostatic intolerance was further classified as OH, postural orthostatic tachycardia syndrome (POTS), or orthoatatic hypertension when the following criteria were met OH was defined as a decrease in systolic BP of at least 20 mm Hg or a decrease in diastolic BP of at least 10 mm Hg with upright tilting; POTS was defined as an increase in HR of at least 30 bpm, or a maximum of 120 bpm was obtained in the upright position without profound hypotension; orthostatic hypertension was realized when tilt study results demonstrated a diastolic BP greater than or equal to 98 mm Hg during orthostatic adjustment. The Valsalva maneuver was performed after the patient rested for 15 minutes. Control resting BP and HR were measured. The patient was then asked to take a deep inspiration and then expire against an aneroid manometer, Maintenance of a pressure Laryngoscope 113: October of 30 mm Hg for 15 seconds was required to pmceed with testing. HR was monitored from the moment of strain onset, at the midportion of the strain phase, at the peak of the straining phase at 15 seconds, immediately on release, and regularly during the recovery phase at 5 to 10 seconds, 10 to 20 seconds, 20 to 30 seconds, 1 minute, and 1.5 minutes. BP was also measured at 30, 60, and 90 second intervals during the recovery phase. Percentage changes in HR h m baseline were calculated. The percentage changes in HR were then plotted on a graph against the testing time interval, with the points of strain onset, mid-strain, peak strain, release, and the recovery phase noted. The graph's coordinates and curve pattern were then compared with a mean pattern established by norrnal control subjects (Fig. 1). The deep breathing test was obtained after 30 seconds of normal breathing, with the HR and BP being monitored. The patient was then instructed to inhale and exhale, deeply and slowly, at a rate of 6 breaths per minute or 5 second inspiratory and expiratory phases. Deep breathing was continued for 3 minutes while HR and BP were recorded. The ratio of maximum and minimum change in HR across resting breathing was identified and then compared with the HR of the deep breathing cycles as a percentage change. These values were then compared with normal standards. The hand grip test was obtained by asking the patient to grip a spring loaded hand grip as hard as possible and hold this grip for 15 seconds. HR and BP responses were monitored. The echo stress test obtained BP and HR responses as a reaction to sympathetic stimulation caused by the delayed auditory feedback (0.15 s delay) of the patient reading a short paragraph. In all cases, the following treatment regimen was initiated. Patients were given a goal of drinking at least 64 ounces of fluid per day. An moderate aerobic exercise program was recommended. Patients were also instructed to avoid stimulants such as caffeine and sweets. No restriction was placed on dietary sodium content. In many cases, patients were encouraged to consume higher salt containing foods. Medications were appropriately prescribed by the patient's internist or cardiologist for patients with hyperadrenergic or hypervagal symptoms and findings. So that we could present vertigo treatment results in a meaningful manner, the guidelines set forth in 1995 by the AAO- HNS for reporting treatment efficacy of Meniere's disease and functional level scale were extrapolated to the vertigo treatment results in this study." Aa stated in these guidelines, at least 18 months time was required for long-term follow-up. The current study group was compared with a control p up that demonstrated identical vestibular and otologic symptoms in the absence of all autonomic dysfunction criteria cited above. Sex, age, incidence of bilateral otologic symptoms, incidence of autonomic symptoms, ECoG results, resting systolic BP, and response to low sodium diet or diuretic therapy were compared. The control group was represented by a possible Meniere's disease population of 131 patients. The diagnosis of possible Meniere's disease was based on the AAO-HNS guidelines. Data obtained from autonomic function testing was not compared because the control population did not undergo this form of testing. Only the subset of OH cases that were diagnosed with orthostatic vital sign checks were included in this comparison. Statistid analysis was performed using the Pearson 2 test or Fisher's exact test for categorical variables and the t test for continuous variables. The criterion for statistical significance was P <.05. Chart review and telephone interview results generated a database for this study, which was compiled using FileMaker Pro, version 5.0 (FileMaker Inc., Santa Clara, CA)

4 10 TILT TEST lzs 85 L 20 9 U c Q 2 10 a! 01 C 5 c o 0 $ s BASELINE EP - Controls BASELINE HR - Controls 70 comols r VALSALVA MANEUVER T 5 ai I al m C 5 L to L 1 BASELINE HR - Controls 71 CONTROLS t t CMtd t PHk Strain t t t Rakan lcxl Post-Straln Phase of Vaisal- t 203a Socoda Maneuver Fig. 1. Control graphs for Tilt Test and Valsalva maneuver. The percent change in heart rate (HR) is plotted against the testing time interval, noting the points of the test phase for each study. The mean blood pressure (~p) responses, according to time and test phase, are plotted along each test curve. Baseline HR for the control groups are included. Patient test results would be plotted in the same manner, allowing comparison to the control curves. t 60 t m Laryngoscope 11 3: October

5 RESULTS The mean age at presentation was 40 years, with a range of 15 to 64 years. Females overwhelmingly outnumbered males 106/7 (94%) in occurrence. Female weight ranged from 98 to 214 pounds, with an average weight of 140 pounds. Male weights ranged from 135 to 205 pounds, with an average weight of 166 pounds. The average height for females was 64 inches, with a range of 59 to 70 inches. The average height for males was 69 inches, with a range of 67 to 71 inches. Chief complaint data are presented in Table I. Several patients reported more than one chief complaint. The majority of patients presented with dizziness in 83 (73%) cases. Thirty-seven (33%) patients presented with an otologic chief complaint: tinnitus, aural fullness, hearing loss (HL), or otalgia. Two patients also described fainting spells independent of vertigo. Disequilibrium data are presented in Table 11. Dizziness was reported and characterized as spontaneous vertigo in all patients. In distinction from vertigo, these patients also described episodes of lightheadedness in 110 (97%) cases or unsteadiness in 111 (98%) cases. Half (50%) of the patients experienced episodes of vertigo that lasted hours in duration, 60 (55%) patients required bed rest, and 48 (56%) patients missed work because of vertigo. There was an additional postural component to vertigo in 49 (53%) cases. Sixty (54%) patients experienced vertigo on a daily basis. Nausea (with or without vomiting) accompanied vertigo in 87 (77%) cases. Otologic symptomatology is illustrated in Table 111. Two patients had preexisting sensorineural HL attributed to a congenital etiology and were not included within the hearing statistics. HL was reported in 46 (41%) patients, characterized as fluctuating in 31 (78%) cases and bilateral in 22 (48%) cases. Tinnitus was the most common otologic symptom described in 97 (86%) patients, most commonly bilateral in 63 (65%) cases, and demonstrated a quality of ringing in 71 (75%) cases, roaring in 42 (44%) cases, pulsating in 6 (6%) cases, or combination thereof. Aural fullness was reported in 93 (82%) cases and was also more commonly bilateral in 59 (63%) cases, Seventy-nine (70%) patients dated their vertigo onset to at least 1 year in duration. The majority of patients had also experienced their HL (56%), tinnitus (63%), and aural fullness (58%) for at least 1 year before initial evaluation. Overall, 74% of patients reported at least one of their otologic symptoms (HL, tinnitus, or aural fullness) to be bilateral. Vertigo was accompanied by at least one otologic Complaint TABLE 1. Chief Complaint (n = 113). n (96) Dizziness 83 (73) Aural fullness 15 (13) Tinnitus 13 (12) Hearing loss 7 (6) Otalgia 2 (2) Fainting 2 (2) Laryngoscope 113: October Vertigo Spontaneous (n = 113) Duration (n = 111) Seconds Minutes Hours Nausea (n = 113) Nausea Nausea and vomiting Additional Factors (n = 93) Postural component Positional component Requiring bed rest (n = 11 0) Missed work (n = 86) Daily occurrence (n = 112) Unsteadiness (n = 113) Lightheadedness (n = 113) TABLE II. Disequilibrium Data. n (96) 113 (100) 25 (23) 30 (27) 56 (50) 87 (77) 35 (31) 49 (53) 12 (13) 60 (55) 48 (56) 60 (54) 1 i 1 (98) llo(97) symptom in 107 (95%) cases, two otologic symptoms in 79 (70%) cases, and three otologic symptoms in 35 (31%) cases. Before the current evaluation, 58 (51%) patients had been previously diagnosed with Meniere's disease and treated with low-sodium diet or diuretic. Vertigo improved in 5 (9%) patients, remained the same in 20 (34%) patients, and worsened in 33 (57%) patients. The most frequent review of systems findings are delineated in Table IV Symptoms and problems common to dysautonomia were demonstrated. Palpitations in 103 (91%) cases, chronic fatigue in 102 (90%) cases, sleeping problems in 92 (81%) cases, and cold extremities in 91 (81%) cases were most frequently reported. Seventy-two (64%) patients had fainted at one time in their life. MVP was reported in either review of systems or past history in TABLE 111. Otoloaic Svmptoms. n (96) Hearing loss (n = 111) 46 (41) Bilateral (n = 46) 22 (48) Unilateral (n = 46) 24 (52) Fluctuating (n = 40) 31 (78) Tinnitus (n = 113) 97 (86) Bilateral (n = 97) 63 (65) Unilateral (n = 97) 34 (35) Ringing (n = 95) 71 (75) Roaring (n = 95) 42 (44) Pulsating (n = 95) 6 (6) Aural fullness (n = 113) 93 (82) Bilateral (n = 93) 59 (63) Unilateral (n = 93) 34 (37)

6 TABLE IV. Review of Systems Data (n = 113). - Palpitations Chronic fatigue Sleeping disorders Cold extremities Frequent headaches Anxiety/panic attacks Gastrointestinal symptoms Medication intolerance Previous painting spell History of mitral valve prolapse 103 (91) 102 (90) 92 (81) 91 (81) 88 (78) 82 (73) 80 (71) 74 (65) 72 (64) 51 (45) 51 (45%) patients. Ten of these patients were referred by cardiologists that specialize in dysautonomia, specifically for evaluation of their vertigo. Two patients had been previously diagnosed as hypoglycemic. Physical examination data are presented in Table V. Otolaryngologic examination was unremarkable in all cases. A systolic click without murmur was audible in 44 patients or 90% of those patients examined for such a finding. Results of orthostatic BP and HR testing demonstrated a mean resting systolic BP of 110 (range ) mm Hg sitting and 101 (range ) mm Hg standing. Forty-two patients or 39% demonstrated a systolic BP of less than or equal to 100 mm Hg during testing. HR averaged 74 (range ) bpm sitting and 83 (range ) bpm standing. A decrease in systolic BP, greater or equal to 20 mm Hg, was demonstrated in 6 of 104 (6%) cases, meeting the criteria for OH. An increase in HR of more than 20 bpm was demonstrated in 10 (10%) additional cases. OH was, therefore, evident in 16 cases or 15%. Audiologic examination revealed normal hearing in all but five patients. A mean pure-tone average of 12 db and a mean speech discrimination score of 96% were demonstrated. The five patients with impaired hearing demonstrated a mean pure-tone average of 43 db, with a range TABLE V. Physical Examination Findings. Otolaryngologic Findings None Systolic click (n = 49) 44 (90%) Orthostatic testing (n = 104) Blood pressure (systolic) Sitting Mean 110 mm Hg Standing mean 101 mm Hg Orthostatic hypotension 6 (6%) Heart rate (beats per minute) Sitting mean 74 bpm Standing mean 83 bpm Orthostatic hypotension 10 (10%) Total orthostatic hypotension 16 (15%) Laryngoscope 1 13: October 2003 of 33 to 50 db. All of the hearing impaired patients demonstrated normal speech discrimination scores. ECoG demonstrated findings suggestive of endolymphatic hydrops in 42 (40%) cases, unilateral and bilateral findings were equally divided. These results are summarized in Table VI. Eighty-seven patients underwent cardiologic workup that included echocardiogram and exercise testing in several cases. These results are also reported in Table VI. Echocardiogram was consistent with hi" in 68 patients or 93% of those tested. Exercise testing results were available for 32 patients. Abnormal HR and BP responses to exercise were noted in 24 (75%) of these cases. EKG was performed in 28 cases, demonstrating sinus rhythm in all cases. Bradycardia was noted in five (18%) patients. Autonomic testing was most commonly obtained from the most recent patients studied. Autonomic testing results are summarized in Table VII. A total of 34 patients were tested, all demonstrating abnormal autonomic function on at least one study. Both screening tilt and extended tilt table results are presented together. Overall orthostatic intolerance was demonstrated in 33 of 34 (97%) tilt studies. Orthostatic intolerance was further differentiated as OH in 13 cases, POTS in 8 cases, and orthostatic hypertension in 2 cases. The extended tilt table test diagnosed orthostatic intolerance in two cases where the screening tilt test was unremarkable. The extended tilt test further differentiated orthostatic intolerance as OH or POTS in four additional cases. The Valsalva maneuver could not be performed in half of the patients undergoing autonomic testing because these patients were unable to sustain the required pressure. The Valsalva maneuver was completed in 17 (50%) patients. Abnormal autonomic regulation was demonstrated in 16 (94%) of these cases, where responses were classified as hypervagal in 63% and hyperadrenergic in 38%. The hand grip, echo stress, and deep breathing tests demonstrated variable results, abnormal for those tested in 38%, 40%, and 1%, respectively. TABLE VI. Workup Results. Audiologic (n = 109) (%) Normal Mean pure tone average Speech discrimination mean Electrocochleography (n = 105) (%) Abnormal Unilateral finding Bilateral finding Echocardiogram (n = 73) (%) Mitral valve prolapse Exercising testing (n = 32) (%) Abnormal EKG (n = 28) (%) Normal Bradycardia EKG = electrocardiogram. 104 (95) 12 db 96% 42 (40) 21 (50) 21 (50) 68 (93) 24 (75) 23 (82) 5 (18) 1663

7 ~ TABLE VII. Autonomic Function Testing. Patients tested 34 Tilt table (n = 34) Orthostatic intolerance 33 (97) Orthostatic hypotension 13 (38) Postural tachycardia 8 (24) Orthostatic hypertension Valsalva (n = 17) 2 (6) Abnormal 16 (94) Hypervagal response 10 (63) Hyperadrenergic response Deep Breathing (n = 29) 6 (38) Abnormal 1 (3) Hand grip (n = 29) Abnormal 11 (38) Echo stress test (n = 25) Abnormal 10 (40) Dizziness during testing (n = 26) 25 (96) Vertigo during testing (n = 22) 17 (77) Otologic symptoms during testing (n = 19) 9 (47) Presyncope during testing (n = 17) 4 (24) Patient symptoms were also documented during tilt table testing in Table VII. Dizziness was reported during testing in 25 of 26 (96%) cases. Vertigo was Specifically reproduced in 17 of 22 (77%) cases. Otologic symptoms such as subjective HL, aural fullness, or tinnitus were reported in 9 of 19 (47%) cases during testing. Either vertigo or otologic symptoms were reported during testing in 81% of cases. Presyncope occurred in 4 of 17 (24%) patients during testing. Syncope was avoided by returning patients to a recumbent position when presyncope was encountered, Treatment medications serotonin reuptake inhibitors, fludrocortisone, ibuprofen, calcium channel blockers, phenobarbital, alphal-adrenergic receptor antagonists, and sympathomimetics. Forty (35%) Patients did not require pharmacotherapy, whereas 73 (65%) patients were treated with medications in addition to the treatment regimen initiated above. This includes medications taken before and after initial evaluation and workup. These medications were frequently adjusted, changed, or combined throughout the treatment course by the Patient s own cardiologist and, therefore, could not be accurately assessed according to individual outcome value. Treatment follow-up is detailed in Table VIII. Follow-up ranged from 1 to 129 months, with a mean of 27 months. Vertigo improved in 93 of 110 (85%) patients, whereas tinnitus and aural fullness improved in 56 of 84 (67%) cases and 59 of 80 (74%) cases, respectively. Conversely, only 2 of 110 (2%) patients experienced worsening of their vertigo. Patient satisfaction was used to reflect the individual s overall autonomic treatment benefit. For most, this represented improvement with regard to their Laryngoscope 113: October TABLE VIII. Treatment Follow-Up. All Patients Long Term (n = 111) (n = 64) Mean follow-up 27 months 40 months Range months months Tinnitus follow-up (%) n = 84 n = 53 Better 56 (67) 36 (68) Unchanged 21 (25) 12 (23) Worse 7 (8) 5 (9) Fullness follow-up (%) n = 80 n = 50 Better 59 (74) 37 (74) Unchanged 16 (20) 10 (20) Worse 5 (6) 3 (6) Vertigo follow-up (YO) n = 110 n = 64 Better 93 (85) 56 (88) Unchanged 15 (14) 6 (9) Worse 2 (2) 2 (3) Patient satisfaction (%) n = 96 n = 56 Yes a7 (91) 49 (88) chief complaint of dizziness, whereas others reported increased energy levels, less chest discomfort, headache improvement, etc. Thus, patient satisfaction with treatment was achieved in 87 of 96 (91%) patients. Sixty-four patients were followed for at least 18 months. Long-term treatment success and satisfaction figures paralleled those for the entire group as demonstrated in Table VIII. Vertigo treatment results are further illustrated as functional levels for the 18-month follow-up group in Table M, following the guidelines set forth by the AAO-HNS. The lower portion of Table M follows each functional level group over time. Of the original 14-level 1 to 2 patients, 13 (93%) remained on levels 1 to 2, and 1 (7%) worsened to levels 3 to 6. Of the original 43-level3 to 6 patients, 14 (33%) remained on levels 3 to 6, and 29 (67%) improved to levels 1 to 2. These results were statistically significant at P <.01. TABLE IX. Dizziness Treatment Results (n = 57). Functional Level Initial Evaluation Follow-Up Level 1 Level 2 Level 3 Level 4 Level 5 Level Follow-Up (P <.01) Initial evaluation Level 1.2 (%) Level 3,4.5.6 (%) Level 1,2 (n = 14) 13 (93) 1 (7) Level 3,4,5,6 (n = 43) 29 (67) 14 (33)

8 TABLE X. Vertigo Treatment Comparison (n = 56). Original Treatment: Low Subsequent Treatment: Sodium/Diuretic (%) Autonomic Regimen (%) Low Sodium/Diuretic (%) Autonomic Regimen (%) Better 5 (9) 48 (86) Same 19 (34) 8 (14) Worse 32 (57) 0 (0) P <.01. Results of previous low-sodium or diuretic therapy are compared with subsequent autonomic treatment results for 56 patients in Table X. With the original medical therapy of low-sodium diet or diuretic, vertigo worsened in 32 (57%) cases, remained unchanged in 19 (34%) cases, and improved in 5 (9%) cases. After an autonomic treatment regimen, the same patients reported vertigo improvement in 48 (86%) cases, remained unchanged in 8 (14%) cases, and no patients reported worsened vertigo. A statistically significant difference was demonstrated between the groups at P <.01. Table XI compares the current study group with that of the control population of possible Meniere's patients. A statistically significant difference was documented for all variables studied with the exception of age, ECoG results, and mean resting systolic BP. DISCUSSION The true incidence of autonomic dysfunction is unknown. Various forms of dysautonomia and orthostatic intolerance are widely reported in today's literature. Autonomic related vertigo, on the other hand, is rarely documented. Within this study period and setting, 5% of all new vertigo workups were found to be autonomically related. Because this study involved an otologic referral center, these cases most likely represent a share of refractory vestibular disorders rather than a true percentage of all vertigo presentations. Yet, the diagnosis of autonomic related vertigo should not be overlooked. Ohashi et al.' documented a 10% incidence of OH in 1,291 patients presenting with complaints of vertigo, dizziness, or disequilibrium. The presentation of autonomic related vertigo in this study often resembled that of Meniere's disease. In fact, half of the study population had been previously diagnosed with Meniere's disease. Rotational vertigo occurred spontaneously in all cases, was accompanied by nausea in TABLE XI. Autonomic Related Vettigo/Control Comparison. Current Study (%), n = 113 Possible Meniere's (%), n = 131 Female sex" 106 (94) 95 (73) Mean age 40? 11, ? 14, Unilateral symptoms* 31 (27) 119 (91) Bilateral symptoms' 82 (74) 12 (9) n = 113 n = 85 Postural dizziness' 49 (53) 8 (9) Palpitations* 103 (91) 7 (8) Chronic fatigue* 102 (90) 20 (24) Sleep difficulty' 92 (81) 18 (21) Cold extremities' 91 (81) 20 (24) Frequent headaches. 88 (78) (10 (12) Anxiety attacks' 82 (73) 5 (6) Gastrointestinal Symptoms* 80 (71) 16 (19) Medication intolerance* 74 (65) 4 (5) Previous fainting* 72 (64) 3 (4) Mitral valve prolapse' 51 (45) 3 (4) Electrocochleography n = 105 n = 131 Abnormal 42 (40) 86 (66) Unilateral findings 21 (50) 40 (47) Bilateral findings 21 (50) 46 (53) Mean systolic blood pressure , , Positive orthostatic testt n = (15%) n = 33 0 (0%) Low sodium + diuretic n = 58 n = 79 Better* 5 (9) 59 (75) Same' 20 (34) 17 (22) Worse' 33 (57) 3 (4) 'P <.001. tp <.01. Laryngoscope 1 13: October

9 77% of cases, and required bed rest and work absence in more than half of all cases. Episodes occurred daily in 54% of patients and lasted hours in duration in 50% of patients. Vertigo was associated with at least one otologic symptom in 95% of cases. There were also important distinctions. Although rotational vertigo was specifically distinguished from other forms of dizziness, an additional postural component was often reported (53%), and distinct lightheadedness was almost universal (97%). Vertigo tended to worsen with low-sodium diet or diuretic. There was a high degree of symptom bilaterality from the time of illness onset, as opposed to a more ultimate degree of bilateral involvement that can be seen with bilateral Meniere's disease. In addition, normal hearing was revealed in all but five cases despite a 41% incidence of perceived HL. In addition to the vertigo and otologic symptoms, these patients frequently reported chronic fatigue, palpitations, difficulty sleeping, previous fainting, and anxiety attacks among other problems listed in Table IV. At first glance, these symptoms could be regarded as vague or nonspecific. However, these symptoms are common to those reported in association with autonomic dysfunction en these results were examined collectively, 22% of all patients reported all nine symptoms listed in Table IV, 75% documented at least six of these symptoms, and 94% documented at least four of these symptoms. A prior history of at least one syncopal episode or fainting spell was common (64%) in this patient population. It must be emphasized that only two patients reported fainting or loss of consciousness to be associated with their current illness but independently of their vertigo. An existing history of syncope would typically preclude referral for otologic evaluation. Fainting was typically reported as an isolated event of the past, described as a response to a specific incident or illness. This information was elicited to further establish evidence or history of faulty autonomic function. A history of MVP was reported by 45% of patients. Mvp is the most common inherited cardiac variation, reported to occur in 5% of the p~pulation.~'~'~ Mvp is significant in this setting because it has been correlated with autonomic dysfun~tion.l~,~~*~~-~~ Jacob et al.,24 in 1997, found a similar incidence of MVP in a smaller group of orthostatic intolerant patients. The mechanism relating this mitral valve variation and autonomic function remains poorly understood. It has been hypothesized that the myotendinous junction of the ventricular papillary muscles contain sensory neuroreceptors that produce afferent signals that could modify autonomic reflex responses. l4 Diagnosis of autonomic dysfunction in a otolaryngologic setting requires a high index of suspicion, starting with a careful history. In addition to a history of vertigo, a description of lightheadedness, postural dizziness, and prior fainting spells are suspect. A history of worsening vertigo with traditional Meniere's treatment could also prove significant. Although otologic and vestibular symptomatology is of primary focus, information obtained from the past medical history and review of systems data are often material to this diagnostic process. A past history Laryngoscope 113: October questionnaire should include MVP, hypoglycemia, panic disorder, irritable bowel syndrome, and low BP because these conditions are often associated or confused with autonomic dysfunction. Review of systems should include the items listed in Table IV. Identification of these symptoms and conditions does not confirm the presence of autonomic pathology but could indicate the need for further workup. Physical examination, as with many vertiginous patients, was unrevealing from an otolaryngologic standpoint. Female sex was predominate, with a 151 ratio, similar to figures found in autonomic dysfunction studies.14 With a mean age of 40 years and mean female weight of 140 pounds, the physical attributes of this population were not consistent with the stereotypical dysautonomic, small young female. Other autonomic dysfunction studies share the finding of a wide range of general physical attributes.14 Examination was also notable for a mid-systolic click, reported in 85% of those examined. A mid-systolic click or a late systolic apical murmur are consistent with MVP and should be sought in the recumbent, seated, and standing positions.lg Orthostatic BP and HR testing was an important screening method for demonstrating autonomic dysfunction within this study. Orthostatic testing can be easily performed in a clinical setting and should be obtained when low BP is documented. The Schellong test is similar to the orthostatic testing protocol used in this study. It has been advocated in several studies as a screening method for OH in the evaluation of dizziness, vertigo, or disequilibrium in association with symptoms of autonomic dysfun~tion.~,~,~~*~~ Re sults met the criteria for OH in 15% of cases in this study. Thirty-nine percent of all patients demonstrated a resting systolic BP no greater than 100 mm Hg. The mean standing systolic BP of 101 mm Hg was also notable. Large reported series have suggested that BP plays an important role in patients with dizziness. Fujikawa et al.,27 in 1993, revealed a high incidence of hypotension in 3,349 dizzy patients, especially in females. Male diagnosis could, therefore, prove more challenging because hypotension and its associated symptoms are less commonly demonstrated in males.28 Wessely et a1.,28 in 1990, screened 7,383 adults, correlating hypotension with dizziness and fatigue. Other than pure tone and speech audiometry, additional otologic tests such as ECoG are optional. Autonomic workup serves to characterize and provide objective evidence of autonomic dysfunction. Testing usually includes an EKG to screen for arrhythmias and potential cardiac disease. Bradycardia can be a sign of a hypemagal state, but it may also represent a normal variant. Echocardiogram further evaluates cardiac function and may demonstrate A". Echocardiogram can be performed in the upright position where MVP is often more pronounced. A normal echocardiogram does not rule out autonomic dysfunction in a symptomatic patient, nor does an abnormal study demonstrating MVP always signify autonomic dysfunction. Exercise testing will often demonstrate exaggerated HR responses. A blunted or reduced increase in BP response to exercise may reflect a hypemagal state or hypovolemia.

10 Autonomic workup is typically directed by a cardiologist specializing in autonomic dysfunction. Formal autonomic testing is designed to measure end-organ responses to standardized physiologic challenges. HR and BP responses are analyzed as a means of assessing the relative magnitude and balance of sympathetic and parasympathetic activity. The tilt table and Valsalva studies are mediated by baroreflex arcs. The hand grip, deep breathing, and echo stress tests provide autonomic data independent of the baroreceptor reflex mechanisms. The hand grip test assesses parasympathetic tone, whereas the echo stress test assesses central and efferent sympathetic function. The importance of a battery of autonomic testing is emphasized. Within this study, formal autonomic testing consistently demonstrated autonomic dysfunction and frequently reproduced symptoms of dizziness and vertigo. me tilt table was this study s most reliable testing modality because all patients completed testing, and results effectively demonstrated orthostatic intolerance in 97% of patients tested. Orthostatic intolerance was further categorized as OH, orthostatic hypertension, or POTS when the appropriate diagnostic criteria were met. The Valsalva maneuver also proved sensitive, but 50% of those undergoing formal autonomic testing could not complete the Valsalva maneuver because of patient inability to sustain the required pressure. When completed, the Valsalva maneuver was helpful in further characterizing the autonomic response as hypervagal or hyperadrenergic. The high overall incidence of OH discovered in this study (21%) is comparable with OH rates of 17% to 25% reported in other autonomic dysfunction series. 14~16 BP measurements also reflect values documented in other autonomic dysfunction studies.29 This study s complex union of vestibular and autonomic dysfunction invites the following questions: 1) Are vestibular and autonomic dysfunction related? 2) If there is a relationship, is the vestibular dysfunction a trigger or consequence of the autonomic dysfunction? To establish the existence of a relationship between the vestibular and autonomic dysfunction, Table XI must be examined. The choice of a possible Meniere s population as a control group was important because the diagnosis of possible Meniere s disease, as defined by the AAO-HNS 1995 guidelines, includes episodic, spontaneous vertigo without documented HL. l1 Thus, the possible Meniere s group was ideally suited as a contrasting match to the patient population of this study. As an added study benefit, both groups were also diagnosed, tested, and treated within the same facility. The compared physical characteristics and autonomic symptoms and findings were statistically different between the two groups. Several of these findings are worthy of comment. Although female cases far exceeded male cases in either group, the greater preponderance of female cases in the current study group is notable and consistent with results found in autonomic dysfunction ~tudies.~.~~ The mean resting systolic BP figures tended to be lower in the current study group, but no statistically significant difference was demonstrated. Although the reported incidence of bilateral Meniere s disease ranges Laryngoscope 11 3: October 2003 widely within the literature, the disparity in bilaterality between these groups is too great given the common clinical setting. Such a variance is not expected within a single study, but from one study to another, where such differences could reflect deviation in diagnostic criteria, geographic or social influences, or clinical bias. The contrasting treatment response to sodium restriction or diuretic arguably highlights the most substantial difference between the current study and control groups. The difference in response between the groups reaches statistical significance, and comparison demonstrates an almost inverse relationship with regard to symptom improvement versus worsening. Although vertigo may not always improve with salt restriction or diuretic, a high incidence of worsening vertigo would not be an expected result. Intolerance to volume depletion, however, is well described by individuals who demonstrate autonomic dysfunction. 14*30*31 These results suggest the following: episodic, spontaneous vertigo tended to worsen with conventional treatment when autonomic dysfunction was evident. The converse relationship was also true: episodic, spontaneous vertigo tended to improve with conventional treatment when autonomic dysfunction was not evident. Therefore, it is highly likely that the autonomic and vestibular dysfunction demonstrated by the patients of this study are related to one another. Given this evidence of an existing autonomicvestibular relationship, cause and effect factors can be sought. The possibility that the described vestibular dysfunction is a trigger for the demonstrated autonomic dysfunction can be supported by compelling evidence of vestibular influence on the sympathetic nervous ~ ystem.~~.~~ As a common example, vertigo typically produces pallor and sweating, mediated by sympathetic outflow to blood vessels in the skin and to sweat glands. Research has examined the potential of a vestibulo-autonomic influence on salivary secretion, HR, and re~piration.~~.~~ Park et al.,36 in 1999, demonstrated the effects of caloric stimulation on gastric motility. In the current study, however, the history of autonomic symptoms preceded the initial episode of vertigo in all cases. These patients also routinely experienced autonomic symptoms in the absence of their vertigo and otologic symptoms. In addition, many patients demonstrated findings more consistent with a hypervagal state as opposed to a hyperadrenergic state. Research has provided little evidence of a vestibular influence on the parasympathetic system. The possibility that vertigo is a consequence of autonomic dysfunction is thus considered. Evidence supporting an autonomic etiology was demonstrated with the consistent reproduction of vertigo during tilt testing in 77% of patients tested. Patients differentiated vertigo from other forms of dizziness that were also encountered during testing. The reproduction of otologic symptoms in 47% of those tested was also notable. It must be understood that vertigo occurred well into the tilt study while the patient was stationary in the upright position for several minutes. Vertigo was neither described when the patients were in motion being tilted nor immediately after the assumption of the upright or supine position. In theory, prolonged upright posture during tilting will produce 1667

11 maximal venous pooling in individuals with autonomic dysfuncti~n.~~*~~ These findings echo those of other studies in the literature. Ohashi et al.,' in 1991, also reported vertigo with postural testing in 41% of a small group of patients with a history of vertigo without well-defined peripheral vestibular disorders. The Ohashi study noted a statistically significant relationship between postural vertigo and autonomic dysfunction. Grubb et al.,' in 1992, reported vertigo with tilting in 71% and tinnitus in 29% of test subjects. Grubb correlated the onset of vertigo to the initial drop in BP during tilt testing. Further evidence of an autonomic mechanism is inferred by the successful treatment results demonstrated in this study. Both vertigo and otologic symptoms responded to an autonomic treatment approach that contained a strategy of blood volume expansion while avoiding salt restriction. Tables VIII, IX, and X demonstrate both short- and long-term vertigo improvement. Of the patients followed long term, 42 (74%) ultimately reported that dizziness had no effect or did not necessitate change in activity (levels 1 or 2). Perhaps even more compelling evidence is demonstrated in the statistically significant results of Table X, where patients originally treated with a low-sodium diet or diuretic found vertigo improvement in the order of 9%, and then the same patients went on to experience vertigo improvement with the autonomic treatment strategy in the order of 86%. Grubb et al.' also reported vertigo resolution with treatment of autonomic dysfunction in all cases, with a mean 26-month follow-up. Within that study, all tilt-positive patients were retested and eventually became tilt-negative, corresponding to successful therapy. The theory that autonomic dysfunction plays a role in the pathophysiology of Meniere's disease has been considered in the literat~re.~~-~' In contrast with previous studies, this analysis does not present evidence supporting an autonomic etiology for Meniere's disease. Such an endeavor would require formal autonomic testing of patients with definite Meniere's disease. Again, 95% of this patient group demonstrated normal hearing and would, therefore, not meet the diagnostic criteria of a definite Meniere's process." As evident in Table XI, the patients of this study exhibited several statistically significant differences from the possible Meniere's population. The Meniere's Patients neither reported nor demonstrated consistent autonomic SYmPtomatology. This distinction allows the author to pursue evidence of an autonomic etiology for a unique group of vertigo patients. Controversy exists as to whether autonomically induced vertigo is mediated centrally or peripherally. The idea of a central process is most commonly based on impaired cerebral aut~regulation.'*~~~~~ Theories of a peripheral mechanism concentrate on autonomic influence of labyrinthine microcirculation.48~49 Another potential peripheral mechanism could involve direct neural modulation of the vestibular neuroepitheli~rn.~~ The results of this study would best support the concept of a peripheral mechanism. The symptom complex of episodic, spontaneous vertigo, HL, ringing or roaring tinnitus, and aural fullness is generally considered peripheral or end organ in origin. Although objective HL was rarely measured, ECoG Laryngoscope 1 13: October findings were consistent with endolymphatic hydrops in 40% of those tested. Various studies report the predictive value of ECoG in the range of 62% to 74% in the diagnosis of Meniere's di~ease.'~"~ Although not conclusive, these ECoG findings would suggest a peripheral process. This study's vertigo treatment success is also more indicative of peripheral disease. A long-term improvement figure of 88% and achievement of high-level function in 74% would not be anticipated with vertigo of central origin. The high incidence of otologic symptom bilaterality would be expected with an autonomic etiology as seen with other systemic and focal illness such as autoimmune inner ear disease, diabetes mellitus, and syphilis. A dilemma then arises in explaining that 27% of patients experienced only unilateral otologic symptoms. Autonomic innervation of the labyrinth is poorly understood but could be similar to that of the pupils, which can react independently of each other. Uemura et al.,40 in 1980, demonstrated a significantly higher rate of myosis with the Mecholyl test during and on the same side of vertiginous attacks in Meniere's patients. The myosis rate of the unaffected side was not different from that of normal subjects. Another explanation could lie in the unknown mechanism(s) that allows one ear versus the other to be more susceptible to otologic processes such as Meniere's disease, sudden sensorineural HL, or fistula formation. Treatment of autonomic related vertigo aimed to improve overall autonomic function as opposed to specifically treating the vestibular or otologic symptoms. This strategy then resulted in long-term vertigo improvement, resembling rates of medical treatment success seen with Meniere's di~ease.'~ Vertigo control was also examined according to differences in workup and testing outcomes within this study. Because all patients did not undergo autonomic testing and those tested did not uniformly demonstrate OH, this patient population can be subdivided into distinct groups for comparison: 1) patients that neither underwent formal autonomic testing nor demonstrated OH with orthostatic testing (no orthostatic intolerance [OI] group); 2) patients that demonstrated 01 with autonomic testing without meeting the criteria for OH (01 without OH group); and 3) patients that demonstrated OH with autonomic or orthostatic testing (OH group). TOgether, these groups comprise the entire patient population. Table XI1 compares physical characteristics, symptoms, clinical findings, and treatment outcome for each subgroup. With the exception of tinnitus, none of the studied variables demonstrated a statistically significant difference in incidence, and, thus, no group was distinct from the others. This includes the rate of vertigo control across all groups. The first step in managing autonomic related vertigo involves ruling out correctable causes of hypovolemia such as anemia, volume depletion, or diuretic use. Next, patient education is fundamental. The explanation that altered autonomic function can result in this symptom complex can be very reassuring. Many of these patients have experienced frustration in their lack of treatment response and in relaying the morbidity of their condition to family and friends. This frustration can result in great anxiety,

12 TABLE XII. Patient Population Comparison. All Patients (n = 113) No 01 (n = 70) 01 without OH (n = 20) OH (n = 23) Mean age 40 years 39 years 39 years 40 years Female sex (%) 106 (94) 68 (97) 17 (85) 21 (91) Mean weight (female) (98-214) 141 t 25 (98-214) ( ) 135 t 27 ( ) Mean height (female) 64 inches 64 inches 65 inches 64 inches Subjective hearing loss (%) 46/111 (41) 31 (44) 6 (30) 9 (39) Tinnitus' (%) 97 (86) 64 (91) 15 (75) 17 (74) Aural fullness (%) 93 (82) 58 (83) 14 (70) 20 (87) Previous fainting (%) 72 (64) 47 (67) 12 (60) 14 (61) Mean systolic sitting BP 110 mm Hg 111 mm Hg 111 mm Hg 109 mm Hg Mean sitting HR 74 bpm 75 bpm 71 bpm 75 bpm ECoG abnormal (%) 42/105 (40) 24/63 (38) 7 (35) 11/21 (52) Vertigo improvement (%) 93/110 (85) 56/69 (81) 18/18 (100) 19 (83) 'p <.05 Mean weight is presented as the mean 2 standard deviation (weight ranges). Incidences are presented as fractions when the number of subjects does not correspond to the given n value. 01 = orthostatic intolerance; OH = orthostatic hypotension; BP = blood pressure; HR = heart rate; ECoG = electrccochleography; bpm = beats per minute. which can then magnify adrenergic responses. As evident in this study, anxiety is a common component (Table IV). Management approaches attempt to expand intravascular volume, improve vascular tone, decrease exaggerated sympathetic or parasympathetic activation, and counteract p-receptor hypersensitivity.2 Success with volume loading has been documented. Jacob et al.,3 in 1997, demonstrated a transient improvement in HR response to 1 L of saline infusion, measured with orthostatic testing in a controlled study. The Jacob study was unique in that a homogeneous population of orthostatic intolerant subjects was studied. Volume expansion can be accomplished on a more practical basis with increased fluid intake and liberal use of sodium. Fludrocortisone, which enhances renal sodium conservation and increases the sensitivity of arterioles to norepinephrine, can be added as a volume ex- Potassium levels should be monitored with long-term use. Patients are also instructed to avoid factors that aggravate volume depletion or effective circulating volume such as extreme heat, dehydration, alcohol consumption, and vasoactive medications such as cold preparations and diet pills. Venous return can be increased with elastic support hose, which work best when waist high to avoid venous pooling in the abdomen." Historically, compliance with waist-high external support is poor because of discomfort. Moderate exercise is encouraged in an attempt to strengthen the blood pumping effect of skeletal muscles that could increase venous return and possibly improve vascular tone. Exercise has also been shown to reverse the decrease in blood volume associated with prolonged bed rest.sg In addition, short-term exercise may correct sensitivity abnormalities found with p-adrenoreceptors.60 Swimming has been proposed as a means of increasing physical conditioning without orthostatic stress.30 Elevating the head of the patient's bed has been shown to decrease early morning symptomatology in patients with supine hypertension. Its effectiveness is thought to result Laryngoscope 11 3: October 2003 from the reduction in renal arterial pressure, inducing increased secretion of renin, which results in sodium retention and increased blood volume. Nocturnal loss of intravascular and interstitial fluid leads to relative hypovolemia that worsens early hour orthostatic intolerance.61*62 Just as individual medication profiles that may include vestibular suppressants, tranquilizers, and antidepressants are rarely included in large vestibular studies, a complete discussion of pharmacotherapy options for autonomic dysfunction is complex and beyond the scope of this study. No single medication has proven universally successful for any given form of autonomic dysfunction nor any vestibular disorder, for that matter. Furthermore, the beneficial effects of a given medication may produce adverse effects with respect to another symptom of the condition. Medication selection depends on each drug's side effect profile and are best selected by a specialist such as a cardiologist. Various medications are used in an attempt to elevate BP. These include sympathomimetics such as midodrine, a peripheral alpha agonist without central effect^.'^ Beta-blockers, such as propranolol, can be effective through negative inotropic effects that lessen the degree of cardiac mechanoreceptor activation associated with abrupt falls in venous return.31 Dopamine antagonists, such as metoclopramide, block the vasodilator action of dopamine. Dihydroergotamine, an alpha adrenergic agent, is a vasoconstrictor that primarily acts on venous capacitance vessel^.'^ Because prostaglandins can have a vasodilatory effect, prostaglandin inhibitors, such as ibuprofen, have been effective.66 Small doses of clonidine block sympathetic activity centrally. Clonidine also has a peripheral a-2 agonist action, acting primarily to venoconstrict." Serotonin reuptake inhibitors increase central nervous system levels of serotonin in the autonomic centers of the medulla and appear to enhance autonomic tone and f~nction.'~*'~ 1669

13 Other treatment considerations include controversy over caffeine intake. Avoiding caffeine is recommended by those who view it as a stimulant of the autonomic system that can be associated with the release of catecholamines. l2 Others have documented improvement in postprandial hypotension using caffeine in patients with autonomic failure." Donnatal in small doses is recommended as an anticholinergic to treat unstable autonomic regulation or hypervagal responsiveness.13 Avoiding sweets may also help alleviate fluctuations in blood sugar that could worsen fatigue and trigger additional autonomic dysfunction." CONCLUSIONS There is a subgroup of vertiginous patients that also demonstrate symptoms and findings consistent with autonomic dysfunction. The most important aspect of patient evaluation remains a high index of clinical suspicion. Autonomic related vertigo can present in a similar fashion to that of possible Meniere's disease with spontaneous rotational vertigo, tinnitus, and aural fullness. These patients also demonstrate important distinctions, including a high incidence of symptom bilaterality, normal hearing, distinct postural vertigo, and lightheadedness. Autonomic dysfunction is suggested by a history of MVF' and various symptoms commonly reported with autonomic disorders, including chronic fatigue, palpitations, sleeping disorders, cold extremities, anxiety, and previous fainting. Vestibular and autonomic symptoms tend to worsen with conventional diuretic and low-sodium diet therapy. Clinically, patient age and weight are not always consistent with the stereotypical dysautonomic, small young female. Low BP is commonly demonstrated but not universal. Orthostatic testing in the clinical setting is a useful screening method for identifying OH. An autonomic testing battery can both characterize and provide further objective evidence of autonomic dysfunction. Orthostatic intolerance is typically revealed with tilt testing. The tilt test was the most sensitive and reliable testing modality in this study. Vertigo improvement was consistently demonstrated with an autonomic treatment approach, suggesting both an autonomic-vestibular relationship and an autonomic influence on the production of vertigo. Evidence of an autonomic influence was further indicated by the reproduction of vertigo and otologic symptoms during tilt testing. A direct versus indirect association has not been established. The management of autonomic related vertigo is multifaceted, with most treatment strategies centering on increasing effective circulating volume. The severity of autonomic dysfunction did not distinguish patients with regard to symptomatology or vertigo treatment success. BIBLIOGRAPHY 1. Paparella MM, Goycoolea MV, Meyerhoff WL. 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