..... , ::IL ELSEVIER

Journal of Vestibular Research, Vol. 8, No. I, pp. 27-34,1998 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved

0957-4271/98 $19.00 + .00

Pll S0957 -4271(97)00034-7

Review

CLINICAL EVIDENCE THAT THE VESTIBULAR SYSTEM PARTICIPATES IN AUTONOMIC CONTROL

Joseph M. Furman,* Rolf G. Jacob,t and Mark S. Redfern:j:

I !

Del'e:rtmeAts ef *OteIElf)'A~ele~y, 1'PsyeRiatf), Otel~AEI-$9telatyA!;J6IemMlA6-lflal:lStfieI~iAeeriA~, ~I University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Reprint address: Joseph M. Furman, MD, PhD, The Eye & Ear Institute Building, 200 Lothrop Street, Suite 500, Pittsburgh, PA 15213. Tel: (412) 647-2117; Fax: (412) 647-2080; E-mail: furman@vms.cis.pitt.edu

both the peripheral vestibular system, that is, the labyrinth, and the central vestibular system, is known to influence autonomic function in several ways that have clinical implications. This paper discusses evidence for vestibular influences on autonomic control from normal human subjects, evidence for vestibular influences on autonomic con­trol from patients, clinical implications of vestibulo­autonomic regulation, and speculations regarding possible clinical implications of vestibulo-auto­nomic control. Situations that provoke vestibular­induced autonomic responses in normal subjects include vestibular laboratory testing, vehicular motion, simulators, and, possibly, exposure to mi­crogravity. Patients with peripheral and central vestibular abnormalities manifest both symptoms and signs of autonomic dysfunction presumably via vestibulo-autonomic connections. Vestibulo­autonomic regulation impacts vestibular diagnos­B@ Iesnng, ciimcai dIagnosIs of BaJance msoroers, anci treatment of haianci: disorders. In addition to \\ eI ;'recognizcL periphent: anel ccntra! vestihular disorders. anxie!~ disorcier,; iJ2 V l rcct'ntl~ becn linked tn vcstibu iar dysrunctior: ir , subse: 0' ;1 ... -

tients. In particular. vestihular d~'sfunction has been linked to panic disorder and agoraphobia. Vestibular-autonomic connections may form a ba­sis for an association between vestihular dysfunc­tion and panic attacks. The importance of vestib­ulo-autonomic regulation in the clinical arena is not fully known. Two speculative areas discussed in this paper include vestibular-induced ortho­static intolerance and the role of vestibular-respi­ratory pathways on sleep apnea. © 1998 Elsevier Science Inc.

27

balance; orthostatic intolerance; phobia.

Introduction

The vestibular system, including both the pe­ripheral vestibular system, that is, the labyrinth, and the central vestibular system, is known to influence autonomic function in several ways that have clinical implications. Figure I illus­trates diagrammatically how input from the ves­tibular labyrinth and other sensory systems combine in the vestibular nuclei to influence so­called vegetative symptoms such as nausea, vomiting, and changes in heart rate and blood pressure. Additionally, sensory signals important PSS spA'. nb".lioR, .8H~ tlu .. hi 1

nuclei. also influence the locus coeruleus. a nor­adrenerf'ic qfucture though t to be important ir panic c1 i ~ ()"Je' and agorull!1c1bia (J) . AnOlile: i---:~I I ··:~l·Y. ~:··~L·t L:j"~ fG" \'·?s : !~u i:.~ · · ~rJt 'l :10 n: i:'

regulation i~ the cerebellum. which i!-> known to influenct the cardio\'a~cular system (2 .) .

This paper is concerned with the clinical il11-plication!-> of vestibular autonomic regulation and will be organized as follows. There will be a discussion of evidence for vestibular influences on autonomic control from normal human sub­jects, evidence for vestibular influences on au­tonomic control from patients, clinical implica­tions of vestibulo-autonomic regulation and,

28

Affective and

Vestibular Nuclei

J. M. Furman et al

Respiratory Canters

Figure 1. An overview of vestibular influences on autonomic control. Ascending projections from the vestibular nuclei to the parabrachial nucleus may participate In producing affective and emotional responses, and dys­function in this pathway may lead to psychiatric disorders such as agoraphobia. A descending pathway from the vestibular nuclei to bralnstem centers that control respiration and circulation may be responsible for adjust­ing blood pressure and respiration during movement and changes in posture.

finally, speculations regarding possible clinical implications of vestibulo-autonomic control.

Evidence for Vestibular Influences on Autonomic Control from Normal

HdiIISII 5d6]@(G

The vestibular system is known to influence the sympathetic nervous system, the parasym-pat e IC nervous sys ern, an e respir 0

system. Although the respiratory system is not formally part of the autonomic nervous system, the involuntary nature of respiratory control and its importance in vomiting prompted its inclu­sion herein. Evidence for vestibular influences on autonomic control from normal human sub­jects includes the occurrence of both autonomic "symptoms," that is, perception on the part of subjects, and "signs," that is, objective findings that can be observed. Vestibular-induced auto-

nomic symptoms include nausea, malaise, drows­iness, abdominal awareness, anxiety, distress, dread, and reduced vigilance. Vestibular-induced autonomic signs include changes in salivation, changes in gastric motility, vomiting, endocrine responses, "cold" sweating, pallor, increased blOOd hOw to §k@1@M hld§Ei@§, Mid CIIMIg8§ hi heart rate and heart rate variability.

Situations that provoke vestibular-induced autonomic responses include clinical vestibular a ora 0 eng, re

tory testing, vehicular motion, simulators. and exposure to microgravity. The latter three cir­cumstances can lead to motion sickness, simu­lator sickness, and space sickness, respectively. The term "sickness" refers to the autonomic signs and symptoms that result from a combina­tion of vestibular stimulation, visual motion, and visual-vestibular interaction. Vestibular-induced motion sickness has been conceptualized as a "poison response" that includes a combination

-

Clinical Evidence for Autonomic Control

of "stomach emptying" and a "stress response" (3). Stomach emptying includes a combination of symptoms of the act of vomiting, arginine­vasopressin (A VP) release, and increased activ­ity in the parasympathetic nervous system. The "stress response" includes symptoms of anxiety or discomfort, endocrine release. and predomi­nantly sympathetic nervous system changes.

There are several issues regarding vestibular­induced autonomic changes that are unresolved.

x'fhese mell!6e-iflEW/iQy&:l1!&ri~aipn&bi"'UCSp­tibility to vestibular-induced autonomic changes, the relative influence of the semicircular canals compared with the otolith organs. and the cause

Evidence for Vestibular Influences on Autonomic Control from Patients

Evidence for vestibular influences on auto­nomic control from patients includes the effects of acute unilateral peripheral vestibular loss, vestibular compensation for unilateral periph­eral loss, and the effects of central vestibular le­sions on autonomic control including lesions both of the brainstem and of the cerebellum. Acutely, unilateral peripheral vestibular disease causes vegetative symptoms such as nausea. vomiting, and malaise. These symptoms and signs are unquestionably related to direct and indirect connection~ from the vestibula .. system [(, til::- autonomIC nervow, system (..j.). ~k' usefuJ­nes\ n' these symptoms and sign~ physiologl­call) i~ uncertain, \"itll the pr, )..:es~ of"\ estibular compensmion" (:'i L which re'lIlt~ in ,I re~()luti(Jn

of vestibulo-ocular and ve~tibulo-spinal imbal­ances. patients typically have a resolution of their vegetative symptoms ane! signs. In partiCll­lar, vomiting typically resolves over a period of hours. Nausea and malaise may be more long­standing and can continue for days to weeks, even in patients who eventually fully recover their functional abilities.

Many patients with central nervous system disorders that adversely affect central vestibular structures have accompanying autonomic symp­toms and signs tll':\ ,n:1\' hI' "dated to the disc'"

29

der primarily, or may be related to the effect of the disorder on central vestibular function. Such disorders as brainstem or cerebellar infarction (6), migraine (7,8), the effects of neurotoxins (9), and neurodegenerative disorders (10), all can affect central vestibular function and/or au­tonomic function . For example. the highly prev-alent nausea and occasional vomiting that ac-companies migraine headache (11) may be due, in part, to abnormalities in vestibulo-autonomic

f.

cOllIlectioDs duriDg J! migrainous ep=is=o""d""e""" -=S~iIru=' ----..... 11--­larly, the autonomic symptoms and signs asso-ciated with lateral medullary infarction (Wal-lenberg's syndrome) may be a result of direct

Clinical Implications of Vestibulo-Autonomic Regulation

Diagnostic Testing of the Vestibular System

Current diagnostic testing methods used in the evaluation of vestibular disorders include caloric testing, rotational testing, and platform posturography. A limitation of each of these methods pertains to autonomic symptoms in­duced' by vestibular stimulation. For caloric testing. in our experience, nausea is induced in most patients and vomiting occurs in about 5% of patients, l\utonomic symptom" require dis­C(\l1linuatio; of caloric te:.;tiJ1~ prior to complt ­tiOI, of hinaural hithcrma: tcstiJ1f in aOl)ut )(,( of (lUi' pal i~nt.-,. Com cnuoJ1a! i'(ltaU,)na icqing,

\\'herei" patien;s are genli:- Sfll!I' wh ~ lc s~ated ir a compUler-C(lIllroJlec, (nUlL ;'areJ~ re:--Ull, ill

autonomic ~ymrtoms thai are severe enough to warrant discontinuation of testing, Another lype of rotational testing. still in the development stage. is designed to assess the otolith-ocular reflex and uses off-vertical axis rotation. For this test, patients are tilted while rotating. Off­vertical axis rotation leads to significant auto­nomic symptoms that ultimately may limit the clinical applicability of this new technique (12). Measures to reduce autonomic symptoms in­_'luclc assuring that the ambient temperature in

30

the test ella! 'I ~ r is below 65°F • .llllllhat total test time is strictly limited. Dynamic posturography rarely induces significant autonomic symptoms. However, future refinements of and additions to platform posturography, including assessment of visually induced sway (13), may lead to sig­nificant autonomic symptoms.

Balance Disorders and AnxieTY Symptoms

Manv vestibular Jisorders .1fe associated with aU[ol1omic sympt(1!:1S and ~ign~. For '=XLlI11!':e. ')e­ripheral vcslibuiar disorders. ~uch as .\r!e:llere·:, Jisease. are often associatet.! with nausea ant.! vomiting in addition [0 vertigo . .-\s :-toted above. presumably, the nausea and vomiting are a result of the influence of peripheral vestibular signals on the autonomic nervous system. Also, as noted above, central vestibular disorders can lead to ab­normal autonomic nervous system activity.

In addition to well-recognized peripheral and central vestibular disorders, certain anxiety dis­orders recently have been linked to vestibular dysfunction in a subset of patients (14,15). In particular, vestibular dysfunction has been linked to panic disorder and agoraphobia (16-21). Panic attacks are characterized by sudden onset of autonomic symptoms, hyperventilation, and dizziness. The autonomic symptoms include heart palpitations, sweating, trembling, hot or cold flashes, and gastrointestinal distress; the symptoms of hyperventilation include shortness of breath, feeling like choking, chest discom-

J. M. Furman et al

malities (22). Based upon the symptol"" 01 pa­tients with anxiety, many are likely to be suffering from alterations in vestibulo-autonomic regula­tion. This idea is supported by the knowledge that patients with bonafide panic attacks have autonomic symptoms as an accompaniment of their attacks.

Patients with panic disorder often develop agoraphobia. characterized by avoidance of sit­uations such as heights. elevators. supermar-

. ket~ . .;hopping malls . ..:ro\vds. theaters. ~tacliLLl11s. rraveiing. bridges. and [unnels (24). The high iJrevaknce !)r' 'eslibui:.u~ dy,,!'unction in ')anic disllrder .. vith igorapilnbia .-uggesls a func' Jonal

. relationship be[ween these ..:onditions. The [)fes­enc~ of such a relationship :~ also supported by findings that panic attacks and agoraphobic avoidance are prevalent among otoneurological patients with balance complaints and objectively demonstrated vestibular dysfunction. Eagger and colleagues (25) found that one third of pa­tients with peripheral vestibular disorders had panic and agoraphobic symptoms. Similarly, Stein and colleagues (26) found a prevalence of panic disorder of 41 % in patients with vestibu­lar disorders; Clark and colleagues (14) found panic attacks in 37% of patients with vestibular disorders as compared to a 0% prevalence of panic in patients with mild hearing loss.

Current theories of the epidemiology of panic disorder include (1) dysregulation of brainstem noradrenergic systems (for example 27-29); (2) involvement of central serotonergic pathways (30); and (3) respiratory dysfunction (31,32).

~ - • ~. • ~~ - . - _.... _ ... . . • • • • • •• ". II _ . • • ~ • . _. ... .. " _.. '." ..... _ , . ..

III I .' I • ....1 .. •• .1 ..1 • • • •• I. • •• .: •• •• •• I.':'

disorders is uncertain, possibly, It IS medIated panic disorder and vestIbular dysfunctIOn. Rela­by autonomic circuits involving the locus co- tionships between the vestibular system and emleas, a sffilet1:1fe that inFffienee:esHallfm~Oll!s*t-Ee""'1'eef'1ry,..! --ls*mAI:l:lEe~tel:1lFFt!elSS--Eo*f-liIflB,ateM'Fe:esS4~;-jftee~F-'ffl*laBIfIHIM:e~8i:lE' BIeOIFlFa~e~F~llf' BlEefHhlM:l:a:lEe~-"".I---part of the brainstem and spinal cord (1). (1) connections between the locus coeruleus ~

A commonly used diagnostic term for pa- and the lateral vestibular nucleus, as well as al­tients with dizziness and anxiety without con- terations in vestibular processing after ionto­comitant symptoms that clearly define a vestib- phoretic administration of clonidine to the locus ular syndrome such as Meniere's disease or coeruleus (33-36); (2) vestibular input to the migraine is "psychogenic dizziness" (22). Ned- raphe nuclei (37-39) as well as serotonergic ef­zelski and colleagues (23) have proffered a defi- fects on vestibular processing (40,41); and (3) nition for psychogenic dizziness. Their definition vestibular-respiratory connections (42-44). Also, is problematic because many patients labeled as the nucleus parabrachialis receives vestibular psychogenic may have vestibular system abnor- and visceral input and is connected with struc-

Clinical Evidence for Autonomic Control

tures of the limbic system, including the amygdala (45). The amygdala and other parts of the limbic system are known to be essential for the condi­tioning of fear responses (46).

Although these neuroanatomical findings sug­gest a relationship between vestibular dysfunc­tion and panic attacks, they may not easily ac­count for the observations. within patients with panic disorder, of a specific relationship be­tHleep vestibular Oysfupctip9 2nd ?scxapilgGiQ avoidance. However, "pseudo-agoraphobic" syn­dromes in patient with vestibular disorders have long been recognized. including "street neurosis"

(50), "space phobia" (51.52) , and "visual vertigo" (53). In larger samples, the most common fears reported by patients with balance disorders in­clude heights (1 4,25 ,54) and boats (1 4). In fact, it has been suggested that the psychiatric condition of height phobia is related to vestibular dysfunc­tion (55).

"Space and motion discomfort" (56) repre­sents a unifying theme among the situations enumerated above. The concept of SMD is based on the notion that, in many patients with chronic, perhaps partially compensated, vestib­ular dysfunction, vestibular symptoms are situa­tion-specific. This situational specificity, in turn. is related to a sensory integration strategy in which visual and proprioceptive information is used to replace the defective information in the vestibular channel. Individuals utilizing thi ~ strategy would be expectcG to be particu larl) sensitive to (a ) inadequ at ~· 0 ; l11 i!-. leadin.g vi sual information (J :'.57 , 0; " tc' in sLal1il lt \ 0:' the ,>uppor: ... urface (SS.S LI I.

SM! may be a con~eq ucnce of increased de­pendenc:c on nOI1\ e~ tibLl l ar spatia; informati on combined wi th II1appropriate sell:.ory integra­tion. The situation~ thal trigger SMD are char­acterized by inadequate or non vestibular spatial cues and include heights. boats, crowds, and the "particularly rich or repetitive visual patterns" (53) occuning in supermarkets, and certain floor, wallpaper, or traffic patterns. We believe that in patients with panic disorder, SMD can contrib­ute to the development of agoraphobic avoid­ance. This theory is supported by our findings I! ..• , I) patients with anxiety disorders selected

31

for prominent SMD showed an increased pos­tural sensitivity to optic flow stimuli (57), and (2) agoraphobics, known to have high levels of SMD (56), exhibited a surface-dependent sway pattern on computerized dynamic posturogra­phy (59).

To summarize, central vestibulo-autonomic relationships, along with the situational speci­ficity of vestibular symptoms leading to SMD, pi9"i98 M:l6 easis fur the role o()f the 'Vestibul1lf'----I.--­system in certain anxiety disorders. Specifically, vestibular-autonomic connections may form a basis for association with panic attacks. Also,

terns is facilitated, including agoraphobia. Fig­ure 2 (I) summarizes these relationships, im­bedded with other possibilities not specifically discussed here. For example, increased arousal and the behavior of hyperventilation, both com­mon in panic disorder, may affect vestibular function (60-62).

The model depicted in Figure 2 (1) is still in­complete. Importantly, we need to further de­velop our understanding of why vestibular dys­function contributes to anxiety disorders in some individuals and not in others. The nature of the underlying vestibulopathy (that is, whether acute or chronic, compensated or uncompensated) and the degree of anxiety proneness (as indicated, for example, by a family history of anxiety dis-orders) are likely moderators of the relation-ship . Even though vestibular dysfunction may no; be the ultimate caLl ~e 0; panic disorder. it appear\ \() contribute to it ~ phenomenoiog:. par-[iculari ~ the dcwiopmeni of agoraollOblu.

Trearl11ent qf Pariellls 'with Balance Disorders

Treatment for vestibular disorders currently includes pharmacotherapy, physical therapy, and surgery. An emerging technology that may be applied to the treatment of patients with diz­ziness and balance disorders is that of virtual environments (63). Autonomic side effects from physical therapy can be a limiting factor in treat­ment options. Similarly, as virtual envim ':ments evolve as an additional treatmellt modality, au-

i,

32 J. M. Furman et al ._--------------------------------

I Other Visceral Input I I ,

Vestibular Dysfunction Autonomic Activity

I t I Hyperventilation I ,

Space / Motion "-

I Panic Disorder I ) I

I Discomfort I

~ J~ Other Agoraphobic

/ \ I I Mechanisms ~

, r

Agoraphobia without Panic

?anlc Disoroer I with Agoraphobia fooo, ~t---------------'

Figure 2. Overview of relationships between vestibular dysfunction and certain anxiety disorders. From Jacob and colleagues (1).

tonomic side effects also are likely to be a limit­ing factor, as with physical therapy, since expo­sure to virtual environments in nonnal subjects is well known to cause autonomic symptoms (64). Such symptoms may be immediate, de­layed, and/or prolonged. Possibly, with improved understanding of vestibulo-autonomic regulation, the side effects of physical therapy or from vir­tual environments can be minimized. Also, phys­ical therapy techniques typically used for patients with vestibular disorders may become useful for a subset of patients with anxiety disorders, par­ticularly those anxious patients with objectifi-

Further Speculations Regarding Clinical Implications

The importance of vestibulo-autonomic reg­ulation in the clinical arena is as yet unknown. Two . peculative areas of application include vestibular-induced orthostatic intolerance and the role of vestibular-respiratory pathways on sleep apnea. Although these issues are only be­ing explored in a very preliminary fashion, orthostatic intolerance experienced by astro­nauts returning to Earth (65) may have as a

component abnormal vestibulo-autonomic reg­ulation. Further research regarding vestibulo­autonomic connection, particularly otolith-auto­nomic influences, may improve our understand­ing of "Earth sickness." Also, although patients with vestibular disorders rarely complain of orthostatic hypotension, they avoid making sud­den changes in posture that would require rapid readjustments in circulation.

Upper airway muscle tone is known to be in­fluenced by head position (43,66-68). Such in­fluences may be mediated by vestibulo-respira­tory circuits. Possibly, by altering the activity in

ameliorated by vestibular stimulation.

Conclusions

In conclusion, vestibulo-autonomic pathways impact the field of vestibular and balance disor­ders. In particular, patients with either periph­eral and central vestibular abnonnalities mani­fest both symptoms and signs of autonomic dysfunction. Vestibular autonomic regulation affects the assessment, diagnosis, and treatment of patients with vestibular disorders.

Clinical Evidence for Autonomic Control 33

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