HISTORY 76 Clinical Evidence of Dysautonomia MICHAEL J. REICHGOTT. Definition Dysaulonomia refers to an abnormality of function of the autonomic nervous system. There are two divisions of the ‘autonomic nervous system: che sympathetic and the para sympathetic, Although the lauer occasionally may be in- volved, abnormal funetion of the sympathetic division produces the most striking symptoms of dysautonomic syn. ‘dromes. The term orthasatc hypotension is often used 38 2 synonym for dysautonomia, It is the most dramatic of the symptoms and is the one that most often brings the patient to the physician, bur i is not an adequate description of the full dysautonomic syndrome. Dysautonomia is nota single disease process. The auto- ppomic nervous system may undergo injury as part of several different degenerative neurologic diseases. These are the primary dysaitonomias, There ate also nonneurologic sys- temic illnesses of a variety of causes in which injury co the autonomic nervous system may occur and become a pre- dominant component. These are the secondary dyautonemie, Finally, side effects of drugs are often manifested as ab- normalities of function of the autonomic nervous system, producing an iatrogenic form of dysautonomia. The many causes of dysautonomia are listed in Table 76.1 Technique Dysautonomia does not produce unique symptoms. ‘The patients individual complaints can each be part of another disease process, It isthe set of symptoms, taken together, that suggests chat a dysauconomic state is present, In ob: taining the history, therefore, three tasks must be accom plished. The physician must: 1, Develop a sufficient body of information to establish that a dysautonomic syndrome acwally exists. 2. Distinguish the secondary dysautonomias, including drug side effects, many of which will improve or dis- appear when the causative problem is treated, from the primary dysauronomias for which there is only symptomatic relief 3. Distinguish among the several forms of primary dys- autonomia, since these have different natural histo- ries and. prognoses The symptoms of primary dysautonomia are listed in Table 76.2, Other than postural syncope, the symptoms are often mild or sublle and may become evident only after a careful and detailed review of systems. Postural dizziness or syncope is the most striking symptom of dysautonomia. It is the most commonly reported, and is ‘usually sufficiently disturbing to be a chief complaint or presenting problem. Note thatthe symptoms evident 10 the Patent are postural dizziness, syncope, or one of the other 389 ‘manifestations of cerebrovascular ischemia noted in Table 76.2. These symptoms are due to orthostatic (postural) hy- potension, but the latter is 2 sign to be elicited on physical examination and is not, strictly speaking, part of the his- torical database. ‘There are many causes in addition to primary dysau- tonomia for postural syncope due to orthostatic hypoten- sion; these are listed in Table 76.8. The terms sympathicotonic and asynpathicotonic have been coined to describe situations in which the autonomic nervous system is normal (the for- ‘mer) and those in which a dysautonomic state exists (the laner). An important point of differentiation becween these two groups of problems is that when the autonomic re- sponse system is functioning normally (the sympathicotonic state), assumption of the upright posture is accompanied by an increase in heart rate. This may be perceived and reported as palpitation, In the asympathicotonie state, the heart rate response is usually impaired along with the other impairments of autonomic function ‘Table 76. The Dysautonomias Primary Familial dysautonomia (Riley-Day syndrome) |diopathic orthostatic hypotension ¢progresive autonomic fall) Mulipe ytem atrophy wih amonomic lure (Shy-Drager syndrome) mse Parkinsons syndrome with autonomic fare Secondary “Amyidoss ‘Autoimmane neuropathies GuillanBarse syndrome Myasthent gras Rheumatoid mba Carcinomatoss autonomic neuropathy Cenral nervous system dseosce ‘Hypothalamic ons Poweron foes fomors Syringomyel ‘Terry yphilis—tabes dors Wernicle yndvome Diabetes melts Metab sees Fabr's disease Pernicious anemia Porphyria ‘Tangier disease Drug Related (ce Table 76.7 for mote detailed tt) ‘Aketot ‘Anudepreseans Antibypertenaives “Tranglzers-amuipychodc agents Modii trom Banner R Autom are a mck of dal dr of he anton meron at Ne York: Onion Univer Pre 183390 ¥ mie avroxonic Table 762 Symptoms of Dysautonomia Syaom = Patapon ms Tipuncadeone ining, dives of von, stmt ge sed spec evercie man dst — om Tg err py, are mane Sera ofcon aie Itiptte fw of id, dy or reropade nie ow faction 0% Imereti, ncaa, eal Dard ting us Data devi fom: Thomas JE, Senger A. Idopathie orotate he pec Arch Neurol ISR 3285-98, ‘Table 763 Causes of Orthostatic Hypotension hicotoie—aonomie datunction: “Fetch eimary dyaonomi Secondary aysautonomias Syapathee ibang drags (ee Tale 76.7) Sympathiotonie—no autonomic dysfunction; characterized by rscyerle ‘Volume deplion Ada clcae Dehydration Berorniage ‘Vasu tticency Parade fainting Pregnangy ‘Thermodaton ‘Variote vine Decondnioning of grant forces Pennfecious Prolonged bed rest Drug induced ‘Ahlan Diuree Navas ota depletion Vasa see racretized by ‘The patient who experiences the postural symptoms as- sociated with orthostatic hypotension describes a sen of dizziness or transient weaknesson arising from the su position, This is especially obvious when the movement is Sudden. The feeling is often described as though a “wave” fof weakness had passed over the individual. The symptom js not accompanied by shortness of breath or chest pain. Palpitation will not occur in the dysautonomie patient. The postural syneope resolves quickly once the head is lowered, nd the symptom can sometimes be prevented by having the patient stand slowly enough to allow the circulatory systein to adjust, When the syndrome is fully developed, however, adjustment does not occur, and severe syncopal C NERVOUS SYSTEM symptoms can be controlled only through use of support ‘garments and therapy to expand the blood volume, ‘As noted, these sympcoms are a manifestation of a sud- den decrease of blood supply to the brain and can have any of the characteristics of transient cerebral ischemia. For ex ample, some patients will experience slurring of speech or dimming of vision rather than the more commonly de- scribed dizainest. In other individuals, particularly with cer tain drug-related secondary dysautonomias, the symptoms present as postexercise syncope or weakness rather than {Just occurring with postural change. At times, even a normal individual will experience pos tural dizziness (e., om a hot day, after a hot bath, or with social drinking). The historian must determine whether postural symptonas are a common occurrence, under what eircumstances they occur, whether the events are increasing in severity oF frequency, and what other symptoms occur in association in order effectively wo sort among the many sand varied cxuse, Urinary tract dysfunction is described by almost two-thirds of the patients with primary dysautonomia. These symp- toms alo are common in individuals with secondary dysau- tonomia, particularly diabetics, The bladder symptoms are very nonspecific; for example, nocturnal frequeney may be part of symptom complex die to congestive heart failure, Urinary tract infection, or bladder outlet obstruction, any ff which are more frequent in occurrence than dysauto- rnomia. It could also be due tothe osmotic duresis that occurs in diabetics more commonly than severe dysautonomia. For these reasons, the historian must carefully evaluate each individual symptom within a complete context ‘A point of differential value in the history pertaining 10 bladder funecion is thatthe dysautonomias, particularly the primary syndromes, may be accompanied by failure of blad- der sensation as well as motor function abnormalities. Thus the dysautonomic patient may not be aware of a distended bladder This sensory abnormality can help differentiate among, the causes of urinaty frequency, since osmotic diuresis and the frequency of congestive failure are accompanied by an apparent sense of urgency. Similarly, the absence of eystic inflammation in the dysautonomic results in frequency ‘vithont dysuria, allowing differentiation from urinary tract infection. ‘The absence of sensation, along with the motor Fianetion abnormalities of the syndrome, also make dysau- tonomic individuals (particularly women) subject to stress ‘oF overflow incontinence, Sexual dyefunction, 2 common occurrence in dysauto- noma, may also be caused by a wide variety of other illnesses (Table 76.4). For many years, this problem had been written, fff as being almost always of psychogenic origin. More re- cently, however, an organic or pharmacologic cause has been established in 80% of impotent men, and more than 50 organic causes of impotence have been identified. rogenic sexval dysfunction caused by side effects of ‘drugs on the autonomic nervous system is a problem of special concern, The drugs involved, particularly the anti- hypertensive agents, are needed for lifelong treatment of an important cardiovascular risk factor. The occurrence of side effects like sexual dysfunction often results in noncome pliance with preseripion and may seriously impair a treat fnient program. Therefore, whenever 2 patient is known 10 be taking a drug with the potential of producing this side effect, the possibility should be explored by careful and sensitive questioning for evidence of sexual performanceTable 764 Organic Causes of Impotence Inflammatory: Urethrits, prostatitis, seminal vesiculiis, . ‘Sati urethral site. gonorthe tubercalos Congenal deformity, Peyronie's disease, ‘hashed obesty, hytecte, pimosis Frosatebiopey,promatectomy (imple oF radia), sbdominoperineal rection, Iphincrerowmy, wala sorgery Aferorderosn arteritn paper, chromboss, embolism enectomy, urethral rupture Myocardial alae, angina pectoris, pulmonary ‘iauffiteney, stems, leukemia, metabolic Alscase, other system less Dysautonomis, peripheral neutopathy, mor ‘or transect ofthe spinal cov, Stayourophi aeralselerons, hile ‘cio spina bifid, syringomyelia Drug abuse leobol,stinulams narcosis), vchotropie agents ranquiizes Seidepretentanipeyc toe), Sncconvalant,aniparkinsontan dros, nthypertensive Pituitary disease, adrenal dscase, thyroid tncae,lypoyonadio, clabees telus, romosomal abnormalities (iets oF ‘Tamers syndrome) ‘Mechanical ostoperative: Qechusive— ‘ascular Traumatic: ‘Endurance: Neurologic Ghemical Endocrine ‘Adapted from: Sith AD. Casts and castifcation f impotence, Ure log sof North Aten 1981;8:70-6 ” difficulties. If these are discovered, the drug regimen should be changed. Specific historical points tend to suggest dysautonomia for some other organie cause for sexual dysfunction. When evaluating impotence, the special clue is the presence or absence of morning crecion. The morning erection i a frequently experienced event in the male. It tends to decline in frequency with age, but sill occurs even inthe older man. Iisa manifestation of sympathetic nervous system activity during the REM sleep cycle; as such, iti a true measure of the competence of the autonomic nervous system. ‘The historian should determine whether the patient has morn- ing erection, its frequency. and whether changes in its char- acter (-e, becoming less turgid) are occurring. Where the history is unclear, itis possible to test fr this phenomenon using objective methods (nocturnal penile tumescence). ‘Another clue inthe differentiation between organic and psychogenic sexual dysfunction i the relationship of arousal and potency to specific sexual partners. Psychogenic sexual dysfunction is often limited to'a specific partner. Iemay ‘manifestation of guilt because of extramarital sexual ac- tivity, anxiety over possible transmission of venereal disease, or may be due to performance ansiety. Organic problems are manifested with all partners. Differentiating among the many causes of organic im- potence is not easy. In inflammatory diseases the presence Of pain may provide a cue. Most ofthe other causes must be differentiated by evaluation ofthis symptom within con- text of the entre history ‘Bowel dysfunction seems to be less often a symptomatically ‘Table 76.7 Drugs Causing Dysautonomic Orthostatic Hypotension ‘Achat MAO itor ‘pase opa Mecoamine tours Phenhornes Beshansine Fhemotanine Coniine Pomc Disenatoe Prone ene ne Gana Figen Canceling “Tasetapan isn Reseping ey Vincine mon for the diabetic to develop nocturnal diarthea or diar- thea alternating with constipation as a manifestation of dysautonomic bowel function. Impotence and retrograde sjaculation are also frequently reported. ‘The occurrence of orthostatic hypotension and postural syncope is a major problers with some drugs (Table 76.7) This side effect will make it impossible to continue t0 use an agent in a therapeutic regimen even if itis producing the desired treatment effect hecause of the risks to the pa tient and the inability of 2 patient to tolerate this problem, “The lst of drags that can cause postural syncope is long, and varied. Some produce this effect through actions in the autonomic nervous system. Others do noe impair autonomic Tunction, but result in diminution of the circulating blood volume. "These drugs share the common characteristic, whether causing autonomic inhibition or producing. pos ‘ural symptoms through volume depletion, that they reduce cardiac output and preload. Drugs that only reduce pe: ripheral vascular resistance (¢g., hydralazine, minoxidil) do ‘not cause orthostatic hypotension. This isan important con- sideration when planning change in therapy in an attempt to alleviate postural syncope as a side effect. ‘The most important consequence of these side effects is probably not the postural syncope or impairment of sexual perlormance per se, but the failure ofthe patient 1o remain ‘compliant with the treatment regimen once a drug is id tified as the cause of discomfort. The mistrust of drugs i often carried over to other agents, and even minor discom. forts are blamed on a drug. Since drugs are needed for lifetime treatment in most of the patients, such compliance failure and the associated unwillingness to trust any agent become an extremely important clinical management prob- lem, Other secondary dysautonomias are relatively uncom= ‘mon. In addition, the symptoms of failure of the autonomic system are only a part of the entire syndrome presented by the patient. Most often, the diagnosis of these illnesses will be stggested by these other symptoms. The full differential agnosis mast be reviewed, however, because the second- ary dysautonomie syndromes are often part of correctable problems and sill resolve with successful treatment or con- trol of the underlying systemic illness. References Appenzeller O, Gos JE. Autonomic deficits in Parkinson's» ‘drome. Arch Neurol 171;24:50-87, [Bannister R. Chronic antonomie failure with postural hypotension. Taneet 1979;2:404-675. GLINICAL EVIDENCE OF DYSAUTONOMIA 397 Bannister R, Ardill , Fentem P, An assessment of various methods ‘of treatment of idiopathic orthosatic hypotension. Q] Med 1969;38:377~95. Bannister R, Oppenheimer DR. Degenerative disease ofthe ner ‘ous sytem. Brain 1972;95:457-74, Bradbury 8, Eggleston C. Postural hypotension: an autopsy upon 3 case. Am Heart J 1025:1:78-8. Edis AJ, Shepherd J. Autonomic control ofthe peripheral vas ‘cular system. Arch Intern Med 1970:125:716-24 Johnson RH, Lee Ge], Oppenheimer DR, etal. Autonomic failure with orthostatic hypotension due to intermediolateral column degeneration. QJ Me 1966;38:276-92. Riley CM, Day RL. Greely DM, etal Cental astonomic dysfunction with defective lacrimation. 1. Report of 5 cases. Pediatrics 1949; 5296878 ‘Sharpey Schafer EP, Taylor FJ. Absent circulatory reflexes in di abetic neuritis. Lancet 1960¢1:869-62 Shy GM, Drager GA. A neurological syndrome associated with ‘orthostatic hypotension, Arch Neurol 1960;2:511-27. ‘Thomas JE, Schirger A. Orthosatic hypotension: etiologic consid ‘rations, diagnosis and treatment. Med Clin North Aes 1968; 52:809-16, ‘Thomas JE, Schirger A. Idiopathic orthostatic hypotension. Arch ‘Neural 1970:22:289-93, ‘Wagner HN. Orthosttic hypotension. Bull Johns Hopkins Hosp 1959; 105;322—59, “iegler MG, Lake GR, Kopin I. The sympathetic nervous system ‘defect in primary orthostae hypotension. N Engl J Med 1977;206:295-97