1.14 Review Article.the Shy-drager Syndrome, r.sandyk
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380 SA MEDICAL JOURNAL VOLUME 63 5 MARCH 1983 Review Article The Shy-Drager syndrome R. SANDYK Summary The association of orthostatic hypotension with signs of progressive neuronal degeneration of the central nervous system particularly affecting the autonomic nervous system is known as the Shy- Drager syndrome. The pathological hallmark of the disease is cell loss in the intermediolateral column of the spinal cord, which is responsible for the major element in the autonomic failure. There is also evi- dence that widespread involvement of the dopami- nergic system may be responsible for the auto- nomic as well as the parkinsonian features encountered. S At, Med J 1983: 63: 380-381. In 1960 Shy and Drager l published a report on the clinical and pathological features of 4 patients with idiopathic orthostatic hypotension and nervous system involvement. Bannister and . Oppenheimer 2 distinguished two pathological subtypes of the syndrome, one in which the intermediolateral column degenera- tion is associated with multisystemic atrophy such as olivoponto- cerebellar degeneration or striatonigral degeneration, and the other in which there are Lewy body inclusions and other features of idiopathic parkinsonism. Clinical manifestations The main clinical features of the syndrome are variations in blood pressure, sphincter dysfunction and impaired potency and libido, somatic neurological manifestations (parkinsonism and upper motor neuron and cerebellar syndromes), secretory dis- turbances and heat intolerance. There are also other miscel- laneous .signs. Variations in blood pressure are the hallmark of the syn- drome. The patient often complains of dizziness and severe anacks of syncope, more intense when standing than when sit- down. Measurement of the blood pressure in the horizontal and the upright positions definitely establishes the diagnosis, for which a demonstrable drop in blood pressure of at least 30/20 mmHg on standing must be present. Sphincter dysfunction is manifested by urinary inconti- nence; faecal incontinence usually follows. Shy and Drager stressed that one of the most common initial complaints in males is of impotence and/or loss of libido; nocturnal diuresis and urinary retention follow. Department of Neurology, Johannesburg Hospital, Johannes- burg R. SANDYK, M.D. (BON!';), (Present address: Department of Clinical Pharmacology, University of the Witwatersrand, Johannesburg) Dare received: 26 February 1982. Somatic neurological manifestations include loss of invo- luntary movements, tremor, muscular weakness and dysarthria. Extrapyramidal symptoms and signs such as cogwheel;rigidity, pill-rolling tremor and a mask-like face are among the most disabling and clinically prominent features of the syndrome. The parkinsonism may resemble that of Parkinson's disease or par- kinsonism of other causation, but it usually appears as a resting as well as an intention tremor, which may be somewhat faster than that in Parkinson's disease. Signs and symptoms of corticobulbar and corti- cospinal tract involvement such as a positive Babinski sign, dysarthria and a brisk jaw jerk are often present, and Thomas and Schirger 3 report that hyperreflexia is one of the most frequent objective neurological abnormalities. Cerebellar involvement leads to intention tremor of the limbs, ataxia and scanning speech. Involvement of the pyramidal-extrapyramidal and cere- bellar systems is usually bilateral and symmetrical. Unilateral predominance of the neurological deficit is occasionally seen, but any exclusive one-sided neurological involvement should raise doubts about the diagnosis. Progressive muscle weakness and fasciculations may occur in the late stage of the illness. Secretory disorders present as marked impairment of sweating, which may occur early. Lacrimation and salivation.are usually unchanged until the advanced stages of the disease, when diminished lacrimation, excessive salivation and seborrhoea may occur. Heat intolerance is a relatively consistent complaint. Some patients may complain of intolerance to cold. These symptoms are caused by poor body temperature regulation secondary to an inadequate response of the thermoreceptors. Miscellaneous signs include iris atrophy, Horner's syn- drome, diplopia, decreased ankle jerks and decreased perception of pain. Emotional instability and mental deterioration usually become obvious late in the course of the illness. The Shy-Drager syndrome affects both sexes but is com- moner in males. The age of onset is usually around 50 years and the symptoms progress slowly over the years'. The prognosis is poor, and on average death occurs within 7-8 years of the onset of the hypotension and 4 years after the onset of the neurological manifestations. In some patients the neurological deficit pre- cedes the postural symptoms. The life expectancy of these patients is undoubtedly shortened. Pathological abnormalities One of the most consistent pathological fmdings in patients with the Shy-Drager syndrome is shrinkage and brownish dis- cobration of the putamen and depigmentation of the substantia nigra and locus ceruleus. examination usually reveals changes in specific areas such as the autonomic ganglia, intermediolateral columns of the spinal cord, dorsal vagal nuclei, inferior olivary nuclei, locus ceruleus, substantia nigra and put- amen. The pathological hallmark of the disease is cell loss in the intermediolateral column of the spinal cord. This is considered the major element in the autonomic failure. 4 Pathological changes in the substantia nigra and striatum are characteristic. The substantia nigra often shows loss of melanin- pigmented neurons and some reactive gliosis as well as Lewy
Transcript of 1.14 Review Article.the Shy-drager Syndrome, r.sandyk
380 SA MEDICAL JOURNAL VOLUME 63 5 MARCH 1983
Review Article
The Shy-Drager syndromeR. SANDYK
Summary
The association of orthostatic hypotension withsigns of progressive neuronal degeneration of thecentral nervous system particularly affecting theautonomic nervous system is known as the ShyDrager syndrome. The pathological hallmark of thedisease is cell loss in the intermediolateral columnof the spinal cord, which is responsible for the majorelement in the autonomic failure. There is also evidence that widespread involvement of the dopaminergic system may be responsible for the autonomic as well as the parkinsonian featuresencountered.
S At, Med J 1983: 63: 380-381.
In 1960 Shy and Drager l published a report on the clinical andpathological features of 4 patients with idiopathic orthostatichypotension and nervous system involvement. Bannister and .Oppenheimer2 distinguished two pathological subtypes of thesyndrome, one in which the intermediolateral column degeneration is associated with multisystemic atrophy such as olivopontocerebellar degeneration or striatonigral degeneration, and theother in which there are Lewy body inclusions and other featuresof idiopathic parkinsonism.
Clinical manifestationsThe main clinical features of the syndrome are variations in
blood pressure, sphincter dysfunction and impaired potency andlibido, somatic neurological manifestations (parkinsonism andupper motor neuron and cerebellar syndromes), secretory disturbances and heat intolerance. There are also other miscellaneous .signs.
Variations in blood pressure are the hallmark of the syndrome. The patient often complains of dizziness and severeanacks of syncope, more intense when standing than when sit~ing down. Measurement of the blood pressure in the horizontaland the upright positions definitely establishes the diagnosis, forwhich a demonstrable drop in blood pressure of at least 30/20mmHg on standing must be present.
Sphincter dysfunction is manifested by urinary incontinence; faecal incontinence usually follows. Shy and Dragerstressed that one of the most common initial complaints in malesis of impotence and/or loss of libido; nocturnal diuresis andurinary retention follow.
Department ofNeurology, Johannesburg Hospital, JohannesburgR. SANDYK, M.D. (BON!';), (Present address: Department of ClinicalPharmacology, University of the Witwatersrand, Johannesburg)
Dare received: 26 February 1982.
Somatic neurological manifestations include loss of involuntary movements, tremor, muscular weakness and dysarthria.Extrapyramidal symptoms and signs such as cogwheel;rigidity,pill-rolling tremor and a mask-like face are among the mostdisabling and clinically prominent features of the syndrome. Theparkinsonism may resemble that of Parkinson's disease or parkinsonism ofother causation, but it usually appears as a resting aswell as an intention tremor, which may be somewhat faster thanthat in Parkinson's disease.
Signs and symptoms of corticobulbar and corticospinal tract involvement such as a positive Babinski sign,dysarthria and a brisk jaw jerk are often present, and Thomas andSchirger3 report that hyperreflexia is one of the most frequentobjective neurological abnormalities. Cerebellar involvementleads to intention tremor of the limbs, ataxia and scanningspeech. Involvement of the pyramidal-extrapyramidal and cerebellar systems is usually bilateral and symmetrical. Unilateralpredominance of the neurological deficit is occasionally seen, butany exclusive one-sided neurological involvement should raisedoubts about the diagnosis. Progressive muscle weakness andfasciculations may occur in the late stage of the illness.
Secretory disorders present as marked impairment ofsweating, which may occur early. Lacrimation and salivation.areusually unchanged until the advanced stages ofthe disease, whendiminished lacrimation, excessive salivation and seborrhoea mayoccur.
Heat intolerance is a relatively consistent complaint. Somepatients may complain of intolerance to cold. These symptomsare caused by poor body temperature regulation secondary to aninadequate response of the thermoreceptors.
Miscellaneous signs include iris atrophy, Horner's syndrome, diplopia, decreased ankle jerks and decreased perceptionof pain. Emotional instability and mental deterioration usuallybecome obvious late in the course of the illness.
The Shy-Drager syndrome affects both sexes but is commoner in males. The age of onset is usually around 50 years andthe symptoms progress slowly over the years'. The prognosis ispoor, and on average death occurs within 7-8 years of the onset ofthe hypotension and 4 years after the onset of the neurologicalmanifestations. In some patients the neurological deficit precedes the postural symptoms. The life expectancy of thesepatients is undoubtedly shortened.
Pathological abnormalitiesOne of the most consistent pathological fmdings in patients
with the Shy-Drager syndrome is shrinkage and brownish discobration of the putamen and depigmentation of the substantianigra and locus ceruleus. Micros~opic examination usuallyreveals changes in specific areas such as the autonomic ganglia,intermediolateral columns of the spinal cord, dorsal vagal nuclei,inferior olivary nuclei, locus ceruleus, substantia nigra and putamen. The pathological hallmark of the disease is cell loss in theintermediolateral column of the spinal cord. This is consideredthe major element in the autonomic failure. 4
Pathological changes in the substantia nigra and striatum arecharacteristic. The substantia nigra often shows loss ofmelaninpigmented neurons and some reactive gliosis as well as Lewy
bodies. The putamen may be involved, but there is a relativesparing of the nucleus caudatus.
Biochemical abnormalitiesThere is evidence that widespread involvement' of the dopa
minergic system, similar to that found in parkinsonism, occurs inthe Shy-Drager syndrome. Reduction in the dopamine concentration in midbrain structures, limbic areas and the hypothalamus has been demonstrated.s A substantial fall in the noradrenaline content, which was more pronounced than in parkinsonianpatients, has been found in several patients with the Shy-Dragersyndrome. The clinical significance of this finding is not clear,but it may relate to both the parkinsonism and the autonomicdisturbance observed in the syndrome.s The autonomic disturbance has been attributed to loss of preganglionic autonomiccells from the intermediolateral co~umns of the spinal cord.However, it is also possible that lesions in supraspinal centres,normally concerned with the control of autonomic outflow, maycontribute to the overall disturbance. Histochemical studieshave shown that the noradrenergic, adrenergic and serotoninergic fibre systems richly innervate brainstem nuclei involved inthe central control of blood pressure and heart rate and thatbulbospinal noradrenergic and serotoninergic fibres terminate inthe intermediolateral columns, where they join with preganglionic autonomic neurons. It is therefore possible that centralnoradrenaline depletion contributes to the autonomic failure,since there is considerable evidence that this amine has an important neurotransmitter role in central pathways subserving a cardiovascular function.
Differential diagnosisParkinson's disease may be diagnosed in patients with ortho
static hypotension, particularly when it precedes the posturalhypotension. In addition some parkinsonian patients have symptoms of dysautonomia. However, the other somatic symptoms inthe Shy-Drager syndrome usually make the diagnosis fairly easy.Progressive supranuclear palsy may resemble the syndrome, butocular involvement is exceptional in the latter. Familial dysautonomia (the Riley-Day syndrome) is a recessive hereditary disorder characterized by blood pressure disturbances, lack of lacrimation, decreased taste, dysphagia and early onset.
The conditions associated with orthostatic hypotension arelisted in Table I.
Treatment of the Shy-Drager syndromeThere have been reports6 of limited and temporary success
with L-dopa treatment in patients with the Shy-Drager syndrome and parkinsonian features. This treatment, either alone orwith cyproheptadine, has also been reported as beneficial inorthostatic hypotension. Simple physical measures such as legsupports in combination with drugs affecting the postganglionic
SA MEDIESE TYDSKRIF DEEL 63 5 MAART 1983 381
TABLE I. CAUSES OF ORTHOSTATIC HYPOTENSION
Endocrine and metabolic disordersDiabetes mellitus with neuropathyAdrenal insufficiencyHypopituitarismPhaeochromocytomaPorphyria
Neurological disordersTabes dorsalisSyringomyeliaEncephalitisMultiple sclerosisParkinson's diseaseHaematomyeliaTransection of the cordCraniopharyngiomaWernicke's diseaseBotulismSubacute combined degeneration of the cordGuillain-Barre syndrome
Miscellaneous causesAmyloidosisProlonged bed restShy-Drager syndrome
DrugsTranquillizersAntihypertensive drugsMonoamine oxidase inhibitorsAdrenergic blocking agents
sympathetic system may be of help in the early stages of theorthostatic hypotension. Fludrocortisone acetate is indicated ifthese methods fail; the starting dose is 0,1 mg/d, graduallyincreased over a period of 3 - 4 weeks to 2 mg/d or until thesymptoms of orthostatic hypotension subside. Ankle oedemaand severe hypertension in the supine position usually limitprolonged administration of the drug.
REFERENCES
1. Shy GM, Drager GA. A neurological syndrome associaled Wilh orrhostalichypolension. Arch Neurol 1960; 2: 511-527.
2. Bannister R, Oppenheimer DR. Degeneralive diseases of the nervous syslemassociated Wilh autonomic failure. Brain 1972; 95: 457-468.
3. Thomas JE, Schirger A. Idiopathic orthostatic hypotension: a study of itsnatural history in 57 neurologically affected palien!s. Arch Neurol 1970; 22:283-289.
4. Graham JG, Oppenheimer DR. Orthostatic hypolension and nicotine sensitivity in a case of 'muiriple syslem atrophy'. J Neurol Neurosurg Psychiacry1969; 32: 28-36.
5. Spokes EGS, Bannister R. Catecholamines and dopamine receptor binding inparkinsonism. In: C1ifford Rose F, Capildeo R, eds. Research Progress inParkinson's Disease. Tunbridge Wells, Ken!: Pitman Medical, 1981: 195-205.
6. Bannister R, Ardill L) Fenrem P. An assessment of various merhos of treatmentof idiopathic hypotension. Q J Med 1969; 38: 377-384.
