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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 ofNeurology, 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-
kinsonismof 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 ofthe 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
bodies. The putamen may be involved, but there is a relative
sparing of the nucleus caudatus.
Biochemical abnormalities
There is evidence that widespread involvement' of the dopa-
minergic system, similar to that found in parkinsonism, occurs in
the Shy-Drager syndrome. Reduction in the dopamine concen-
tration in midbrain structures, limbic areas and the hypothala-
mus has been demonstrated.
s
Asubstantial fall in the noradrena-
line content, which was more pronounced than in parkinsonian
patients, has been found in several patients with the Shy-Drager
syndrome. The clinical significance of this finding is not clear,
but it may relate to both the parkinsonism and the autonomic
disturbance observed in the syndrome.
s
The autonomic distur-
bance has been attributed to loss of preganglionic autonomic
cells from the intermediolateral c o ~ u m n s of the spinal cord.
However, it is also possible that lesions in supraspinal centres,
normally concerned with the control of autonomic outflow, may
contribute to the overall disturbance. Histochemical studies
have shown that the noradrenergic, adrenergic and serotoniner-
gic fibre systems richly innervate brainstem nuclei involved in
the central control of blood pressure and heart rate and that
bulbospinal noradrenergic and serotoninergic fibres terminate in
the intermediolateral columns, where they join with preganglio-
nic autonomic neurons. It is therefore possible that central
noradrenaline depletion contributes to the autonomic failure,
since there is considerable evidence that this amine has an impor-
tant neurotransmitter role in central pathways subserving a car-
diovascular function.
Differential diagnosis
Parkinson's disease may be diagnosed in patients with ortho-
static hypotension, particularly when it precedes the postural
hypotension. In addition some parkinsonian patients have symp-
toms of dysautonomia. However, the other somatic symptoms in
the Shy-Drager syndrome usually make the diagnosis fairly easy.
Progressive supranuclear palsy may resemble the syndrome, but
ocular involvement is exceptional in the latter. Familial dysauto-
nomia (the Riley-Day syndrome) is a recessive hereditary dis-
order characterized by blood pressure disturbances, lack of lac-
rimation, decreased taste, dysphagia and early onset.
The conditions associated with orthostatic hypotension are
listed in Table I.
Treatment of the Shy-Drager syndrome
There have been reports
6
of limited and temporary success
with L-dopa treatment in patients with the Shy-Drager syn-
drome and parkinsonian features. This treatment, either alone or
with cyproheptadine, has also been reported as beneficial in
orthostatic hypotension. Simple physical measures such as leg
supports 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 disorders
Diabetes mellitus with neuropathy
Adrenal insufficiency
Hypopituitarism
Phaeochromocytoma
Porphyria
Neurological disorders
Tabes dorsalis
Syringomyelia
Encephalitis
Multiple sclerosis
Parkinson's disease
Haematomyelia
Transection of the cord
Craniopharyngioma
Wernicke's disease
Botulism
Subacute combined degeneration of the cord
Guillain-Barre syndrome
Miscellaneous causes
Amyloidosis
Prolonged bed rest
Shy-Drager syndrome
Drugs
Tranquillizers
Antihypertensive drugs
Monoamine oxidase inhibitors
Adrenergic blocking agents
sympathetic system may be of help in the early stages of the
orthostatic hypotension. Fludrocortisone acetate is indicated if
these methods fail; the starting dose is 0,1 mg/d, gradually
increased over a period of 3 - 4 weeks to 2 mg/d or until the
symptoms of orthostatic hypotension subside. Ankle oedema
and severe hypertension in the supine position usually limit
prolonged administration of the drug.
REFERENCES
1. Shy GM, Drager GA. A neurological syndrome associaled Wilh orrhostalic
hypolension. Arch Neurol 1960; 2: 511-527.
2. Bannister R, Oppenheimer DR. Degeneralive diseases of the nervous syslem
associated Wilh autonomic failure. Brain 1972; 95: 457-468.
3. Thomas JE, Schirger A. Idiopathic orthostatic hypotension: a study of its
natural history in 57 neurologically affected palien!s. Arch Neurol 1970; 22:
283-289.
4. Graham JG, Oppenheimer DR. Orthostatic hypolension and nicotine sensi-
tivity in a case of 'muiriple syslem atrophy'. J Neurol Neurosurg Psychiacry
1969; 32: 28-36.
5. Spokes EGS, Bannister R. Catecholamines and dopamine receptor binding in
parkinsonism. In: C1ifford Rose F, Capildeo R, eds. Research Progress in
Parkinson's Disease. Tunbridge Wells, Ken!: Pitman Medical, 1981: 195-205.
6. Bannister R, Ardill L) Fenrem P. An assessment of various merhos of treatment
of idiopathic hypotension. QJ Med 1969; 38: 377-384.