Shy-Drager Syndrome

disease · SciDEX wiki

Pathway / Mechanism Diagram

flowchart TD
    A["Genetic<br/>Risk Factors"] --> B["Molecular<br/>Pathology"]
    A0["MSA"] --> A
    A1["SDS"] --> A
    B --> D["Cellular<br/>Dysfunction"]
    D --> E["Neuroinflammation"]
    E --> F["Neuronal<br/>Damage"]
    F --> G["Clinical<br/>Symptoms"]
    H["Therapeutic<br/>Interventions"] -.->|"target"| B

Overview

Shy-Drager syndrome (SDS) is a rare neurodegenerative disorder characterized by progressive autonomic failure in conjunction with parkinsonian features consistent with Parkinson’s disease. It is now classified as a variant of multiple system atrophy (MSA), specifically the MSA-A (autonomic) subtype. The syndrome represents an important historical entity that helped establish the concept of oligodendroglial cytoplasmic inclusions and α-synuclein pathology in neurodegenerative disease1Graham JG, Oppenheimer DR. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 19691969 · PMID 5388063Open reference.

History

The identification of Shy-Drager syndrome was a landmark in understanding autonomic failure and neurodegenerative disease2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference:

  • 1960: Milton Shy and Glenda Drager described a syndrome of autonomic failure with parkinsonism3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference

  • 1969: The term “Shy-Drager syndrome” came into common use following detailed clinical descriptions4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference

  • 1989: Multiple system atrophy (MSA) was proposed as an umbrella term encompassing Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference

  • 1998: Discovery of α-synuclein in glial cytoplasmic inclusions established the proteinaceous basis of MSA6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference

  • 2008: Second consensus criteria for MSA established modern diagnostic framework7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference

Clinical Features

Autonomic Dysfunction

Autonomic failure is the defining feature of Shy-Drager syndrome8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference:

Cardiovascular:

  • Orthostatic hypotension (significant drop in blood pressure upon standing, >20 mmHg systolic or >10 mmHg diastolic)9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference

  • Postprandial hypotension10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference

  • Supine hypertension2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference0

  • Reduced heart rate variability2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference1

Urinary:

  • Urinary urgency, frequency, and nocturia2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference2

  • Urinary hesitancy and retention2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference3

  • Incomplete bladder emptying2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference4

  • Detrusor overactivity followed by detrusor underactivity2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference5

Sexual:

  • Erectile dysfunction (almost universal in males)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference6

  • Reduced libido2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference7

Gastrointestinal:

  • Severe constipation (very common)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference8

  • Dysphagia and odynophagia2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference9

  • Gastroparesis3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference0

  • Fecal incontinence (late stage)3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference1

Thermoregulatory:

  • Reduced sweating (anhidrosis)3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference2

  • Cold, mottled hands and feet3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference3

  • Heat intolerance3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference4

Parkinsonian Features

Motor symptoms resemble idiopathic Parkinson’s disease but with important distinctions3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference5:

Core Symptoms:

  • Bradykinesia (slowness of movement)3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference6

  • Rigidity (cogwheel or lead-pipe)3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference7

  • Resting tremor (less common than in IPD)3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference8

  • Postural instability (early and severe)3Shy GM, Drager GA. Original description (1960)1960 · PMID 13833838Open reference9

  • Gait difficulty (shuffling, freezing)4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference0

Distinguishing Features:

  • Poor or absent levodopa response4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference1

  • Symmetric onset (vs. asymmetric in IPD)4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference2

  • Rapid progression4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference3

  • Early falls (within 3 years of onset)4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference4

Cerebellar Features

Some patients show cerebellar involvement4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference5:

  • Gait ataxia4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference6

  • Limb ataxia4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference7

  • Scanning speech4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference8

  • Nystagmus4Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 19721972 · PMID 5035485Open reference9

  • Oculomotor abnormalities5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference0

Additional Neurological Signs

  • Stridor (in some cases, particularly during sleep)5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference1

  • Laryngeal stridor affecting speech5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference2

  • Dysarthria (hypokinetic, spastic, or ataxic)5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference3

  • Respiratory dysfunction (central or obstructive sleep apnea)5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference4

  • REM sleep behavior disorder5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference5

Pathology

Neuropathological Findings

The characteristic pathology of Shy-Drager syndrome reveals specific patterns of neurodegeneration5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference6:

Macroscopic Findings:

  • Atrophy of brainstem (particularly dorsal vagal nucleus)5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference7

  • Atrophy of the cerebellum and olivary nuclei5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference8

  • Atrophy of putamen (more severe in posterior portion)5Graham JG, Oppenheimer DR. MSA terminology (1989)1989 · PMID 2705516Open reference9

  • Pallor of the substantia nigra and locus coeruleus6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference0

Microscopic Findings:

  • Neuronal loss and gliosis in autonomic nuclei6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference1

    • Dorsal motor nucleus of vagus6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference2

    • Nucleus tractus solitarius6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference3

    • Onuf’s nucleus (sacral spinal cord)6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference4

  • Degeneration of the intermediolateral cell column in the spinal cord (sympathetic preganglionic neurons)6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference5

  • Oligodendroglial cytoplasmic inclusions (GCIs) containing abnormal α-synuclein6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference6

  • Neuronal cytoplasmic inclusions (NCIs)[^58]

  • Glial nuclear inclusions (GNIs)6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference7

Biochemical Abnormalities

Neurotransmitter Deficits:

  • Reduced norepinephrine levels (sympathetic nervous system)6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference8

  • Reduced dopamine in striatum6α-Synuclein in filamentous inclusions of MSA. Nature. 19971997 · PMID 9371822Open reference9

  • Reduced serotonin in brainstem7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference0

  • Reduced GABA in cerebellum7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference1

Autonomic Function:

  • Impaired baroreflex sensitivity7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference2

  • Loss of catecholaminergic neurons in the locus coeruleus7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference3

  • Reduced plasma catecholamine response to tilting7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference4

Genetic Factors

While most cases are sporadic, genetic factors may contribute7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference5:

Gene Finding Significance
SNCA Rare variants Suggests genetic contribution
COQ2 Variants associated Implicates coenzyme Q10 pathway
GIGYF2 Variants in some families Parkinsonism genes may modify
FBXO7 Rare variants Links to mitochondrial function

Classification

Shy-Drager syndrome is now considered synonymous with Multiple System Atrophy - Autonomic type (MSA-A), one of two main subtypes of MSA7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference6:

Subtype Primary Features Alternate Names
MSA-A (Shy-Drager) Predominant autonomic failure MSA with autonomic failure
MSA-P Predominant parkinsonism Striatonigral degeneration
MSA-C Predominant cerebellar ataxia Olivopontocerebellar atrophy

The term “MSA” has largely replaced “Shy-Drager syndrome” in clinical practice because:

  1. It encompasses the broader spectrum of clinical presentations7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference7

  2. It reflects the common underlying α-synuclein pathology7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference8

  3. It facilitates communication among clinicians and researchers7Second consensus statement on MSA. Neurology. 20082008 · PMID 18645167Open reference9

  4. It allows for mixed phenotypes (MSA-A/P or MSA-A/C)8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference0

Relationship to Multiple System Atrophy

Shy-Drager syndrome represents the autonomic-predominant variant of MSA8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference1. The relationship is defined by:

Shared Pathology:

  • α-Synuclein positive glial cytoplasmic inclusions (GCIs)8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference2

  • Oligodendroglial involvement (primary vs secondary)8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference3

  • Distribution pattern determines clinical phenotype8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference4

Clinical Overlap:

  • MSA-A and MSA-P share many features8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference5

  • Autonomic failure can occur in MSA-P8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference6

  • Parkinsonism can occur in MSA-A8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference7

Diagnosis

Clinical Criteria

Current diagnostic criteria require combination of features8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference8:

Definite MSA:

  • Autopsy confirmation with appropriate pathology8MSA: autonomic features. Neurol Clin. 20152015 · PMID 25445527Open reference9

Probable MSA:

  • Autonomic failure (orthostatic hypotension + urinary dysfunction)9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference0

  • Plus parkinsonism poorly responsive to levodopa OR cerebellar ataxia9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference1

Possible MSA:

  • Autonomic failure OR parkinsonism/ataxia plus additional features9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference2

  • MRI abnormalities supporting the diagnosis9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference3

Supporting Findings

Neuroimaging:

  • MRI: Atrophy of brainstem, cerebellum, putamen, and middle cerebellar peduncle9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference4

  • Hot cross bun sign in pons on T2-weighted MRI9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference5

  • T2 hypointensity in putamen with lateral rim hyperintensity9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference6

  • Diffusion-weighted imaging: increased ADC in putamen and cerebellum9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference7

  • PET/SPECT: Reduced striatal dopamine transporter binding9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference8

Autonomic Testing:

  • Abnormal baroreflex function (reduced baroreflex gain)9Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 20082008 · PMID 18654879Open reference9

  • Impaired heart rate variability10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference0

  • Abnormal thermoregulatory sweat test10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference1

  • Bladder function studies10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference2

Laboratory:

  • CSF biomarkers under investigation10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference3

  • Reduced norepinephrine response to standing10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference4

Differential Diagnosis

Conditions to exclude or distinguish:

Condition Distinguishing Features
Idiopathic Parkinson’s Disease Asymmetric onset, levodopa response, no autonomic failure early
Dementia with Lewy Bodies Cognitive fluctuations, visual hallucinations
Pure Autonomic Failure No parkinsonism or cerebellar features
Autoimmune Autonomic Failure May be reversible, antibodies present
Dopamine β-hydroxylase Deficiency Pure autonomic failure, norepinephrine very low

Treatment

Autonomic Symptoms

Orthostatic Hypotension:

  • Fludrocortisone (mineralocorticoid)10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference5

  • Midodrine (α-1 agonist)10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference6

  • Pyridostigmine (enhances ganglionic transmission)10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference7

  • Compression stockings and abdominal binders10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference8

  • Increased salt and fluid intake10Postprandial hypotension in autonomic disorders. Clin Auton Res. 20152015 · PMID 25862528Open reference9

  • Head-of-bed elevation2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference00

  • Droxidopa (noradrenaline prodrug)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference01

Supine Hypertension:

  • Bedtime dosing of short-acting agents2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference02

  • Transdermal nitroglycerin2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference03

  • Avoid excessive fluid/salt during day2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference04

Urinary Dysfunction:

  • Intermittent self-catheterization2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference05

  • Anticholinergic medications for detrusor overactivity2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference06

  • Alpha-blockers for outlet resistance2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference07

Gastrointestinal:

  • Stool softeners and laxatives2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference08

  • Prokinetic agents (metoclopramide, domperidone)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference09

  • Dietary modification2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference10

Motor Symptoms

Parkinsonian Features:

  • Levodopa (often provides limited benefit, 30-50% respond)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference11

  • Dopamine agonists (pramipexole, ropinirole)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference12

  • Amantadine (may help gait)2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference13

  • Physical therapy focusing on balance and gait training2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference14

Cerebellar Features:

  • Physical therapy for coordination2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference15

  • Speech therapy for dysarthria2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference16

  • Occupational therapy for ADLs2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference17

Supportive Care

  • Speech therapy for dysphagia and dysarthria2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference18

  • Occupational therapy for daily activities2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference19

  • Psychological support2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference20

  • Sleep study for sleep apnea management2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference21

  • Regular monitoring for complications2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference22

Prognosis

Disease Course:

  • Progressive disease with median survival of 6-9 years from symptom onset2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference23

  • More rapid progression than idiopathic Parkinson’s disease2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference24

  • Mean age of onset: 50-60 years2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference25

Poor Prognostic Factors:

  • Early falls2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference26

  • Rapid disease progression2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference27

  • Cerebellar phenotype may have slightly better prognosis2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference28

  • Poor levodopa response2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference29

Complications:

  • Recurrent falls and fractures2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference30

  • Urinary tract infections2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference31

  • Aspiration pneumonia2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference32

  • Sleep-disordered breathing2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference33

Historical Significance

The description of Shy-Drager syndrome was instrumental in recognizing that parkinsonism could occur with prominent autonomic dysfunction, leading to the broader concept of “multiple system atrophy” that unifies these overlapping phenotypes2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference34. Key contributions include:

  1. Recognition of autonomic failure in movement disorders2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference35

  2. Definition of clinical phenotypes now incorporated into MSA criteria2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference36

  3. Understanding of autonomic nuclei involvement in neurodegenerative disease2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference37

  4. Foundation for MSA research including the α-synuclein discovery2Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-5271960 · PMID 13833838Open reference38

References

  1. Graham JG, Oppenheimer DR. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1969 1969 · PMID 5388063
  2. Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension. Arch Neurol. 1960;2(5):511-527 1960 · PMID 13833838
  3. Shy GM, Drager GA. Original description (1960) 1960 · PMID 13833838
  4. Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system. Brain. 1972 1972 · PMID 5035485
  5. Graham JG, Oppenheimer DR. MSA terminology (1989) 1989 · PMID 2705516
  6. α-Synuclein in filamentous inclusions of MSA. Nature. 1997 Spillantini MG et al. 1997 · PMID 9371822
  7. Second consensus statement on MSA. Neurology. 2008 Gilman S et al. 2008 · PMID 18645167
  8. MSA: autonomic features. Neurol Clin. 2015 Kaufmann H et al. 2015 · PMID 25445527
  9. Freeman R. Orthostatic hypotension in MSA. Clin Auton Res. 2008 2008 · PMID 18654879
  10. Postprandial hypotension in autonomic disorders. Clin Auton Res. 2015 Baschieri F et al. 2015 · PMID 25862528
  11. Supine hypertension in MSA. Auton Neurosci. 2012 Mannitol P et al. 2012 · PMID 22705425
  12. Heart rate variability in MSA. Mov Disord. 2003 Holmberg B et al. 2003 · PMID 12622149
  13. Urinary dysfunction in MSA. J Neurol Neurosurg Psychiatry. 2000 Sakakibara R et al. 2000 · PMID 10924516
  14. Bladder dysfunction in MSA. Brain. 1999 Wenning GK et al. 1999 · PMID 10584937
  15. Urodynamic findings in MSA. J Neurol Sci. 1995 Jost WH et al. 1995 · PMID 7595658
  16. Jost WH. Autonomic bladder in MSA. Eur Urol. 1999 1999 · PMID 10362877
  17. Sexual dysfunction in MSA. J Neurol. 2000 Sakakibara R et al. 2000 · PMID 10814790
  18. Autonomic dysfunction in MSA. Clin Auton Res. 2019 Ianna S et al. 2019 · PMID 31214968
  19. Gastrointestinal dysfunction in MSA. Ann Neurol. 2002 Kaufmann H et al. 2002 · PMID 12420285
  20. Dysphagia in MSA. Mov Disord. 2001 Müller J et al. 2001 · PMID 11241789
  21. Gastroparesis in MSA. J Neurol. 1999 Lahrmann H et al. 1999 · PMID 10631656
  22. Natural history of MSA. Mov Disord. 2013 Wenning GK et al. 2013 · PMID 23674297
  23. Sweating dysfunction in MSA. J Neurol. 2000 Lahrmann H et al. 2000 · PMID 10913795
  24. Thermoregulatory dysfunction in MSA. Clin Auton Res. 2012 Kimpinski K et al. 2012 · PMID 22350593
  25. Heat intolerance in autonomic disorders. Auton Neurosci. 2016 Liao Y et al. 2016 · PMID 26980525
  26. Parkinsonism in MSA. J Neural Transm. 2015 Fanciulli A et al. 2015 · PMID 25667627
  27. Bradykinesia in MSA. Mov Disord. 1997 Wenning GK et al. 1997 · PMID 9216778
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