Multiple System Atrophy Differential Diagnoses
- Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD more...
Diagnostic Considerations
MSA and Parkinson disease
Parkinsonian symptoms can occur frequently in multiple system atrophy (MSA). Approximately 10% of patients with a diagnosis of Parkinson disease are found to have MSA at autopsy. About 29-33% of patients with isolated, late-onset cerebellar ataxia will eventually develop MSA.
Clinical differentiation of Parkinson disease from MSA is extremely difficult. MSA is suggested by the following characteristics:
- Disability progresses rapidly
- Patients are poorly responsive to levodopa
- Autonomic features such as urinary retention or incontinence or orthostatic hypotension are pronounced
- Rigidity and bradykinesia are out of proportion to tremor
- Speech is affected severely (dysarthrophonia, severe dysarthria)
- Aspiration, inspiratory gasps, and stridor are present
Preliminary results of an ongoing comparison study indicate that autonomic indices are significantly more abnormal in MSA than in Parkinson disease.[16]
Wenning et al developed a predictive model based on established pathologic data from patients with MSA and Parkinson disease.[17] The model contains the following features:
- Poor response to levodopa
- Autonomic features
- Speech or bulbar dysfunction
- Absence of dementia
- Absence of levodopa-induced confusion
- Falls
Table 6 (below) further outlines some distinctive features of MSA and Parkinson disease.
Table 6. Differential Diagnosis of MSA and Parkinson Disease[18] (Open Table in a new window)
| Characteristic | MSA | Parkinson Disease |
| Response to chronic levodopa therapy* | Poor or unsustained motor response because of loss of postsynaptic dopamine receptors Initial improvement in 30% of patients with MSA, but 90% were unresponsive over a longer time; 50% develop levodopa-induced dyskinesia of orofacial and neck muscles | Good response |
| Effects on striatonigral transmission | Presynaptic and postsynaptic; dopaminergic cell bodies in substantia nigra and their terminals in striatum, as well as their striatal target cells, have reduced dopamine receptors | Presynaptic |
| Symmetry of movement disorder | Possibly asymmetrical | No data |
| Progression of symptoms | Rapid | Slow |
| Postural instability and falling** | Early Fast progression Worsen >20% of UPDRS scale** | Late Less progression (< 10%) |
| Progress of disability | Relatively fast disability; 30% decrease of activities of daily living in 1 year; 40% of patients in a wheelchair within 5 years (wheel chair sign) | Relatively slow disability |
| Abnormal speech | Severely affected speech in 30% of patients with MSA Dysarthrophonia and severe dysarthria are common | Less affected |
| Abnormal Respiration | Abnormal aspiration, inspiratory gasps, and stridor in 60% of patients with MSA Stridor caused by paralysis of vocal cord occurs especially at night but is also present during day | Less common |
| Lewy bodies (hyaline eosinophilic cytoplasmic neuronal inclusions) | Not present*** | Primarily in substantia nigra |
| Cytoplasmic inclusions (immunocytochemical reaction with antibodies to alpha synuclein) | Glial inclusions; argyrophilic cellular inclusions in oligodendrocytes | Absent |
| Thermoregulation, skin perfusion | Cold hands and decrease of warm-up after cold-pack stimulus | Normal |
| Caudate-putamen index of dopamine uptake (on positron emission tomography [PET] scanning) | Decreased in putamen and caudate | Decreased in putamen with smaller decrease in caudate |
| Growth hormone release with intravenous (IV) injection of clonidine | No release; dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit) | Increase of growth hormone, intact function |
| * A positive response to levodopa is defined as a significant improvement of motor features during 3 months’ application of escalating doses of levodopa with a peripheral decarboxylase inhibitor.[6] ** Postural instability as defined by item 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor examination).[6] *** Pakiam et al reported that patients with diffuse Lewy-body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling some proposed criteria for the striatonigral form of MSA.[19] | ||
MSA and PAF
Patients with MSA who present with only autonomic and urinary dysfunction can be incorrectly identified as having pure autonomic failure (PAF).
Bradbury and Eggleston first described PAF as idiopathic hypotension,[20] but current criteria imply failure of the autonomic nervous system in the absence of extrapyramidal, pyramidal, or cerebellar abnormalities. MSA is distinct from PAF.
The sympathetic and parasympathetic systems are centrally impaired in MSA, whereas the involvement is peripheral in PAF. The progression of MSA is faster than that of PAF, and the prognosis is poor.
Lewy bodies are common in PAF at many sites, even occasionally in the heart, but they are not present in MSA. (Exception: In 1999, Pakiam et al reported 1 case in which a patient with diffuse Lewy-body disease presented with parkinsonism and prominent autonomic dysfunction, fulfilling proposed criteria for the striatonigral form of MSA.[19] ) Instead of Lewy bodies, patients with MSA have oligodendroglial cytoplasmic inclusions. Low plasma norepinephrine levels also usually indicate PAF.
Table 7, below, summarizes the distinctive features of MSA and PAF. Early (eg, years 1-2) in the disease process, the distinction may be difficult, but distinguishing findings are usually evident during follow-up care.
Table 7. Differential Diagnosis of MSA and PAF (Open Table in a new window)
| Characteristic | MSA | Pure Autonomic Failure |
| CNS involvement | Multiple involvement | Unaffected |
| Site of lesion | Mainly preganglionic, central; degeneration of intermediolateral cell columns; ganglionic neurons relatively intact | Mainly postganglionic; loss of ganglionic neurons |
| Progression | Fast; median survival 6.5-9.5 years | Slow; some patients survive >10-30 years |
| Prognosis | Poor | Good |
| Extrapyramidal involvement | Common | Not present |
| Cerebellar involvement | Common | Not present |
| Gastrointestinal symptoms | Uncommon | Absent, except constipation |
| Plasma supine norepinephrine level | Normal | Reduced |
| Antidiuretic hormone (ADH) response to tilt | Impaired because of catecholaminergic denervation of hypothalamus (but normal ADH response to osmotic stimuli) | Maintained |
| Adrenocorticotropic hormone and beta-endorphin response to hypoglycemia | Impaired because of central cholinergic dysfunction or dysfunction of adrenergic input to paraventricular nucleus | Normal |
| Growth hormone release with clonidine IV injection | No release, dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit) | Increase of growth hormone; intact function |
| Substance P, catecholamine, 5-HT, and acetylcholine markers in cerebrospinal fluid | Decreased levels | No data |
| Lewy bodies | Mostly absent | Present in autonomic neurons |
| BP response to oral water intake | Increased | Increased but variable |
| BP response to ganglionic blockade | Profound decrease | Modest decrease |
MSA and PSP
Progressive supranuclear palsy (PSP), also known as the Steele-Richardson-Olszewski syndrome, is characterized by neuronal degeneration and neurofibrillary tangles affecting the pons and midbrain. The clinical picture of PSP may be similar to that of MSA. Cardiovascular autonomic dysfunction is an exclusionary feature in the diagnosis of PSP.[21]
Analysis of the horizontal and vertical eye movements may help to distinguish PSP from MSA. Patients with PSP demonstrate slowing of saccades, which is not the situation in MSA. The trajectories of saccades made to diagonal target jumps are deviated toward the horizontal plane; because of the vertical hypometria, this is more pronounced in patients with PSP than in those with MSA. The patient with PSP may be prone to falls because of impaired downward gaze.
Persons with PSP and those with MSA demonstrate different responses to pharmacologic and physiologic stimuli in autonomic function tests.[21]
MSA and corticobasal ganglionic degeneration
Corticobasal ganglionic degeneration is pathologically characterized by enlarged, achromatic neurons in cortical areas and nigral and striatal neuronal degeneration. The onset is typically unilateral, with marked rigidity-dystonia of the involved arm; this differs from MSA.
Cortical signs of apraxia, alien-limb phenomena, cortical sensory loss, and cortical reflex myoclonus are helpful to distinguish between corticobasal ganglionic degeneration and MSA.
MSA and cerebrovascular syndromes
Cerebrovascular syndromes (eg, multi-infarct lesions in the brain) may demonstrate features similar to those of MSA. Dementia is not common in MSA. Brain MRI helps to exclude cerebrovascular diseases.
Other conditions
Other disorders to consider in the differential diagnosis of MSA include the following:
- Fragile X-associated tremor/ataxia syndrome (FXTAS)
- Mitochondrial cytopathies
- Paraneoplastic Disease
- Neurosarcoidosis
Differential Diagnoses
- Chorea in Adults
- Cortical Basal Ganglionic Degeneration
- Fragile X-associated tremor/ataxia syndrome (FXTAS)
- Hallervorden-Spatz Disease
- Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes
- Mitochondrial cytopathies
- Multiple Sclerosis
- Neuroacanthocytosis
- Neuroacanthocytosis Syndromes
- Neurosarcoidosis
- Neurosyphilis
- Olivopontocerebellar Atrophy
- Paraneoplastic Disease
- Parkinson Disease
- Parkinson Disease in Young Adults
- Parkinson-Plus Syndromes
- Pelizaeus-Merzbacher Disease
Wenning GK, Jellinger KA. The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol. 2005;109:129-40. [Medline].
Gilman S, Low P, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin Auton Res. Dec 1998;8(6):359-62. [Medline].
Ubhi K, Low P, Masliah E. Multiple system atrophy: a clinical and neuropathological perspective. Trends Neurosci. Nov 2011;34(11):581-90. [Medline]. [Full Text].
Geser F, Wenning GK, Seppi K. Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG). Mov Disord. Feb 2006;21(2):179-86. [Medline].
Wenning GK, Tison F, Seppi K, et al. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord. Dec 2004;19(12):1391-402. [Medline].
Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. Aug 26 2008;71(9):670-6. [Medline].
Robertson D, Biaggioni I, Burnstock, Low, PA, Paton JFR. Primer on the Autonomic Nervous System. San Diego, Calif: Elsevier; 2012:1-702.
Nee LE, Gomez MR, Dambrosia J, et al. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res. Mar 1991;1(1):9-13. [Medline].
Hara K, Momose Y, Tokiguchi S, Shimohata M, Terajima K, Onodera O. Multiplex families with multiple system atrophy. Arch Neurol. Apr 2007;64(4):545-51. [Medline].
Nirenberg MJ, Libien J, Vonsattel JP, Fahn S. Multiple system atrophy in a patient with the spinocerebellar ataxia 3 gene mutation. Mov Disord. Jan 15 2007;22(2):251-4. [Medline].
Benarroch EE, Schmeichel AM, Dugger BN, Sandroni P, Parisi JE, Low PA. Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia. Neurology. Jul 14 2009;73(2):106-12. [Medline].
Papatsoris AG, Papapetropoulos S, Singer C, Deliveliotis C. Urinary and erectile dysfunction in multiple system atrophy (MSA). Neurourol Urodyn. 2008;27(1):22-7. [Medline].
Köllensperger M, Stampfer-Kountchev M, Seppi K, Geser F, Frick C, Del Sorbo F. Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment. Eur J Neurol. Jan 2007;14(1):66-72. [Medline].
Lahrmann H, Cortelli P, Hilz M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol. Sep 2006;13(9):930-6. [Medline].
Takamori M, Hirayama M, Kobayashi R. Altered venous capacitance as a cause of postprandial hypotension in multiple system atrophy. Clin Auton Res. Feb 2007;17(1):20-5. [Medline].
Lipp A, Sandroni P, Ahlskog JE, Fealey RD, Kimpinski K, Iodice V, et al. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol. Jun 2009;66(6):742-50. [Medline].
Wenning GK, Ben-Shlomo Y, Magalhaes M, et al. Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry. Feb 1995;58(2):160-6. [Medline].
Iodice V, Lipp A, Ahlskog JE, Sandroni P, et al. Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests. J Neurol Neurosurg Psychiatry. Jan 6 2012;[Medline].
Pakiam AS, Bergeron C, Lang AE. Diffuse Lewy body disease presenting as multiple system atrophy. Can J Neurol Sci. May 1999;26(2):127-31. [Medline].
Bradbury S, Eggleston C. Postural hypotension: a report of three cases. Am Heart J. 1925;1:73-85.
Kimber J, Mathias CJ, Lees AJ, et al. Physiological, pharmacological and neurohormonal assessment of autonomic function in progressive supranuclear palsy. Brain. Jul 2000;123 ( Pt 7):1422-30. [Medline].
Nagayama H, Hamamoto M, Ueda M, Nagashima J, Katayama Y. Reliability of MIBG myocardial scintigraphy in the diagnosis of Parkinson's disease. J Neurol Neurosurg Psychiatry. Feb 2005;76(2):249-51. [Medline].
Kikuchi A, Baba T, Hasegawa T, Sugeno N, Konno M, Takeda A. Differentiating Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test. Parkinsonism Relat Disord. Nov 2011;17(9):698-700. [Medline].
Tsukamoto K, Matsusue E, Kanasaki Y, Kakite S, Fujii S, Kaminou T, et al. Significance of apparent diffusion coefficient measurement for the differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and Parkinson's disease: evaluation by 3.0-T MR imaging. Neuroradiology. Jan 25 2012;[Medline].
Massano J, Costa F, Nadais G. Teaching neuroImage: MRI in multiple system atrophy: "hot cross bun" sign and hyperintense rim bordering the putamina. Neurology. Oct 7 2008;71(15):e38. [Medline].
Pellecchia MT, Barone P, Mollica C, Salvatore E, Ianniciello M, Longo K, et al. Diffusion-weighted imaging in multiple system atrophy: a comparison between clinical subtypes. Mov Disord. Apr 15 2009;24(5):689-96. [Medline].
Lewis SJ, Pavese N, Rivero-Bosch M, et al. Brain monoamine systems in multiple system atrophy: A positron emission tomography study. Neurobiol Dis. Jan 12 2012;[Medline].
Sharabi Y, Eldadah B, Li ST. Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes. Clin Neuropharmacol. May-Jun 2006;29(3):97-105. [Medline].
Shibao C, Gamboa A, Abraham R. Clonidine for the treatment of supine hypertension and pressure natriuresis in autonomic failure. Hypertension. Mar 2006;47(3):522-6. [Medline].
- Table 1. Historical Milestones in the Definition of Terms for MSA
- Table 2a. Main Features for the Diagnosis of MSA
- Table 2b. Additional Features for the Diagnosis of Possible MSA*
- Table 3. Characteristics That Do Not Support the Diagnosis of MSA
- Table 4. Diagnostic Categories of MSA
- Table 5. Clinicopathologic Correlations
- Table 6. Differential Diagnosis of MSA and Parkinson Disease[18]
- Table 7. Differential Diagnosis of MSA and PAF
- Table 8. Differences Between GCIs in MSA and Other Pathologic Inclusions and Structures
- Table 9. Drugs Used to Manage Orthostatic Hypotension in MSA
| Term | Period | Authors | Comments |
| Olivopontocerebellar atrophy (OPCA) | 1900 | Dejerine and Thomas | Introduction of the term olivopontocerebellar atrophy |
| Orthostatic hypotension (OH) | 1925 | Bradbury and Eggleston | Introduction of autonomic failure as a clinical syndrome |
| Shy-Drager syndrome (SDS) | 1960 | Shy and Drager | Origin of this term as a neuropathologic entity with parkinsonism and autonomic failure with OH |
| Striatonigral degeneration (SND) | 1960 | Van der Eecken et al | Description of SND |
| Multiple system atrophy (MSA) | 1969 | Graham and Oppenheimer | Introduction of the term MSA, which represents SDS, SND, and OPCA as 1 entity |
| Glial cytoplasmic inclusions (GCIs) | 1989 | Papp et al, Matsuo et al | Discovery of GCIs as hallmark of MSA |
| Alpha-synuclein inclusion | 1998 | Spillantini et al, Wakabayashi et al | Alpha-synuclein immunostaining as a sensitive marker of MSA |
| MSA classification | 1996-1999 | Consensus Committee | Classification of MSA based on clinical domains and features and neuropathology |
| Unified MSA Rating Scale (UMSARS) | 2003 | European MSA Study Group | Unified MSA Rating Scale as a standard to define MSA symptoms[4, 5] |
| Second consensus for MSA | 2007 | Consensus Committee | New definition of MSA with simplified criteria |
| Clinical Domain | Feature | Comment |
| Autonomic dysfunction | Severe orthostatic hypotension (OH)
| OH is defined as blood pressure fall by at least 30mm Hg systolic and 15mm Hg diastolic within 3 minutes of standing from a previous 3-minute interval in the recumbent position.** |
| Urogenital dysfunction | Urinary incontinence (UI) or incomplete bladder emptying | UI is defined as persistent, involuntary, partial or total bladder emptying. ED usually occurs before symptomatic OH.*** |
| Erectile dysfunction (ED) in men | ||
| Parkinsonian features (87% incidence *) | Bradykinesia (BK) | BK is slowness of voluntary movement with progressive reduction in speed and amplitude during repetitive actions. PI not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction. |
| Rigidity | ||
| Postural instability (PI) | ||
| Tremor - Postural, resting, or both | ||
| Cerebellar dysfunction (54% incidence *) | Gait ataxia (GA) | GA is a wide-based stance with steps of irregular length and direction. Sustained gaze-evoked nystagmus |
| Ataxic dysarthria | ||
| Limb ataxia | ||
| Oculomotor dysfunction | ||
| *Incidence of clinical features recorded during the lifetimes of 203 patients (Gilman et al[2] ). **OH caused by drugs, food, temperature, deconditioning, or diabetes are excluded. ***ED does not count in the definition of onset of disease, because it is a general feature in older people. | ||
| Category | Additional Features |
| Possible MSA-P Possible MSA-C |
|
| Possible MSA-P |
|
| Possible MSA-C |
|
| *Modified from second consensus[6] | |
| Procedure | Nonsupporting Features |
| History taking |
|
| Physical examination |
|
| Laboratory study |
|
| Category | Definition |
| Possible MSA | A sporadic, progressive, adult (>30y) with onset disease* characterized by the following:
|
| Probable MSA | A sporadic, progressive, adult (>30y) with onset disease* characterized by the following:
|
| Definitive MSA | A sporadic, progressive, adult (>30y) with onset disease pathologically confirmed by presence of high density GCIs in association with degenerative changes in striatonigral and olivopontocerebellar pathways |
| *Disease onset is defined as the initial presentation of any parkinsonian or cerebellar motor problems or autonomic features (except erectile dysfunction). | |
| Clinical Symptom | Pathologic Findings and Location of Damage or Cell Loss |
| Orthostatic hypotension | Primary preganglionic damage of intermediolateral cell columns |
| Urinary incontinence (not retention) | Preganglionic cell loss in spinal cord (intermediolateral cell columns), related to detrusor hyperreflexia caused mainly by loss of inhibitory input to pontine micturition center (rather than to external urethral sphincter denervation alone) |
| Urinary retention caused by detrusor atonia | Sacral intermediolateral cell columns |
| Cerebellar ataxia | Cell loss in inferior olives, pontine nuclei, and cerebellar cortex |
| Pyramidal signs | Pyramidal tract demyelination |
| Extensor plantar response | Pyramidal tract lesion |
| Hyperreflexia | Pyramidal tract lesion |
| Motor abnormalities | GCIs in cortical motor areas or basal ganglia |
| Akinesia | Putamen, globus pallidus |
| Rigidity | Putaminal (not nigral) damage |
| Limb and gait ataxia | Inferior olives, basis pontis |
| Decreased or absent levodopa responsiveness | Striatal cell loss, loss of D1 and D2 receptors in striatum or impaired functional coupling of D1 and D2 receptors |
| Nystagmus | Inferior olives, pontine nuclei |
| Dysarthria | Pontine nuclei |
| Laryngeal stridor | Severe cell loss in nucleus ambiguus or biochemical defect causing atrophy of posterior cricoarytenoid muscles |
| Excessive daytime sleepiness | Loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons[11] |
| Adapted from Wenning et al and other sources. | |
| Characteristic | MSA | Parkinson Disease |
| Response to chronic levodopa therapy* | Poor or unsustained motor response because of loss of postsynaptic dopamine receptors Initial improvement in 30% of patients with MSA, but 90% were unresponsive over a longer time; 50% develop levodopa-induced dyskinesia of orofacial and neck muscles | Good response |
| Effects on striatonigral transmission | Presynaptic and postsynaptic; dopaminergic cell bodies in substantia nigra and their terminals in striatum, as well as their striatal target cells, have reduced dopamine receptors | Presynaptic |
| Symmetry of movement disorder | Possibly asymmetrical | No data |
| Progression of symptoms | Rapid | Slow |
| Postural instability and falling** | Early Fast progression Worsen >20% of UPDRS scale** | Late Less progression (< 10%) |
| Progress of disability | Relatively fast disability; 30% decrease of activities of daily living in 1 year; 40% of patients in a wheelchair within 5 years (wheel chair sign) | Relatively slow disability |
| Abnormal speech | Severely affected speech in 30% of patients with MSA Dysarthrophonia and severe dysarthria are common | Less affected |
| Abnormal Respiration | Abnormal aspiration, inspiratory gasps, and stridor in 60% of patients with MSA Stridor caused by paralysis of vocal cord occurs especially at night but is also present during day | Less common |
| Lewy bodies (hyaline eosinophilic cytoplasmic neuronal inclusions) | Not present*** | Primarily in substantia nigra |
| Cytoplasmic inclusions (immunocytochemical reaction with antibodies to alpha synuclein) | Glial inclusions; argyrophilic cellular inclusions in oligodendrocytes | Absent |
| Thermoregulation, skin perfusion | Cold hands and decrease of warm-up after cold-pack stimulus | Normal |
| Caudate-putamen index of dopamine uptake (on positron emission tomography [PET] scanning) | Decreased in putamen and caudate | Decreased in putamen with smaller decrease in caudate |
| Growth hormone release with intravenous (IV) injection of clonidine | No release; dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit) | Increase of growth hormone, intact function |
| * A positive response to levodopa is defined as a significant improvement of motor features during 3 months’ application of escalating doses of levodopa with a peripheral decarboxylase inhibitor.[6] ** Postural instability as defined by item 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor examination).[6] *** Pakiam et al reported that patients with diffuse Lewy-body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling some proposed criteria for the striatonigral form of MSA.[19] | ||
| Characteristic | MSA | Pure Autonomic Failure |
| CNS involvement | Multiple involvement | Unaffected |
| Site of lesion | Mainly preganglionic, central; degeneration of intermediolateral cell columns; ganglionic neurons relatively intact | Mainly postganglionic; loss of ganglionic neurons |
| Progression | Fast; median survival 6.5-9.5 years | Slow; some patients survive >10-30 years |
| Prognosis | Poor | Good |
| Extrapyramidal involvement | Common | Not present |
| Cerebellar involvement | Common | Not present |
| Gastrointestinal symptoms | Uncommon | Absent, except constipation |
| Plasma supine norepinephrine level | Normal | Reduced |
| Antidiuretic hormone (ADH) response to tilt | Impaired because of catecholaminergic denervation of hypothalamus (but normal ADH response to osmotic stimuli) | Maintained |
| Adrenocorticotropic hormone and beta-endorphin response to hypoglycemia | Impaired because of central cholinergic dysfunction or dysfunction of adrenergic input to paraventricular nucleus | Normal |
| Growth hormone release with clonidine IV injection | No release, dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit) | Increase of growth hormone; intact function |
| Substance P, catecholamine, 5-HT, and acetylcholine markers in cerebrospinal fluid | Decreased levels | No data |
| Lewy bodies | Mostly absent | Present in autonomic neurons |
| BP response to oral water intake | Increased | Increased but variable |
| BP response to ganglionic blockade | Profound decrease | Modest decrease |
| GCIs in MSA | Lewy Bodies in Parkinson Disease | Neurofibrillary Pathology in Alzheimer Disease | Glial Lesions in Corticobasal and Progressive Supranuclear Palsy | |
| Shape | Sickle shaped to flame shaped to ovoid, various neurofibrillary tangles | Target-shaped inclusions | Tangles | Tufted astrocytes, coiled bodies |
| Membrane | No limiting membrane; tubular profiles and electrodense granules | Present | Present | Present |
| Ultrastructure | Loosely aggregated filaments | No data | No data | Astrocytic plaques |
| Immunocytochemistry | Ubiquitin positive, alpha-B-crystallin (synuclein) positive, alpha- and beta-tubulin positive, tau-protein positive | Hyaline eosinophilic cytoplasmic neuronal inclusions, ubiquitin | No data | Absence of phosphorylated tau |
| Localization | In oligodendroglial cells and neurons | In neuronal cells and oligodendroglial cells | No data | No data |
| Class | Drug | Description or Mechanism |
| Corticosteroids | Fludrocortisone (Florinef) | Mineralocorticoid; sodium retention, primarily in extravascular compartment, causes tissue edema to venous capacitance bed in lower extremity. With this edema, venous bed accommodates decreased volume of blood in an upright posture (high doses, late effect); increases sensitivity to norepinephrine (even with small doses) |
| Sympathomimetic amines | Midodrine | Alpha1-adrenoreceptor agonist acts directly on vasculature, causes venous and arteriolar vasoconstriction |
| Droxidopa (investigational) | Droxidopa is a synthetic precursor of norepinephrine. It acts by conversion to norepinephrine in the body. | |
| Recombinant erythropoietin (EPO) | Epoetin alfa | Increases sensitivity to pressor effects of angiotensin II; increases plasma endothelin level; increases cytosolic free calcium in vascular smooth muscle; increases intravascular volume |
| NSAIDs | Indomethacin, ibuprofen | Inhibition of vasodilator prostaglandins proposed but not proven |
| Antihistamines | Diphenhydramine, cimetidine | Reduce vasodilatation caused by histamine release |
| Somatostatin analogs | Octreotide | Reduce splanchnic capacitance |
| Vasopressin agonists | Desmopressin (DDAVP) | Vasopressin analogs; no effect on V1 receptors, which are responsible for vasopressin-induced vasoconstriction; acts on V2 receptors on renal tubuli, which are responsible for antidiuretic effect; prevents nocturnal diuresis, raises BP in morning |
| Other sympathomimetics | Yohimbine | Alpha2-adrenoreceptor antagonist |
| Caffeine | Adenosine receptor antagonist |
Print
