Multiple System Atrophy Treatment & Management

  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Apr 6, 2012
 

Approach Considerations

The cause of multiple system atrophy (MSA) remains unknown, and no current therapy can reverse or halt progression of the disease. The extrapyramidal and cerebellar aspects of the disease are debilitating and difficult to treat.

Nonpharmacologic treatment

  • Constipation - A high-fiber diet, bulk laxative, lactulose, and suppositories can prevent constipation
  • Stridor - Speech therapy is often useful to improve swallowing and communication
  • Deconditioning - Physical therapy and an aquatic exercise program (hypotension does not occur while patients are in water) prevent physical deconditioning of the patient unless the movement disorder aspect of the illness so impairs balance that this is not advisable
  • Urinary incontinence - Intermittent self catheterization or suprapubic or urethral catheterization can improve symptoms of urinary incontinence
  • Falls - As the disease progresses, the risk of falls increases; proper gait instruction and precautions are critical to prevent falls and resultant injury

Pharmacologic treatment

Drug therapy is directed mainly toward alleviation of symptoms of the movement disorder and orthostatic hypotension. Urinary incontinence, constipation, erectile dysfunction, and supine hypertension can also be addressed through pharmacologic therapy. (See Table 9.)

Surgical care

An atrial pacemaker may be used in patients with profound bradycardia in addition to orthostatic hypotension as a means of preventing the hypotension. However, this treatment is rarely undertaken and is rarely helpful.

Consider tracheostomy with the utmost care for intermittent respiratory stridor. Cricopharyngeal myotomy or gastrostomy has been used in patients with severe dysphagia, but its value is uncertain.

Consultations

Physical therapists, occupational therapists, speech therapists, and social workers can offer considerable practical help.

Diet

An essentially normal diet is recommended, with the following guidelines:

  • Increased salt and fluid intake maintains plasma volume
  • Small, frequent meals may help patients for whom postprandial hypotension is a significant problem
  • A high-fiber diet, bulk laxatives, and suppositories prevent constipation

Activity

Exercise of muscles of the lower extremities and abdomen, water aerobics at hip level (not swimming, as it causes polyuria), and postural training, in combination with drug therapy, are useful.

Inpatient evaluation and tailoring of therapy are often important. However, if patients are restricted to bedrest, their functional mobility can decrease rapidly. Therefore, initiate physical therapy if the patient must remain in the hospital for longer than 2 days.

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Nonpharmacologic Treatment of Hypotension and Hypertension

Orthostatic hypotension

The earliest symptom that brings patients to medical attention usually is orthostatic hypotension. Orthostatic hypotension leads to curtailing of physical activity, with all of the problems of deconditioning that consequently occur. Without an adequate upright BP, keeping patients active and on an exercise regimen is extremely difficult; therefore, management of orthostatic hypotension is one of the major tasks in the treatment of patients with MSA.

Mechanical maneuvers, such as leg-crossing, squatting, abdominal compression, bending forward, and placing 1 foot on a chair, can be effective in preventing episodes of orthostatic hypotension. Wearing an external support garment that comes to the waist improves venous return and preload to the heart during standing but loses effectiveness if the patient also wears it while supine. Increased salt and fluid intake and tilted sleeping with the head elevated increase the circulatory plasma volume.

Postprandial hypotension

Small, frequent meals attenuate BP drop after eating. Intake of water half an hour before meals or drinking coffee can counteract postprandial hypotension.

Supine hypertension

The management of patients with orthostatic hypotension and supine hypertension can be challenging, but adequate BP control is often achieved with the following treatment strategy:

  • Use of over-the-counter medication with pressor effects
  • Avoidance of fluid intake at bedtime
  • Not using elastic stockings when supine
  • Not using pressor agents before bedtime
  • Raising the head of the bed 6-9 inches
  • Resting on a semirecumbent chair with feet on the floor during the day
  • Snacking before bedtime
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Contributor Information and Disclosures
Author

André Diedrich, MD, PhD  Research Associate Professor of Medicine and Biomedical Engineering, Autonomic Dysfunction Center, Vanderbilt University School of Medicine

André Diedrich, MD, PhD is a member of the following medical societies: American Autonomic Society and American Heart Association

Disclosure: Nothing to disclose.

Coauthor(s)

David Robertson, MD  Director, Clinical and Translational Research Center, Vanderbilt Institute for Clinical and Translational Research, Principal Investigator, Autonomic Rare Disease Clinical Research Consortium, Elton Yates Professor of Medicine, Pharmacology, and Neurology, Vanderbilt University School of Medicine

David Robertson, MD is a member of the following medical societies: American Heart Association and Association of American Physicians

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Additional Contributors

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Wenning GK, Jellinger KA. The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol. 2005;109:129-40. [Medline].

  2. 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].

  3. 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].

  4. 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].

  5. 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].

  6. 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].

  7. Robertson D, Biaggioni I, Burnstock, Low, PA, Paton JFR. Primer on the Autonomic Nervous System. San Diego, Calif: Elsevier; 2012:1-702.

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. Bradbury S, Eggleston C. Postural hypotension: a report of three cases. Am Heart J. 1925;1:73-85.

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

  27. 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].

  28. Sharabi Y, Eldadah B, Li ST. Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes. Clin Neuropharmacol. May-Jun 2006;29(3):97-105. [Medline].

  29. 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].

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Table 1. Historical Milestones in the Definition of Terms for MSA
TermPeriodAuthorsComments
Olivopontocerebellar atrophy (OPCA)1900Dejerine and ThomasIntroduction of the term olivopontocerebellar atrophy
Orthostatic hypotension (OH)1925Bradbury and EgglestonIntroduction of autonomic failure as a clinical syndrome
Shy-Drager syndrome (SDS)1960Shy and DragerOrigin of this term as a neuropathologic entity with parkinsonism and autonomic failure with OH
Striatonigral degeneration (SND)1960Van der Eecken et alDescription of SND
Multiple system atrophy (MSA)1969Graham and OppenheimerIntroduction of the term MSA, which represents SDS, SND, and OPCA as 1 entity
Glial cytoplasmic inclusions (GCIs)1989Papp et al, Matsuo et alDiscovery of GCIs as hallmark of MSA
Alpha-synuclein inclusion1998Spillantini et al, Wakabayashi et alAlpha-synuclein immunostaining as a sensitive marker of MSA
MSA classification1996-1999Consensus CommitteeClassification of MSA based on clinical domains and features and neuropathology
Unified MSA Rating Scale (UMSARS)2003European MSA Study GroupUnified MSA Rating Scale as a standard to define MSA symptoms[4, 5]
Second consensus for MSA2007Consensus CommitteeNew definition of MSA with simplified criteria
Table 2a. Main Features for the Diagnosis of MSA
Clinical DomainFeatureComment
Autonomic



dysfunction



Severe orthostatic hypotension (OH)
  • Asymptomatic
  • Symptomatic
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 dysfunctionUrinary incontinence (UI) or incomplete bladder emptyingUI 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.



Table 2b. Additional Features for the Diagnosis of Possible MSA*
CategoryAdditional Features
Possible



MSA-P



Possible



MSA-C



  • Babinski sign with hyperreflexia
  • Stridor
Possible



MSA-P



  • Rapidly progressive parkinsonism
  • Poor response to levodopa
  • Postural instability within 3 years of motor onset
  • Gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
  • Dysphagia within 5 years of motor onset
  • Atrophy on magnetic resonance imaging (MRI) of putamen, middle cerebellar peduncle, pons, or cerebellum
  • Hypometabolism on 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scanning in putamen, brainstem, or cerebellum
Possible



MSA-C



  • Parkinsonism (bradykinesia and rigidity)
  • Atrophy on MRI of the putamen, middle cerebellar peduncle, or pons
  • Hypometabolism on FDG-PET in the putamen
  • Presynaptic striatonigral dopaminergic denervation on single-photon emission computed tomography (SPECT) or PET scanning
*Modified from second consensus[6]
Table 3. Characteristics That Do Not Support the Diagnosis of MSA
ProcedureNonsupporting Features
History taking
  • Symptomatic onset at < 30 years
  • Onset after age 75 years
  • Family history of ataxia or parkinsonism
  • Systemic diseases or other identifiable causes for features listed in Table 2a
  • Hallucinations unrelated to medication
  • Dementia
Physical examination
  • Classic parkinsonian pill-rolling rest tremor
  • Clinically significant neuropathy
  • Prominent slowing of vertical saccades or vertical supranuclear gaze palsy
  • Evidence of focal cortical dysfunction, such as aphasia, alien limb syndrome, and parietal dysfunction
Laboratory study
  • Metabolic, molecular genetic, and imaging evidence of alternative cause of features listed in Table 2a
  • White matter lesions suggesting multiple sclerosis
Table 4. Diagnostic Categories of MSA
CategoryDefinition
Possible MSAA sporadic, progressive, adult (>30y) with onset disease* characterized by the following:
  • Parkinsonism or cerebellar syndrome
  • At least 1 feature of autonomic or urogenital dysfunction
  • At least 1 of the additional features from Table 2b
Probable MSAA sporadic, progressive, adult (>30y) with onset disease* characterized by the following:
  • Autonomic failure involving urinary dysfunction
  • Poorly levodopa-responsive parkinsonism or cerebellar dysfunction
Definitive MSAA 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).
Table 5. Clinicopathologic Correlations
Clinical SymptomPathologic Findings and Location of Damage or Cell Loss
Orthostatic hypotensionPrimary 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 atoniaSacral intermediolateral cell columns
Cerebellar ataxiaCell loss in inferior olives, pontine nuclei, and cerebellar cortex
Pyramidal signsPyramidal tract demyelination
Extensor plantar responsePyramidal tract lesion
HyperreflexiaPyramidal tract lesion
Motor abnormalitiesGCIs in cortical motor areas or basal ganglia
AkinesiaPutamen, globus pallidus
RigidityPutaminal (not nigral) damage
Limb and gait ataxiaInferior olives, basis pontis
Decreased or absent levodopa responsivenessStriatal cell loss, loss of D1 and D2 receptors in striatum or impaired functional coupling of D1 and D2 receptors
NystagmusInferior olives, pontine nuclei
DysarthriaPontine nuclei
Laryngeal stridorSevere cell loss in nucleus ambiguus or biochemical defect causing atrophy of posterior cricoarytenoid muscles
Excessive daytime sleepinessLoss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons[11]
Adapted from Wenning et al and other sources.
Table 6. Differential Diagnosis of MSA and Parkinson Disease[18]
CharacteristicMSAParkinson 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 transmissionPresynaptic 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 disorderPossibly asymmetricalNo data
Progression of symptomsRapidSlow
Postural instability and falling**Early



Fast progression



Worsen >20% of UPDRS scale**



Late



Less progression (< 10%)



Progress of disabilityRelatively 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 speechSeverely affected speech in 30% of patients with MSA



Dysarthrophonia and severe dysarthria are common



Less affected
Abnormal RespirationAbnormal 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 oligodendrocytesAbsent
Thermoregulation, skin perfusionCold hands and decrease of warm-up after cold-pack stimulusNormal
Caudate-putamen index of dopamine uptake (on positron emission tomography [PET] scanning)Decreased in putamen and caudateDecreased in putamen with smaller decrease in caudate
Growth hormone release with intravenous (IV) injection of clonidineNo 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]



Table 7. Differential Diagnosis of MSA and PAF
CharacteristicMSAPure Autonomic Failure
CNS involvementMultiple involvementUnaffected
Site of lesionMainly preganglionic, central; degeneration of intermediolateral cell columns; ganglionic neurons relatively intactMainly postganglionic; loss of ganglionic neurons
ProgressionFast; median survival 6.5-9.5 yearsSlow; some patients survive >10-30 years
PrognosisPoorGood
Extrapyramidal involvementCommonNot present
Cerebellar involvementCommonNot present
Gastrointestinal symptomsUncommonAbsent, except constipation
Plasma supine norepinephrine levelNormalReduced
Antidiuretic hormone (ADH) response to tiltImpaired because of catecholaminergic denervation of hypothalamus (but normal ADH response to osmotic stimuli)Maintained
Adrenocorticotropic hormone and beta-endorphin response to hypoglycemiaImpaired because of central cholinergic dysfunction or dysfunction of adrenergic input to paraventricular nucleusNormal
Growth hormone release with clonidine IV injectionNo 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 fluidDecreased levelsNo data
Lewy bodiesMostly absentPresent in autonomic neurons
BP response to oral water intakeIncreasedIncreased but variable
BP response to ganglionic blockadeProfound decreaseModest decrease
Table 8. Differences Between GCIs in MSA and Other Pathologic Inclusions and Structures
GCIs in MSALewy Bodies in Parkinson DiseaseNeurofibrillary Pathology in Alzheimer DiseaseGlial Lesions in Corticobasal and Progressive Supranuclear Palsy
ShapeSickle shaped to flame shaped to ovoid, various neurofibrillary tanglesTarget-shaped inclusionsTanglesTufted astrocytes, coiled bodies
MembraneNo limiting membrane; tubular profiles and electrodense granulesPresentPresentPresent
UltrastructureLoosely aggregated filamentsNo dataNo dataAstrocytic plaques
ImmunocytochemistryUbiquitin positive, alpha-B-crystallin (synuclein) positive, alpha- and beta-tubulin positive, tau-protein positiveHyaline eosinophilic cytoplasmic neuronal inclusions, ubiquitinNo dataAbsence of phosphorylated tau
LocalizationIn oligodendroglial cells and neuronsIn neuronal cells and oligodendroglial cellsNo dataNo data
Table 9. Drugs Used to Manage Orthostatic Hypotension in MSA
ClassDrugDescription or Mechanism
CorticosteroidsFludrocortisone (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 aminesMidodrineAlpha1-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 alfaIncreases sensitivity to pressor effects of angiotensin II; increases plasma endothelin level; increases cytosolic free calcium in vascular smooth muscle; increases intravascular volume
NSAIDsIndomethacin, ibuprofenInhibition of vasodilator prostaglandins proposed but not proven
AntihistaminesDiphenhydramine, cimetidineReduce vasodilatation caused by histamine release
Somatostatin analogsOctreotideReduce splanchnic capacitance
Vasopressin agonistsDesmopressin (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 sympathomimeticsYohimbineAlpha2-adrenoreceptor antagonist
CaffeineAdenosine receptor antagonist
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