Multiple System Atrophy

Multiple system atrophy (MSA) is a degenerative[1] neurological disorder. MSA is associated with the degeneration of nerve cells in specific areas of the brain. This cell degeneration causes problems with movement, balance and other autonomic functions of the body such as bladder control. The cause of MSA is unknown and no specific risk factors have been identified.[2] Around 55% of cases occur in men, with typical age of onset in the late 50s to early 60s.[3]
The overall prevalence of MSA is estimated at 4.6 cases per 100,000 people.[4]

Symptoms

MSA is characterized by a combination of the following, which can be present in any combination:[5][6]
When autonomic failure predominates, the term Shy-Drager syndrome is sometimes used, although this term is no longer current, given the terminology changes which are explained below.[7] This syndrome was named after Dr Milton Shy and Dr Glenn Drager, who identified it in 1960, but the American Autonomic Society and the American Academy of Neurology redefined it as multiple system atrophy with autonomic phenomena in 1996.[8][9][10]
A variant with combined features of MSA and Lewy body dementia may also exist. [11]

Initial Presentation

The most common first sign of MSA is the appearance of an “akinetic-rigid syndrome” (i.e. slowness of initiation of movement resembling Parkinson’s disease) found in 62% at first presentation. Other common signs at onset include problems with balance (found in 22%), followed by genito-urinary problems (9%). For men, the first sign can be erectile dysfunction(unable to achieve or sustain an erection). Both men and women often experience problems with their bladders including urgency, frequency, incomplete bladder emptying or an inability to pass urine (retention). About 1 in 5 MSA patients will suffer a fall in their first year of disease.[3]

Symptoms as Disease Progresses

As the disease progresses three groups of symptoms predominate. These are:
  1. Parkinsonism (slow, stiff movement, writing becomes small and spidery)
  2. Cerebellar dysfunction (difficulty coordinating movement and balance)
  3. Autonomic dysfunction (impaired automatic body functions) including:
Other symptoms such as double vision[12] can occur. Not all patients experience all of these symptoms.

Prognosis

MSA usually progresses more quickly than Parkinson’s disease.[13] There is no remission from the disease. The remaining lifespan after the onset of symptoms is on average about 9 years.[14] Almost 80% of patients are disabled within 5 years of onset of the motor symptoms, and only 20% survive past 12 years.[15] Rate of progression differs in every case and speed of decline may vary widely in individual patients.

Treatment

There is no discovered cure for MSA, so treatment involves treating the symptoms.
Management by rehabilitation professionals (physiotherapistsoccupational therapistsspeech therapists, and others) for problems with walking/movement, daily tasks, and speech problems is essential. Also social workers can help with coping with disability and access to health care services, both for the person with MSA as well as his/her family caregivers.
Ongoing care from a neurologist specialized in “movement disorders” is recommended as the complex symptoms of MSA are often not familiar to less-specialized health care professionals.
One particularly serious problem, the drop in blood pressure upon standing up (with risk of fainting thus injury from falling) often responds to fludrocortisone, a synthetic mineralocorticoid. Another common drug treatment is midodrine (an alpha-agonist.) Non-drug treatments include “head-up tilt” (elevating the head of the whole bed by about 10 degrees), salt tablets or increasing salt in the diet, generous intake of fluids, and pressure (elastic) stockings. Avoidance of triggers of low blood pressure (e.g. hot weather, alcohol, dehydration) are crucial..[16]
Hospice/homecare services can be very useful as disability progresses.
Levdopa (L-Dopa), a drug used in the treatment of Parkinson’s disease, fails to improve the parkinsonian symptoms of most MSA patients. A recent trial reported that only 1.5% of MSA patients experienced a > 50% improvement when taking levodopa, and even this was a transient effect lasting less than one year. Poor response to L-Dopa has been suggested as a possible element in the differential diagnosis of MSA from Parkinson’s disease.
A recent study conducted in Europe failed to find an effect for the drug riluzole in treating MSA or PSP.[3]

Histopathology

In some cases, a diagnosis of MSA can only be confirmed post-mortem. When brain tissue of a person with MSA is examined under a microscope, structures called glial cytoplasmicinclusion bodies are visible. The presence of these inclusions (also known as Papp-Lantos bodies) in the movement, balance and automatic control centres of the brain are the defining histopathologic hallmark of MSA. Recent studies have shown that major fillamentous component of glial and neuronal cytoplasmic inclusions is alpha-synuclein.[17] Mutations in this substance may play a role in the disease. [18]

Terminology

Many terms have historically been used to refer to this disorder, based on the predominant systems presented. These include Olivopontocerebellar atrophy (OPCA), Orthostatic hypotension (OH), Shy-Drager syndrome (SDS), and Striatonigral degeneration (SND).
These terms and their distinctions have been dropped in recent (1996 onwards) medical usage[19] and replaced with MSA subtype naming, but are helpful to understanding the older literature about this disease:
Name
Characteristics
Abbreviation
Striatonigral degeneration
predominating Parkinson’s-like symptoms
MSA-p, “p” = parkinsonian subtype
SporadicOlivopontocerebellar atrophy (OPCA)
characterized by progressive ataxia (an inability to coordinate voluntary muscular movements) of the gait and arms and dysarthria (difficulty in articulating words)
MSA – c, “c” = cerebellar dysfunction subtype
Shy-Drager syndrome
characterized by Parkinsonism plus a more pronounced failure of the autonomic nervous system.[20]. This subtype was referred to in the 1996 Consensus Statement as MSA-a, “a” = autonomic dysfunction subtype.[21]
The current terminology and diagnostic criteria for the disease were established at a 2007 conference of experts on the disease and set forth in the “Second consensus statement on the diagnosis of multiple system atrophy.”[22]
The Second Consensus Statement defines two categories of MSA, based on the predominant symptoms of the disease at the time of evaluation. These are:
  • MSA with predominant parkinsonism (MSA-P) MSA-P is defined as MSA where extrapyramidal features predominate. The term striatonigral degeneration, parkinsonian variant is sometimes used for this category of MSA.
  • MSA with cerebellar features (MSA-C). MSA-C is defined as MSA where cerebellar ataxia predominates. It is sometimes termed sporadic olivopontocerebellar atrophy.
  1. ^ multiple system atrophy at Dorland’s Medical Dictionary
  2. ^ “National Study Seeks Cause of Baffling, Fatal Disorder Called Multiple System Atrophy”. UCSD Health Sciences Communications Healthbeat. December 5, 2003. Retrieved 2008-07-01.
  3. a b c Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, Leigh PN (2008). “Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: The NNIPPS Study”Brain 132 (Pt 1): 156.doi:10.1093/brain/awn291PMID 19029129.
  4. ^ (November 2008) Prevalence of rare diseases : Bibliographic dataOrphanet, 20. (Report). Retrieved on 2009-01-19.
  5. ^ Swan L, Dupont J (May 1999). “Multiple system atrophy”Phys Ther 79 (5): 488–94. PMID 10331752.
  6. ^ Burn DJ, Jaros E (December 2001). “Multiple system atrophy: cellular and molecular pathology”MP, Mol. Pathol. 54 (6): 419–26. PMID 11724918PMC 1187133.
  7. ^ Jellinger KA (2007). “More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains”Acta Neuropathologica 114 (3): 299–303.doi:10.1007/s00401-007-0227-4PMID 17476513.
  8. ^ “Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy”. Neurology 46 (5): 1470. 1996. PMID 8628505.
  9. ^ synd/875 at Who Named It?
  10. ^ Shy GM, Drager GA (1960). “A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study”. Arch. Neurol. 2: 511–27. PMID 14446364.
  11. ^ Sikorska B, Papierz W, Preusser M, Liberski PP, Budka H. (2007). “Synucleinopathy with features of both multiple system atrophy and dementia with Lewy bodies.”. Neuropathology and Applied Neurobiology 33 (1): 126–9. doi:10.1111/j.1365-2990.2006.00817.xPMID 17239015.
  12. ^ NINDS NIH MSA with Orthostatic Hypotension
  13. ^ Bower J, Maraganore D, McDonnell S, Rocca W (1997). “Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990″. Neurology 49 (5): 1284–8.PMID 9371909.
  14. ^ msa at NINDS Multiple System Atrophy
  15. ^ Watanabe H, Saito Y, Terao S, et al. (May 2002). “Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients”Brain 125 (Pt 5): 1070–83. doi:10.1093/brain/awf117.PMID 11960896.
  16. ^ Aminoff MJ, Greenberg DA, Simon RP. “Chapter 7. Movement Disorders”Clinical Neurology (6th ed.).
  17. ^ Arima K, Uéda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (November 1998). “NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy”. Acta Neuropathol. 96 (5): 439–44. doi:10.1007/s004010050917PMID 9829806.
  18. ^ Al-Chalabi A, Dürr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, Morrison KE, Renton A, Sussmuth SD, Landwehrmeyer BG, Ludolph A, Agid Y, Brice A, Leigh PN, Bensimon G; NNIPPS Genetic Study Group. (Sep 2009). “Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy.”. PLoS OnePMID 19771175.
  19. ^ The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (1996). “Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy.”. Neurology 46 (5): 1470. PMID 8628505.
  20. ^ Shy GM, Drager GA (1960). “A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study”. Arch. Neurol. 2: 511–27. PMID 14446364.
  21. ^ The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (1996). “Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy.”. Neurology 46 (5): 1470. PMID 8628505.
  22. ^ Gillman, S. (2008). “Second consensus statement on the diagnosis of multiple system atrophy”. Neurology 71 (9): 670-6. PMID 18725592.