Multiple system atrophy

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Multiple system atrophy
Classification and external resources
ICD-10 G90.3
ICD-9 333.0
OMIM 146500
DiseasesDB 8441
MedlinePlus 000757
eMedicine neuro/671
Patient UK Multiple system atrophy
MeSH D019578

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 or blood-pressure regulation. 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] MSA often presents with some of the same symptoms as Parkinson's disease. However, MSA patients generally show minimal if any response to the dopamine medications used for Parkinson's.

Prevalence[edit]

The overall prevalence of MSA is estimated at 4.6 cases per 100,000 people.[4][5] This disease is more common in men than in women, with studies showing ratios ranging from between 1.4:1[6] to ratios as high as 1.9:1.[7]

Symptoms[edit]

MSA is characterized by a combination of the following, which can be present in any combination:[7][8] Because people with MSA often suffer "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinson's disease) found in 62% at first presentation it is sometimes grouped with diseases referred to as Parkinson plus syndrome.[citation needed]

When autonomic failure predominates, the term Shy–Drager syndrome is sometimes used, although this term is no longer current, given the terminology changes which are explained below.[9][10][11][12]

A variant with combined features of MSA and Lewy body dementia may also exist.[13]

Initial presentation[edit]

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 (cerebellar ataxia) found in 22% at first presentation, followed by genito-urinary problems (9%). For men, the first sign can be erectile dysfunction (inability 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[edit]

As the disease progresses one of 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 nervous system dysfunction (impaired automatic body functions) including:

Other symptoms such as double vision can occur.[15] Not all patients experience all of these symptoms.

Some patients (20% in one study) experience significant cognitive impairment as a result of MSA.[16]

Prognosis[edit]

MSA usually progresses more quickly than Parkinson's disease.[5] There is no remission from the disease. The average remaining lifespan after the onset of symptoms in patients with MSA is 7.9 years.[5] Almost 80% of patients are disabled within five years of onset of the motor symptoms, and only 20% survive past 12 years.[17] Rate of progression differs in every case and speed of decline may vary widely in individual patients.

O’Sullivan and colleagues (2008) identified early autonomic dysfunction to be the most important early clinical prognostic feature regarding survival in MSA. Patients with concomitant motor and autonomic dysfunction within three years of symptom onset had a shorter survival duration, in addition to becoming wheelchair dependent and bed-ridden at an earlier stage than those who developed these symptoms after three years from symptom onset. Their study also showed that when patients with early autonomic dysfunction develop frequent falling, or wheelchair dependence, or severe dysphagia, or require residential care, there is a shorter interval from this point to death.[18]

Diagnosis[edit]

Alpha synuclein immunohistochemistry showing many glial inclusions.

Diagnosis of MSA can be challenging because there is no test that can definitively make or confirm the diagnosis in a living patient. Clinical diagnostic criteria were defined in 1998[19] and updated in 2007.[20] Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult.[21]

A definitive diagnosis can only be made pathologically on finding abundant glial cytoplasmic inclusions in the central nervous system.[22]

Treatment[edit]

There is no discovered cure for MSA, so treatment involves controlling the symptoms.

Ongoing care from a neurologist specialized in "movement disorders" is recommended[by whom?] 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 and thus injury from falling) often responds to fludrocortisone, a synthetic mineralocorticoid.[citation needed] Another common drug treatment is midodrine (an alpha-agonist).[citation needed] 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 (such as hot weather, alcohol, dehydration) are crucial.[23]

Hospice/homecare services can be very useful as disability progresses.

Levodopa (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 less than 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 November, 2008 study conducted in Europe failed to find an effect for the drug riluzole in treating MSA or PSP.[3]

A July, 2012, study suggested that mesenchymal stem cell therapy could delay the progression of neurological deficits in patients with MSA-cerebellar type, suggesting the potential of mesenchymal stem cell therapy as a treatment candidate of MSA.[24]

Rehabilitation[edit]

Management by rehabilitation professionals (physiatrists, physiotherapists, occupational therapists, speech therapists, and others) for problems with walking/movement, daily tasks, and speech problems is essential.

Physiotherapy can help to maintain the patient’s mobility and will help to prevent contractures.[6] Instructing patients in gait training will help to improve their mobility and decrease their risk of falls.[25] A physiotherapist may also prescribe mobility aids such as a cane or a walker to increase the patient’s safety.[25] Other ways a physiotherapist can help to improve the patient’s safety are to teach them to move and transfer from sitting to standing slowly to decrease risk of falls and limit the effect of postural hypotension.[25] Instruction in ankle pumping helps to return blood in the legs to the systemic circulation.[25] To further control the postural hypotension, raising the head of the bed by 8 in (20.3 cm) while sleeping may be indicated as well as the use of elastic compression garments.[7]

Speech and language therapists may assist in assessing, treating and supporting speech (dysarthria) and swallowing difficulties (dysphagia). Early intervention of swallowing difficulties is particularly useful to allow for discussion around tube feeding further in the disease progression.{doubtful - citation needed} At some point in the progression of the disease, fluid and food modification may be suggested. Speech changes mean that alternative communication may be needed, for example communication aids or word charts.

Social workers and occupational therapists can also help with coping with disability through the provision of equipment and home adaptations, services for caregivrs and access to healthcare services, both for the person with MSA as well as family caregivers.

Histopathology[edit]

Multiple-system atrophy can be explained as cell loss and gliosis or a proliferation of astrocytes in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar.[6] Currently, a confirmed diagnosis of MSA can only be made post-mortem as glial cytoplasmic inclusion bodies are visible. When brain tissue of a person with MSA is examined under a microscope, these glial structures are visible, confirming the diagnosis. 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 the major filamentous component of glial and neuronal cytoplasmic inclusions is alpha-synuclein.[26] Mutations in this substance may play a role in the disease.[27] Tau proteins have been found in some GCIs.[28]

Terminology[edit]

Many terms have historically been used to refer to this disorder, based on the predominant systems presented. These include olivopontocerebellar atrophy (OPCA), Shy–Drager syndrome (SDS), and striatonigral degeneration (SND), which were once considered to be separate disorders.[29]

These terms and their distinctions have been dropped in recent (1996 onwards) medical usage[10] and replaced with MSA and its subtypes, but are helpful to understanding the older literature about this disease:

Historical Name Characteristics Abbreviation and modern name
Striatonigral degeneration predominating Parkinson's-like symptoms MSA-P, "p" = parkinsonian subtype
Sporadic olivopontocerebellar 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.[12] This terminology fell out of favour[30] and was not specified in the 2007 consensus paper.[20] The earlier consensus of 1998[19] referred to MSA-A, "a" = autonomic dysfunction subtype but this subtype is no longer used.

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."[31]

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.

Genomics[edit]

One study by Sasaki et al found a correlation between the deletion of genes in a specific genetic region and the development of MSA in a group of Japanese patients.[32] The region in question includes the SHC2 gene which, in mice and rats, appears to have some function in the nervous system. The authors of this study hypothesized that there may be a link between the deletion of the SHC2 and the development of MSA. (See Copy-number variation for a general discussion of gene copy deletion and the variation in the number of copies of one or more sections of the DNA.)

A follow-up study in the U.S. by a different group of scientists was unable to replicate this finding in american MSA patients.[33] The authors of the U.S. study concluded that "Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds."

References[edit]

  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): 156–71. doi:10.1093/brain/awn291. PMC 2638696. PMID 19029129. 
  4. ^ (PDF) Prevalence of rare diseases : Bibliographic data (Report). Orphanet. November 2008. p. 20. http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf. Retrieved 2009-01-19.
  5. ^ a b c 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. doi:10.1212/wnl.49.5.1284. PMID 9371909. 
  6. ^ a b c Wenning GK, Colosimo C, Geser F, Poewe W (February 2004). "Multiple system atrophy". Lancet Neurol 3 (2): 93–103. doi:10.1016/S1474-4422(03)00662-8. PMID 14747001. 
    Wenning GK, Colosimo C, Geser F, Poewe W (March 2004). "Erratum". Lancet Neurol 3 (3): 137. doi:10.1016/S1474-4422(04)00695-7. 
  7. ^ a b c Swan L, Dupont J (May 1999). "Multiple system atrophy". Phys Ther 79 (5): 488–94. PMID 10331752. 
  8. ^ Burn DJ, Jaros E (December 2001). "Multiple system atrophy: cellular and molecular pathology". MP, Mol. Pathol. 54 (6): 419–26. PMC 1187133. PMID 11724918. 
  9. ^ 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/s00401-007-0227-4. PMID 17476513. 
  10. ^ a b 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. doi:10.1212/wnl.46.5.1470. PMID 8628505. 
  11. ^ synd/875 at Who Named It?
  12. ^ a b Shy GM, Drager GA (1960). "A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study". Arch. Neurol. 2: 511–27. doi:10.1001/archneur.1960.03840110025004. PMID 14446364. 
  13. ^ 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.x. PMID 17239015. 
  14. ^ Gilman S, Koeppe RA, Chervin RD, et al. (July 2003). "REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA". Neurology 61 (1): 29–34. doi:10.1212/01.wnl.0000073745.68744.94. PMID 12847152. 
  15. ^ NINDS NIH MSA with Orthostatic Hypotension
  16. ^ Brown RG, Lacomblez L, Landwehrmeyer BG, Bak T, Uttner I, Dubois B, Agid Y, Ludolph A, Bensimon G, Payan C, Leigh NP; for the NNIPPS Study Group (August 2010). "Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy". Brain 133 (Pt 8): 2382–93. doi:10.1093/brain/awq158. PMID 20576697. 
  17. ^ 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. 
  18. ^ O`Sullivan, S. S.; Massey, L. A., Williams, D. R., Silveira-Moriyama, L., Kempster, P. A., Holton, J. L., Revesz, T. & Lees, A. J. (2008). "Clinical outcomes of progressive supranuclear palsy and multiple system atrophy". Brain 131 (5): 1362–72. doi:10.1093/brain/awn065. PMID 18385183. 
  19. ^ a b Gilman, S; Low, PA; Quinn, N; Albanese, A; Ben-Shlomo, Y; Fowler, CJ; Kaufmann, H; Klockgether, T; Lang, AE; Lantos, PL; Litvan, I; Mathias, CJ; Oliver, E; Robertson, D; Schatz, I; Wenning, GK (Feb 1, 1999). "Consensus statement on the diagnosis of multiple system atrophy.". Journal of the neurological sciences 163 (1): 94–8. doi:10.1016/s0022-510x(98)00304-9. PMID 10223419. 
  20. ^ a b Gilman, S; Wenning, GK; Low, PA; Brooks, DJ; Mathias, CJ; Trojanowski, JQ; Wood, NW; Colosimo, C; Dürr, A; Fowler, CJ; Kaufmann, H; Klockgether, T; Lees, A; Poewe, W; Quinn, N; Revesz, T; Robertson, D; Sandroni, P; Seppi, K; Vidailhet, M (Aug 26, 2008). "Second consensus statement on the diagnosis of multiple system atrophy.". Neurology 71 (9): 670–6. doi:10.1212/01.wnl.0000324625.00404.15. PMC 2676993. PMID 18725592. 
  21. ^ Vanderbilt Autonomic Dysfunction Cente. "Multiple System Atrophy / Shy Drager Syndrome". Retrieved May 29, 2010. 
  22. ^ Papp MI, Kahn JE, Lantos PL. (Dec 1989). "Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration,olivopontocerebellar atrophy and Shy-Drager syndrome)". J Neurol Sci. 94 (1–3): 79–100. doi:10.1016/0022-510X(89)90219-0. PMID 2559165. 
  23. ^ Aminoff MJ, Greenberg DA, Simon RP. "Chapter 7. Movement Disorders". Clinical Neurology (6th ed.). 
  24. ^ Lee, Phil Hyu; Lee, Ji E.; Kim, Han-Soo; Song, Sook K.; Lee, Hye Sun; Nam, Hyo Suk; Cheong, June-Won; Jeong, Yong; Park, Hae-Jeong; Kim, Dong Joon; Nam, Chung Mo; Lee, Jong Doo; Kim, Hyun Ok; Sohn, Young H. (2012). "A randomized trial of mesenchymal stem cells in multiple system atrophy". Annals of Neurology 72 (1): 32–40. doi:10.1002/ana.23612. PMID 22829267. 
  25. ^ a b c d Hardy, Joanne (2008). "Multiple system atrophy: pathophysiology, treatment and nursing care". Nursing Standard 22 (22): 50–56. doi:10.7748/ns2008.02.22.22.50.c6359. PMID 18333558. 
  26. ^ 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/s004010050917. PMID 9829806. 
  27. ^ Al-Chalabi, A; Dürr, A; Wood, NW; Parkinson, MH; Camuzat, A; Hulot, JS; Morrison, KE; 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. et al. (Sep 2009). "Genetic Variants of the α-Synuclein Gene SNCA Are Associated with Multiple System Atrophy". In Heutink, Prof. Peter. PLoS ONE 4 (9): e7114. doi:10.1371/journal.pone.0007114. PMC 2743996. PMID 19771175. 
  28. ^ Piao YS, Hayashi S, Hasegawa M, Wakabayashi K, Yamada M, Yoshimoto M, Ishikawa A, Iwatsubo T, Takahashi H. (Mar 2001). "Co-localization of alpha-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of long duration". Acta Neuropathol. 101 (3): 285–93. PMID 11307630. 
  29. ^ Ahmed, Z.; Asi, YT.; Sailer, A.; Lees, AJ.; Houlden, H.; Revesz, T.; Holton, JL. (Feb 2012). "The neuropathology, pathophysiology and genetics of multiple system atrophy". Neuropathol Appl Neurobiol 38 (1): 4–24. doi:10.1111/j.1365-2990.2011.01234.x. PMID 22074330. 
  30. ^ Schatz, IJ (Jul 1, 1996). "Farewell to the "Shy-Drager syndrome".". Annals of Internal Medicine 125 (1): 74–5. doi:10.7326/0003-4819-125-1-199607010-00012. PMID 8644992. 
  31. ^ Gillman, S.; Wenning, GK; Low, PA; Brooks, DJ; Mathias, CJ; Trojanowski, JQ; Wood, NW; Colosimo, C et al. (2008). "Second consensus statement on the diagnosis of multiple system atrophy". Neurology 71 (9): 670–6. doi:10.1212/01.wnl.0000324625.00404.15. PMC 2676993. PMID 18725592. 
  32. ^ Sasaki H, Emi M, Iijima H, et al. (2011). "Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy". Mol Brain 4: 24. doi:10.1186/1756-6606-4-24. PMC 3141657. PMID 21658278. 
  33. ^ Ferguson, MC; Garland, EM; Hedges, L; Womack-Nunley, B; Hamid, R; Phillips JA, 3rd; Shibao, CA; Raj, SR; Biaggioni, I; Robertson, D (Feb 2014). "SHC2 gene copy number in multiple system atrophy (MSA).". Clinical autonomic research : official journal of the Clinical Autonomic Research Society 24 (1): 25–30. doi:10.1007/s10286-013-0216-8. PMID 24170347. 

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