Multiple system atrophy

From Ganfyd

(Redirected from MSA)
Jump to: navigation, search

Contents

Introduction

Multiple System Atrophy (MSA) is the condition most often confused with idiopathic Parkinson's disease[1], if it should choose to present as the Parkinsonian variant MSA-P. That Parkinson's own Case 1[2] probably had MSA-P[3] did not help generations of doctors.

Info bulb.pngThe term multiple system atrophy was coined by Graham and Oppenheimer in 1969[4]

Pathology

It is characterised by glial alpha-synuclein cytoplasmic inclusions on histological examination[5]. This allowed the reclassification of

  • Striatonigral degeneration (SND) now known as MSA-P
  • Olivopontocerebellar atrophy (OPCA) now known as MSA-C
  • Shy-Drager syndrome now known as MSA-A

as variants of the same condition. There is cell loss and gliosis (without Lewy bodies) in:

Epidemiology

  • MSA-P in >4.5/100,000[6]
  • Mean age of onset 54 years with survival after diagnosis often between 5 to 7 years[7]

Associations

  • Familial (suggesting polygenetic factors)[8]
  • Metal dusts and fumes[9]
  • Plastic monomers and additives[10]
  • Organic solvents[11]
  • Pesticides[12]

Clinical

LogoKeyPointsBox.pngRed flags suggesting MSA:[13]

A better clinical approach to MSA is to note that

  • Autonomic failure is present in three quarters.
  • Cerebellar presentations (MSA-C) are easy to confuse with other presentations of cerebellar syndrome
    • Cerebellar ataxia is present ultimately in over 50%
  • Parkinsonian presentations (MSA-P) are easy to confuse with Parkinson's disease.
    • Parkinsonism is present in ultimately nearly 90%
    • The respose to levodopa is poor (not the case in a proven minority !)
  • Severe dementia is very rare. However a cause for expert misclassification on post mortem is that patient had dementia.
  • Pyramidal signs are ultimately found in almost 50%
  • Early features predictive of MSA-P are:[14]
    1. Autonomic features
    2. Poor initial levodopa response
    3. Early motor fluctuations
    4. Initial rigidity
  • Features at death predictive of MSA-P are:[15]
    1. Falls
    2. Absence of levodopa induced confusion
    3. Speech or bulbar dysfunction
    4. Poor response to levodopa
    5. Autonomic features
    6. Absence of dementia

Diagnostic Criteria

Diagnostic approach and criteria for differential diagnosis from other similar presentations have been defined for MSA.[16] These are (slightly reworded):

  • Possible MSA-P
    • Parkinsonism
      • Plus two from separate other domains.
      • Poor levodopa response plus one other domain
  • Possible MSA-C
    • Cerebellar dysfunction
      • plus two from separate other domains.
  • Probable MSA-P
    • Autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism.
  • Probable MSA-C
      • Autonomic failure/urinary dysfunction plus cerebellar dysfunction.
  • Definite MSA
    • High density of alpha-synuclein-positive GCIs
    • Degeneration in nigrostriatal (SND) and olivopontocerebellar pathways (OPCA).

With domains as follows:

Autonomic and urinary dysfunction

  • Criterion
    • Orthostatic fall in blood pressure by 30 mmHg systolic or 15 mmHg diastolic or
    • Persistent urinary incontinence with erectile dysfunction in men
  • Feature
    • Orthostatic hypotension (by 20 mmHg systolic or 10 mmHg diastolic)
    • Urinary incontinence or incomplete bladder emptying

Parkinsonism

  • Criterion
  • Feature
    • Bradykinesia (progressive reduction in rigidity speed and amplitude of voluntary movements during repetitive actions)
    • Rigidity
    • Postural instability (loss of primary postural reflexes)
    • Tremor (postural, resting or both)

Cerebellar dysfunction

  • Criterion
    • Gait ataxia plus one of:
      • Ataxic dysarthria
      • Limb ataxia
      • Sustained gaze-evoked nystagmus
  • Feature
    • Gait ataxia (wide based stance with irregular steps)
    • Ataxic dysarthria
    • Limb ataxia
    • Sustained gaze-evoked nystagmus

Corticospinal tract dysfunction

  • Feature
    • Extensor plantar responses with hyperreflexia

Applying these criteria does not have the positive predictive value of a neurologist experienced in the condition.[17]

Investigations

  • MRI (interpreted by an experienced neuroradiologist !)
    • worsening serial pontine atrophy
    • Diffusion-weighted cal distinguish from PSP[18]
    • T2 putamen signal loss has good specificity 0.91 and sensitivity 0.64 with right scanner and neuroradiologist.
  • SPECT
  • Autonomic function
  • Clonidine test - release of growth hormone[22]

Treatment

References

  1. GK Wenning, F. Tison, Y. Ben Shlomo, SE Daniel,NP Quinn: Multiple System Atrophy: A Review of 203 Pathologically Proven Cases. Movement Disorders 1997, 12(2): 133-147.
  2. Parkinson J: An Essay on the Shaking Palsy. London, Sherwood, Neely and Jones, 1817
  3. Quinn, N: Multiple system atrophy, in Movement Disorders 3. Edited by Marsden CD. Fahn S. Oxford: Butterworth-Heinemann. 1994, 263-281.
  4. Graham JG, Oppenheimer DR. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1969 Feb;32(1):28-34.
  5. Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M. Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies. Neurosci Lett. 1998;251(3):205-8.
  6. Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet 1999;354:1771-5.
  7. Kaufmann H. Multiple System Atrophy Current Opinion in Neurology 1998, 11:351-355
  8. Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res. 1991 Mar;1(1):9-13
  9. Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res. 1991 Mar;1(1):9-13
  10. Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res. 1991 Mar;1(1):9-13
  11. Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res. 1991 Mar;1(1):9-13
  12. Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res. 1991 Mar;1(1):9-13
  13. Wenning GK, Geser F. Diagnosis and Treatment of Multiple System Atrophy: an Update. ACNR 2004;3(6):5-10
  14. Wenning GK, Ben-Shlomo Y, Hughes A, Daniel SE, Lees A, Quinn NP. What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease? J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):434-40.
  15. Wenning GK, Ben-Shlomo Y, Hughes A, Daniel SE, Lees A, Quinn NP. What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease? J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):434-40.
  16. Gilman S, Low PA, Quinn N, et al: Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999 Feb 1; 163(1): 94-8
  17. Litvan I, Booth V, Wenning GK, Bartko JJ, Goetz CG, McKee A, Jankovic J, Jellinger K, Lai EC, Brandel JP, Verny M, Chaudhuri KR, Pearce RK, Agid Y. Retrospective application of a set of clinical diagnostic criteria for the diagnosis of multiple system atrophy.J Neural Transm. 1998;105(2-3):217-27.
  18. Nicoletti G, Lodi R, Condino F, Tonon C, Fera F, Malucelli E, et al. Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy. Brain : a journal of neurology 2006;129:2679-87. (Direct link – subscription may be required.)
  19. Cilia R, Marotta G, Benti R, Pezzoli G, Antonini A. Brain SPECT imaging in multiple system atrophy. J Neural Transm. 2005 Dec;112(12):1635-45.
  20. Shinotoh H. Neuroimaging of PD, PSP, CBD and MSA-PET and SPECT studies. Journal of neurology 2006;253 Suppl 3:iii30-iii34. (Direct link – subscription may be required.)
  21. Wenning GK, Colosimo C, Geser F, Poewe W: Multiple System Atrophy. Lancet Neurol 2004; 3: 93-103
  22. Kimber JR, Watson L, Mathias CJ. Distinction of idiopathic Parkinson's disease from multiple-system atrophy by stimulation of growth-hormone release with clonidine. The Lancet 1997; 349:1877-1881
  23. Colosimo C, Albanese A, Hughes AJ, de Bruin VM, Lees AJ. Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease. Arch Neurol 1995;52:294-298
  24. Wright RA, Kaufmann H, Perera R, et al: A double blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology 1998
  25. Winkler AS, Landau S, Watkins P, Chaudhuri KR. Observations on haematological and cardiovascular effects of erythropoietin treatment in multiple system atrophy with sympathetic failure. Clin Auton Res. 2002 Jun;12(3):203-6.
Personal tools