Clinical features and autonomic testing predict survival in multiple system atrophy

Elizabeth Coon, David M. Sletten, Mariana D. Suarez, Jayawant Mandrekar, J. Eric Ahlskog, James Howard Bower, Joseph Y. Matsumoto, Michael H. Silber, Eduardo E. Benarroch, Robert D. Fealey, Paola Sandroni, Phillip Anson Low, Wolfgang Singer

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P <0.001). Median disease duration from symptom onset to death was 7.51 years (95% confidence interval 7.18-7.78) while time from diagnosis to death was 3.33 years (95% confidence interval 2.92-3.59). There was no difference in survival between motor subtypes of multiple system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P <0.0001); (ii) bladder symptoms (hazard ratio 1.96, P <0.0001); (iii) urinary catheterization within 3 years of symptom onset (hazard ratio 1.67, P <0.003); (iv) orthostatic intolerance within 1 year of symptom onset (hazard ratio 1.28, P <0.014); (v) older age of onset (hazard ratio 1.02, P = 0.001); and (vi) degree of autonomic failure as measured by a validated composite autonomic severity score (hazard ratio 1.07, P <0.0023). We conclude that carefully selected clinical features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as prognostic marker.

Original languageEnglish (US)
Pages (from-to)3623-3631
Number of pages9
JournalBrain
Volume138
Issue number12
DOIs
StatePublished - Dec 1 2015

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Multiple System Atrophy
Survival
Parkinsonian Disorders
Cerebellar Ataxia
Age of Onset
Orthostatic Intolerance
Confidence Intervals
Urinary Catheterization

Keywords

  • ataxia
  • autonomic
  • multiple system atrophy
  • parkinsonism

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Clinical features and autonomic testing predict survival in multiple system atrophy. / Coon, Elizabeth; Sletten, David M.; Suarez, Mariana D.; Mandrekar, Jayawant; Ahlskog, J. Eric; Bower, James Howard; Matsumoto, Joseph Y.; Silber, Michael H.; Benarroch, Eduardo E.; Fealey, Robert D.; Sandroni, Paola; Low, Phillip Anson; Singer, Wolfgang.

In: Brain, Vol. 138, No. 12, 01.12.2015, p. 3623-3631.

Research output: Contribution to journalArticle

Coon, E, Sletten, DM, Suarez, MD, Mandrekar, J, Ahlskog, JE, Bower, JH, Matsumoto, JY, Silber, MH, Benarroch, EE, Fealey, RD, Sandroni, P, Low, PA & Singer, W 2015, 'Clinical features and autonomic testing predict survival in multiple system atrophy', Brain, vol. 138, no. 12, pp. 3623-3631. https://doi.org/10.1093/brain/awv274
Coon, Elizabeth ; Sletten, David M. ; Suarez, Mariana D. ; Mandrekar, Jayawant ; Ahlskog, J. Eric ; Bower, James Howard ; Matsumoto, Joseph Y. ; Silber, Michael H. ; Benarroch, Eduardo E. ; Fealey, Robert D. ; Sandroni, Paola ; Low, Phillip Anson ; Singer, Wolfgang. / Clinical features and autonomic testing predict survival in multiple system atrophy. In: Brain. 2015 ; Vol. 138, No. 12. pp. 3623-3631.
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N2 - Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P <0.001). Median disease duration from symptom onset to death was 7.51 years (95% confidence interval 7.18-7.78) while time from diagnosis to death was 3.33 years (95% confidence interval 2.92-3.59). There was no difference in survival between motor subtypes of multiple system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P <0.0001); (ii) bladder symptoms (hazard ratio 1.96, P <0.0001); (iii) urinary catheterization within 3 years of symptom onset (hazard ratio 1.67, P <0.003); (iv) orthostatic intolerance within 1 year of symptom onset (hazard ratio 1.28, P <0.014); (v) older age of onset (hazard ratio 1.02, P = 0.001); and (vi) degree of autonomic failure as measured by a validated composite autonomic severity score (hazard ratio 1.07, P <0.0023). We conclude that carefully selected clinical features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as prognostic marker.

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