PracticeUpdate Neurology February 2019

EXPERT OPINION 22

Young-Onset Multiple System Atrophy By Sonja W. Scholz MD, PhD Dr. Scholz is Assistant Clinical Investigator and Chief of the Neurodegenerative Diseases Research Unit, Neurogenetics Branch at the National Institutes of Neurological Disorders and Stroke, National Institutes of Health in Bethesda, Maryland. This commentary is based upon the article Young-onset multiple system atrophy: Clinical and pathological features by Batla et al.

D istinguishing rare diseases from common conditions with overlapping symp- tomatology is the art of clinical neurology. This is particularly true for individuals whose features deviate from our textbook definitions of disease; for example, earlier-than-expected age at onset. This can lead to high misdiagnosis rates and long, frustrating diagnostic odysseys for patients. Multiple system atrophy (MSA) is a disabling neurodegenerative condition with heterogeneous clinical presentations that typically begins in the sixth decade of life. 1 The disease rarely manifests prior to age 40, and we simply do not know much about the clinical features of these young-onset patients. In a recent study in the journal Movement Disorders , Batla and colleagues addressed this gap in our knowledge by examining the clinicopathological features of 22 young-on- set MSA patients. 2 Of these individuals, 8 were pathologically confirmed, whereas the remaining cases were probable MSA patients based on clinic consensus criteria. 3 The most pertinent observations from this study were as follows: 1. On initial presentation, young-onset MSA patients commonly presented with levodo- pa-responsive parkinsonism, autonomic dysfunction, cerebellar features and dystonia (particularly anterocollis). 2.In contrast to patients with young-onset Parkinson’s disease, young-onset MSA patients also frequently had pyramidal signs, such as brisk reflexes or Babinski signs. 3. Postural tremor and orofacial dyskinesia were more common in MSA patients, whereas levodopa-induced dyskinesia was more prevalent in patients with Parkinson’s disease. 4. Cognition was notably preserved in all MSA patients. These observations offer us the opportunity to distinguish young-onset Parkinson’s disease from young-onset MSA with higher accuracy. This is, of course, important for patients and their families, and helps to guide clinical management. In the future, as disease-modifying agents come to market, making the distinction between the two forms of neurodegeneration will be even more clinically relevant. From a scientific perspective, it is fascinating to consider the reasons why these patients develop what is essentially a late-onset disease at a much earlier time point. Perhaps, this occurs more commonly than we previously appreciated, and Batla and colleagues’ work will lead to an increased recognition of such cases among the general population. References 1. Wenning GK, Geser F, Krismer F, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 2013;12(3):264-274. 2. Batla A, De Pablo-Fernandez D, Erro R, et al. Young-onset multiple system atrophy: Clinical and pathological features. Mov Disord 2018;33(7):1099-1107. 3. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71(9):670-676. www.practiceupdate.com/c/72743

" From a scientific perspective, it is fascinating to consider the reasons why these patients develop what is essentially

a late-onset disease at a much earlier time point.

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