Prognostic Indicators Within Parkinson's Plus Syndromes
Abstract & Commentary
By Claire Henchcliffe, MD, DPhil Assistant Professor, Department of Neurology and Neuroscience, Weill Medical College, Cornell University. Dr. Henchcliffe reports that she is on the speaker's bureau for GlaxoSmithKline, Teva, Boehringer Ingelheim, Schwarz Pharma, and Allergan.
Synopsis: This study of patients with PSP and MSA diagnosed at autopsy, 70% of whom were correctly diagnosed during their lifetime, suggests differences in disease subtypes that impact upon prognosis and response to treatment.
Source: O'Sullivan SS, et al. Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain 2008;131(Pt 5):1362-1372.
O'sullivan and colleagues have performed a careful retrospective analysis of medical records of patients with neuropathology-confirmed progressive supranuclear palsy (PSP) or multiple system atrophy (MSA) identified from all cases that came to autopsy between 1987 and 2007 at the Queen Square Brain Bank for Neurological Disorders. Of the 110 cases of PSP identified, only 72% had correct clinical diagnoses prior to death. The mean age of onset was 65.6 ± 8.4 years, with a mean survival of 8.0 ± 4.1 years. Male gender and older age of onset were independent predictors of shorter survival time. Of the 83 MSA cases identified by pathology, 70% had received a correct clinical diagnosis during their lifetime. Autonomic failure was documented in 42/83 (53%) within 2 years of onset of MSA. Mean age of MSA onset was younger than in PSP (56.8 ± 10.2 years, p<0.001), but survival was similar (7.9 ± 2.8 years). Those with MSA were more likely to be levodopa-responsive (62.9% vs. 33.7%) but response was not sustained in either group after 2 years (MSA: 34.3%; PSP: 27.7%). Within the PSP group, two subtypes were identified: 1) Richardson syndrome (RS), a "classic" PSP with early cognitive dysfunction, falls, and supranuclear gaze palsy; and 2) PSP-parkinsonism (PSP-P) with asymmetric onset and tremor. The RS subgroup had a significantly shorter survival time compared with PSP-P, reaching pre-specified clinical milestones (including falls, cognitive impairment, and dysphagia) earlier, and with more rapid progression to wheelchair requirement and residential care. Within the MSA group, the presence of early autonomic symptoms did not affect the frequency or rapidity of reaching any of these milestones, but was associated with shorter survival (p=0.0014). Comparing milestones between MSA and PSP, the most common milestone for each was frequent falls (PSP: 63.6%; MSA: 39.3%), followed by cognitive impairment in PSP (15.4%) vs. urinary catheterization in MSA (29.4%).
Commentary
PSP and MSA are Parkinson's-plus syndromes sometimes clinically mistaken for Parkinson's disease; however, they have a distinct pathology and prognosis. Diagnoses during a patient's lifetime are made almost exclusively on a clinical basis, with limitations well-illustrated by an approximately 30% misdiagnosis rate when compared with pathology in this study. Diagnosis on clinical grounds is further complicated by the existence of disease subtypes. In this study, the authors chose to examine MSA with and without prominent early autonomic dysfunction and PSP with predominant parkinsonism (PSA-P) or RS. Using the gold standard for diagnosis, autopsy examination, individuals with MSA and PSP had similar survival after disease onset, but PSP was more debilitating in this population. Furthermore, early levodopa response did not affect disease duration. Shorter survival times were predicted by the presence of early autonomic dysfunction in MSA, and by the RS subtype of PSP. These data should aid in better counseling our patients regarding prognosis, and also highlight disease features to help formulate more informed differential diagnoses. However, a number of caveats still apply. First, there may be referral bias regarding which patients come to autopsy (e.g., they could represent more severe and complex cases with worse prognoses than the average). Second, clinical features were identified retrospectively, raising the concern that milestones may be misreported or underreported in the reviewed charts. The importance of prospective studies cannot be overemphasized if we are to advance the understanding of these disorders and optimize patient care.
This study of patients with PSP and MSA diagnosed at autopsy, 70% of whom were correctly diagnosed during their lifetime, suggests differences in disease subtypes that impact upon prognosis and response to treatment.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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