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Course in Parkinson disease subtypes

A 39-year clinicopathologic study

From the Division of Neurology (A.H.R., M.L.R., A.R.), Parkinson’s Disease and Movement Disorder Program, University of Saskatchewan/Saskatoon Health Region; College of Medicine (A.V.), University of Saskatchewan; and Division of Neuropathology (C.A.R.), Department of Pathology, Saskatoon Health Region/University of Saskatchewan, Canada.

Address correspondence and reprint requests to Dr. Ali H. Rajput, Room 1663, Royal University Hospital, Saskatoon, Saskatchewan S7N 0W8, Canada ali.rajput{at}saskatoonhealthregion.ca

Background: Individual variations in the course of Lewy body Parkinson disease (PD) are well known. Patients have been classified into different clinical subtypes to identify differences in the course among the subgroups. Several studies indicate that the outcome is more favorable in tremor dominant (TD) cases but others report no difference. A majority of progression studies are based on cross-sectional single point data or short-term clinical observations. The lack of longitudinally followed autopsy-confirmed PD cohort remains a major weakness in the literature. Biochemical studies of brain indicate most pronounced abnormalities in akinetic/rigid (AR) and the least in TD cases. We postulate that PD course in these subtypes is concordant with the biochemical findings.

Objective: To compare the course in TD, mixed (MX), and AR subtypes of PD.

Methods: Longitudinal clinical follow-up and autopsy studies were performed on 166 patients with PD over 39 years (1968–2006). Patients were classified into TD, AR, and MX based on the entire clinical course. Only the pathologically confirmed PD cases were included.

Results: Sixty-six percent of cases had MX, 26% AR, and 8% TD profile. The age at onset was younger (p < 0.001) and progression to Hoehn & Yahr stage 4 was slower (p = 0.016) in the TD cases. Dementia was most common in AR (p = 0.039) and the least common in TD. In general, the course was most favorable in TD, followed by MX and AR subgroups.

Conclusion: The three subtypes of Parkinson disease have different courses which are concordant with the differences in brain biochemical abnormalities.

Abbreviations: AR = akinetic/rigid; CBG = corticobasal ganglia degeneration; ET = essential tremor; H&Y = Hoehn & Yahr; LB = Lewy body; LD = levodopa; MDCS = Movement Disorder Clinic Saskatoon; MSA = multiple system atrophy; MX = mixed; PD = Parkinson disease; PIGD = postural instability and gait difficulty dominant; PSP = progressive supranuclear palsy; SN = substantia nigra; TD = tremor dominant; UPDRS = Unified Parkinson’s Disease Rating Scale.

Disclosure: Author disclosures are provided at the end of the article.

Received October 24, 2008. Accepted in final form April 6, 2009.