WASHINGTON, DC—The motor subtype classification of patients with Parkinson’s disease may shift over time, according to research presented at the 67th Annual Meeting of the American Academy of Neurology. Patients primarily shift from a tremor-dominant classification to a classification characterized by postural instability, gait difficulty, and rigidity. The shift is driven by a steady increase in gait and balance scores, while tremor scores remain stable as the disease progresses.
Friedrich Rainer von Coelln, Dr. med., Assistant Professor of Neurology at University of Maryland School of Medicine in Baltimore, and colleagues determined the motor subtype classifications of 1,185 patients using a naturalistic database at the Maryland Parkinson’s Disease and Movement Disorders Center. Researchers collected data through questionnaires and clinical scales whenever patients who agreed to be included in the database came to their clinic. Researchers applied three motor subtype classification algorithms published by Jankovic, Schiess, and Eggers, respectively. Although each algorithm calculates subtypes differently, all three algorithms use Unified Parkinson’s Disease Rating Scale items and similar motor subtype labels.
Friedrich Rainer von Coelln, Dr. med.
Algorithms to Determine Motor Subtype
The two motor subtypes defined by Jankovic in 1990—the tremor-dominant type and the postural instability/gait difficulty (PIGD) type—have been used in many subsequent studies as the major Parkinson’s disease motor subtypes, Dr. von Coelln said. “Several alternative algorithms have been proposed, in particular by Dr. Schiess et al in 2000 and also by Dr. Eggers in 2011. Both of these defined a tremor-dominant subtype as well, and an akinetic-rigid [AR] subtype somewhat similar to the PIGD subtype defined by Jankovic and coauthors.” In addition to the tremor-dominant and PIGD/AR subtypes, each algorithm also includes a mixed or indeterminate subtype.
Dr. von Coelln and colleagues performed consecutive cross-sectional analyses of the 1,185 patients, determining the frequency of motor subtypes in five-year intervals of disease duration. The frequency of subtypes varied widely between the three algorithms, despite their almost identical subtype labels.
Across all three algorithms, cross-sectional analyses showed a marked decline of tremor-dominant frequency with disease duration, while PIGD/AR frequency increased. Comparing those with less than five years since diagnosis to those with more than 15 years since diagnosis, the percentage of patients with the tremor-dominant subtype decreased from 7% to 44% early in the disease to 2% to 7% late in the disease.
The percentage of patients with the PIGD/AR subtype changed from 46% to 69% early in the disease, to 80% to 91% more than 15 years after diagnosis.
Results From a Longitudinal Analysis
The investigators also performed a longitudinal analysis of 178 patients with five-year follow-up data, comparing motor subtypes of patients within five years of diagnosis and at follow-up at least five years later. In the analysis, 15% to 38% of the tremor-dominant patients shifted to the mixed subtype, and 46% to 50% of the tremor-dominant patients shifted to the PIGD/AR subtype, resulting in an overall shift of 64% to 85% of tremor-dominant patients into a different motor subtype at follow-up at least five years later.
Limited motor subtype fidelity should be taken into account, the researchers concluded. “Understanding the stability of these subtypes over time is critical to establish their value in research, including investigations of biomarker–phenotype correlations,” Dr. von Coelln said.
—Jake Remaly