Mary Ann Thenganatt1, Joseph Jankovic1. 1. Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas.
Abstract
IMPORTANCE: It is increasingly evident that Parkinson disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. OBJECTIVE: To evaluate available evidence, based on findings from clinical, imaging, genetic and pathologic studies, supporting the differentiation of PD into subtypes. EVIDENCE REVIEW: We performed a systematic review of articles cited in PubMed between 1980 and 2013 using the following search terms: Parkinson disease, parkinsonism, tremor, postural instability and gait difficulty, and Parkinson disease subtypes. The final reference list was generated on the basis of originality and relevance to the broad scope of this review. FINDINGS: Several subtypes, such as tremor-dominant PD and postural instability gait difficulty form of PD, have been found to cluster together. Other subtypes also have been identified, but validation by subtype-specific biomarkers is still lacking. CONCLUSIONS AND RELEVANCE: Several PD subtypes have been identified, but the pathogenic mechanisms underlying the observed clinicopathologic heterogeneity in PD are still not well understood. Further research into subtype-specific diagnostic and prognostic biomarkers may provide insights into mechanisms of neurodegeneration and improve epidemiologic and therapeutic clinical trial designs.
IMPORTANCE: It is increasingly evident that Parkinson disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. OBJECTIVE: To evaluate available evidence, based on findings from clinical, imaging, genetic and pathologic studies, supporting the differentiation of PD into subtypes. EVIDENCE REVIEW: We performed a systematic review of articles cited in PubMed between 1980 and 2013 using the following search terms: Parkinson disease, parkinsonism, tremor, postural instability and gait difficulty, and Parkinson disease subtypes. The final reference list was generated on the basis of originality and relevance to the broad scope of this review. FINDINGS: Several subtypes, such as tremor-dominant PD and postural instability gait difficulty form of PD, have been found to cluster together. Other subtypes also have been identified, but validation by subtype-specific biomarkers is still lacking. CONCLUSIONS AND RELEVANCE: Several PD subtypes have been identified, but the pathogenic mechanisms underlying the observed clinicopathologic heterogeneity in PD are still not well understood. Further research into subtype-specific diagnostic and prognostic biomarkers may provide insights into mechanisms of neurodegeneration and improve epidemiologic and therapeutic clinical trial designs.
Authors: Pei-Hsin Kuo; Shi-Rui Gan; Jie Wang; Raymond Y Lo; Karla P Figueroa; Darya Tomishon; Stefan M Pulst; Susan Perlman; George Wilmot; Christopher M Gomez; Jeremy D Schmahmann; Henry Paulson; Vikram G Shakkottai; Sarah H Ying; Theresa Zesiewicz; Khalaf Bushara; Michael D Geschwind; Guangbin Xia; S H Subramony; Tetsuo Ashizawa; Sheng-Han Kuo Journal: Parkinsonism Relat Disord Date: 2017-10-23 Impact factor: 4.891