Objective: To analyze the differential response to subthalamic Deep brain stimulation (STN-DBS) among different Parkinson’s disease (PD) phenotypes, as per the new PD subtype classification [1].

Background: A new PD categorization in 3 different clusters has been proposed, which validity was recently confirmed by life-course longitudinal data. However, the differential response to therapies of the 3 PD subtypes has not still investigated.

Method: We retrospectively analyzed data of PD patients treated with STN-DBS. According to the recently validated classification [1], we analyzed semiquantitative severity scores of multiple features and converted them into 4 domains: motor dysfunction (tremor, bradykinesia, rigidity, and postural instability), autonomic dysfunction (urinary symptoms, constipation, gastrointestinal tract dysfunction symptoms, orthostatic hypotension, sweating, erectile dysfunction), RBD, and cognitive dysfunction. PD subtypes were classified as:
-Mild-motor predominant (MM): motor and all nonmotor scores <75th percentile;
-Diffuse-malignant (DM): either motor score ≥75th percentile and at least 1 nonmotor score ≥75th percentile or all 3 nonmotor scores ≥75th percentile;
-Intermediate (IN): patients not meeting criteria for other subtypes.
The STN-DBS outcome was evaluated as the maintenance of Schwab & England (S&E) score ≥70% within 8-23 months after surgery. Mann-Whitney, ANCOVA, and logistic regression were used for analyses.

Results: We included 154 patients: 26.6% were categorized as MM, 50.7% IN, and 22.7% DM phenotype. No pre-surgical difference was found in age, PD duration, age at PD onset, LEDD, UPDRS-III response to levodopa, motor fluctuations, and S&E score among the 3 groups.
After a mean follow-up of 14.2±3.5 months, the MM phenotype had a significantly greater probability of maintaining independence when compared to the DM phenotype (OR:9.489; p:0.040); the IM phenotype showed a mild, non-significantly higher probability than DM (OR:1.712; p:0.380). The three phenotypes significantly differed in the S&E score (MM: 90.1±2.1; IN: 86.2±1.4; DM: 80.9±2.1; p:0.006) after correcting for age at onset, disease duration, and LEDD. The DM phenotype showed significant differences vs. the MM and IM phenotypes (p:0.004 and p:0.038).

Conclusion: The new PD phenotype classification may serve to inform the patient selection and prognostic counseling in candidates for STN-DBS.

References: [1] De Pablo-Fernández E, Lees AJ, Holton JL, Warner TT. Prognosis and Neuropathologic Correlation of Clinical Subtypes of Parkinson Disease. JAMA Neurol. 2019 Apr 1;76(4):470-479.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinson-disease-phenotype-classification-predicts-the-outcome-of-deep-brain-stimulation/