In Early Parkinson, Quality of Life is Predictive of DBS Outcomes

Michael Schuepbach, MD, from the Department of Neurology at Hopital Piticute-Salpecirctrire, in Paris, France

Michael Schüpbach, MD

The findings of a recent study have suggested that the 39-item Parkinson’s Disease Questionnaire summary index (PDQ-39-SI) may have some predictive value in determining future outcomes for patients with Parkinson disease who undergo deep brain stimulation (DBS).¹

Ultimately, the results of the secondary analysis of the EARLYSTIM study data revealed that a lower quality of life (higher PDQ-39-SI score) at baseline was correlated to the change in PDQ-39-SI score in both the group that received subthalamic nucleus DBS (n = 124) and the best medical treatment group (n = 127) after 2 years (P <.05). No other correlations were found for any other baseline characteristics.

Michael Schüpbach, MD, from the Department of Neurology at Hôpital Pitié-Salpêtrière, in Paris, France, and coauthors concluded that the results should prompt the systematic inclusion of disease-specific quality of life evaluations when selecting patients with Parkinson for DBS.

“Impaired [quality of life] as subjectively evaluated by the patient is the most important predictor of benefit in patients with [Parkinson] and early motor complications, fulfilling objective gold standard inclusion criteria for [subthalamic-DBS],” they wrote.

EARLYSTIM was a prospective, randomized trial comparing subthalamic DBS with best medical treatment alone over 24 months. The cohort was “intended to broadly represent the group of relatively young patients with PD and early motor complications as seen in daily practice,” according to the investigators. They noted that in such a population, the potential for improvement is more modest than in advanced patients with Parkinson.

The results showed that the change in the quality of life over the study period correlated with baseline PDQ-39-SI in the investigators’ regression model (P <.001 for both groups), though the effect was more pronounced for the DBS group (P <.0262 for interaction).

Four categories were fleshed out for baseline PDQ-39-SI values (0-15; 15-30; 30-45; and >45) for the 2 groups. At baseline, those in the DBS group that had a score of 15-30, 30-45, or >45 all experienced a statistically significant change from baseline, with respective changes at 24 months of 7.1, 12.6, and 21.1 points (P <.05 compared to best medical treatment). Comparatively, those in the best medical treatment group with similar baseline values saw respective changes of -1.2, 1.7, and 7.4 points.

These changes in PDQ-39-SI scores were independent of age, disease duration, motor complication duration, the severity of parkinsonian motor signs in “off” and “on” medications (as measured by the Unified Parkinson Disease Rating Scale-III scores), the severity of levodopa-induced complications, and “off” time at baseline.

Notably, Schüpbach and colleagues noted that “levodopa response of the motor score (UPDRS III) at baseline was not predictive for the change of the [quality of life] outcome between baseline and 24 months in the DBS-group or in the [best medical treatment] control group.”

The investigators debated if the benefit from subthalamic DBS produced a floor effect with a minimum level of disease-related suffering to be prerequisite for the possible advantage from the intervention. They found that in the subgroup of patients with PDQ-39-SI scores <15, there was no difference between the quality of life for the outcome between groups. Interestingly enough, the DBS group in this sub-analysis actually had worse average outcomes.

“However, this post hoc secondary analysis must be taken with reserve, especially since the subgroup with PDQ-39-SI ratings under 15 was very small and some individuals in this group had an excellent improvement of [quality of life] with [DBS] and would wrongly have been barred from a beneficial treatment if a strict cutoff level for the indication of STN-DBS had been applied,” Schüpbach and colleagues wrote. As such, in those with very low baseline ratings on the PDQ-39-SI, the progression of quality of life impairment which naturally occurs may overshadow the improvements from DBS.

On the other hand, they concluded that select patients “with very modest impairment” of their quality of life appear to gain less from DBS. “If they choose to undergo neurosurgery, they may do it for the wrong reasons and have expectations that are unrealistic,” and could lead to disappointment which could be reflected on the PDQ-39-SI, they noted. Therefore, a thorough assessment of the motives for neurosurgery and expectations of DBS are required if the impairment of quality of life is modest.

Importantly, Schüpbach and colleagues noted that the highly selected patient population is a limitation of the study. As well, they suggested that due to the fact that operated patients in the EARLYSTIM study had an excellent average baseline levodopa response (63.5% ±16.2), poor quality of life in patients in the absence of levodopa responsive motor symptoms “should not be regarded as an indication for surgery.”

REFERENCE

1. Schüpbach WMM, Tonder L, Schnitzler A, et al. Quality of life predicts outcome of deep brain stimulation in early Parkinson disease. Neurology. 2019;92(10). Published online February 8, 2019. https://doi.org/10.1212/WNL.0000000000007037.