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Within the first 2 years of DBS treatment, patients with Parkinson experienced improvements in freezing of gait and other axial signs in off periods compared to best medical treatment.
Paul Krack, MD, PhD
Compared to best medical treatment, deep brain stimulation (DBS) may be able to improve outcomes related to freezing of gait and other gait outcomes in patients with Parkinson disease who have early motor complications.
These secondary results of the EARLYSTIM trial suggest that DBS of the subthalamic nucleus can significantly improve the freezing of gait, doing so within 24 months for those treated with it by reducing it by 18% for a group of 124 patients. Additionally, axial signs improved in the stimulation group compared to the best medical treatment group (P <.01) in both medication-off and medication-on conditions.
The investigation, which included Paul Krack, MD, PhD, professor of neurology, chief physician, and head, Movement Disorder Center, University Hospital Bern, compared the use of DBS (n = 124) to best medical treatment (n = 127).
“Our study was of high quality, with randomization of a large number of patients and randomization to a control group with best medical treatment,” Krack and colleagues wrote. “The patients were treated with routine, high-frequency stimulation parameters and were implanted at common, center-specific stereotactic coordinates for subthalamic nucleus-DBS. Programming of DBS parameters was not specifically aimed at improving FOG. Therefore, this trial provides higher-class evidence compared to most other DBS studies, which focused on axial signs and freezing of gait.”
Krack and colleagues concluded that the findings demonstrate a clear benefit during the first 2 years and noted that any concern that freezing of gait may worsen in this patient population because of earlier DBS is “not supported” by these data and that the findings “are important for Parkinson disease patient counseling.”
In total, at baseline, both the best medical treatment group and the DBS group had freezing of gait occur in 52% of patients. After 2 years, the DBS group experienced a decrease of this percentage to 34%, while the best medical group’s percentage remained steady at 52% (P = .018). The effect of DBS on freezing of gait was observed to be similar at 5 months and 12 months of follow-up.
The DBS group featured 55 patients who were freezers, with 60% (n = 33) of them turning into nonfreezers, compared to only 27% (n = 15) of their 56 counterparts in the best medical treatment group. This, Krack and colleagues detailed, is of particular interest due to the observation of a reduction in the mean levodopa equivalent daily dose of 39% in the DBS group compared to an increase of 21% in the best medical treatment group.
The results of this EARLYSTIM analysis also showed that the 15 of those who were freezers at baseline and had become nonfreezers by 24 months in the best medical treatment group had an average levodopa equivalent daily dose of 1,132.13 mg/day (standard deviation, 302.9), corresponding to an increase of 54.1%. In the DBS group, those who transitioned from freezers to nonfreezers (n = 31) had an average levodopa daily dose at 24 months of 498.9 mg/day (SD, 382.1), corresponding to a decrease of 34.2%.
“Yet in both treatment groups, the proportion of patients developing freezing of gait over the course of 24 months, most likely attributable to disease progression, was the same and amounted to roughly 12% of patients. We interpret this finding as the natural course of disease with an increasing incidence of freezing of gait independent of therapy,” Krack and colleagues wrote. As well, the severity of freezing of gait between groups was significantly less in the DBS group (odds ratio [OR], 3.96 [±1.50]; P = .0003)
The study did not reveal a change in Unified Parkinson’s Disease Rating Scale-II (UPDRS-II) q14best scores between baseline and 24 months for either group (DBS, P = .55; best medical treatment, P = .57). The gait subscore of the Parkinson’s Disease Questionnaire (PDQ-39) improved from 6.40 ±0.23 at baseline to 4.50 ±0.25 at 24 months (P <.0001), but did not change significantly for the best medical treatment group in the same time frame (baseline: 6.50 ±0.23; 24 months: 6.70 ±0.25; P = .81). The difference in mean change between the DBS group and BMT group of 2.30 ±0.17 was also significant (P <.0001).
“Our study illustratively confirms clinical experience that the spectrum of freezing of gait outcomes after DBS shows unfavorable (i.e., no effect) and favorable outcomes,” the investigators wrote. “A severe increase of freezing of gait after DBS, as described in paradoxical freezing of gait, was not observed in this cohort of patients.”
Barbe MT, Tonder L, Krack P, et al. Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease With Early Motor Complications. Movement Dis. Published online November 22, 2019. doi: 10.1002/mds.27892.