Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson's Disease

Geetanjali Gera, Zain Guduru, Tritia Yamasaki, Julie A Gurwell, Monica J Chau, Anna Krotinger, Frederick A Schmitt, John T Slevin, Greg A Gerhardt, Craig van Horne, Jorge E Quintero, Geetanjali Gera, Zain Guduru, Tritia Yamasaki, Julie A Gurwell, Monica J Chau, Anna Krotinger, Frederick A Schmitt, John T Slevin, Greg A Gerhardt, Craig van Horne, Jorge E Quintero

Abstract

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna.

Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson's disease.

Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD.

Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months.

Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results.

Keywords: Parkinson’s disease; balance; cell therapy; deep brain stimulation; gait.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Participants inclusion flowchart.
Figure 2
Figure 2
(A) UPDRS III (B) UPDRS III Item-29 (Gait) (C) Hoehn and Yahr and (D) UPDRS III Item-30 (Postural Stability) clinical scales at baseline (0 month), 6 and 24 months post-surgery. Group means (SE), and example subjects: Parkinson’s disease (PD) subject 1 (UPDRS = 54), and PD subject 2 (UPDRS = 39).
Figure 3
Figure 3
(A) Cadence (B) Velocity (C) Step length (less) and (D) Step length (more) affected sides at baseline(0 month), 6 and 24 months post-surgery. Group means (SE), and example subjects: Parkinson’s disease (PD) subject 1 (UPDRS = 54), and PD subject 2 (UPDRS = 39).

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