Characterization and localization of upper and lower extremity motor improvements in STN DBS for Parkinson's disease

https://doi.org/10.1016/j.parkreldis.2021.11.036Get rights and content

Highlights

  • Subthalamic DBS improves tremor > rigidity > bradykinesia

  • Improvement in UE rigidity > LE rigidity; tremor and bradykinesia are the same

  • Loci for maximal effect in UE and LE cardinal signs overlap

  • Differences in STN DBS responses are likely due to downstream network effects

Abstract

Introduction

Subthalamic deep brain stimulation (STN DBS) may have differential effects on cardinal motor signs of Parkinson's disease (PD) in the upper and lower extremities. In addition, sites of maximally effective DBS for each sign and extremity may be distinct. Our study seeks to elucidate these structure-function relationships.

Methods

We applied an ordinary least squares linear regression model to measure motor effects of STN DBS on upper (UE) and lower (LE) extremity tremor, rigidity, and bradykinesia. We then applied an atlas-independent electrical-field model to identify sites of maximally effective stimulation for each sign and each extremity. Distances between sites and statistical power to resolve differences were calculated.

Results

In our study population (n = 78 patients), STN DBS improved all cardinal motor signs (β = 0.64, p < .05). Improvement magnitudes were tremor > rigidity > bradykinesia. Effects of STN DBS on UE versus LE signs were statistically equal for tremor and bradykinesia, but greater for UE rigidity than LE rigidity (β = 0.19, p < .05). UE maximal-effect loci were lateral, anterior, and dorsal to LE loci, but were not statistically resolved, despite sufficient statistical power to resolve differences of ≤0.48 mm (p < .05) between maximally effective loci of stimulation.

Conclusion

STN DBS produces differential effects on UE and LE rigidity, but not for tremor or bradykinesia. This finding is not explained by distinct UE and LE loci of maximally effective stimulation. Instead, we hypothesize that downstream effects of STN DBS on motor networks and limb biomechanics are responsible for observed differences in UE and LE responses.

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder with heterogeneous clinical features in terms of symmetry, upper and lower extremity involvement, and severity [1,2]. Subthalamic nucleus deep brain stimulation (STN DBS) is a well-established therapy for medically intractable PD. The complex, differential effects of PD on motor networks, as well as its variable clinical presentation, raise the question whether upper (UE) and lower (LE) extremities respond in similar fashion to STN DBS, and where loci of maximally effective stimulation may be located. To date, few studies have investigated the differential effect of STN DBS on UE and LE motor signs [3]. Local field potential recordings from DBS electrodes illustrate a differential somatotopic organization of UE and LE processing regions within the STN in both the spatial and the spectral domains [4]. Single-track microelectrode recording (MER) of unit activity during passive repetitive movements show UE-responsive cells are lateral, anterior, and dorsal to LE-responsive cells [5]. However, whether similar somatotopic differentiation occurs in clinical responsiveness to STN stimulation remains unknown.

To characterize and to localize STN DBS effects on UE and LE, this study first examined the responses of cardinal motor signs (tremor, rigidity, and bradykinesia) to STN DBS. Following this differential analysis, an atlas-independent, fully individualized computational electric field model was applied to identify loci of maximal effect for UE and LE motor improvement for each cardinal sign.

Section snippets

Patient population

We performed a cross-sectional study to investigate the cardinal motor responses of 78 patients with advanced PD, treated with STN DBS between 2007 and 2018. All patients provided informed consent under the Medical Institutional Review Board of the University of Michigan. The detailed selection criteria for patients undergoing STN DBS has been previously reported [6].

DBS procedure

DBS surgery was performed in two stages: Non-segmented DBS electrode (Medtronic 3389) insertion and pulse generator placement.

Patient demographics and motor outcomes

Among 78 patients (56 males and 22 females), 75 underwent STN DBS bilaterally and 3 unilaterally, yielding 153 leads (131 monopolar, 20 bipolar, and 2 double monopolar) and 312 extremities. Each extremity was examined in one region for rigidity and tremor, three subregions (finger, wrist, and forearm) for bradykinesia in upper extremity, and two subregions (toe and leg) for bradykinesia in lower extremity. Therefore, the overall number of examinations was 1404. The average disease duration was

Discussion

STN DBS unequally improves all three cardinal motor signs of PD. Improvement magnitudes are tremor > rigidity > bradykinesia. Not all patients exhibit each cardinal symptom. At the same time, a large minority of patients experience either no change (17%–40%) or worsening (1%–10%) with STN DBS (Table 2).

Our study finds differences in clinical responses for upper and lower extremity rigidity to STN DBS. Upper and lower extremity tremor and bradykinesia respond similarly to STN DBS. Observed

Conclusion

This study provides an analytical model to assess the clinical motor improvement in each cardinal sign of PD for upper and lower extremities and identifies the loci of maximal stimulation effect. An observed difference in motor improvement between UE and LE rigidity is not explained by stimulation localization, but may be associated with downstream neuronal and non-neuronal pathophysiological components of rigidity.

Declaration of competing interest

None.

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