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