Predictive factors affecting early deterioration of axial symptoms after subthalamic nucleus stimulation in Parkinson’s disease

doi:10.1016/j.parkreldis.2010.07.008

Parkinsonism & Related Disorders

Volume 16, Issue 9, November 2010, Pages 582-584

https://doi.org/10.1016/j.parkreldis.2010.07.008 Get rights and content

Abstract

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment option for medically refractory Parkinson’s disease (PD). However, some patients show deterioration of axial symptoms within a short time after surgery. We studied 43 patients who underwent bilateral STN-DBS and investigated predictive factors affecting early deterioration of axial symptoms. Among 43 patients, 16 patients showed obvious deterioration of axial symptoms within three years of surgery. Multiple logistic regression analysis indicated that the significant independent variables related to early deterioration of axial symptoms were rapidly progressive short duration of the disease and advanced age at surgery. These results suggest that patients with rapidly progressing PD, who need early surgical intervention, tend to show early deterioration of axial symptoms after STN-DBS.

Introduction

Recently, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be the most promising surgical treatment for medically refractory Parkinson’s disease (PD). STN-DBS effectively improves cardinal motor symptoms of PD and fluctuations, and also reduces the need for antiparkinsonian medication. Recent long-term studies revealed that the effects of STN-DBS are sustained over time. However, some patients show deterioration of axial symptoms such as gait disturbance or postural instability within a short time after surgery. [1], [2], [3], [4], [5], [6]. In the present study, we investigated predictive factors affecting early deterioration of axial symptoms among our patients after bilateral STN-DBS.

Section snippets

Patients and assessments

We studied 43 patients who underwent bilateral STN-DBS for motor complications resulting from levodopa and were followed for more than 3 years post surgery. All patients underwent bilateral surgery in one-stage at Nagoya City University Hospital between November 2003 and December 2005. Quadripolar DBS electrodes (Activa 3389; Medtronic, Minneapolis, MN) were implanted into the STN stereotactically under MRI guidance with physiological refinement by microelectrode recording. The DBS lead was

Results

The results of univariate analysis between patients with and without early deterioration of axial symptoms are summarized in Table 1. Only duration of the disease up to surgery was significantly different between the two groups. It was significantly shorter in patients with early deterioration of axial symptoms after STN-DBS (P = 0.0008).

The results of multiple logistic regression analysis are summarized in Table 2. The significant independent variables related to early deterioration of axial

Discussion

STN-DBS has been widely performed for medically refractory PD and its beneficial long-term effect has been demonstrated. STN-DBS can maintain improvement in motor symptoms such as tremor, rigidity, and bradykinesia over a long period. Nevertheless, some patients develop deterioration in axial symptoms such as freezing of gait and postural instability after a few years, in spite of experiencing some improvement in the early period after surgery [1], [2], [3], [4], [5], [6]. In general, these

Acknowledgment

We would like to thank the physical and occupational therapists for their commitment and dedication in this study. They are Mitsuya Horiba, Yutaka Yamashita, Fumiyasu Ishii, Maria Mizuguchi, Takehiko Yamanaka, Miwako Shimizu.

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Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease
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Cited by (14)

Identifying subtypes of treatment effects of subthalamic nucleus deep brain stimulation on motor symptoms in patients of late-stage Parkinson's disease with cluster analysis
2022, Brain Hemorrhages
Citation Excerpt :
These results indicate the existence of some responders to STN-DBS in late-stage PD patients. However, previous studies also pointed out that some of the PD patients who accepted STN-DBS presented progressed axial symptoms, decreased executive function, and reduced speaking fluency.8–10 Some of the patients even presented more severe cognitive disorders when compared with the responders.11
Parkinson's disease (PD) presents clinical heterogeneity in late-stage patients who show a varied responsivity to subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms. To explore the heterogeneity of STN-DBS effect on motor symptoms in late-stage PD patients and to categorize the patients, basic characteristics, preoperative motor symptoms, and motor symptoms one month and one year after the operation of 28 late-stage PD patients were collected and analyzed with agglomerative hierarchical clustering. Preoperative motor complications, non-motor symptoms, and late-stage related manifestations were also collected and compared among the clusters. The analysis revealed three patient clusters with different motor features: 1) high response; 2) low response, and 3) moderate response with fast progression. Clinical characteristics showed significant differences in disease duration, postoperative UPDRS-III, decrease in UPDRS-III, and index of progression. Patterns of the six major motor symptoms can clearly differentiate the three clusters. Preoperative dyskinesia, memory decline, and visual hallucination were also found to differ in the three clusters. The current study identified three clusters of late-stage PD patients showing distinct responses to STN-DBS on motor symptoms. These clustering patterns may relate with diverse dopaminergic/non-dopaminergic impairments and hopefully help to categorize late-stage PD patients and to select adequate STN-DBS candidates.
Bilateral subthalamic deep brain stimulation is an effective and safe treatment option for the older patients with Parkinson's disease
2018, Clinical Neurology and Neurosurgery
Citation Excerpt :
First of all, age itself is a risk for the progression of PD [25,26], and combined pathologies are more common in older patients [27,28]. Additionally, axial symptoms, including gait disturbance, postural instability and speech problems, are expected to poorly respond to DBS, and older patients had more axial symptoms compared to younger PD patients [9,29,30]. Therefore, it is important to select PD patients with great levodopa response, considering limited response from dopaminergic medications in possible combined pathologies such as vascular parkinsonism.
We aimed to provide evidence that subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and safe treatment option for older patients with Parkinson’s disease (PD).
Bilateral STN DBS was performed in 55 patients with PD from 2012 to 2016 at Samsung Medical Center. We divided them into two groups based on the age at DBS: younger group (<65 years, n = 38) and older group (≥65 years, n = 17). For evaluating effectiveness, we compared pre- and post-DBS Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 and 4 scores and levodopa equivalent daily dose (LEDD) between the two groups. Additionally, surgery-related complications in each group were assessed.
The mean age of the younger group was 56.7 ± 5.7 and that of the older group was 68.5 ± 2.9. More female patients underwent STN DBS in the younger group, but there were no differences in baseline characteristics. In terms of effectiveness, UPDRS part 3 and 4 scores and LEDD significantly improved 6 months after DBS in both groups. In terms of safety, 1 complication was observed in the younger group (2.6%), while 2 complications, including 1 subject with intracerebral hemorrhage, were observed in the older group (11.8%, p = 0.225).
Based on our results, STN DBS can be applied in well-selected older patients with PD as well as in younger patients. However, despite the lack of statistical significance, more attention should be paid on surgical complications in the older group.
Subthalamic Stimulation Improves Quality of Life of Patients Aged 61 Years or Older With Short Duration of Parkinson's Disease
2018, Neuromodulation
Citation Excerpt :
On the other hand, the authors of the EARLYSTIM study proposed their strategy as a possibility to prevent social, occupational, and professional withdrawal and prolong the phase of good QoL at a critical point in the disease course (6,7,32). Age has repeatedly been implied as a negative predictor for DBS outcomes, e.g., surgical complications (33), motor functions (34), QoL, and axial signs (10,35). However, recently its role as a rigid exclusion criterion was questioned when similar complication rates were reported between elderly (>75 years) and younger patients (33) although this study focused on all targets, not just the STN.
The optimal timing of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD) is a topic of ongoing debate. In patients with short disease duration an improvement of quality of life (QoL) has been demonstrated for patients aged younger than 61 years. However, this has not been systematically investigated in older patients yet. We hypothesized that patients aged 61 years or older experience a significant QoL improvement after STN-DBS with no difference in effect sizes for groups of patients with short and longer disease duration.
From four centers (Cologne, London, Manchester, Venice) we identified “older patients” aged 61 years or older with short (≤8 years) or longer disease duration and compared QoL, motor impairment, complications, medication requirements, and Mini-Mental State Examination (MMSE) on baseline and five months after surgery.
Mean age/disease duration in 21 subjects with shorter disease duration were 65.5/6.3 years compared to 66.8/14.6 in 33 subjects with longer disease duration. The short disease duration group was affected by less baseline motor complications (p = 0.002). QoL in the short/longer disease duration group improved by 35/20% (p = 0.010/p = 0.006), motor complications by 40/44% (p = 0.018/p < 0.001), and medication requirements by 51/49% (both p < 0.001). MMSE remained unchanged in both groups.
Patients aged 61 years or older benefited from STN-DBS regardless of short (≤8 years) or longer (>8 years) disease duration. Our results contribute to the debate about DBS selection criteria and timing and call for prospective confirmation in a larger cohort.
The impact of age and disease duration on the long term outcome of neurostimulation of the subthalamic nucleus
2014, Parkinsonism and Related Disorders
Citation Excerpt :
Similar to our results, a stronger progression of non-dopaminergic axial and postural manifestations in older DBS patients was found in several studies [6–8]. One study demonstrated that patients with advanced stage tend to develop early axial deterioration after DBS-STN due to more rapid disease progression [21]. Moreover, older PD patients [22] and older persons [23] are associated with progressive deterioration of gait and postural impairment contributing to patients' disability.
Selection of patients with Parkinson's disease for neurostimulation of subthalamic nucleus (STN-DBS) is still poorly studied.
To identify the impact of age and disease duration on the outcome of bilateral STN-DBS.
110 operated patients in a single center covering a large range of age and disease duration were retrospectively included and followed for up-to 5 years. Standardized UPDRS assessments were obtained at 0.5–1 and 3–5 years. Patients were stratified into three age groups (≤55, 56–64 and ≥65 years) and the middle age group was further stratified into 2 disease duration subgroups (<15years, ≥15 years).
The age groups had comparable baseline data except for the predefined differences. Compared to baseline early and late intra-group “Med Off-Stim On” motor scores were significantly improved for all groups (p < 0.001). Mood/cognition were significantly improved in younger two groups (p = 0.008, 0.019) at 0.5–1 year. Inter-group comparisons showed significantly worse early and late axial scores for older patients (p < 0.05). All groups had comparable postoperative improvement except for the older group which had significantly less improvement of early UPDRS-II, late UPDRS-I, and early and late PIGD/axial scores. Different disease durations had no effect on the outcome except for worse Schwab and England Off-score in longer duration group (p = 0.02). Side effects of surgery and long-term management were similar.
STN-DBS is an efficient treatment of advanced PD for all treated age-groups. Provided strict inclusion criteria are respected, older age and longer disease duration are associated with slightly worse effects mainly on L-dopa-resistant symptoms.
Axial impairment and falls in Parkinson’s disease: 15 years of subthalamic deep brain stimulation
2022, npj Parkinson's Disease
Challenges in PD Patient Management After DBS: A Pragmatic Review
2018, Movement Disorders Clinical Practice

View all citing articles on Scopus

^☆: The review of this paper was entirely handled by an Associate Editor, Eng-King Tan.

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Predictive factors affecting early deterioration of axial symptoms after subthalamic nucleus stimulation in Parkinson’s disease☆

Abstract

Introduction

Section snippets

Patients and assessments

Results

Discussion

Acknowledgment

Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease

N Engl J Med

Bilateral deep brain stimulation in Parkinson’s disease: a multicentre study with 4 years follow-up

Brain

Evolution of Parkinson’s disease during 4 years of bilateral deep brain stimulation of the subthalamic nucleus

Mov Disord

Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease

J Neurol

Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease: five year follow-up

J Neurol

Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson’s disease: long-term observation

Mov Disord