Bilateral Subthalamic Nucleus Deep Brain Research Articles

Disentangling Bradykinesia and Rigidity in Parkinson Disease: Evidence from Short- and Long-Term Subthalamic Nucleus Deep Brain Stimulation.

Bradykinesia and rigidity are considered closely related motor signs in Parkinson disease (PD), but recent neurophysiological findings suggest distinct pathophysiological mechanisms. This study aims to examine and compare longitudinal changes in bradykinesia and rigidity in PD patients treated with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). In this retrospective cohort study, the clinical progression of appendicular and axial bradykinesia and rigidity was assessed up to 15 years after STN-DBS in the best treatment conditions (ON medication and ON stimulation). The severity of bradykinesia and rigidity was examined using ad hoc composite scores from specific subitems of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III). Short- and long-term predictors of bradykinesia and rigidity were analyzed through linear regression analysis, considering various preoperative demographic and clinical data, including disease duration and severity, phenotype, motor and cognitive scores (eg, frontal score), and medication. A total of 301 patients were examined before and 1 year after surgery. Among them, 101 and 56 individuals were also evaluated at 10-year and 15-year follow-ups, respectively. Bradykinesia significantly worsened after surgery, especially in appendicular segments (p < 0.001). Conversely, rigidity showed sustained benefit, with unchanged clinical scores compared to preoperative assessment (p > 0.05). Preoperative motor disability (eg, composite scores from the UPDRS-III) predicted short- and long-term outcomes for both bradykinesia and rigidity (p < 0.01). Executive dysfunction was specifically linked to bradykinesia but not to rigidity (p < 0.05). Bradykinesia and rigidity show long-term divergent progression in PD following STN-DBS and are associated with independent clinical factors, supporting the hypothesis of partially distinct pathophysiology. ANN NEUROL 2024.

Neurocognitive changes at different follow-up times after bilateral subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

BackgroundBilateral deep thalamic nucleus brain stimulation (STN-DBS) surgery is often used to treat the motor symptoms of patients with Parkinson's disease. The change of neurocognitive symptoms in patients is, however, still unclear. ObjectiveWe aimed at analyzing the deterioration of neurocognitive symptoms in patients with Parkinson's disease after deep brain stimulation surgery under different follow-up times. MethodsA comprehensive literature review was conducted using Pubmed, Cochrane Library, and Web of Science to screen eligible study records, the meta-analysis was performed using an inverse variance method and a random-effects model. Additionally, the areas of analysis include five: cognition, executive function, memory capacity, and verbal fluency (phonetic fluency and semantic fluency). They were analyzed for changes at six and twelve months postoperatively compared to baseline. The Meta-analysis has been registered with PROSPERO under the registration number: CRD42022308786. ResultsIn terms of overall cognitive performance, executive function, and memory capacity, the original studies show a trend of improvement in these areas at 12 months postoperatively compared with 6 months, at variance, patients did not improve or deteriorated in phonetic fluency(d = −0.42 at both 6-month and 12-month follow-up) and semantic fluency from 6 to 12 months postoperatively. ConclusionIn terms of most neurocognitive symptoms, including cognitive ability, executive function, and learning memory capacity, bilateral STN-DBS surgery appears to be safe at relatively long follow-up times. However, postoperative phonetic and semantic fluency changes should still not be underestimated, and clinicians should pay more attention to patients' changes in both.

The impact of bilateral subthalamic nucleus deep brain stimulation on dyskinesia and levodopa equivalent daily dose in advanced Parkinson’s disease

Abstract OBJECTIVE: To assess the effect of bilateral subthalamic nucleus deep brain stimulation (B/L STN DBS) on the progression of dyskinesia and the levodopa equivalent daily dose (LEDD) in advanced Parkinson’s disease (APD) patients 6 months postoperatively. METHODS: Seventeen APD patients aged 21–80 years with the minimum modified Hoen &amp; Yahr score of 2 while off medication and poor motor function underwent B/L STN DBS from January 2021 to December 2021. They were assessed preoperatively and 6 months postoperatively using the Unified dyskinesia rating scale (UDysRS) and Unified Parkinson’s Disease Rating Scale Part IV (UPDRS IV) for dyskinesia and LEDD dosage. RESULTS: Significant improvement was observed postoperatively in both UDysRS (pre-op 66.53 ± 24.59, post-op 30.88 ± 12.01; P = 0.000) and UPDRS IV (pre-op 9.24 ± 1.75, post-op 5.76 ± 1.39; P = 0.000) scores. The overall clinical improvement using UDysRS was 52.23 ± 16.23%. Each subscale of UDysRS showed significant improvement postoperatively: ON dyskinesia (pre-op 21 ± 7.7, post-op 13.76 ± 5.79; P &lt; 0.05); OFF dystonia (pre-op 8.53 ± 3.26, post-op 4.94 ± 2.70; P &lt; 0.05); impairment (face, pre-op 2.47 ± 2.52, post-op 0.29 ± 0.98, P &lt; 0.05; neck and trunk, pre-op 6.29 ± 4.55, post-op 0.59 ± 0.87, P &lt; 0.05; arms, pre-op 13.06 ± 5.86, post-op 5.76 ± 3.7, P &lt; 0.05; and legs, pre-op 7.18 ± 5.12, post-op 1.29 ± 1.57, P &lt; 0.05); and disability (pre-op 8 ± 3.46, post-op 4.24 ± 2.25; P &lt; 0.05), suggesting high clinical significance. LEDD (pre-op 673.41 ± 212.69 mg, post-op 386.82 ± 133.01 mg; P = 0.000) showed significant reduction in dosage 6 months postoperatively. LEDD reduction and dyskinesia improvement showed mild-to-moderate positive correlation (r = 0.404). CONCLUSION: B/L STN DBS helps in improving dyskinesia by reducing LEDD in APD patients.

The efficacy analysis of neurosurgical robot-assisted DBS in the treatment of elderly Parkinson's disease

Objective: To investigate the surgical efficacy of neurosurgery robot deep brain stimulation(DBS) in the treatment of elderly Parkinson's disease(PD). Methods: The clinical data of elderly patients (≥75 years) with PD who underwent neurosurgical robot-assisted DBS surgery in the Department of Neurosurgery of the General Hospital of Northern Theater Command from September 2016 to September 2022 were collected retrospectively. Operation time, electrode implantation duration, postoperative pneumocephalus volume, electrode implantation accuracy, the Tao's DBS surgery scale, perioperative complications were analyzed.The unified Parkinson's disease rating scales (UPDRS), UPDRS-Ⅲ, tremor, rigidity, bradykinesia, axial, Barthel Activities of Daily Living (ADL-Barthel), Levodopa Equivalent Daily Dose (LEDD), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores and mortality were assessed respectively before operation, 6, 12 and 24 months after operation and last follow-up. Results: A total of 25 elderly patients were enrolled, including 14 males and 11 females, aged(78.3±3.2) years. Nine patients had underlying diseases. Nine patients (36%) underwent bilateral Globus Pallidus pars Interna deep brain stimulation (GPi-DBS) and 16 patients (64%) underwent bilateral subthalamic nucleus deep brain stimulation (STN-DBS).The operation time was (1.56±0.19) hours, the electrode implantation duration was (1.01±0.19) hours, the pneumocephalus volume was 9.8(4.7, 23.3) cm3, and the electrode implantation accuracy was (0.84±0.24) mm, the Tao's DBS surgery scale was (80.2±6.2).The follow-up time [M(Q1, Q3)] was 57.3(27.9, 75.7) months. No serious complications such as intracranial hemorrhage, infection or poor wound healing occurred during the perioperative period. The improvement rate of UPDRS, UPDRS-Ⅲ, rigidity, bradykinesia, and LEDD at 6 months after surgery was significantly higher than that at 24 months after surgery and at the last follow-up (all P<0.05); the improvement rate of axial symptoms, ADL-Barthel score, and MoCA score at 6 months after surgery was significantly higher than that at the last follow-up (P<0.05). HAMD and HAMA scores showed no significant improvement during follow-up after surgery (both P>0.05). At the last follow-up, 12 patients died, with death time of (35.1±20.2) months after operation, and the death age of [M(Q1, Q3)] 80(79, 83)years. Conclusions: Robot-assisted DBS surgery for elderly patients with PD is accurate and safe, and the postoperative symptoms are significantly improved, and they can benefit from neuromodulation for long term, and the risks are controllable.

Deep brain stimulation in a pediatric dystonia patient with cochlear implants and mitochondrial disorder: novel application of a frameless stereotactic system and navigating the anesthesia choice and neurosurgical complexities. Illustrative case.

This report presents a case of medically refractory dystonia in a pediatric patient successfully treated with bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) while under general anesthesia by using microelectrode recordings (MERs) with intraoperative computed tomography (CT). The patient was an 18-year-old female with primary dystonia secondary to mitochondrial Leigh syndrome. Her past medical history was significant for complex partial epilepsy and hearing loss treated with cochlear implants. Her cochlear implants precluded anatomical targeting via magnetic resonance imaging. Additionally, the patient could not tolerate awake surgery with MER. The decision was made to proceed with bilateral STN DBS with intraoperative CT with the patient under general anesthesia. The patient's cochlear implants made standard frame placement difficult, so navigation was performed with the Nexframe system. Recordings were obtained with the patient under general anesthesia with ketamine, dexmedetomidine, and remifentanil. At the 3- and 6-month follow-ups, the patient demonstrated marked improvement in dystonia without neurological complications. This is the first case of dystonia secondary to Leigh syndrome treated with DBS. Additionally, the authors describe the novel use of the Nexframe for DBS lead placement in a pediatric patient. This demonstrates that STN DBS with the use of MER and intraoperative CT can be a safe and effective method of treating dystonia in certain pediatric patients.

Long-term effects of subthalamic nucleus deep brain stimulation on speech in Parkinson’s disease

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on speech are still debated, particularly in the long-term follow-up. The objective of this study was to evaluate the long-term effects of bilateral STN-DBS on speech in a cohort of advanced PD patients treated with bilateral STN-DBS. Each patient was assessed before surgery through a neurological evaluation and a perceptual-acoustic analysis of speech and re-assessed in the long-term in different stimulation and drug conditions. The primary outcome was the percentage change of speech intelligibility obtained by comparing the postoperative on-stimulation/off-medication condition with the preoperative off-medication condition. Twenty-five PD patients treated with bilateral STN-DBS with a 5-year follow-up were included. In the long-term, speech intelligibility stayed at the same level as preoperative values when compared with preoperative values. STN-DBS induced a significant acute improvement of speech intelligibility (p < 0.005) in the postoperative assessment when compared to the on-stimulation/off-medication and off-stimulation/off-medication conditions. These results highlight that STN-DBS may handle speech intelligibility even in the long-term.

Profiling the low-beta characteristics of the subthalamic nucleus in early- and late-onset Parkinson's disease.

Low-beta oscillation (13-20 Hz) has rarely been studied in patients with early-onset Parkinson's disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson's disease (LOPD). We enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group. We found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500-650 ms, p = 0.008), while LOPD had higher proportion of short burst (200-350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300-460 Hz) amplitude (p = 0.019). We found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies?

PurposeTo investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. Materials and methodsTwenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were ‘stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)’. These tests reported the centre of pressure data ‘ellipse area, perimeter, front/back and mediolateral standard deviations’. ResultsThere were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward–backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). ConclusionThis study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges.

Development and Validation of a Prediction Model for Anxiety Improvement after Deep Brain Stimulation for Parkinson Disease

Parkinson's disease (PD) represents one of the most frequently seen neurodegenerative disorders, while anxiety accounts for its non-motor symptom (NMS), and it has greatly affected the life quality of PD cases. Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can effectively treat PD. This study aimed to develop a clinical prediction model for the anxiety improvement rate achieved in PD patients receiving STN-DBS. The present work retrospectively enrolled 103 PD cases undergoing STN-DBS. Patients were followed up for 1 year after surgery to analyze the improvement in HAMA scores. Univariate and multivariate logistic regression were conducted to select factors affecting the Hamilton Anxiety Scale (HAMA) improvement. A nomogram was established to predict the likelihood of achieving anxiety improvement. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and calibration curve analysis were conducted to verify nomogram performance. The mean improvement in HAMA score was 23.9% in 103 patients; among them, 68.9% had improved anxiety, 25.2% had worsened (Preop) anxiety, and 5.8% had no significant change in anxiety. Education years, UPDRS-III preoperative score, and HAMA preoperative score were independent risk factors for anxiety improvement. The nomogram-predicted values were consistent with real probabilities. Collectively, a nomogram is built in the present work for predicting anxiety improvement probability in PD patients 1 year after STN-DBS. The model is valuable for determining expected anxiety improvement in PD patients undergoing STN-DBS.

Effects of the combined treatment of bilateral subthalamic nucleus stimulation and levodopa on balance and mobility in Parkinson's disease.

<p>Background and purpose &ndash; To evaluate the efficacy of the combined therapy of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and dopaminergic medication on balance and mobility in patients with Parkinson&rsquo;s disease (PD).</p>. <p>Eighteen PD patients under bilateral STN-DBS stimulation therapy, were enrolled in this study. Unified Parkinson&rsquo;s Disease Rating Scale (UPDRS) was applied to assess the patients&rsquo; clinical characteristics. UPDRS part III postural instability/gait disorder (PIGD) scores (sum of items 3.9-3.13) and UPDRS part III postural stability item (item 3.12) were calculated separately. Patients were evaluated with Berg Balance Scale (BBS), Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go (TUG) test, dual-task TUG test, and Forward Functional Reach (FFR) Test in two conditions: Stimulation-ON (stim-ON)/Medication-ON (Med-ON) and Stimulation-OFF (Stim-OFF)/Med-ON.</p>. <p>The mean age of patients was 59.5&plusmn;9.1 (R: 41-71) years. The UPDRS part III total score and PIGD subsection score significantly improved after stimulation (p=0.001), but the postural instability item of the UPDRS part III did not change significantly (p=0.1). There were no significant differences between the Stim-ON/Med-ON and Stim-OFF/Med-ON conditions, in terms of total Mini-BESTest total scores, total BBS score, FFR test score (p&gt;0.05 for all of them). TUG test was significantly improved in the Stim-ON/Med-ON condition compared to Stim-OFF/Med-ON condition (p=0.03), but DT-TUG test did not change (p=0.1).&nbsp;</p>. <p>Combined bilateral STN-DBS and dopaminergic medication therapy had an additional improvement on motor symptoms and mobility performance, but not on balance and dual-task mobility.&nbsp;</p>.

Deep brain stimulation for Parkinson's disease: A case for patient empowerment

Deep brain stimulation for Parkinson's disease: A case for patient empowerment

The altered spontaneous neural activity in patients with Parkinson's disease and its predictive value for the motor improvement of deep brain stimulation

BackgroundThis study aims to investigate the altered spontaneous neural activity in patients with Parkinson's disease (PD) revealed by amplitudes of low-frequency fluctuations (ALFF) of resting-state fMRI, and the feasibility of using ALFF as neuroimaging predictors for motor improvement after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). MethodsFourty-four patients and 44 healthy controls were included in this study. First, the ALFF of patients with PD was compared with that of controls; then significant clusters were correlated with motor improvement after DBS (unified Parkinson's disease rating scale (UPDRS-III)) and other clinical variables. Second, regression and classification of the machine learning models were conducted to predict motor improvement after DBS. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the classification model. ResultsCompared with healthy controls, patients with PD showed increased ALFF in the bilateral motor area and decreased ALFF in the bilateral temporal cortex and cerebellum. The Hoehn-Yahr stages correlated with ALFF within the bilateral cerebellum (p = 0.021), and UPDRS-III improvement correlated with ALFF in the left (p < 0.001) and right (p = 0.005) motor areas. The regression model showed a significant correlation between the predicted and observed UPDRS-III changes (R = 0.65, p < 0.001). The ROC analysis revealed an area under the curve (AUC) of 0.94 which differentiated moderate and superior DBS responders. ConclusionThe results revealed altered ALFF patterns in patients with PD and their correlations with clinical variables. Both binary and continuous ALFF can potentially serve as predictive biomarkers for DBS response.

Language and verbal fluency outcome after bilateral subthalamic Nucleus Deep Brain Stimulation in Parkinson's disease

BackgroundLanguage disorders in Parkinson's Disease (PD) following bilateral subthalamic Nucleus Deep Brain Stimulation (STN-DBS) are common. ObjectiveTo assess STN-DBS impact on language and observe clinical and anatomical predictors of poor outcome. MethodsWe prospectively included PD patients undergoing STN-DBS. We performed a neuropsychological evaluation focusing on language before (V0), 3 days after (V1), and 3 months after (V2) surgery. Patients performed all assessments in ON drug condition, V1 with the stimulation turned OFF to evaluate the lesion effect, and V2 with the stimulation turned ON to evaluate the stimulation effect. Electrodes and active contact locations were determined with MRI-Atlas fusion. The stimulation parameters and the total electrical energy delivered (TEED) were recorded for each patient. Results18 PD patients consecutively operated were included. We identified a decline in phonemic verbal fluency (VFP) at V1 and V2 (p = 0.023 and 0.032 respectively), as well as in semantic verbal fluency (VFS) (p = 0.025 and 0.019, respectively). There was a significant slowdown in the verbs naming test (p = 0.048). No other language alteration was recorded. There was no correlation between demographic or clinical factors and verbal fluency (VF) evolution. Active contact location within substantia nigra was associated with VFP worsening (p = 0.047), while elevated TEED on the left-sided electrode was associated with VFS decline (p = 0.021). ConclusionVF was significantly altered following STN-DBS. Location outside the dorsolateral sensorimotor STN, and high stimulation power appeared to promote this decline. Other language domains remained stable.

Added value of the instrumented Timed-Up and Go test (iTUG) in the long-term assessment of PD patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS)

STN-DBS is an effective long-term treatment in PD, improving a broad spectrum of symptoms, including tremor, rigidity, and bradykinesia (Fig. 1a) together with dopaminergic treatment. Among axial symptoms, gait disorders are common in PD. This study examines the long-term effects of different combinations of these two treatments in a cohort of advanced PD patients by means of the iTUG. Observational study on consecutive PD patients previously treated with bilateral STN-DBS. Disease severity was assessed using the UPDRS part III. Accelerometric data were acquired using an inertial sensor (G-WALK, BTS Bioengineering). Three iTUG trials were recorded in each of four stimulation and drug conditions: on-stimulation/off-medication, off-stimulation/off-medication, on-stimulation/on- medication and while preforming a cognitive task (counting backward, DUAL TASK) with both stimulation and medication on. Data were segmented into six phases (e.g., rising from chair, walking) as in [1]. A set of indices was computed including durations, RMS amplitudes, peak accelerations, peak angular velocities, indices of symmetry (improved Harmonic Ratio) and smoothness (Spectral Arc) [1]. A one-way non-parametric ANOVA was carried out, with the condition as a factor, followed by paired comparisons when appropriated. Statistical significance was set at 5% for all analyses. Twenty-five patients were re-evaluated 3 to 7 years after STN-DBS surgery, with a mean five-year postoperative follow-up. Clinical characteristics were age 64(5) y, 8/17 F/M, PD duration 16(5) y, distance from STN-DBS intervention 5(1) y, median (IQR) UPDRS-III 12(12), WHS 5(1), FAC 5(2). Most patients were able to perform the test in all conditions. Both STN-DBS alone and the combination of STN-DBS and medications led to an improvement of clinical motor scores and most iTUG parameters (p<0.001). In particular: 1) the elevation/sitting gestures and the turn phases differently improved in the different conditions; 2) on average, the effect of the DUAL TASK condition led to indices similar to those in the off-off condition 3) data from the DUAL TASK condition suggest the existence of two subgroups of patients, whose performance is either affected or not affected by the cognitive task ( Fig. 1 ). The protocol resulted feasible. Our results indicate that both STN-DBS and levodopa can improve walking ability even in the long-term after surgery. Results during DUAL TASK suggest the use of attentional strategies in the rehabilitation of selected patients, as indicated in the EU physiotherapy guidelines for PD [2]. A rehabilitative intervention should be strongly recommended in those patients whose performance in DUAL TASK becomes so impaired as in the STIM-OFF/MED-OFF, as measured by the iTUG. In conclusion, the iTUG test could be used in PD patients with STN-DBS to support the selection of tailored rehabilitative interventions and to identify patients whose performance is highly affected during cognitive tasks.

Freezing of Gait in Parkinson's Disease Patients Treated with Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Long-Term Overview.

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (≥5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and revaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the pre-operative off-medication assessment (z = −1.930; p = 0.05) but not in the on-stimulation/off-medication (z = −0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = −2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG.

Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson's Disease: 10 Years and Beyond

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. To investigate the survival rate and long-term outcome of DBS. We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

Pre-operative cognitive burden as predictor of motor outcome following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.

Long‐term efficacy of bilateral subthalamic deep brain stimulation in the parkinsonism of SCA 3: A rare case report

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited disorder that manifests as a mixture of cerebellar ataxia, parkinsonism, and polyneuropathy; in type IV SCA3, pure parkinsonism is the only symptom. Currently, no disease-modifying treatment is available, but variable responses to antiparkinsonism agents have been reported. However, the benefits of deep brain stimulation (DBS) for treating parkinsonism in this subtype of SCA3remain unclear. A 39-year-old male patient with a rare disorder of type IV SCA3 presented with pure parkinsonism including unilateral resting tremor, rigidity, and bradykinesia at the age of 30 years. Young-onset Parkinson disease was diagnosed at the age of 32 years. His family history revealed a mild ataxia in his father since the age of 55 years. Genetic testing confirmed an expanded CAG repeated number, with 66 in this case and 63 in his father for SCA3mutation. Excellent response to levodopa and dopamine agonists in the first 3years was noted, but wearing-off phenomena, levodopa-induced dyskinesia, and severe impulse control disorders later developed. To alleviate drug-induced complications, he received bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in the absence of cerebellar signs, depression, and cognitive impairment. As of 2019, no impulsive control disorders, motor fluctuations, or DBS-related complications were observed during a 4-year follow-up, with 66% Unified Parkinson's Disease Rating Scale Part III reduction at medication OFF state noted, whereas levodopa equivalent daily dosage decreased by almost half. STN-DBS may be considered as adjunct treatment for severe dopa-related motor/nonmotor complications in patients with parkinsonian phenotype of SCA 3.

A Clinical Study of Patients with Primary Parkinson's Disease Undergoing Bilateral Deep Brain Stimulation (STN-DBS) Surgery in the Subthalamic Nucleus under General Anesthesia

To assess the efficacy and safety of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) under general anesthesia and to provide the basis for clinical research related to DBS surgeries under general anesthesia. A total of 60 patients with primary Parkinson's disease who underwent DBS surgery between January 2019 and December 2021at West China Hospital were enrolled for the study. Among them, 30 had the surgery while they were asleep, i.e., under general anesthesia, and 30, while they were awake, i.e., under local anesthesia. All the patients underwent bilateral STN-DBS surgery. Bispectral index (BIS) was used to monitor and control the depth of anesthesia. Microelectrode recording (MER) technology was used to record the characteristic signals of the bilateral subthalamic nuclei and verify their location during the operation. All patients completed the implantation of deep electrodes, connecting wires, and implantable stimulation generator (IPG) at one time. Postoperative thin-slice CT scans were done to reconstruct electrode images and to verify the accuracy of electrode implantation. The Unified Parkinson's Disease Rating Scale-Ⅲ (UPDRS-Ⅲ) was used to evaluate the preoperative vs. postoperative improvement in motor symptoms, and the results of intraoperative MER and the occurrence of surgery-related complications were documented and analyzed. All patients successfully completed the implantation surgery. The electrodes were accurately implanted at the right position and there was no significant difference between the general anesthesia group and the local anesthesia group in UPDRS-Ⅲ scores and medication dosage differences before and after the operation. No intracranial hemorrhage, cerebral infarction, or infection occurred after the operation, and 5 patients had temporary mental and behavioral abnormalities, which disappeared within 48 hours after the operation. The postoperative therapeutic effect of STN-DBS surgery for primary Parkinson's disease under general anesthesia is comparable to that of the traditional STN-DBS surgery under local anesthesia. When the operation is performed under general anesthesia, the incidence of surgery and anesthesia-related complications is low if patients are managed strictly, and patients would also experience improved surgical comfort.

Nomogram for Predicting Depression Improvement after Deep Brain Stimulation for Parkinson's Disease.

Background: Parkinson’s disease is a common neurodegenerative disease, with depression being a common non-motor symptom. Bilateral subthalamic nucleus deep brain stimulation is an effective method for the treatment of Parkinson’s disease. Thus, this study aimed to establish a nomogram of the possibility of achieving a better depression improvement rate after subthalamic nucleus deep brain stimulation in patients with Parkinson’s disease. Methods: We retrospectively analyzed 103 patients with Parkinson’s disease who underwent subthalamic nucleus deep brain stimulation and were followed up for the improvement of their Hamilton Depression scale scores 1 year postoperatively. Univariate and multivariate logistic regression analyses were used to select factors affecting the improvement rate of depression. A nomogram was then developed to predict the possibility of achieving better depression improvement. Furthermore, the discrimination and fitting performance was evaluated using a calibration diagram, receiver operating characteristics, and decision curve analysis. Results: The mean and median improvement rates of Hamilton Depression scores were 13.1 and 33.3%, respectively. Among the 103 patients, 70.8% had an improved depression, 23.3% had a worsened depression, and 5.8% remained unchanged. Logistic multivariate regression analysis showed that age, preoperative Parkinson’s Disease Questionnaire, Hamilton Anxiety, and Hamilton Depression scores were independent factors for the possibility of achieving a better depression improvement rate. Based on these results, a nomogram model was developed. The nomogram had a C-index of 0.78 (95% confidence interval: 0.69–0.87) and an area under the receiver operating characteristics of 0.78 (95% confidence interval: 0.69–0.87). The calibration plot and decision curve analysis further demonstrated goodness-of-fit between the nomogram predictions and actual observations. Conclusion: We developed a nomogram to predict the possibility of achieving good depression improvement 1 year after subthalamic nucleus deep brain stimulation in patients with Parkinson’s disease, which showed a certain value in judging the expected depression improvement of these patients.