Structural and functional correlates of the response to deep brain stimulation at ventral capsule/ventral striatum region for treatment-resistant depression.

BACKGROUND: Though deep brain stimulation (DBS) shows increasing potential in treatment-resistant depression (TRD), the underlying neural mechanisms remain unclear. Here, we investigated functional and structural connectivities related to and predictive of clinical effectiveness of DBS at ventral capsule/ventral striatum region for TRD. METHODS: Stimulation effects of 71 stimulation settings in 10 TRD patients were assessed. The electric fields were estimated and combined with normative functional and structural connectomes to identify connections as well as fibre tracts beneficial for outcome. We calculated stimulation-dependent optimal connectivity and constructed models to predict outcome. Leave-one-out cross-validation was used to validate the prediction value. RESULTS: Successful prediction of antidepressant effectiveness in out-of-sample patients was achieved by the optimal connectivity profiles constructed with both the functional connectivity (R=0.49 at p<10-4; deviated by 14.4±10.9% from actual, p<0.001) and structural connectivity (R=0.51 at p<10-5; deviated by 15.2±11.5% from actual, p<10-5). Frontothalamic pathways and cortical projections were delineated for optimal clinical outcome. Similarity estimates between optimal connectivity profile from one modality (functional/structural) and individual brain connectivity in the other modality (structural/functional) significantly cross-predicted the outcome of DBS. The optimal structural and functional connectivity mainly converged at the ventral and dorsal lateral prefrontal cortex and orbitofrontal cortex. CONCLUSIONS: Connectivity profiles and fibre tracts following frontothalamic streamlines appear to predict outcome of DBS for TRD. The findings shed light on the neural pathways in depression and may be used to guide both presurgical planning and postsurgical programming after further validation.

Subthalamic and Pallidal Stimulations in Patients with Parkinson's Disease: Common and Dissociable Connections.

OBJECTIVE: The subthalamic nucleus (STN) and internal globus pallidus (GPi) are the most effective targets in deep brain stimulation (DBS) for Parkinson's disease (PD). However, the common and specific effects on brain connectivity of stimulating the 2 nuclei remain unclear. METHODS: Patients with PD receiving STN-DBS (n = 27, 6 women, mean age 64.8 years) or GPi-DBS (n = 28, 13 women, mean age 64.6 years) were recruited for resting-state functional magnetic resonance imaging to assess the effects of STN-DBS and GPi-DBS on brain functional dynamics. RESULTS: The functional connectivity both between the somatosensory-motor cortices and thalamus, and between the somatosensory-motor cortices and cerebellum decreased in the DBS-on state compared with the off state (p < 0.05). The changes in thalamocortical connectivity correlated with DBS-induced motor improvement (p < 0.05) and were negatively correlated with the normalized intersection volume of tissues activated at both DBS targets (p < 0.05). STN-DBS modulated functional connectivity among a wider range of brain areas than GPi-DBS (p = 0.009). Notably, only STN-DBS affected connectivity between the postcentral gyrus and cerebellar vermis (p < 0.001) and between the somatomotor and visual networks (p < 0.001). INTERPRETATION: Our findings highlight common alterations in the motor pathway and its relationship with the motor improvement induced by both STN- and GPi-DBS. The effects on cortico-cerebellar and somatomotor-visual functional connectivity differed between groups, suggesting differentiated neural modulation of the 2 target sites. Our results provide mechanistic insight and yield the potential to refine target selection strategies for focal brain stimulation in PD. ANN NEUROL 2021;90:670-682.

Asleep Deep Brain Stimulation in Patients With Isolated Dystonia: Stereotactic Accuracy, Efficacy, and Safety.

OBJECTIVES: Lead placement for deep brain stimulation (DBS) is routinely performed using neuroimaging or microelectrode recording (MER). Recent studies have demonstrated that DBS under general anesthesia using an imaging-guided target technique ("asleep" DBS) can be performed accurately and effectively with lower surgery complication rates than the MER-guided target method under local anesthesia ("awake" DBS). This suggests that asleep DBS may be a more acceptable method. However, there is limited direct evidence focused on isolated dystonia using this method. Therefore, this study aimed to investigate the clinical outcomes and targeting accuracy in patients with dystonia who underwent asleep DBS. MATERIALS AND METHODS: We examined 56 patients (112 leads) with isolated dystonia who underwent asleep DBS targeting in the globus pallidus internus (GPi) and subthalamic nucleus (STN). The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were assessed preoperatively and at 12-month follow-up (12 m-FU). The lead accuracy was evaluated by comparing the coordinates of the preoperative plan with those of the final electrode implantation location. Other measures analyzed included stimulation parameters and adverse events (AEs). RESULTS: For both GPi and STN cohorts, mean BFMDRS motor scores were significantly lower at 12 m-FU (8.9 ± 10.9 and 4.6 ± 5.7 points) than at baseline (22.6 ± 16.4 and 16.1 ± 14.1 points, p < 0.001). The mean difference between the planned target and the distal contact of the leads was 1.33 ± 0.54 mm for the right brain electrodes and 1.50 ± 0.57 mm for the left, determined by Euclidian distance. No perioperative complications or AEs related to the device were observed during the complete follow-up. However, AEs associated with stimulation occurred in 12 and 6 patients in the GPi and STN groups, respectively. CONCLUSIONS: Asleep DBS may be an accurate, effective, and safe method for treating patients with isolated dystonia regardless of the stimulation target.

Effectiveness and safety of neuroablation for severe and treatment-resistant obsessive-compulsive disorder: a systematic review and meta-analysis.

Background: Several neuroablative procedures are available for severe and treatment-resistant obsessive-compulsive disorder (OCD), but limited knowledge about their relative clinical advantages and disadvantages poses obstacles for treatment decision-making. Methods: We searched PubMed, Embase, Scopus, Web of Knowledge and the Cochrane Library for reports up to February 2019. We reviewed the literature on the effectiveness (assessed using the Yale-Brown Obsessive Compulsive Scale [Y-BOCS]) and safety of various neuroablative interventions for severe and treatment-resistant OCD. Results: We included 23 studies involving 487 patients in the systematic review; 21 studies with 459 patients entered meta-analysis. Overall, neuroablation achieved a response rate (proportion of patients with ≥ 35% reduction in Y-BOCS) of 55%. Most of the adverse events (88.4%) were mild and transient. The top 3 adverse events were headache (14.9%), cognitive deficits (9.1%) and behaviour problems (8.1%). Severe or permanent adverse events included personality changes (2.3%) and brain edema or brain cyst (1.5%). The response rates associated with capsulotomy, limbic leucotomy and cingulotomy were 59% (95% confidence interval [CI] 54-65), 47% (95% CI 23-72) and 36% (95% CI 23-50), respectively. Interventions with different coverages of the dorsal part of the internal capsule were associated with different adverse-event profiles but were unlikely to modify clinical effectiveness. Limitations: The level of evidence of most included studies was relatively low. Conclusion: Ablative surgeries are safe and effective for a large proportion of patients with severe and treatment-resistant OCD. Among the available procedures, capsulotomy seemed to be the most effective. Further research is needed to improve clinical effectiveness and minimize risks.

Spinal Cord Stimulation with Surgical Lead Improves Pain and Gait in Parkinson's Disease after a Dislocation of Percutaneous Lead: A Case Report.

Spinal cord stimulation (SCS) is receiving increasing interests for treating pain and gait disorders in patients with Parkinson's disease (PD). In an SCS study, it is hard to apply a double-blind approach, especially at low frequencies, as the stimulation normally induces paresthesia which can be perceived by the patient. We herein demonstrate a case treated with SCS in which a blinding design was accomplished by an accidental dislocation of a stimulation lead. A 73-year-old man with PD was admitted to our hospital because of relapsed low back pain. This was due to the dislocation of a previously implanted SCS lead, which caused a decrease in its effectiveness in alleviating pain (from 81 to 43% measured by King's Parkinson's Disease Pain Scale) and improving gait (from 35 to 28% measured by the timed up and go test). A second SCS surgery using a paddle lead solved this problem, with improvements in pain and gait rebounded to 81 and 45%. In this case, the paresthesia induced by SCS (using either a paddle lead or percutaneous leads) was below the threshold of perception when the patient was sitting and standing, and a dislocation of one previously implanted percutaneous lead did not cause evident changes in his sensation of paresthesia. At last follow-up, the patient's quality of life had improved by 40% as measured by the 8-item Parkinson's Disease questionnaire (PDQ-8). This study could serve partly as a proof that low-frequency SCS is effective in improving pain as well as gait problems in PD patients, which was unlikely a result of a placebo effect.

[Clinical features of patients with primary biliary cirrhosis].

OBJECTIVE: To determine features of the clinical manifestation in patients with primary biliary cirrhosis (PBC), and to provide a scientific basis for diagnosis of PBC.
 METHODS: A total of 102 patients with PBC treated in the Second Xiangya Hospital, Central South University, from January 2013 to January 2015 were retrospectively analyzed. The patients' general condition, clinical manifestations, serum biochemical and immunological parameters were detected.
 RESULTS: Of the 102 PBC patients, 91 (89.21%) patients were female. The main symptoms in these patients were fatigue, poor appetite, dry mouth, nausea, vomiting, pruritus, stomachache, and abdominal distension. The major signs were jaundice, splenomegaly, hepatomegaly, edema, and ascites. The main features of serum biochemical parameters in these patients included the increase of alkaline phosphatase and gamma glutamyltranspeptidase (GGT), especially the GGT. The anti-mitochondrial antibodies-M2 (AMA-M2) in 81 and 21 patients was positive and negative, respectively. The differences between the AMA-MA positive and negative groups were not statistically significant (P>0.05). According to clinical manifestation, 102 patients were classified into 2 groups: A non-cirrhosis group (n=56) and a cirrhosis group (n=46). The positive rates in these 2 groups, such as ANA, AMA-M2, anti-gp210, anti-Sp100, anti-Ro52, anti-PML, were 54.35%, 89.13%, 41.30%, 13.04%, 43.38% and 10.87% vs 57.14%, 71.43%, 42.86%, 12.5%, 51.79% and 3.71%, respectively, with no significant difference between them (P>0.05). However, there was significant difference in the positive rate of anti-3E-EPO between the above 2 groups (86.78% vs 58.93%, P<0.05). The positive rates of AMA-M2 and anti-3E-EPO in 30 patients diagnosed by hepatic histopathological examination were higher than those of other antibodies.
 CONCLUSION: PBC mainly affects middle-aged women, and its clinical manifestation is various. The autoantibody tests play an important role in diagnosis of PBC. Checking for AMA-A2 and anti-3E-BPO can improve the positive rate of PBC. Liver histopathological examination may provide useful information on disease severity, which can determine the histological stage when the patient's serum autoantibodies are negative.

Parameter-based analysis of clinical efficacy of combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

OBJECTIVE: Treatment-resistant depression (TRD) is a severely disabling psychiatric condition that responds poorly to conventional treatments. Deep brain stimulation (DBS) has been proposed for the treatment of patients with TRD in numerous studies. Several deep brain nuclei are considered as potential targets for TRD-DBS, but their clinical efficacy needs further validation. This study carried out dual-target combined stimulation of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) to investigate the effectiveness of the treatment for TRD patients. METHODS: An 8-contact DBS electrode was used in the study with a surgical path that crossed the BNST and NAc targets. Stimulation parameters and the corresponding severity of symptoms evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17) and other scales were obtained at each follow-up. The accuracy of electrode positions, the effect of combined stimulation, and the corresponding stimulation parameters were evaluated. Sweet spot prediction models were used to assess the effective stimulation sites in the treatment. RESULTS: The study included 23 TRD patients undergoing DBS at a single center from March 2021 to May 2023. At the last follow-up (range 4-24 months), 14 patients had responded to the treatment (HAMD-17 score improved ≥ 50%), 7 of whom had achieved clinical remission (HAMD-17 score ≤ 7). Electrode position analysis suggested that the BNST may be more important for the improvement of depressive symptoms than the NAc. Overlapped volumes of volume of tissue activated (VTA) and BNST were significantly correlated with absolute (ρleft = -0.377, p < 0.001; ρright = -0.251, p < 0.001) and percent (ρleft = -0.249, p < 0.001; ρright = -0.098, p = 0.102) changes in HAMD-17 score. The sweet spot model of HAMD-17 improvement also suggested that the VTA overlap with the dorsal side of BNST was associated with the impact on depressive symptoms (t = -4.10, p < 0.05). CONCLUSIONS: Combined BNST-NAc stimulation of TRD can effectively improve depressive symptoms, in which the BNST seems to have a dominant therapeutic effect. The results of this study not only help to optimize the DBS programming parameters, but also offer an opportunity to further understand the differences between the two targets. In the future, larger prospective cohorts are needed to verify the results of combined BNST-NAc DBS.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

Background: Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD). Aims: The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD. Methods: Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations. Results: Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age. Conclusions: Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST-NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

Value of functional connectivity in outcome prediction for pallidal stimulation in Parkinson disease.

OBJECTIVE: Functional connectivity shows the ability to predict the outcome of subthalamic nucleus deep brain stimulation (DBS) in Parkinson disease (PD). However, evidence supporting its value in predicting the outcome of globus pallidus internus (GPi) DBS remains scarce. In this study the authors investigated patient-specific functional connectivity related to GPi DBS outcome in PD and established connectivity models for outcome prediction. METHODS: The authors reviewed the outcomes of 21 patients with PD who received bilateral GPi DBS and presurgical functional MRI at the Ruijin Hospital. The connectivity profiles within cortical areas identified as relevant to DBS outcome in the literature were calculated using the intersection of the volume of tissue activated (VTA) and the local structures as the seeds. Combined with the leave-one-out cross-validation strategy, models of the optimal connectivity profile were constructed to predict outcome. RESULTS: Connectivity between the pallidal areas and primary motor area, supplementary motor area (SMA), and premotor cortex was identified through the literature as related to GPi DBS outcome. The similarity between the connectivity profile within the primary motor area, SMA, pre-SMA, and premotor cortex seeding from the VTA-GPi intersection from an out-of-sample patient and the constructed in-sample optimal connectivity profile predicts GPi DBS outcome (R = 0.58, p = 0.006). The predictions on average deviated by 13.1% ± 11.3% from actual improvements. On the contrary, connectivity profiles seeding from the GPi (R = -0.12, p = 0.603), the VTA (R = 0.23, p = 0.308), the VTA outside the GPi (R = 0.12, p = 0.617), or other local structures were found not to be predictive. CONCLUSIONS: The results showed that patient-specific functional connectivity seeding from the VTA-GPi intersection could help in GPi DBS outcome prediction. Reproducibility remains to be determined across centers in larger cohorts stratified by PD motor subtype.

BOLD frequency-dependent alterations in resting-state functional connectivity by pallidal deep brain stimulation in patients with Parkinson's disease.

OBJECTIVE: Functional MRI (fMRI) has been used to investigate the therapeutic mechanisms underlying deep brain stimulation (DBS) for Parkinson's disease (PD). However, the alterations in stimulation site-seeded functional connectivity induced by DBS at the internal globus pallidus (GPi) remain unclear. Furthermore, whether DBS-modulated functional connectivity is differentially affected within particular frequency bands remains unknown. The present study aimed to reveal the alterations in stimulation site-seeded functional connectivity induced by GPi-DBS and to examine whether there exists a frequency band effect in blood oxygen level-dependent (BOLD) signals related to DBS. METHODS: Patients with PD receiving GPi-DBS (n = 28) were recruited for resting-state fMRI with DBS on and DBS off under a 1.5-T MR scanner. Age- and sex-matched healthy controls (n = 16) and DBS-naïve PD patients (n = 24) also received fMRI scanning. The alterations in stimulation site-seeded functional connectivity in the stimulation-on state versus stimulation-off state, as well as the relationship between alterations in connectivity and improvement in motor function induced by GPi-DBS, were examined. Furthermore, the modulatory effect of GPi-DBS on the BOLD signals within the 4 frequency subbands (slow-2 to slow-5) was investigated. Finally, the functional connectivity of the motor-related network, consisting of multiple cortical and subcortical regions, was also examined among the groups. In this study, p < 0.05 with Gaussian random field correction indicates statistical significance. RESULTS: Functional connectivity seeding from the stimulation site (i.e., the volume of tissue activated [VTA]) increased in the cortical sensorimotor areas and decreased in the prefrontal regions with GPi-DBS. Alterations in connectivity between the VTA and the cortical motor areas were correlated with motor improvement by pallidal stimulation. The alterations in connectivity were dissociable between the frequency subbands in the occipital and cerebellar areas. The motor network analysis indicated decreased connectivity among most cortical and subcortical regions but increased connectivity between the motor thalamus and the cortical motor area in patients with GPi-DBS compared with those in DBS-naïve patients. The DBS-induced decrease in several cortical-subcortical connectivities within the slow-5 band correlated with motor improvement with GPi-DBS. CONCLUSIONS: These findings indicate that the alterations in functional connectivity from the stimulation site to the cortical motor areas, as well as multiple connectivities among the motor-related network, were associated with the efficacy of GPi-DBS for PD. Furthermore, the changing pattern of functional connectivity within the 4 BOLD frequency subbands is partially dissociable.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

A systematic review of brain morphometry related to deep brain stimulation outcome in Parkinson's disease.

While the efficacy of deep brain stimulation (DBS) is well-established in Parkinson's Disease (PD), the benefit of DBS varies across patients. Using imaging features for outcome prediction offers potential in improving effectiveness, whereas the value of presurgical brain morphometry, derived from the routinely used imaging modality in surgical planning, remains under-explored. This review provides a comprehensive investigation of links between DBS outcomes and brain morphometry features in PD. We systematically searched PubMed and Embase databases and retrieved 793 articles, of which 25 met inclusion criteria and were reviewed in detail. A majority of studies (24/25), including 1253 of 1316 patients, focused on the outcome of DBS targeting the subthalamic nucleus (STN), while five studies included 57 patients receiving globus pallidus internus (GPi) DBS. Accumulated evidence showed that the atrophy of motor cortex and thalamus were associated with poor motor improvement, other structures such as the lateral-occipital cortex and anterior cingulate were also reported to correlated with motor outcome. Regarding non-motor outcomes, decreased volume of the hippocampus was reported to correlate with poor cognitive outcomes. Structures such as the thalamus, nucleus accumbens, and nucleus of basalis of Meynert were also reported to correlate with cognitive functions. Caudal middle frontal cortex was reported to have an impact on postsurgical psychiatric changes. Collectively, the findings of this review emphasize the utility of brain morphometry in outcome prediction of DBS for PD. Future efforts are needed to validate the findings and demonstrate the feasibility of brain morphometry in larger cohorts.

Effects of Bilateral Subthalamic Nucleus Stimulation on Depressive Symptoms and Cerebral Glucose Metabolism in Parkinson's Disease: A 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography Study.

Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor symptoms in Parkinson's disease (PD), as well as potentially improving otherwise intractable comorbid depressive symptoms. To address the latter issue, we evaluated the severity of depressive symptoms along with the severity of motor symptoms in 18 PD patients (mean age, 58.4 ± 5.4 years; 9 males, 9 females; mean PD duration, 9.4 ± 4.4 years) with treatment-resistant depression (TRD) before and after approximately 1 year of STN-DBS treatment. Moreover, to gain more insight into the brain mechanism mediating the therapeutic action of STN-DBS, we utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess cerebral regional glucose metabolism in the patients at baseline and 1-year follow-up. Additionally, the baseline PET data from patients were compared with PET data from an age- and sex-matched control group of 16 healthy volunteers. Among them, 12 PD patients underwent post-operative follow-up PET scans. Results showed that the severity of both motor and depressive symptoms in patients with PD-TRD was reduced significantly at 1-year follow-up. Also, patients used significantly less antiparkinsonian medications and antidepressants at 1-year follow-up, as well as experiencing improved daily functioning and a better quality of life. Moreover, relative to the PET data from healthy controls, PD-TRD patients displayed widespread abnormalities in cerebral regional glucose metabolism before STN-DBS treatment, which were partially recovered at 1-year follow-up. Additionally, significant correlations were observed between the patients' improvements in depressive symptoms following STN-DBS and post-operative changes in glucose metabolism in brain regions implicated in emotion regulation. These results support the view that STN-DBS provides a promising treatment option for managing both motor and depressive symptoms in patients who suffer from PD with TRD. However, the results should be interpreted with caution due to the observational nature of the study, small sample size, and relatively short follow-up.

Mapping Motor Pathways in Parkinson's Disease Patients with Subthalamic Deep Brain Stimulator: A Diffusion MRI Tractography Study.

INTRODUCTION: This study assessed the safety of postoperative diffusion tensor imaging (DTI) with on-state deep brain stimulation (DBS) and the feasibility of reconstruction of the white matter tracts in the vicinity of the stimulation site of the subthalamic nucleus (STN). The association between the impact of DBS on the nigrostriatal pathway (NSP) and the treatment effect on motor symptoms in Parkinson's disease (PD) was then evaluated. METHODS: Thirty-one PD patients implanted with STN-DBS (mean age: 66 years; 25 male) were scanned on a 1.5-T magnetic resonance imaging (MRI) scanner using the DTI sequence with DBS on. Twenty-three of them were scanned a second time with DBS off. The NSP, dentato-rubro-thalamic tract (DRTT), and hyperdirect pathway (HDP) were generated using both deterministic and probabilistic tractography methods. The DBS-on-state and off-state tractography results were validated and compared. Afterward, the relationships between the characteristics of the reconstructed white matter tracts and the clinical assessment of PD symptoms and the DBS effect were further examined. RESULTS: No adverse events related to DTI were identified in either the DBS-on-state or off-state. Overall, the NSP was best reconstructed, followed by the DRTT and HDP, using the probabilistic tractography method. The connection probability of the left NSP was significantly lower than that of the right side (p < 0.05), and a negative correlation (r = -0.39, p = 0.042) was identified between the preoperative symptom severity in the medication-on state and the connection probability of the left NSP in the DBS-on-state images. Furthermore, the distance from the estimated left-side volume of tissue activated (VTA) by STN-DBS to the ipsilateral NSP was significantly shorter in the DBS-responsive group compared to the DBS-non-responsive group (p = 0.046). CONCLUSIONS: DTI scanning is safe and delineation of white matter pathway is feasible for PD patients implanted with the DBS device. Postoperative DTI is a useful technique to strengthen our current understanding of the therapeutic effect of DBS for PD and has the potential to refine target selection strategies for brain stimulation.

For some more seriously affected Parkinson's disease (PD) patients, drugs are no longer effective in treating their symptoms. An alternate treatment is to use deep brain stimulation (DBS), a commonly used neurosurgical therapy for PD patients. For those DBS treatments targeting the subthalamic nucleus (STN), the electrical stimulation used may impact nearby white matter tracts and alter the effectiveness of the DBS treatment. The nigrostriatal pathway (NSP), dentato-rubro-thalamic tract, and hyperdirect pathway are three white matter tracts near the STN. They are all relevant to motor symptoms in PD. This study examined whether imaging these tracts using magnetic resonance imaging (MRI) is safe and feasible in the presence of DBS leads. The relationships between the fiber-tracking characteristics and distance to the DBS leads were then evaluated. For this purpose, 31 PD patients with stimulation-on were scanned on a 1.5 T MRI scanner using a diffusion tensor imaging sequence. A total of 23 subjects underwent another scan using the same sequence with stimulation-off. No adverse events related to diffusion tensor imaging were found. Among the white matter tracts near the STN, the NSP was best delineated, followed by the dentato-rubro-thalamic tract and the hyperdirect pathway. The connection probability of the left NSP was significantly lower than that of the right side as were the subject's motor symptoms. The closer the distance between the NSP and the stimulation location, the better the DBS outcome. These findings indicate that imaging white matter tracts with DBS on is safe and useful in mapping DBS outcomes.

Deep Brain Stimulation-Induced Transient Effects in the Habenula.

The habenula, located in the epithalamus, has been implicated in various psychiatric disorders including mood disorders and schizophrenia. This study explored the transient effects of deep brain stimulation in the habenula. Each of the four patients (two with bipolar disorder and two with schizophrenia) was tested with eight deep brain stimulation contacts. Patients were examined via transient electrical stimulation 1 month after deep brain stimulation surgery. The pulse width was 60 µs and the voltage ranged from 0 V to a maximum of 10 V, increasing in increments of 1 V. Each patient received stimulation at two frequencies, 60 and 135 Hz. A total of 221 out of 385 active trials elicited stimulation-induced effects. The three most common transient effects were numbness, heart rate changes, and pain. The incidence of numbness, heart rate changes, pain, and involuntary movements increased with the increase in stimulation voltage. Through contralateral stimulation, numbness was triggered in all parts of the body except the scalp. The obtained stimulus-response maps suggested a possible somatosensory organization of the habenula.

Subthalamic Stimulation for Camptocormia in Parkinson's Disease: Association of Volume of Tissue Activated and Structural Connectivity with Clinical Effectiveness.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been reported to be effective for camptocormia in Parkinson's disease (PD). However, the association between clinical effectiveness and the stimulated volumes or structural connectivity remains unexplored. OBJECTIVE: To investigate the effectiveness of STN-DBS for treating camptocormia in PD and its association with volumes of tissue activated (VTA) and structural connectivity. METHODS: We reviewed video recordings of patients who had undergone STN-DBS. The total and upper camptocormia (TCC and UCC) angles were measured to quantify changes in camptocormia. The Movement Disorders Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) was used to assess motor symptoms. Pre- and postoperative brain images were collected for modeling volume of VTA and structural connectivity using Lead-DBS software. RESULTS: Participants included 36 patients with PD (8 with TCC-camptocormia and 2 with UCC-camptocormia) treated with bilateral STN-DBS. After surgery, patients showed a significant improvement in postural alignment at follow-up (mean follow-up duration: 6.0±2.2 months). In the entire sample, higher structural connectivity to the right supplementary motor area (SMA) and right lateral premotor cortex along the dorsal plane (PMd) was associated with larger postsurgical improvements in axial signs and TCC angles after stimulation was turned on. In patients diagnosed with camptocormia, larger improvement in camptocormia angles after STN-DBS was associated with a larger VTA overlap with STN (R = 0.75, p = 0.032). CONCLUSION: This study suggests that both VTA overlap with STN and structural connectivity to cortical motor regions are associated with the effectiveness of STN-DBS for managing camptocormia in PD.

Recharging Difficulty With Pulse Generator After Deep Brain Stimulation: A Case Series of Five Patients.

Background: Deep brain stimulation (DBS) is a well-established treatment for a variety of movement disorders. Rechargeable cell technology was introduced to pulse generator more than 10 years ago and brought great benefits to patients. However, with the widespread use of rechargeable implanted pulse generators (r-IPGs), a new hardware complication, when charging the r-IPG has been difficult, was encountered. Objective: The aims of this study were to report five cases confronted with r-IPG charging difficulty postoperatively and to explore the predisposing factors and treatment strategies for this rare complication. Methods: We retrospectively reviewed our DBS patient database for those who were implanted with r-IPGs. From 2012, we identified a total of 1,226 patients, with five of them experiencing charging difficulties after surgery. Detailed patient profiles and clinical procedures were scrutinized and reviewed. Results: All the charging problems were resolved by reoperation. Cases 1 and 2 required their r-IPGs to be anchored to the muscle and fascia. Cases 3 and 4 had their r-IPGs inserted in the wrong orientation at the initial surgery, which was resolved by turning around the r-IPGs at the revision surgery. Case 5, in which we propose that the thick subcutaneous fat layer blocked the connection between the r-IPG and the recharger, required a second operation to reposition the r-IPG in a shallow layer underneath the skin. For all cases, the charging problems were resolved without reoccurrences to date. Conclusion: Our case series indicates a novel hardware complication of DBS surgery, which had been rarely reported before. In this preliminary study, we describe several underlying causes of this complication and treatment methods.

Pallidal stimulation as treatment for camptocormia in Parkinson's disease.

Camptocormia is a common and often debilitating postural deformity in Parkinson's disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.

Weight Change After Subthalamic Nucleus Deep Brain Stimulation in Patients With Isolated Dystonia.

Purpose: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment method for advanced Parkinson's disease (PD) and isolated dystonia and provides marked improvement of major motor symptoms. In addition, non-motor effects have been reported including weight gain (WG) in patients with PD after STN-DBS. However, it is still unclear whether patients with isolated dystonia also experience WG. Methods: Data from 47 patients with isolated dystonia who underwent bilateral STN-DBS surgery between October 2012 and June 2019 were retrospectively collected. The severity of dystonia was assessed via the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Changes in the body mass index (BMI) and BFMDRS score were analyzed using paired Student's t-tests. Regression analysis was performed to identify factors that affected the BMI after surgery. Results: Postoperative WG was observed in 78.7% of patients. The percentage of overweight and obese patients increased from 25.5% (before STN-DBS) to 48.9% (at the last follow-up). The mean BMI and mean percentage change in BMI increased by 1.32 ± 1.83 kg/m2 (P < 0.001) and 6.28 ± 8.34%, respectively. BMI increased more in female than in male patients. At the last follow-up, BFMDRS movement and disability scores improved by 69.76 ± 33.23% and 65.66 ± 31.41%, respectively (both P < 0.001). The final regression model analysis revealed that sex and preoperative BMI alone were independently associated with BMI change (P < 0.05). Conclusions: STN-DBS is associated with postoperative WG with patients with isolated dystonia. WG is more prominent in female patients and is associated with preoperative weight but not with the efficacy of STN-DBS on motor symptoms.