Diffusion tensor imaging in pediatric patients with dystonia.

BACKGROUND: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia. METHODS: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies. RESULTS: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus. CONCLUSION: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

Incidence and Management of Hardware-Related Wound Infections in Spinal Cord, Peripheral Nerve Field, and Deep Brain Stimulation Surgery: A Single-Center Study.

INTRODUCTION: Neuromodulation using deep brain stimulation (DBS), spinal cord stimulation (SCS), and peripheral nerve field stimulation (PNFS) to treat neurological, psychiatric, and pain disorders is a rapidly growing field. Infections related to the implanted hardware are among the most common complications and result in health-related and economic burden. Unfortunately, conservative medical therapy is less likely to be successful. In this retrospective study, we aimed to identify characteristics of the infections and investigated surgical and antimicrobial treatments. METHODS: A retrospective analysis was performed of patients with an infection related to DBS, SCS, and/or PNFS hardware over an 8-year period at our institution. Data were analyzed for type of neurostimulator, time of onset of infection following the neurosurgical procedure, location, and surgical treatment strategy. Surgical treatment of infections consisted of either a surgical wound revision without hardware removal or a surgical wound revision with partial or complete hardware removal. Data were further analyzed for the microorganisms involved, antimicrobial treatment and its duration, and clinical outcome. RESULTS: Over an 8-year period, a total of 1,250 DBS, 1,835 SCS, and 731 PNFS surgeries were performed including de novo system implantations, implanted pulse generator (IPG) replacements, and revisions. We identified 82 patients with infections related to the neurostimulator hardware, representing an incidence of 3.09% of the procedures. Seventy-one percent of the patients had undergone multiple surgeries related to the neurostimulator prior to the infection. The infections occurred after a mean of 12.2 months after the initial surgery. The site of infection was most commonly around the IPG, especially in DBS and SCS. The majority (62.2%) was treated by surgical wound revision with simultaneous partial or complete removal of hardware. Microbiological specimens predominantly yielded Staphylococcus epidermidis (39.0%) and Staphylococcus aureus (35.4%). After surgery, antimicrobials were given for a mean of 3.4 weeks. The antimicrobial regime was significantly shorter in patients with hardware removal in comparison to those who only had undergone surgical wound revision. One intracranial abscess occurred. No cases of infection-related death, sepsis, bacteremia, or intraspinal abscesses were found. CONCLUSION: Our data did show the predominance of S. epidermidis and S. aureus as etiologic organisms in hardware-related infections. Infections associated with S. aureus most likely required (partial) hardware removal. Aggressive surgical treatment including hardware removal shortens the duration of antimicrobial treatment. Clear strategies should be developed to treat hardware-related infections to optimize patient management and reduce health- and economic-related burden.

Connectivity in deep brain stimulation for self-injurious behavior: multiple targets for a common network?

Self-injurious behavior (SIB) is associated with diverse psychiatric conditions. Sometimes (e.g., in patients with autism spectrum disorder or acquired brain injuries), SIB is the most dominant symptom, severely restricting the psychosocial functioning and quality of life of the patients and inhibiting appropriate patient care. In severe cases, it can lead to permanent physical injuries or even death. Primary therapy consists of medical treatment and if implementable, behavioral therapy. For patients with severe SIB refractory to conventional therapy, neuromodulation can be considered as a last recourse. In scientific literature, several successful lesioning and deep brain stimulation targets have been described that can indicate a common underlying neuronal pathway. The objectives of this study were to evaluate the short- and long-term clinical outcome of patients with severe, therapy refractory SIB who underwent DBS with diverse underlying psychiatric disorders and to correlate these outcomes with the activated connectivity networks. We retrospectively analyzed 10 patients with SIB who underwent DBS surgery with diverse psychiatric conditions including autism spectrum disorder, organic personality disorder after hypoxic or traumatic brain injury or Tourette syndrome. DBS targets were chosen according to the underlying disorder, patients were either stimulated in the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus or ventrolateral thalamus. Clinical outcome was measured 6 months after surgery and at long-term follow-up after 10 or more years using the Early Rehabilitation Barthel index (ERBI) and time of restraint. Connectivity patterns were analyzed using normative connectome. Based on previous literature the orbitofrontal cortex, superior frontal gyrus, the anterior cingulate cortex, the amygdala and the hippocampus were chosen as regions of interest. This analysis showed a significant improvement in the functionality of the patients with DBS in the short- and long-term follow-up. Good clinical outcome correlated with higher connectivity to the amygdala and hippocampus. These findings may suggest a common pathway, which can be relevant when planning a surgical procedure in patients with SIB.

Corrigendum: Women in Neuromodulation: Innovative Contributions to Stereotactic and Functional Neurosurgery.

[This corrects the article DOI: 10.3389/fnhum.2021.756039.].

Proceedings of the 10th annual deep brain stimulation think tank: Advances in cutting edge technologies, artificial intelligence, neuromodulation, neuroethics, interventional psychiatry, and women in neuromodulation.

The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis.

Background: Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus-nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus-parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and commonalities between those targets need to be compared systematically. Objective: Therefore, we evaluated whether DBS is effective in reducing TS symptoms and target-specific differences. Methods: A PubMed literature search was conducted according to the PRISMA guidelines. Eligible literature was used to conduct a systematic review and meta-analysis. Results: In total, 65 studies with 376 patients were included. Overall, Yale Global Tic Severity Scale (YGTSS) scores were reduced by more than 50 in 69% of the patients. DBS also resulted in significant reductions of secondary outcome measures, including the total YGTSS, modified Rush Video-Based Tic Rating Scale (mRVRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Becks Depression Inventory (BDI). All targets resulted in significant reductions of YGTSS scores and, with the exception of the CM-Pf, also in reduced YBOCS scores. Interestingly, DBS of pallidal targets showed increased YGTSS and YBOCS reductions compared to thalamic targets. Also, the meta-analysis including six randomized controlled and double-blinded trials demonstrated clinical efficacy of DBS for TS, that remained significant for GPi but not thalamic stimulation in two separate meta-analyses. Conclusion: We conclude that DBS is a clinically effective treatment option for patients with treatment-refractory TS, with all targets showing comparable improvement rates. Future research might focus on personalized and symptom-specific target selection.

Connectivity Patterns of Deep Brain Stimulation Targets in Patients with Gilles de la Tourette Syndrome.

Since 1999, several targets for deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) have emerged showing similar success rates. Studies using different tractography techniques have identified connectivity profiles associated with a better outcome for individual targets. However, GTS patients might need individualized therapy. The objective of this study is to analyze the connectivity profile of different DBS targets for GTS. We identified standard target coordinates for the centromedian nucleus/nucleus ventro-oralis internus (CM/Voi), the CM/parafascicular (CM-Pf) complex, the anteromedial globus pallidus internus (amGPi), the posteroventral GPi (pvGPi), the ventral anterior/ventrolateral thalamus (VA/VL), and the nucleus accumbens/anterior limb of the internal capsule (Nacc/ALIC). Probabilistic tractography was performed from the targets to different limbic and motor areas based on patient-specific imaging and a normative connectome (HCP). Our analysis showed significant differences between the connectivity profiles of standard DBS targets (p < 0.05). Among all targets, the pvGPi showed the strongest connection to the sensorimotor cortex, while the amGPi showed the strongest connection to the prefrontal cortex in patient-specific imaging. Differences were observed between the connectivity profiles when using probabilistic tractography based on patient data and HCP. Our findings showed that the connectivity profiles of different DBS targets to major motor and limbic areas differ significantly. In the future, these differences may be considered when planning DBS for GTS patients employing an individualized approach. There were compelling differences in connectivity profiles when using different tractography techniques.

1.2 kHz High-Frequency Stimulation as a Rescue Therapy in Patients With Chronic Pain Refractory to Conventional Spinal Cord Stimulation.

OBJECTIVES: We aimed to investigate the efficacy of new subperception stimulation paradigms including 1.2 kHz-high-frequency stimulation (HFS) and advanced-HFS field-shaping algorithm (dorsal horn HFS [DHHFS]) in refractory cases which initially benefited from conventional spinal cord stimulation (SCS) and lost the effect throughout time. MATERIALS AND METHODS: In the context of a rescue-therapy, patients underwent externalization of the implanted SCS-leads and were tested with multiple combinations of new SCS paradigms. Pain intensity was analyzed using the numeric rating scale (NRS), and data were collected preoperatively and at multiple postoperative follow-ups. RESULTS: Thirty-seven patients underwent externalization of the leads. Mean preoperative NRS-score was 8.1/10 points (SD ± 0.9) for the ON-stimulation period. Patients received a combination of either tonic, burst and 1.2 kHz-HFS, or burst and 1.2 kHz-HFS, DHHFS, or 1.2 kHz-HFS and DHHFS, or 1.2 kHz-HFS alone. The mean postoperative NRS-score after the testing-phase was 3.8/10 points (SD ± 2.5), showing a 48.0% mean reduction (p < 0.001). In total, 29 patients reported a significant reduction above 50% in NRS-scores and therefore were reimplanted with new generators that could deliver the new paradigms. Eight patients underwent full SCS-system explantation. The patients who continued with the new paradigms (n = 29) reported mean NRS-scores of 3.5/10 points (SD ± 1.7) 12 months postoperatively, still showing a significant reduction of 43.3% when compared to preoperative scores (p < 0.001). CONCLUSION: Rescue-therapy with combination of multiple waveforms, including tonic, burst, 1.2 kHz-HFS, and DHHFS, was associated with a significant pain relief in patients with failed conventional SCS. This approach is a safe and efficient and should be considered before explantation of the SCS-system.

Women in Neuromodulation: Innovative Contributions to Stereotactic and Functional Neurosurgery.

Stereotactic neurosurgery emerged in the mid-20th century following the development of a stereotactic frame by Spiegel and Wycis. Historically women were underrepresented in clinical and academic neurosurgery. There is still a significant deficit of female scientists in this field. This article aims to demonstrate the career and scientific work of some of the most important women who contributed to the development of stereotactic and functional neurosurgery. Exceptional women from all over the world, represented in this review, assisted the evolution of modern stereotactic and functional neurosurgery as neurosurgeons, neuropathologists, neurologists, neurophysiologists and occupational therapists. Fortunately, we could conclude that in the last two decades the number of female researchers has increased significantly.

Modulation of Fibers to Motor Cortex during Thalamic DBS in Tourette Patients Correlates with Tic Reduction.

Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the connectivity of the primary motor cortex and supplementary motor area with the striatum and thalamus, suggesting an abnormal connectivity of the cortico-striatum-thalamocortical-pathways in TS. Deep brain stimulation (DBS) of the centromedian nucleus-nucleus ventrooralis internus (CM-Voi complex) in the thalamus is an effective treatment for refractory TS patients. We investigated the connectivity of activated fibers from CM-Voi to the motor cortex and its correlation between these projections and their clinical outcome. Seven patients with TS underwent CM-Voi-DBS surgery and were clinically evaluated preoperatively and six months postoperatively. We performed diffusion tensor imaging to display the activated fibers projecting from the CM-Voi to the different motor cortex regions of interest. These analyses showed that the extent of tic reduction during DBS is associated with the degree of stimulation-dependent connectivity between CM-Voi and the motor cortex, and in particular, an increased density of projections to the presupplementary motor area (preSMA). Non-responder patients displayed the largest amount of active fibers projecting into cortical areas other than motor cortex compared to responder patients. These findings support the notion that an abnormal connectivity of thalamocortical pathways underlies TS, and that modulation of these circuits through DBS could restore the function and reduce symptoms.

Radiofrequency denervation for treatment of sacroiliac joint pain-comparison of two different ablation techniques.

The radiofrequency treatment (RFD) for sacroiliac joint pain (SIP) is well-established, but there is still scarce evidence on its clinical outcome. The classical monopolar RFD is limited by a high recurrence rate. This might be caused by an incomplete denervation of the dorsal rami. The Simplicity III probe was invented to optimise pain fibre recruitment by its multi-electrode design. However, the clinical superiority of this procedure was never proven. The aim of this study was to illustrate the effectiveness of RFD and to compare both denervation techniques. One hundred twenty-one patients were included, and their clinical course was analysed. Fifty-seven patients received conventional treatment with multiple percutaneous monopolar RFDs (monolesion probe group, MoLG) and 64 patients with the Simplicity III probe (multilesion probe group, MuLG). All patients were followed 1, 3, 6 and 12 s after RFD. Clinical outcome scores were analysed (numeric pain rating scale (NPRS), Roland-Morris Disability Questionnaire, Oswestry Disability Index (ODI), Odom's criteria, Short Form 36 score). The MuLG showed a clearly advanced improvement concerning the clinically relevant pain relief (≥ 50%) (1 month/3 months /6 months/12 months = 72%, 55%, 36%, 27% vs. 1 month/3 months/6 months/12 months = 39%, 28%, 16%, 11%) as well as an advanced improvement of pain-associated disability and a higher satisfaction rating compared to the MoLG (NPRSMuLG_preop = 8,3; NPRSMuLG_12months = 5.8; NPRSMoLG_preop = 7,7; NPRSMoLG_12months = 5.8; ODIMuLG_preop = 52; ODIMuLG_12months = 42; ODIMoLG_preop = 52; ODIMoLG_12months = 47; ODOMSMuLG_good/excellent = 54%; ODOMSMoLG_good/excellent = 28%). RFD of the SIP with the Simplicity III probe is effective and delivers a distinct pain reduction even after 1 year of treatment. This technique shows clear advantages compared to the conventional monolesion technique and is a useful treatment for patients with recurrent SIP.

Treatment results for lumbar epidural lipomatosis: Does fat matter?

PURPOSE: The lumbar epidural lipomatosis (LEL) is a rare disease that can cause sciatic pain syndrome or neurological deficits comparable to symptoms caused by a classical spinal canal stenosis. In severe cases surgical decompression was conducted. However, the outcome after decompressive surgery has only been investigated in small case series. In this study we compared the outcome of LEL patients after microsurgery with the outcome of patients with classical spinal stenosis (CSS). METHODS: Patients with LEL (n = 38) and patients with CSS (n = 51), who received microsurgical decompression, were followed in a prospective observational study for 3 years. The clinical results including the Oswestry Disability Index, Numeric Pain Rating Scale (NRS), Roland and Morris Disability Questionnaire, the Short Form-36 Score and the Walking Distance were analysed and compared between both groups. RESULTS: Patients with LEL improved significantly after microsurgical decompression in a 3-year follow-up concerning back pain, leg pain and pain-associated disability equal to patients with CSS (NRSback_LEL_preop. = 6.4; NRSback_CSS_preop. = 6.3; NRSback_LEL_3-years = 3.2; NRSback_CSS_3-years = 3.6; NRSleg_LEL_preop. = 6.3; NRSleg_CSS_preop. = 6.5; NRSleg_LEL_3-years = 2.5; NRSleg_CSS_3-years = 2.9; ODILEL_preop. = 52.7; ODICSS_preop = 51.8; ODILEL_3-years = 32.3; ODICSS_3-years = 27.6). The microsurgical decompression had a positive effect on the health-related quality of life, and patient satisfaction was high in both groups (LEL group-71%, CSS group-69%). CONCLUSIONS: LEL can influence the quality of life dramatically and cause a high degree of disability. A surgical decompression is a safe and effective procedure with a good clinical outcome comparable to the results in patients with an osteoligamentous spinal stenosis. Therefore, microsurgical decompression can be recommended in patients with LEL if conservative treatment fails. These slides can be retrieved under Electronic Supplementary Material.

Pathological gambling in Parkinson's disease: what are the risk factors and what is the role of impulsivity?

The incidence of pathological gambling in Parkinson's patients is significantly greater than in the general population. A correlation has been observed between dopamine agonist medication and the development of pathological gambling. However, scientists conjecture that the affected patients have underlying risk factors. Studies analysing Parkinson's patients have detected that patients who developed pathological gambling are younger, score higher on novelty-seeking tests, are more impulsive and are more likely to have a personal or family history of alcohol addiction. In addition, some genetic variations have been associated with the susceptibility of developing pathological gambling, which include mutations of DRD3, 5-HTTLPR and GRIN2B. Studies focusing on neurofunctional discrepancies between Parkinson's patients with and without pathological gambling have found increased functional activation and dopamine release in regions associated with the mesolimbic reward system. Furthermore, there is also evidence showing increased processing of reward and decreased activation elicited by punishment, suggesting altered learning processes. Furthermore, the role of deep brain stimulation of the nucleus subthalamicus (STN DBS) is controversial. In most Parkinson's patients, pathological gambling resolved after the initiation of the STN DBS, which might be explained by discontinuation or decrease in dopamine agonist medication. However, it has been also shown that some patients are more impulsive while the STN DBS is activated. These differences may depend on the DBS localization in the more limbic or motor part of the STN and their regulative effects on impulsivity. Further research is needed to clarify susceptibility factors for the development of pathological gambling in Parkinson's patients.