Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

Abstract Deep brain stimulation (DBS) has been successfully used to treat movement disorders, such as Parkinson's disease, for more than 25 years and heralded the advent of electrical neuromodulation to treat diseases with dysregulated neuronal circuits. DBS is now superseding ablative techniques, such as stereotactic radiofrequency lesions. While serendipity has played a role in developing DBS as a therapy, research during the past two decades has shown that electrical neuromodulation is far more than a functional lesion that can be switched on and off. This understanding broadens the field to enable new types of stimulation, clinical indications, and research. This review highlights the complex effects of DBS from the single cell to the neuronal network. Specifically, we examine the electrical, cellular, molecular, and neurochemical mechanisms of DBS as applied to Parkinson's disease and other emerging applications

Early Complications and Cement Leakage in Elderly Patients Who Have Undergone Intraoperative Computed Tomography (CT)-Guided Cement Augmented Pedicle Screw Placement: Eight-Year Single-Center Experience.

OBJECTIVE: To assess early complications, mortality rate, and cement leakage in elderly patients who had undergone navigation-based pedicle screw placement of the thoracic and lumbar spine. METHODS: Eighty-six patients older than 65 years of age who had received cement-augmented pedicle screws for various conditions were retrospectively included between May 2008 and December 2016. Complications, mortality, and cement leakage were determined. All patients had a radiograph as a control. In patients with cement leakage seen on radiographs, a computed tomography scan of the surgical area was also obtained. RESULTS: Average age was 73.4 years (range 65-86 years). A total of 319 vertebral bodies with 637 screws were inserted, of which 458 screws were cement-augmented; 348 (76%) of the augmented screws were placed in the lumbar spine and 110 (24%) in the thoracic spine. Cement leakage occurred in 55 of 86 patients, of whom 52 (60%) were asymptomatic. In all cases with cement leakage (asymptomatic or symptomatic), cement could be found in the perivertebral veins: in the inferior vena cava in 25%, in the epidural space in 7%, in the azygos vein in 5%, and in pulmonary arteries in 7%. CONCLUSIONS: Our study confirms that the use of cement correlates with a high risk of cement leakage in elderly patients. Using computed tomography navigation for screw placement did not reduce the risk of venous cement leakage, but leakage into the epidural space or through a cortical defect seems to be low

Anterior Access to the Cervicothoracic Junction via Partial Sternotomy: A Clinical Series Reporting on Technical Feasibility, Postoperative Morbidity, and Early Surgical Outcome

Surgical access to the cervicothoracic junction (CTJ) is challenging. The aim of this study was to assess technical feasibility, early morbidity, and outcome in patients undergoing anterior access to the CTJ via partial sternotomy. Consecutive cases with CTJ pathology treated via anterior access and partial sternotomy at a single academic center from 2017 to 2022 were retrospectively reviewed. Clinical data, perioperative imaging, and outcome were assessed with regards to the aims of the study. A total of eight cases were analyzed: four (50%) bone metastases, one (12.5%) traumatic instable fracture (B3-AO-Fracture), one (12.5%) thoracic disc herniation with spinal cord compression, and two (25%) infectious pathologic fractures from tuberculosis and spondylodiscitis. The median age was 49.9 years (range: 22–74 y), with a 75% male preponderance. The median Spinal Instability Neoplastic Score (SINS) was 14.5 (IQR: 5; range: 9–16), indicating a high degree of instability in treated cases. Four cases (50%) underwent additional posterior instrumentation. All surgical procedures were performed uneventfully, with no intraoperative complications. The median length of hospital stay was 11.5 days (IQR: 9; range: 6–20), including a median of 1 day in an intensive care unit (ICU). Two cases developed postoperative dysphagia related to stretching and temporary dysfunction of the recurrent laryngeal nerve. Both cases completely recovered at 3 months follow-up. No in-hospital mortality was observed. The radiological outcome was unremarkable in all cases, with no case of implant failure. One case died due to the underlying disease during follow-up. The median follow-up was 2.6 months (IQR: 23.8; range: 1–45.7 months). Our series indicates that the anterior approach to the cervicothoracic junction and upper thoracic spine via partial sternotomy can be considered an effective option for treatment of anterior spinal pathologies, exhibiting a reasonable safety profile. Careful case selection is essential to adequately balance clinical benefits and surgical invasiveness for these procedures

Morbidity and Mortality in Patients over 90 Years of Age Following Posterior Stabilization for Acute Traumatic Odontoid Type II Fractures: A Retrospective Study with a Mean Follow-Up of Three Years.

Odontoid type II fractures represent the most common cervical spine injuries in the elderly. The decision for surgical treatment in very elderly patients is still controversial. The aim of this study was to assess morbidity and mortality in patients over 90 years of age undergoing CT-guided posterior stabilization for unstable odontoid type II fractures. A total of 15 patients with an acute traumatic odontoid type II fracture who received surgical treatment for unstable odontoid type II fractures were retrospectively analyzed. Complications, morbidity, and mortality as well as length of ICU and hospital stay were determined. Clinical follow-up evaluation was based on outpatient presentation and information from family members and general practitioners. Finally, we conducted a comparison of complications rates between patients over 90 years of age and patients between 65 and 89 years old with a type II odontoid fracture after CT-guided posterior stabilization in our institution. The mean age was 91.4 years. Patients were predominately female (87%). In-hospital deaths did not occur. The average length of the hospital stay was 13.4 days and 1.9 days for the ICU. Blood transfusion was necessary in two patients (13%). Two patients (13%) developed urinary tract infection, one patient (7%) a delirium, and another epistaxis (7%). One patient (7%) developed pneumonic sepsis and fully recovered within several weeks. The mean follow-up was 36 months (range 9-72 months). Implant-related complications developed in one patient (7%). Five patients died during the follow-up period, with an average time to death of 26.6 months. Postoperative bracing was not needed in any of the patients. Posterior stabilization of unstable odontoid fractures type II using CT-guided navigation in patients over 90 years of age is a safe and effective procedure with low complications and mortality rates

A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation: the Multi Recharge Trial

OBJECTIVE Rechargeable neurostimulators for deep brain stimulation have been available since 2008, promising longer battery life and fewer replacement surgeries compared to non-rechargeable systems. Long-term data on how recharging affects movement disorder patients are sparse. This is the first multicenter, patient-focused, industry-independent study on rechargeable neurostimulators. METHODS Four neurosurgical centers sent a questionnaire to all adult movement disorder patients with a rechargeable neurostimulator implanted at the time of the trial. The primary endpoint was the convenience of the recharging process rated on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence, and complication rates. Endpoints were compared for several subgroups. RESULTS Datasets of 195 movement disorder patients (66.1% of sent questionnaires) with Parkinson's disease (PD), tremor, or dystonia were returned and included in the analysis. Patients had a mean age of 61.3 years and the device was implanted for a mean of 40.3 months. The overall convenience of recharging was rated as "easy" (4). The mean charge burden was 122 min/wk and showed a positive correlation with duration of therapy; 93.8% of users felt confident recharging the device. The rate of surgical revisions was 4.1%, and the infection rate was 2.1%. Failed recharges occurred in 8.7% of patients, and 3.6% of patients experienced an interruption of therapy because of a failed recharge. Convenience ratings by PD patients were significantly worse than ratings by dystonia patients. Caregivers recharged the device for the patient in 12.3% of cases. Patients who switched from a non-rechargeable to a rechargeable neurostimulator found recharging to be significantly less convenient at a higher charge burden than did patients whose primary implant was rechargeable. Age did not have a significant impact on any endpoint. CONCLUSIONS Overall, patients with movement disorders rated recharging as easy, with low complication rates and acceptable charge burden

Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease

This commentary provides an overview of the putamen as an established target site for gene therapy in treating aromatic l‐amino acid decarboxylase (AADC) deficiency and Parkinson’s disease, two debilitating neurological disorders that involve motor dysfunction caused by dopamine deficiencies. The neuroanatomy and the function of the putamen in motor control provide good rationales for targeting this brain structure. Additionally, the efficacy and safety of intraputaminal gene therapy demonstrate that restoration of dopamine synthesis in the putamen by using low doses of adeno‐associated viral vector serotype 2 to deliver the hAADC gene is well tolerated. This restoration leads to sustained improvements in motor and nonmotor symptoms of AADC deficiency and improved uptake and conversion of exogenous l‐DOPA into dopamine in Parkinson’s patients