Stereotactic frame-based biopsy of infratentorial lesions via the suboccipital-transcerebellar approach with the Zamorano-Duchovny stereotactic system-a retrospective analysis of 79 consecutive cases.

OBJECTIVE: Lesions of the posterior fossa (brainstem and cerebellum) are challenging in diagnosis and treatment due to the fact that they are often located eloquently and total resection is rarely possible. Therefore, frame-based stereotactic biopsies are commonly used to asservate tissue for neuropathological diagnosis and further treatment determination. The aim of our study was to assess the safety and diagnostic success rate of frame-based stereotactic biopsies for lesions in the posterior fossa via the suboccipital-transcerebellar approach. METHODS: We performed a retrospective database analysis of all frame-based stereotactic biopsy cases at our institution since 2007. The aim was to identify all surgical cases for infratentorial lesion biopsies via the suboccipital-transcerebellar approach. We collected clinical data regarding outcomes, complications, diagnostic success, radiological appearances, and stereotactic trajectories. RESULTS: A total of n = 79 cases of stereotactic biopsies for posterior fossa lesions via the suboccipital-transcerebellar approach (41 female and 38 male) utilizing the Zamorano-Duchovny stereotactic system were identified. The mean age at the time of surgery was 42.5 years (± 23.3; range, 1-87 years). All patients were operated with intraoperative stereotactic imaging (n = 62 MRI, n = 17 CT). The absolute diagnostic success rate was 87.3%. The most common diagnoses were glioma, lymphoma, and inflammatory disease. The overall complication rate was 8.7% (seven cases). All patients with complications showed new neurological deficits; of those, three were permanent. Hemorrhage was detected in five of the cases having complications. The 30-day mortality rate was 7.6%, and 1-year survival rate was 70%. CONCLUSIONS: Our data suggests that frame-based stereotactic biopsies with the Zamorano-Duchovny stereotactic system via the suboccipital-transcerebellar approach are safe and reliable for infratentorial lesions bearing a high diagnostic yield and an acceptable complication rate. Further research should focus on the planning of safe trajectories and a careful case selection with the goal of minimizing complications and maximizing diagnostic success.

Gene therapy for aromatic L-amino acid decarboxylase deficiency: Requirements for safe application and knowledge-generating follow-up.

The autosomal recessive defect of aromatic L-amino acid decarboxylase (AADC) leads to a severe neurological disorder with manifestation in infancy due to a pronounced, combined deficiency of dopamine, serotonin and catecholamines. The success of conventional drug treatment is very limited, especially in patients with a severe phenotype. The development of an intracerebral AAV2-based gene delivery targeting the putamen or substantia nigra started more than 10 years ago. Recently, the putaminally-delivered construct, Eladocagene exuparvovec has been approved by the European Medicines Agency and by the British Medicines and Healthcare products Regulatory Agency. This now available gene therapy provides for the first time also for AADC deficiency (AADCD) a causal therapy, leading this disorder into a new therapeutic era. By using a standardized Delphi approach members of the International Working Group on Neurotransmitter related Disorders (iNTD) developed structural requirements and recommendations for the preparation, management and follow-up of AADC deficiency patients who undergo gene therapy. This statement underlines the necessity of a framework for a quality-assured application of AADCD gene therapy including Eladocagene exuparvovec. Treatment requires prehospital, inpatient and posthospital care by a multidisciplinary team in a specialized and qualified therapy center. Due to lack of data on long-term outcomes and the comparative efficacy of alternative stereotactic procedures and brain target sites, a structured follow-up plan and systematic documentation of outcomes in a suitable, industry-independent registry study are necessary.

Mortality, complication risks, and clinical outcomes after surgical treatment of spinal epidural abscess: a comparative analysis of patients aged 18-64 years, 65-79 years, and ≥ 80 years, with a 3-year follow-up.

Spinal epidural abscess (SEA) with pyogenic vertebral osteomyelitis (PVO) is a rare illness with a steadily increasing incidence. However, comparative analyses of young and older patients with SEA are lacking. We aimed to compare the clinical course of patients aged 18-64 years, 65-79 years, and ≥ 80 years undergoing surgery for SEA. Clinical and imaging data were retrospectively collected from the institutional database between September 2005 and December 2021. Ninety-nine patients aged 18-64 years, 45 patients aged 65-79 years, and 32 patients ≥ 80 years were enrolled. Patients ≥ 80 years presented with a poorer baseline history (9.2 ± 2.4), as indicated by the CCI, than their younger counterparts (18-74 years: 4.8 ± 1.6;6.5 ± 2.5; p < 0.001). Patients aged 65-79 years and 80 years had a significantly longer length of stay. In-hospital mortality was significantly higher in those aged ≥ 80 years compared to their younger counterparts (≥ 80 years, n = 3, 9.4% vs. 18-64 years, n = 0, 0.0%; 65-79 years, n = 0, 0.0%; p < 0.001), while no differences in 90-day mortality or 30-day readmission were observed. After surgery, a significant decrease in C-reactive protein levels and leukocytes and amelioration of motor scores were observed in all the groups. Of note, older age (> 65 years), presence of comorbidities, and poor preoperative neurological condition were significant predictors of mortality. Surgical management led to significant improvements in laboratory and clinical parameters in all age groups. However, older patients are prone to multiple risks, requiring meticulous evaluation before surgery. Nevertheless, the risk profile of younger patients should not be underestimated. The study has the limitations of a retrospective design and small sample size. Larger randomized studies are warranted to establish the guidelines for the optimal management of patients from every age group and to identify the patients who can benefit from solely conservative management.

Reevaluating age restrictions of spinal metastasis surgery in elderly groups with over 2-year follow-up.

This study aimed to compare and assess clinical outcomes of spinal metastasis with epidural spinal cord compression (MESCC) in patients aged 65-79 years and ≥ 80 years with an acute onset of neurological illness who underwent laminectomy. A second goal was to determine morbidity rates and potential risk factors for mortality. This retrospective review of electronic medical records at a single institution was conducted between September 2005 and December 2020. Data on patient demographics, surgical characteristics, complications, hospital clinical course, and 90-day mortality were also collected. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). A total of 99 patients with an overall mean age of 76.2 ± 3.4 years diagnosed with MESCC within a 16-year period, of which 65 patients aged 65-79 years and 34 patients aged 80 years and older were enrolled in the study. Patients aged 80 and over had higher age-adjusted CCI (9.2 ± 2.1) compared to those aged 65-79 (5.1 ± 1.6; p < 0.001). Prostate cancer was the primary cause of spinal metastasis. Significant neurological and functional decline was more pronounced in the older group, evidenced by Karnofsky Performance Index (KPI) scores (80+ years: 47.8% ± 19.5; 65-79 years: 69.0% ± 23.9; p < 0.001). Despite requiring shorter decompression duration (148.8 ± 62.5 min vs. 199.4 ± 78.9 min; p = 0.004), the older group had more spinal levels needing decompression. Median survival time was 14.1 ± 4.3 months. Mortality risk factors included deteriorating functional status and comorbidities, but not motor weakness, surgical duration, extension of surgery, hospital or ICU stay, or complications. Overcoming age barriers in elderly surgical treatment in MSCC patients can reduce procedural delays and has the potential to significantly improve patient functionality. It emphasizes that age should not be a deterrent for spine surgery when medically necessary, although older MESCC patients may have reduced survival.

Outcomes of cervical spinal stenosis surgery in patients aged ≥ 65 years based on insurance status: a single-center cohort study from a tertiary center in Germany.

OBJECTIVE: The prevalence of degenerative disorders of the spine, such as cervical spinal stenosis with cervical spine myelopathy (CSM) in the geriatric population, has rapidly increased worldwide. To date, there has been no systematic analysis comparing outcomes in older patients suffering from progressive CSM and undergoing surgery depending on their health insurance status. We sought to compare the clinical outcomes and complications after anterior cervical discectomy and fusion (ACDF) or posterior decompression with fusion in patients aged ≥ 65 years with multilevel cervical spinal canal stenosis and concomitant CSM with special focus on their insurance status. METHODS: Clinical and imaging data were retrieved from patients' electronic medical records at a single institution between September 2005 and December 2021. Patients were allocated into two groups with respect to their health insurance status: statutory health insurance (SHI) vs. private insurance (PI). RESULTS: A total of 236 patients were included in the SHI group and 100 patients in the privately insured group (PI) group. The overall mean age was 71.7 ± 5.2 years. Regarding comorbidities, as defined with the age-adjusted CCI, SHI patients presented with higher rates of comorbidities as defined by a CCI of 6.7 ± 2.3 and higher prevalence of previous malignancies (9.3%) when compared to the PI group (CCI 5.4 ± 2.5, p = 0.051; 7.0%, p = 0.048). Both groups underwent ACDF (SHI: 58.5% vs. PI: 61.4%; p = 0.618), and the surgical duration was similar between both groups. Concerning the intraoperative blood transfusion rates, no significant differences were observed. The hospital stay (12.5 ± 1.1 days vs. 8.6 ± 6.3 days; p = 0.042) and intenisve care unit stay (1.5 ± 0.2 days vs. 0.4 ± 0.1 days; p = 0.049) were significantly longer in the PI group than in the SHI group. Similar in-hospital and 90-day mortality rates were noted across the groups. The presence of comorbidities, as defined with the age-adjusted CCI, poor neurological status at baseline, and SHI status, was significant predictor for the presence of adverse events, while the type of surgical technique, operated levels, duration of surgery, or blood loss was not. CONCLUSIONS: Herein, we found that surgeons make decisions independent of health insurance status and aim to provide the most optimal therapeutic option for each individual; hence, outcomes were similar between the groups. However, longer hospitalization stays were present in privately insured patients, while SHI patients presented on admission with poorer baseline status.

Emergency surgical decompression for spontaneous spinal epidural hematoma in octogenarians: risk factors, clinical outcomes, and complications.

PURPOSE: Spontaneous spinal epidural hematoma (SSEH) is a rare but disabling disease. Although several cases have been reported in the literature, their treatment remains unclear, especially in patients with advanced age. We, therefore, aimed to describe the clinical outcomes of cervical SSEH in octogenarians with an acute onset of neurological illness undergoing laminectomy. METHODS: Electronic medical records from a single institution between September 2005 and December 2020 were retrieved. Data on patient demographics, neurological conditions, functional status, surgical characteristics, complications, hospital course, and 90-day mortality were also collected. RESULTS: Twenty-two patients aged ≥ 80 years with SSEH undergoing laminectomy were enrolled in this study. The mean Charlson comorbidity index was 9.1 ± 2.0, indicating a poor baseline reserve. Ten individuals (45.5%) were taking anticoagulant agents with a pathologic partial thromboplastin time (PTT) of 46.5 ± 3.4 s. Progressive neurological decline, as defined by the motor score (MS), was observed on admission (63.8 ± 14.0). The in-hospital and 90-day mortality were 4.5% and 9.1%, respectively. Notably, the MS (93.6 ± 8.3) improved significantly after surgery (p < 0.05). Revision surgery was necessary in 5 cases due to recurrent hematoma. Anticoagulant agents and pathological PTT are significant risk factors for its occurrence. Motor weakness and comorbidities were unique risk factors for loss of ambulation. CONCLUSIONS: Laminectomy and evacuation of the hematoma in octogenarians with progressive neurological decline induce clinical benefits. Emergent surgery seems to be the "state of the art" treatment for SSEH. However, potential complications associated with adverse prognostic factors, such as the use of anticoagulants, should be considered.

Anterior cervical discectomy and fusion with plate versus posterior screw fixation after traumatic subaxial fractures in octogenarians: complications and outcomes with a 2-year follow-up.

INTRODUCTION: Surgical intervention for management of spinal instability after traumatic subaxial fractures in octogenarians requires a clear consensus on optimal treatments. This study aimed to provide a guide for more efficient management through comparison and assessment of clinical outcomes and complications of anterior cervical discectomy and fusion with plate (pACDF) and posterior decompression fusion (PDF) instrumentation alone in patients aged 80 years. METHODS: A single institution retrospective review of electronic medical records was undertaken between September 2005 and December 2021. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). Logistic regression was used to identify potential risk factors for ACDF complications. RESULTS: The rate of comorbidities were similarly high between the pACDF (n=13) and PDF (n=15) groups (pACDF: 8.7 ± 2.4 points vs. 8.5 ± 2.3 points; p=0.555). Patients in the PDF group had significantly longer surgical duration (235 ± 58.4 min vs. 182.5 ± 32.1 min; p<0.001) and significantly higher volumes of intraoperative blood loss (661.5 ± 100.1 mL vs. 487.5 ± 92.1 mL; p<0.001). The in-hospital mortality was 7.7% for the pACDF group and 6.7% for the PDF group. On day 90, the mortality rate increased in both groups from baseline (pACDF: 15.4% vs. PDF: 13.3; p>0.05). Motor scores (MS) improved significantly after surgery in both groups (pACDF: preOP MS: 75.3 ± 11.1 vs. postOP MS: 82.4 ± 10.1; p<0.05; PDF: preOP MS: 80.7 ± 16.7 vs. postOP MS: 89.5 ± 12.1; p<0.05). Statistically significant predictors for postoperative complications included longer operative times (odds ratio 1.2, 95% confidence interval 1.1-2.1; p=0.005) and larger volume of blood loss (odds ratio 1.5, 95% confidence interval 1.2-2.2; p=0.003). CONCLUSIONS: Both pACDF and PDF can be considered safe treatment strategies for octogenarians with a poor baseline profile and subaxial fractures as they lead to patients substantial neurological improvements, and they are accompanied with low morbidity and mortality rates. Operation duration and intraoperative blood loss should be minimized to increase the degree of neurological recovery in octogenarian patients.

Perioperative morbidity and mortality in octogenarians sustaining traumatic osteoporotic type 4 and 5 thoracolumbar and lumbar fractures: a retrospective study with 3 years follow-up.

PURPOSE: This study aimed to guide the more efficient management of type 4 and 5 thoracolumbar or lumbar osteoporotic fractures (OF) in patients aged 80 years and older with an acute onset of neurological decline. This aim was achieved by assessing the clinical course and morbidity and mortality rates and identifying potential risk factors for patient mortality METHODS: Electronic medical records were retrieved from a single institution pertaining to the period between September 2005 and December 2020. Data on patient demographics, neurological conditions, surgical characteristics, complications, hospital course, and 90-day mortality were also collected. RESULTS: Over a 16-year period, 35 patients aged ≥80 years diagnosed with thoracolumbar and lumbar OF were enrolled in the study. The mean Charlson comorbidity index (CCI) was >6, indicating a poor baseline reserve (9.4 ± 1.9), while cardiovascular diseases were the most prevalent among comorbidities. The mean surgical duration was 231.6 ± 89.3 min, with a mean blood loss of 694.4± 200.3 mL. The in-hospital was 8.6% and 90-day mortality rates at 11.4%. Two patients underwent revision surgery for deep wound infection. Intraoperative and postoperative radiography and computed tomography (CT) imaging revealed correct screw placement. Proper alignment of the thoracolumbar spine was achieved in all the patients. Unique risk factors for mortality included the presence of comorbidities and the occurrence of postoperative complications. CONCLUSIONS: Emergent instrumentation in patients with acute onset of neurological decline and potentially unstable spines due to thoracolumbar and lumbar OF improved functional outcomes at discharge. Age should not be a determinant of whether to perform surgery.

Adverse events in spine surgery: a prospective analysis at a large tertiary center in Germany.

STUDY DESIGN: Prospective study OBJECTIVES: The occurrence of adverse events (AEs) during surgery is a major cause of increased economic costs, disability, or even death. This study aimed to prospectively identify and quantify AEs in patients undergoing spinal surgery at a neurosurgical tertiary care hospital. METHODS: Patients who underwent spinal surgery and were discharged between January 2019 and December 2022 were enrolled prospectively. Each patient underwent a peer-reviewed AE evaluation at discharge. An AE was defined as any event that occurred up to 30 days postoperatively and resulted in an undesirable outcome. Patients were allocated to four groups according to spinal pathology (degenerative, oncologic, traumatic, and infectious). RESULTS: During the study period, 1778 patients with a mean age of 55.4 ± 10.5 years underwent surgery. Elective surgery was performed in 90.8% (1615/1778) of patients, while emergency surgery was performed in 9.2% (163/1778). The overall rate of surgery-related AEs was relatively low (8.7%). Degenerative pathologies were the most frequent reasons for surgery (78.5%, 1396/1778). Wound infection was the most prevalent AE in patients with degenerative diseases (1.4%), of which 1.1% required revision surgery. Wound infection, dural leakage, and new neurological deficits had the same prevalence (2.1%) in patients with spinal tumors. Among patients with spinal trauma, two presented with postoperative epidural bleeding and underwent emergency surgery. Postoperative wound infection was the most prevalent AE in this group (9.5%), with 7.0% of affected patients requiring revision surgery. The overall rate of non-surgery-related AEs was 4.3%, and the overall mortality rate was low (0.4%). CONCLUSION: AEs in spinal surgery remained low, with a prevalence of 8.7%. Documentation of AEs as part of clinical routine may be a key tool for identifying the occurrence of surgery-related and non-surgery-related AEs.

ACDF versus corpectomy in octogenarians with cervical epidural abscess: early complications and outcomes with 2 years of follow-up.

PURPOSE: Cervical spinal epidural abscess (CSEA) is a rare condition, manifesting as rapid neurological deterioration and leading to early neurological deficits. Its management remains challenging, especially in patients older than 80 years. Therefore, we aimed to compare the clinical course and determine morbidity and mortality rates after anterior cervical discectomy and fusion (ACDF) versus corpectomy in octogenarians with ventrally located CSEA at two levels. METHODS: In this single-center retrospective review, we obtained the following from electronic medical records between September 2005 and December 2021: patient demographics, surgical characteristics, complications, hospital clinical course, and 90-day mortality rate. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). RESULTS: Over 16 years, 15 patients underwent ACDF, and 16 patients underwent corpectomy with plate fixation. Between the two groups, patients who underwent corpectomy had a significantly poorer baseline reserve (9.0 ± 2.6 vs. 10.8 ± 2.7; p = 0.004) and had a longer hospitalization period (16.4 ± 13.1 vs. 10.0 ± 5.3 days; p = 0.004) since corpectomy lasted significantly longer (229.6 ± 74.9 min vs. 123.9 ± 47.5 min; p < 0.001). Higher in-hospital and 90-day mortality and readmission rates were observed in the corpectomy group, but the difference was not statistically significant. Both surgeries significantly improved blood infection parameters and neurological status at discharge. Revision surgery due to pseudoarthrosis was required in two patients after corpectomy. CONCLUSIONS: We showed that both ACDF and corpectomy for ventrally located CSEA can be considered as safe treatment strategies for patients aged 80 years and above. However, the surgical approach should be carefully weighed and discussed with the patients and their relatives.

Decompression only versus fusion in octogenarians with spinal epidural abscesses: early complications, clinical and radiological outcome with 2-year follow-up.

Despite increased life expectancy due to health care quality improvements globally, pyogenic vertebral osteomyelitis (PVO) treatment with a spinal epidural abscess (SEA) remains challenging in patients older than 80 years. We aimed to assess octogenarians for PVO prevalence with SEA and compare after-surgery clinical outcomes of decompression and decompression and instrumentation. A retrospective review of electronic medical records at a single institution was conducted between September 2005 and December 2020. Patient demographics, surgical characteristics, complications, hospital course, and 90-day mortality were collected. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). Over 16 years, 35 patients aged ≥80 years with PVO and SEA were identified. Eighteen patients underwent surgical decompression ("decompression group"), and 17 underwent surgical decompression with instrumentation ("instrumentation group"). Both groups had a CCI >6 (mean±SD, 8.9±2.1 vs. 9.6±2.7, respectively; p=0.065). Instrumentation group patients had a significantly longer hospital stay but no ICU stay. In-hospital and 90-days mortality rates were similar in both groups. The mean follow-up was 26.6±12.4 months. No further surgeries were performed. Infection levels and neurological status were improved in both groups at discharge. At the second-stage analysis, significant improvements in the blood infection parameters and the neurological status were detected in the decompression group. Octogenarians with PVO and SEA have a high adverse events risk after surgical procedures. Surgical decompression might contribute to earlier clinical recovery in older patients. Thus, the surgical approach should be discussed with patients and their relatives and be carefully weighed.

Spinal Meningioma Surgery in Octogenarians: Functional Outcomes and Complications over a 2-Year Follow-Up Period.

Background and Objectives: Population aging in industrial nations has led to an increased prevalence of benign spinal tumors, such as spinal meningiomas (SMs), in the elderly. The leading symptom of SM is local pain, and the diagnosis is confirmed after acute neurological decline. However, little is known about the optimal treatment for this frail patient group. Therefore, this study sought to assess the clinical outcome, morbidity, and mortality of octogenarians with SMs and progressive neurological decline undergoing surgery and to determine potential risk factors for complications. Materials and Methods: Electronic medical records dated between September 2005 and December 2020 from a single institution were retrieved. Data on patient demographics, neurological conditions, functional status, degree of disability, surgical characteristics, complications, hospital course, and 90-day mortality were collected. Results: Thirty patients aged ≥80 years who were diagnosed with SMs underwent posterior decompression via laminectomy and microsurgical tumor resection. The patients presented with a poor baseline history (mean CCI 8.9 ± 1.6 points). Almost all SMs were located in the thoracic spine (n = 25; 83.3%). Progressive preoperative neurological decline was observed in 21/30 (n = 21; 70%) patients with McCormick Scores (mMCS) ≥3, and their mean motor score (MS) was 85.9 ± 12.3. in the in-hospital and 90-day mortality rates were 6.7% and 10.0%, respectively. The MS (93.6 ± 8.3) and mMCS (1.8 ± 0.9) improved significantly postoperatively (p < 0.05). The unique risk factor for complications was the severity of comorbidities. Conclusions: Decompressive laminectomy and tumor removal in octogenarians with progressive neurological decline improved patient functional outcomes at discharge. Surgery seems to be the "state of the art" treatment for symptomatic SMs in elderly patients, even those with poor preoperative clinical and neurologic conditions, whenever there is an acceptable risk from an anesthesiological point of view.

CT-Navigated Spinal Instrumentations-Three-Dimensional Evaluation of Screw Placement Accuracy in Relation to a Screw Trajectory Plan.

Background and Objectives: In the literature, spinal navigation and robot-assisted surgery improved screw placement accuracy, but the majority of studies only qualitatively report on screw positioning within the vertebra. We sought to evaluate screw placement accuracy in relation to a preoperative trajectory plan by three-dimensional quantification to elucidate technical benefits of navigation for lumbar pedicle screws. Materials and Methods: In 27 CT-navigated instrumentations for degenerative disease, a dedicated intraoperative 3D-trajectory plan was created for all screws. Final screw positions were defined on postoperative CT. Trajectory plans and final screw positions were co-registered and quantitatively compared computing minimal absolute differences (MAD) of screw head and tip points (mm) and screw axis (degree) in 3D-space, respectively. Differences were evaluated with consideration of the navigation target registration error. Clinical acceptability of screws was evaluated using the Gertzbein−Robbins (GR) classification. Results: Data included 140 screws covering levels L1-S1. While screw placement was clinically acceptable in all cases (GR grade A and B in 112 (80%) and 28 (20%) cases, respectively), implanted screws showed considerable deviation compared to the trajectory plan: Mean axis deviation was 6.3° ± 3.6°, screw head and tip points showed mean MAD of 5.2 ± 2.4 mm and 5.5 ± 2.7 mm, respectively. Deviations significantly exceeded the mean navigation registration error of 0.87 ± 0.22 mm (p < 0.001). Conclusions: Screw placement was clinically acceptable in all screws after navigated placement but nevertheless, considerable deviation in implanted screws was noted compared to the initial trajectory plan. Our data provides a 3D-quantitative benchmark for screw accuracy achievable by CT-navigation in routine spine surgery and suggests a framework for objective comparison of screw outcome after navigated or robot-assisted procedures. Factors contributing to screw deviations should be considered to assure optimal surgical results when applying navigation for spinal instrumentation.

Correction to: Novel mutations in KMT2B offer pathophysiological insights on childhood-onset progressive dystonia.

Rapid progress has recently been made in the elucidation of the genetic basis of childhood-onset inherited generalized dystonia (IGD) due to the implementation of genomic sequencing methodologies. We identified four patients with childhood-onset IGD harboring novel disease-causing mutations in lysine-specific histone methyltransferase 2B gene (KMT2B) by whole-exome sequencing. The main focus of this paper is to gain novel pathophysiological insights through understanding the molecular consequences of these mutations.The disease course is mostly progressive, evolving from lower limbs into generalized dystonia, which could be associated with dysarthria, dysphonia, intellectual disability, orofacial dyskinesia, and sometimes distinct dysmorphic facial features. In two patients, motor performances improved after bilateral implantation of deep brain stimulation in the globus pallidus internus (GPi-DBS). Pharmacotherapy with trihexyphenidyl reduced dystonia in two patients.We discovered three novel KMT2B mutations. Our analyses revealed that the mutation in patient 1 (c.7463 A > G, p.Y2488C) is localized in the highly conserved FYRC domain of KMT2B. This mutation holds the potential to alter the inter-domain FYR interactions, which could lead to KMT2B instability. The mutations in patients 2 and 3 (c.3602dupC, p.M1202Dfs*22; c.4229delA, p.Q1410Rfs*12) lead to predicted unstable transcripts, likely to be subject to degradation by non-sense mediated decay.Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Novel mutations in KMT2B offer pathophysiological insights into childhood-onset progressive dystonia.

Rapid progress has recently been made in the elucidation of the genetic basis of childhood-onset inherited generalized dystonia (IGD) due to the implementation of genomic sequencing methodologies. We identified four patients with childhood-onset IGD harboring novel disease-causing mutations in lysine-specific histone methyltransferase 2B gene (KMT2B) by whole-exome sequencing. The main focus of this paper is to gain novel pathophysiological insights through understanding the molecular consequences of these mutations. The disease course is mostly progressive, evolving from lower limbs into generalized dystonia, which could be associated with dysarthria, dysphonia, intellectual disability, orofacial dyskinesia, and sometimes distinct dysmorphic facial features. In two patients, motor performances improved after bilateral implantation of deep brain stimulation in the globus pallidus internus (GPi-DBS). Pharmacotherapy with trihexyphenidyl reduced dystonia in two patients. We discovered three novel KMT2B mutations. Our analyses revealed that the mutation in patient 1 (c.7463A > G, p.Y2488C) is localized in the highly conserved FYRC domain of KMT2B. This mutation holds the potential to alter the inter-domain FYR interactions, which could lead to KMT2B instability. The mutations in patients 2 and 3 (c.3596_3697insC, p.M1202Dfs*22; c.4229delA, p.Q1410Rfs*12) lead to predicted unstable transcripts, likely to be subject to degradation by non-sense-mediated decay. Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early.

Accuracy and revision rate of intraoperative computed tomography point-to-point navigation for lateral mass and pedicle screw placement: 11-year single-center experience in 1054 patients.

High accuracy in intraoperative computed tomography (iCT) navigation utilizing an intraoperatively acquired dataset for screw placement in the spine has been reported in the literature. To further improve the accuracy and counteract any intraoperative movement of predefined registration points, we introduce an iCT point-to-point navigation, where marker screws are inserted intraoperatively to increase patient safety. In all, 1054 patients who underwent iCT point-to-point navigation for lateral mass and pedicle screw placement were retrospectively analyzed between 09/2005 and 09/2016. Implant-related complications such as screw misplacement, screw loosening, and revision rate were determined. Furthermore, we investigated the rate of complications and the clinical outcome. In total, 6059 screws were inserted in 1054 patients. There were 553 (52.5%) female and 501 (47.5%) male patients. Average age was 63.5 years, mean BMI 27.5 (SD 13.9). Here, 1427 (23.5%) screws were inserted in the cervical, 995 (16.4%) in the thoracic, 3167 (52.3%) in the lumbar, and 470 (7.8%) in the sacral spine. Eight patients required a revision procedure for screw misplacement (0.8%). Total screw misplacement rate was 0.3% (16/6059). With the use of reference markers in iCT-based, spinal, point-to-point navigation, we achieved a high accuracy of screw placement with a low revision rate (0.8%) and a total screw misplacement rate of 0.3%.

Rechargeable Internal Pulse Generators as Initial Neurostimulators for Deep Brain Stimulation in Patients With Movement Disorders.

INTRODUCTION: Rechargeable internal pulse generators (r-IPGs) for deep brain stimulation (DBS) promise a longer battery life and cost effectiveness compared to non-rechargeable IPGs. However, patients need to learn to check the battery capacity and perform the recharging process to ensure continuous therapy. METHODS: n = 35 consecutive adult patients with movement disorders that underwent DBS electrode placement with implantation of a r-IPG were assessed with a questionnaire. They were asked to report on their recharging routine, user confidence, satisfaction, and adverse events. Patients were asked to assess the level of difficulty of the individual steps and the overall recharging process on an ordinal scale awarding 1-5 points. RESULTS: 89% (n = 31) patients responded and were available for data analysis. n = 21 patients received DBS for Parkinson's Disease, n = 8 for essential tremor and n = 2 for dystonia at a mean age of 63.3 years. The mean follow-up was 21.2 months. n = 7 patients have partners or nursing services check and recharge the IPG. The recharging takes an average of 57.6 min. 90.3% felt confident using their IPG after a mean of 2.1 weeks and 1.6 training sessions. 97% of patients prefer their r-IPG over a conventional one. n = 3 patients experienced inability to recharge their IPG at some point. One patient experienced battery depletion and interruption of stimulation because of inability to recharge. The overall recharging process was rated as "easy" with a score of 4.0 out of 5 points. Each individual step was also rated as "easy" with a median score of 4.0 out of 5. Old age was not associated with more adverse events or a lower rating for the recharging process. CONCLUSIONS: Choosing a r-IPG during initial DBS surgery is safe and associated with a low number of adverse events even in older patients. The vast majority of patients consider handling and recharging the IPG as "easy." Most of the patients undergoing DBS for movement disorders will benefit from the advantages of r-IPGs.

Spatial Distortion in MRI-Guided Stereotactic Procedures: Evaluation in 1.5-, 3- and 7-Tesla MRI Scanners.

BACKGROUND: Magnetic resonance imaging (MRI) is replacing computed tomography (CT) as the main imaging modality for stereotactic transformations. MRI is prone to spatial distortion artifacts, which can lead to inaccuracy in stereotactic procedures. OBJECTIVE: Modern MRI systems provide distortion correction algorithms that may ameliorate this problem. This study investigates the different options of distortion correction using standard 1.5-, 3- and 7-tesla MRI scanners. METHODS: A phantom was mounted on a stereotactic frame. One CT scan and three MRI scans were performed. At all three field strengths, two 3-dimensional sequences, volumetric interpolated breath-hold examination (VIBE) and magnetization-prepared rapid acquisition with gradient echo, were acquired, and automatic distortion correction was performed. Global stereotactic transformation of all 13 datasets was performed and two stereotactic planning workflows (MRI only vs. CT/MR image fusion) were subsequently analysed. RESULTS: Distortion correction on the 1.5- and 3-tesla scanners caused a considerable reduction in positional error. The effect was more pronounced when using the VIBE sequences. By using co-registration (CT/MR image fusion), even a lower positional error could be obtained. In ultra-high-field (7 T) MR imaging, distortion correction introduced even higher errors. However, the accuracy of non-corrected 7-tesla sequences was comparable to CT/MR image fusion 3-tesla imaging. CONCLUSION: MRI distortion correction algorithms can reduce positional errors by up to 60%. For stereotactic applications of utmost precision, we recommend a co-registration to an additional CT dataset.

Surgical management of ventrally located cervical epidural abscess: A comparative analysis between patients aged 18-64 years and ≥65 years.

Background: We aimed to compare the clinical course of patients aged 18-65 years and ≥65years who underwent anterior cervical discectomy and fusion (ACDF) or corpectomy for ventrally located CSEA. Methods: Clinical and imaging data were retrospectively collected from the institutional database between September 2005 and December 2021. Results: A total of 35 and 26 patients aged 18-64 and ≥ 65 years, respectively who were diagnosed with ventrally located CSEA were included. The overall mean age was 63.9 ± 3.2 years, with a predominance of the male sex (n = 43/61, 70.5%). Patients aged ≥65 years presented with significantly higher rates of comorbidities (10.3 ± 2.8), as indicated by the CCI, than their younger counterparts (18-64 years: 6.2 ± 2.6; p < 0.001). No differences in the surgical approach or characteristics were observed among the groups. Notably, patients aged ≥65 years had a significantly longer intensive care unit as well as overall hospital stay. In-hospital and 90-day mortality were similar across both groups. Following both types of surgery, a significant improvement was observed in the blood infection parameters and neurological status at discharge compared with the baseline measurements. Older age, higher rates of comorbidities, and higher grades of disability were significant predictors for mortality. Conclusions: Emergency surgical evacuation should be undertaken for CSEA in the presence of acute neurological deterioration regardless of the age. Factors, such as age, comorbidities, and neurological status on admission appear to be important predictors of disease outcomes. However, the risk profile of younger patients should not be underestimated.

High Rate of Pulmonary Cement Embolism after Cement-Augmented Pedicle Screw Fixation: A 12-Year Single-Center Study.

BACKGROUND: The global trend toward increased life expectancy because of remarkable improvements in health care quality has drawn increased attention to osteoporotic fractures and degenerative spine diseases. Cement-augmented pedicle screw fixation has been established as the mainstay treatment for patients with poor bone quality. This study aimed to determine the number of patients with cement leakage and pulmonary cement embolism (PCE) as detected on thoracic computed tomography (CT), and to assess the potential risk factors for PCE. METHODS: Patients undergoing cement-augmented pedicle screw placement in our institution between May 2008 and December 2020 were included. Data regarding baseline characteristics, complications, and cement leakage rates were collected. Indications for the performance of a postoperative thoracic CT due to the suspicion of PCE were intra- or postoperative complications, or postoperative oxygen supplementation. Moreover, PCE was accidently diagnosed because the thoracic CT was performed for medical reasons other than the suspicion of PCE (tumor staging, severe pneumonia, or exacerbated chronic pulmonary obstructive disease). RESULTS: A total of 104 patients with a mean age of 72.8 years (standard deviation of 6.7) were included. Of 802 screws, 573 were cement augmented. Of the 104 patients, 44 (42.3%) underwent thoracic CT scans to diagnose PCE; additionally, 67 (64.4%) demonstrated cement leakage, of whom 27 developed PCE and 4 were symptomatic. Cement-augmented thoracic screws were a risk factor for PCE (odds ratio: 1.5; 95% confidence interval: 1.2-2.1; p = 0.004). CONCLUSIONS: This study showed a high prevalence of cement leakage after cement-augmented pedicle screw insertion, with a relatively frequent incidence of PCE, as tracked by thoracic CT scans. Cement-augmented thoracic screw placement was a unique risk factor for PCE.