Florian Wilhelmy

Background: Electric-field-informed regression provides high-resolution transcranial magnetic stimulation (TMS) motor maps, but conventional nonlinear fitting is too slow to update the map during acquisition, so sessions rely on predefined stimulation budgets, despite sub-stantial inter-individual variability in the data required for stable localization. Objective: To develop a real-time analysis updating a posterior probability map between pulses and compare its hotspots with finger-tapping functional MRI (fMRI). Methods: We analyzed two independent cohorts (12 and 13 participants, one newly collected), analyzing each hand muscle independently. We replaced the conventional per-element sigmoid fit with Spearman’s rank correlation coefficient and transformed the resulting score map into a posterior probability map using marginal-likelihood evidence. Acquisition stopped once posterior mass within 5 mm of the hotspot passed a preset confidence level. Results: The Spearman and linear scores updated the region of interest within milliseconds, versus tens of seconds for sigmoid fitting. Spearman more closely matched the full-data sigmoid hotspot in recorded sessions and converged faster and more precisely to the true source in virtual subjects. Across both fast scores, at a confidence level of 0.85 the stopping criterion was met after a median of 74-159 pulses, with 26-454 across individual problems. FDI hotspots lay 8.3 ± 4.3 mm from the fMRI center of gravity, in the precentral hand region. Conclusions: Rank correlation reduces computation time without loss of accuracy relative to sigmoid fitting. The resulting posterior probability map provides a session-specific stopping criterion in place of a fixed pulse budget.

Transcranial magnetic stimulation (TMS) motor mapping increasingly relies on electric-field (E-field) modeling to localize cortical targets, but many candidate coil placements induce highly redundant cortical patterns. We frame prospective coil-sequence design as a subset-selection problem and compare farthest-point sampling, determinant-based objectives, and related controls in virtual mapping experiments across 12 realistic head models. Across convergence, matrix-diagnostic, and manifold-coverage analyses, the best-performing objectives combined low between-stimulation redundancy with preserved inter-element separability on the cortex; objectives that maximized one of these at the expense of the other fell below random sampling. An RBF-kernelized D-optimal objective matched FPS in mapping accuracy while using ∼15 fewer unique scalp positions per 100 pulses, suggesting reduced arm-reconfiguration cost on robotic TMS platforms. A singular-spectrum analysis of the candidate library provides a low-cost a-priori indicator that predicts when discretization choices fall below the diversity floor required for stable mapping. These results recast prospective TMS mapping as a limited manifold-coverage problem and offer concrete design rules for sample-efficient, robotically efficient sequence planning. Algorithm implementations are available as part of the open-source pynibs tool-box at https://gitlab.gwdg.de/tms-localization/pynibs/-/tree/dev/pynibs/optimization .

Zusammenfassung: Die kindliche Skoliose ist eine der häufigsten Erkrankungen des Bewegungsapparates, die mit einer seitlichen Verkrümmung der Wirbelsäule und einer begleitenden Rotation der Wirbelkörper einhergeht. Die Prävalenz idiopathischer Skoliosen variiert weltweit, doch ist die Notwendigkeit einer frühzeitigen Diagnosestellung und adäquaten Therapie unerlässlich. Besonders herausfordernd wird die Behandlung, wenn eine sekundäre Skoliose aufgrund von neurologischen oder strukturellen Anomalien vorliegt. Die Ätiologie der Skoliose ist vielfältig, wobei idiopathische Formen den größten Anteil ausmachen. Weniger häufig treten jedoch auch sekundäre Skoliosen auf, die durch neurologische Störungen, kongenitale Fehlbildungen oder neurodegenerative Erkrankungen bedingt sind. Die Diagnostik und Therapie dieser sekundären Formen der Skoliose stellen nicht nur die Orthopäden, sondern auch Neurochirurgen vor große Herausforderungen. Daher erfordert die Behandlung ein hohes Maß an interdisziplinärer Zusammenarbeit. In diesem Artikel werden drei interdisziplinär relevante Krankheitsbilder beschrieben, die eine Skoliose bedingen, koinzident auftreten und ihren Verlauf beeinflussen können und bei ihrer Therapie berücksichtigt werden müssen: die Chiari-I-Malformation (CM), die Diastematomyelie (DM) und das Tethered Cord-Syndrom (TC). Zu jedem Krankheitsbild wird der neurologische Zusammenhang zur Skoliose erläutert und sowohl diagnostische als auch therapeutische Maßnahmen anhand aktueller Literatur vorgestellt. Die Bedeutung des interdisziplinären Ansatzes zwischen Orthopädie und Neurochirurgie steht dabei Im Fokus.

Posterior fossa (PF) tumors are the most common neoplastic entity in pediatric neurosurgery. Children suffering from PF tumors regularly present with hydrocephalus and CSF diversion is a crucial point of treatment. There is an ongoing debate about external ventricular drainage (EVD) management before surgery and its influence on ongoing hydrocephalus treatment afterwards. Beyond onco-surgical aspects, the prevention of shunt-dependency is an important goal in posterior fossa surgery. Various predictors for shunt-dependency after posterior fossa surgery in children have been suggested. Because these predictors may only apply to small subsets of children, and their reliability has been questioned, we evaluated a straightforward, potentially automated, and unbiased method for shunt prediction. In this retrospective radiomic study we analyzed 60 pediatric patients with posterior fossa tumors. Exclusion criteria were age under two years, missing MRI data, tumor location non-exclusive to the PF, traumatic brain injury and less than 6 months follow-up. Ultimately, 36 children met the inclusion criteria. We performed a volumetric assessment of various skull and brain compartments before and after surgery focused on ventricle-brain ratio (VBR). We dichotomized for potential predictors and performed ROC analyses. We evaluated the prognostic parameters for shunt dependency, including supratentorial transependymal edema and VBR, as well as pre- and postoperative radiomic measurements as early prognostic tools. The cutoff in ventricle volume for CSF diversion was 60.9 ml (AUC 0.788, p = 0.001). The radiomic-based prediction of shunt dependency with VBR-scoring showed an AUC of 0.783. Postoperative reduction in ventricle size, depicted by the deltaVBR scoring, showed an AUC of 0.719 in predicting shunt-free survival. Perioperative CSF diversion did correlate with postoperative persistent HCP, whereas the odd’s ratio for shunting was decreased, but not significantly lower, when CSF diversion was undertaken perioperatively (AUC = 0.618, OR = 0.273, CI = 0.029–2.577). Ventricle-brain ratio may be a potential predictor for the necessity of CSF diversion. In our cohort, radiomic predictors performed better than hydrocephalus categorization, modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) or transependymal edema alone. VBR pre- and deltaVBR postoperatively may be potential tools to predict the need for shunting in pediatric posterior fossa tumor patients. The decision for pre- or intraoperative CSF diversion showed no correlation and no influence on persistent hydrocephalus.

Background: Cerebellar Mutism Syndrome (CMS) is a neurological complication of posterior fossa (PF) tumour surgery in children, and postoperative speech impairment (POSI) is the cardinal symptom of CMS. The role of tumour volume on the risk of POSI remains unexplored. This study investigates the association between tumour volume and the risk of POSI. Methods: We included 360 patients from the European CMS study with available preoperative T1-weighted contrast-enhanced brain MRI. Speech status was assessed within two weeks postoperatively and categorised into three levels: habitual speech, severely reduced speech, and mutism. Tumour volumes were calculated using the BrainLab Elements SmartBrush™, a semi-automated segmentation tool. We used proportional odds models to estimate the odds ratio (OR) with adjustments for tumour location, pathology, and age. Based on the primary analysis, a risk stratification model for medulloblastoma patients was constructed, and the optimal volume cut-off was determined with Youden’s Index. Results: We found no effect of the overall tumour volume on the risk of POSI. This result did not change when adjusted for tumour location, pathology, and age. We found an association between tumour volume of medulloblastoma and the risk of POSI (unadjusted OR of 1.04 per increase in cm³ (95% CI 1.01;1.07, p = 0.01)), which did not change when adjusting for tumour location and age. The risk stratification cut-off for the tumour volume of medulloblastoma was calculated to be 16,5 cm³. Patients with medulloblastoma and preoperative tumour volumes below 16,5 cm³ had an absolute risk of 13% for POSI (low-risk group), whereas patients with preoperative tumour volumes above 16,5 cm³ had an absolute risk of 50% for POSI (high-risk group). Conclusion: Our data showed an association between preoperative tumour volume and the risk of POSI in children with medulloblastoma, while no association was found for the volume of other tumour types. We suggest a straightforward cut-off risk model for assessing the risk of POSI in children with medulloblastoma based on preoperative tumour volume. This approach can aid clinicians in informing patients and parents about the complications related to CMS following PF tumour surgery in children. Clinical Trials: ID NCT02300766 (October 2014).

Severe traumatic brain injury (TBI) with acute subdural hematoma (SDH) is common in neurosurgical care. Especially due to demographic development, it becomes increasingly coincident with preexisting therapeutic anticoagulation and comorbidity, such as atrial fibrillation or coagulative disorders. High-velocity trauma mechanisms become rarer, while low-impact trauma to the skull with acute-on-chronic subdural hemorrhage gets relatively more frequent. In this study we elucidate the timing of perioperative prophylactic AC and its influence on morbidity and mortality as well as complications after neurosurgical treatment. We focused especially on postoperative intracranial hemorrhage (PH) and thromboembolic events (TE). For this retrospective data analysis, 259 patients who suffered from severe TBI with consecutive subdural hematoma between 01/01/2014 and 31/12/2019 were included. We followed up for the length of stay. We assessed various biographical and clinical data for risk factors and focused on the connection between time-point of AC and adverse events. Subgroup analyses were performed for TE and PH that either required surgical intervention or was managed conservatively with radiological follow-up. Statistical analysis was performed using receiver operating characteristic curve analyses, Mann-Whitney U Test, Chi-square test, Fisher’s exact test and univariate binomial logistic regression. P-values below 0.05 were considered statistically significant. TE were relatively rare in this cohort (n = 14, 5.4%). The more common adverse event was PH (n = 34, 13.1%), with a total of 28 patients (10.8%) needing surgical revision. Though PH was correlated to a delay in AC (p = 0.010), there was no correlation between early prophylactic AC and PH (p = 0.287) or TE (p = 0.444), respectively. Furthermore, only 4 patients had been administered AC before the PH. In this context, AC was delayed purposely after PH, explaining the significant correlation between PH and delayed AC. Occurrence of PH significantly decreased overall survival (p = 0.022), while TE did not (p = 0.357). Prophylactic AC within 24–48 h after surgery did not result in more frequent PH. Our data on AC timing suggest that PH is not caused by prophylactic AC.

Background: PTEN hamartoma tumor syndrome (PHTS) has evolved into an umbrella term for a range of syndromes, characterized by loss-of-function variants in the phosphatase and tensin homolog (PTEN) tumor suppressor gene on chromosome 10q23.31. This can result in a lifelong tumor predisposition in patients. Often, the syndrome is diagnosed in early childhood because of macrocephaly, dermatological findings, or development delay. Since the correlation between phenotype and genotype is weak, and the penetrance is age-dependent, this poses the question of the appropriate timing of potentially invasive and burdensome examinations for early cancer detection. Case: The present report describes an infant with cleft palate associated with PHTS, a rare occurrence, though the initial report of Cowden syndrome already pointed to oromaxillofacial abnormalities. The recent pediatric literature is reviewed to assess which clinical symptoms should raise suspicion of PHTS and may then lead to early genetic counseling. Conclusion: Since the amount of prospective data remains limited, and the estimation of tumor risk during infancy and adulthood is very difficult, we advocate for early and broad genetic testing in suspected cases, to gain more insights into this rare disease and allow for better counseling for patients and their families.

In the perioperative management of patients with glioblastoma (GBM), physicians face the question of whether and when to administer prophylactic or therapeutic anticoagulation (AC). In this study, we investigate the effects of the timing of postoperative heparinization on thromboembolic events (TE) and postoperative hemorrhage (bleeding, PH) as well as the interactions between the two in the context of an underlying intracerebral malignancy. For this retrospective data analysis, 222 patients who underwent surgery for grade IV glioblastoma, IDH-wildtype (2016 CNS WHO) between 01/01/2014 and 31/12/2019 were included. We followed up for 12 months. We assessed various biographical and clinical data for risk factors and focused on the connection between timepoint of AC and adverse events. Subgroup analyses were performed for pulmonary artery embolism (PE), deep vein thrombosis, and postoperative intracranial hemorrhage (PH) that either required surgical intervention or was controlled radiologically only. Statistical analysis was performed using Mann–Whitney U-Test, Chi-square test, Fisher’s exact test and univariate binomial logistic regression. p values below 0.05 were considered statistically significant. There was no significant association between prophylactic AC within 24 h and more frequent major bleeding (p = 0.350). AC in patients who developed major bleeding was regularly postponed by the physician/surgeon upon detection of the re-bleeding; therefore, patients with PH were anticoagulated significantly later (p = 0.034). The timing of anticoagulant administration did not differ significantly between patients who experienced a thromboembolic event and those who did not (p = 0.634). There was considerable overlap between the groups. Three of the six patients (50%) with PE had to be lysed or therapeutically anticoagulated and thereafter developed major bleeding (p < 0.001). Patients who experienced TE were more likely to die during hospitalization than those with major bleeding (p = 0.022 vs. p = 1.00). Prophylactic AC within 24 h after surgery does not result in more frequent bleeding. Our data suggests that postoperative intracranial hemorrhage is not caused by prophylactic AC but rather is a surgical complication or the result of antithrombotic therapy. However, thromboembolic events worsen patient outcomes far more than postoperative bleeding. The fact that bleeding may occur as a complication of life-saving lysis therapy in the setting of a thromboembolic event should be included in this cost–benefit consideration.