Ulrich-Wilhelm Thomale

Hydrocephalus, a condition characterized by disrupted cerebrospinal fluid (CSF) dynamics, has historically and mainly relied on ventriculoperitoneal shunt (VPS) systems for treatment. Despite considerable advances in the field, ranging from early valve-less systems to adjustable pressure valves and anti-hydrostatic devices, shunt failure rates remain high, and optimal, individualized CSF drainage remains challenging to achieve. Since hardly any objective feedback measures of shunt function are integrated in the shunt system in order to achieve physiologic like CSF drainage, it somehow remains to be a black box. In response to the aforementioned challenge, the concept of a “smart shunt” has emerged, with the objective of establishing a self-regulating system. The objective of this systematic literature review is twofold: firstly, to analyze existing research on smart shunts; secondly, to synthesize this research in order to highlight any advancements. In order to achieve these objectives, a systematic literature review was conducted in accordance with the PRISMA guidelines, yielding a total of 135 potentially relevant articles. Following the elimination of duplicates and a more thorough evaluation, 22 articles were deemed pertinent for additional scrutiny. Furthermore, a patent search was conducted, which identified ten relevant results. While technological advances render the realization of a smart shunt increasingly feasible, financial challenges remain and further interdisciplinary research and clinical validation are essential to translate this concept into a reliable, personalized treatment option for patients with hydrocephalus.

Focal cortical dysplasias (FCDs) are one of the most common structural causes of drug-resistant epilepsy in children but are frequently subtle and difficult to detect on conventional MRI. Many automated lesion detection methods have therefore been proposed to support neuroradiological assessment. In this study, we externally validated two recently developed deep-learning approaches for FCD detection, MELD Graph and 3D-nnUNet, in a pediatric cohort. In this retrospective single-center study, brain MRI scans of 71 children evaluated for epilepsy were analyzed, including 35 MRI-positive patients with suspected FCD and 36 MRI-negative cases based on the primary radiology reports. Both models were applied to standard 3D T1-weighted and 3D FLAIR images. Detected lesions were reviewed by an experienced pediatric neuroradiologist and classified as true positive, false positive, or false negative. Clinical semiology and EEG findings were additionally evaluated for cases with false-positive detections. At the lesion level, MELD Graph achieved a precision of 0.85 and recall of 0.52, while 3D-nnUNet achieved a precision of 0.91 and recall of 0.48. In the MRI-negative patients, MELD Graph produced more false-positive detections than 3D-nnUNet (0.53 vs. 0.14 false-positive lesions per patient). At the patient level, MELD Graph showed slightly higher sensitivity than 3D-nnUNet (0.63 vs. 0.54), whereas 3D-nnUNet demonstrated markedly higher specificity (0.86 vs. 0.56). Improved FLAIR image quality was associated with trends toward improved model performance. Both models demonstrated high precision but moderate sensitivity, indicating that they are valuable decision-support tools but cannot replace expert neuroradiological evaluation. Optimized MRI acquisition protocols are needed to further improve automated lesion detection in pediatric epilepsy.

Disturbances of neurovascular coupling (NVC) contribute to metabolic derailment and neurological symptoms associated with epilepsy. While postictal arterial constriction can be alleviated by inhibitors of voltage gated calcium channels (VGCCs), less is knownregarding seizure-associated electrical signals in higher-order capillaries and their role in determining pericyte tone during seizures. Here we investigated electrical signaling within the ex vivo neurovascular unit (NVU) derived from rat and human brain tissue. We focused on electrical signal transduction between pericytes and endothelial cells and the potential role of VGCCs in vasomotion. Using dye coupling and paired patch-clamp recordings, we showed that morphologically heterogeneous groups of mid-capillary pericytes build a functional syncytium with endothelial cells. Coupling was asymmetric, allowing for directed propagation of electrical signals. Regardless of their morphology, mid-capillary pericytes responded with depolarization and constriction to metabotropic receptor (GPCR) activation (by thromboxane, norepinephrine and UDP-glucose). However, depolarization via the patch pipette induced neithe r Ca ²⁺ -influx nor constriction, suggesting lack of contribution of VGCCs to vasomotion. On inducing epileptiform activity, A2a adenosine receptors and inwardly rectifying potassium channels hyperpolarized the capillary syncytium, followed by repeated depolarizations due to seizure-associated potassium increase in the parenchyma. Thus, while mid-capillary pericytes are contractile, their tone does not rely on their membrane potential and VGCCs. However, syncytial coupling allows for transmission of seizure-associated hyper- and depolarizing signals to upstream feeding arterioles.

Study Aims The surgical treatment of symptomatic Arnold-Chiari malformation type I (CM-I) typically involves decompression of the posterior cranial fossa. A full-endoscopic approach is emerging as an alternative to traditional microsurgical techniques. However, this method presents challenges in intraoperative assessment of the decompression extent, potentially resulting in inadequate decompression. In neurosurgery, ultrasound is gaining increasing importance, as it avoids ionizing radiation and enables real-time examination. The aim of this anatomical study is to evaluate the suitability of ultrasound for assessing defect size compared to radiography and CT during uniportal full-endoscopic decompression of the posterior fossa. Material and Methods Six fresh-frozen adult human cadavers underwent endoscopic decompression of the posterior fossa. The endoscope used featured an oval shaft with a diameter of 9.3 mm, a working length of 177 mm, a 20° viewing angle, and an eccentric 5.6 mm working channel. Computed tomography (CT), X-rays, and ultrasound images were obtained before and after decompression for measurement purposes. Results The average endoscopic decompression in the sagittal plane as measured by ultrasound was 26 ± 2 mm, with fluoroscopy 27 ± 1 mm and using CT 26 ± 1 mm. A statistically significant Pearson correlation was found between ultrasound and CT (r = 0.94, p < 0.01); between ultrasound and fluoroscopy (r = 0.9, p < 0.05); and between fluoroscopy and CT (r = 0.8, p < 0.05). The average endoscopic decompression in the axial plane as measured by ultrasound was 37 ± 2 mm, with fluoroscopy 26 ± 2 mm and using CT 36 ± 1 mm. A statistically significant Pearson correlation was found only between ultrasound and CT (r = 0.95, p < 0.01). Conclusion The full-endoscopic approach enables effective decompression of the posterior fossa in an experimental setup. Intraoperative ultrasound proves reliable in assessing the extent of decompression, showing good correlation with X-rays and CT. This technique holds promise for wider use in CM-I treatment, particularly in pediatric neurosurgery, where ultrasound offers a radiation-free method for intraoperative evaluation of defect size.

Purpose: This study validated VParNet and nnU-Net for ventricular segmentation in pediatric hydrocephalus, a condition characterized by irregular and asymmetric ventricular shapes. Methods: Manual segmentation of 139 MRI scans (ages range 2.6–20.3 years) was performed for the four ventricles and the aqueduct. A five-fold cross-validation was conducted for both models. VParNet was tested with its original weights and after retraining on pediatric data. nnU-Net was extended to also segment the aqueduct. Performance was evaluated using the Dice Similarity Coefficient (DSC), Intraclass Correlation Coefficient (ICC), and Minimal Detectable Change (MDC). Results: VParNet preprocessing failed in 20.9% of cases, requiring subject exclusion. Both models showed good to excellent segmentation accuracy and reliability (DSC: 0.87–0.95; ICC: 0.81–1.0). Retraining VParNet improved DSC scores. MDC values (0.05–3.0) indicated high sensitivity for the lateral and third ventricles and acceptable sensitivity for the fourth ventricle. Aqueduct segmentation remained challenging (nnU-Net: DSC = 0.68; ICC = 0.81; MDC = 0.04). Conclusion: All tested models performed well in pediatric hydrocephalus segmentation, with no fundamental differences in overall performance. However, nnU-Net demonstrated key advantages due to its lack of preprocessing requirements, which allow the successful handling of even the most challenging subjects. These features make it easily implementable for clinical applications, providing fast and reliable ventricular segmentation and quantification.

Purpose: Neuroendoscopic lavage (NEL) has been described for post-hemorrhagic hydrocephalus management in intraventricular hemorrhage (IVH) of prematurity in European cohorts. We describe an initial single-center series from the USA. Methods: A retrospective review was performed for premature infants with IVH that underwent NEL at our institution between 2020 and 2023. Patient characteristics, clinical variables, and radiological assessments were collected. Results: Eleven patients (five female) with IVH grade III/IV underwent 13 procedures. Mean gestational age (GA) was 25 weeks and 2 days. Mean birth weight (BW) was 0.83 kg (kg). Average age at NEL was 40.4 ± 21.5 days, and mean weight was 1.51 ± 0.3 kg. Mean frontal horn index decreased from 0.68 to 0.56 after NEL ( p < 0.001). Cerebrospinal fluid infection was diagnosed in 18.2%, secondary hemorrhage in 18.2%, and seizures in 27.3% of patients. One patient died postoperatively with refractory coagulopathy. Conversion to ventriculoperitoneal shunt at six-month follow-up was 8/11 (72.7%), with 50% 1-year revision-free shunt survival. No patients required a multi-catheter system. Rates of comorbidities and shunt dependency showed very strong positive correlations: hyaline membrane disease rate ( R ² = 0.950), necrotizing enterocolitis ( R ² = 0.999), and persistent ductus arteriosus ( R ² = 0.975). Prematurity and shunt dependency showed a moderate to strong negative correlation: GA ( R ² = 0.527) and BW ( R ² = 0.344). Conclusion: Extreme prematurity and comorbidities are associated with increased shunt dependency. However, NEL may decrease the development of complex multiloculated hydrocephalus and the need for multiple catheter systems. Larger, long-term studies are needed to define optimal timing and criteria for NEL and its benefits and impact on neurodevelopment in this fragile population.

Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one-third of cases. Even when a structural lesion is identified as the epileptogenic focus, understanding the underlying genetic causes is crucial to guide both counseling and treatment decisions. Both somatic and germline DNA variants may contribute to the lesion itself and/or influence the severity of symptoms. We therefore used whole exome sequencing (WES) to search for potentially pathogenic somatic DNA variants in brain samples from children with lesional epilepsy who underwent epilepsy surgery. WES was performed on 20 paired DNA samples extracted from both lesional brain tissue and reference tissue from the same patient, such as leukocytes or fibroblasts. The paired WES data were jointly analyzed using GATK Mutect2 to identify somatic single nucleotide variants (SNVs) or insertions/deletions (InDels), which were subsequently evaluated in silico for their disease-causing potential using MutationTaster2021. We identified known pathogenic somatic variants in five patients (25%) with variant allele frequencies (VAF) ranging from 3–35% in the genes MTOR, TSC2, PIK3CA, FGFR1, and PIK3R1 as potential causes of cortical malformations or central nervous system (CNS) tumors. Depending on the VAF, we used different methods such as Sanger sequencing, allele-specific qPCR, or targeted ultra-deep sequencing (amplicon sequencing) to confirm the variant. In contrast to the usually straightforward confirmation of germline variants, the validation of somatic variants is more challenging because current methods have limitations in sensitivity, specificity, and cost-effectiveness. In our study, WES identified additional somatic variant candidates in additional genes with VAFs ranging from 0.7–7.0% that could not be validated by an orthogonal method. This highlights the importance of variant validation, especially for those with very low allele frequencies.