Andreas Pfnür

Background: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is incompletely understood and may involve intrathecal immune activation. Cytotoxic natural killer (NK) cells can rapidly respond to SAH and promote neuroinflammation, whereas regulatory T cells (Tregs) may counteract excessive immune activation. This study investigates the NK/Treg ratio in cerebrospinal fluid (CSF) and peripheral blood (PB) as a potential immunological marker associated with DCI. Methods: In this prospective, observational, single-center study, CSF and peripheral blood samples from 21 patients with aneurysmal SAH admitted between 2023 and 2024 were analyzed. Longitudinal dynamics of NK cells and Tregs were assessed by flow cytometry at predefined time points from day 1 to day 14 after hemorrhage. The NK/Treg ratio was calculated for each compartment and time point, and its association with DCI was explored. Results: Twenty-one patients were included, of whom 16 were female (76.2%). The mean age was 55.9 years (standard deviation [SD] 13.3). Median WFNS and modified Fisher grades at admission were 3 (range 1–5) and 3 (range 1–4), respectively. DCI occurred in 10 patients (47.6%), with a median onset of 8.5 days after hemorrhage (range 4–12). Longitudinal dynamics of NK cells and Tregs in CSF and peripheral blood were assessed using flow cytometry. On day 3, the CSF NK/Treg ratio was higher in patients who later developed DCI compared with patients without DCI (mean 5556.6 [SD 12266.0] vs. 161.8 [SD 195.2]). CSF ratios remained numerically higher at later time points, whereas changes in peripheral blood were modest. In exploratory analyses of clinical covariates, lower modified Fisher grades (1–3 vs. 4) were associated with increased NK/Treg ratios in CSF at day 1 ( p = 0.046) and day 2 ( p = 0.007), possibly indicating that the elevation was not merely a reflection of subarachnoid blood burden. Conclusions: Patients who developed DCI showed an early intrathecal shift in the balance between NK cells and Tregs, reflected by a higher CSF NK/Treg ratio around day 3. This pattern was more pronounced in CSF than in peripheral blood, suggesting a compartment-specific immune alteration associated with DCI. Although the small sample size, high variability, and limited statistically significant findings preclude definitive conclusions, these data support the hypothesis that early CSF immune dysregulation may contribute to DCI after SAH. CSF-based immune profiling, including the NK/Treg ratio, may therefore represent a promising exploratory approach for DCI risk stratification. Larger prospective multicenter studies with standardized CSF sampling are required to validate these exploratory findings.

Background: Decompressive craniectomy (DC) is a life-saving intervention for refractory intracranial pressure (ICP). While outcomes in adults are well documented, pediatric data, especially concerning pupillomotor dysfunction, remain limited. Anisocoria is generally considered a marker of severe neurological compromise, but its clinical relevance in children undergoing DC has not been adequately studied. Methods: We retrospectively reviewed 25 pediatric patients treated with DC between 2004 and 2024. Demographic, radiological and clinical data included age, sex, hospital stay, operative time, etiology, side of craniectomy, preoperative midline (ML) shift, Marshall score, Rotterdam score, Glasgow Coma Scale (GCS) and pupillary status before surgery. Functional outcomes were assessed using the pediatric version of the Glasgow Outcome Scale Extended (pGOS-E) at discharge, after 3 months, 1, 2 and 4 years. Results: The majority of patients were school-aged children with a median age of 10 (range 0–17) years. Traumatic brain injury accounted for 16 cases and represented the leading etiology for DC. Pupillomotor dysfunction (anisocoria or bilateral fixed pupillary dilatation) was observed in 15 of 25 patients, 47% of whom died during hospitalization, demonstrating a significant association with in-hospital mortality (p = 0.02). However, survivors with primary pupillomotor dysfunction demonstrated a favorable recovery at 12 months with a median pGOS-E of 6 (range 4–8), indicating moderate disability. A preoperative ML-shift > 5 mm was not associated with lower pGOS-E scores during follow-up (p > 0.05). Bone flap autolysis was observed in 12 out of 14 children (86%) receiving autologous cranioplasty, and 8 (57%) patients required revision surgery with synthetic material. Conclusions: In pediatric patients, pupillomotor dysfunction is associated with higher early mortality but does not reliably exclude favorable long-term outcomes. Compared with adult cohorts, children appear to have a greater potential for neurological recovery, suggesting that severe initial clinical findings alone should not preclude timely surgical intervention.

Aneurysmal subarachnoid hemorrhage (SAH) involves a significant influx of blood into the cerebrospinal fluid, representing a severe form of stroke. Despite advancements in aneurysm closure and neuro-intensive care, outcomes remain impaired due to cerebral vasospasm and delayed cerebral ischemia (DCI). Previous pharmacological therapies have not successfully reduced DCI while improving overall outcomes. As a result, significant efforts are underway to better understand the cellular and molecular mechanisms involved. This review focuses on the activation and effects of immune cells after SAH and their interactions with neurotoxic and vasoactive substances as well as inflammatory mediators. Particular attention is given to clinical studies highlighting the roles of natural killer (NK) cells and regulatory T cells (Treg) cells. Alongside microglia, astrocytes, and oligodendrocytes, NK cells and Treg cells are key contributors to the inflammatory cascade following SAH. Their involvement in modulating the neuro-inflammatory response, vasospasm, and DCI underscores their potential as therapeutic targets and prognostic markers in the post-SAH recovery process. We conducted a systematic review on T cell- and natural killer cell-mediated inflammation and their roles in cerebral vasospasm and delayed cerebral ischemia. We conducted a meta-analysis to evaluate outcomes and mortality in studies focused on NK cell- and T cell-mediated mechanisms.

Zusammenfassung: Hintergrund Das neurogene Thoracic-Outlet-Syndrom (nTOS) beschreibt einen Symptomkomplex, der durch die Einengung der nervalen Strukturen an der oberen Thoraxapertur ausgelöst wird. Typische Symptome sind Schmerzen, Taubheit und motorische Schwäche der betroffenen Extremität. Die Inzidenz von nTOS beträgt 2–3/100000 und ist am höchsten im Alter von 25–40 Jahren. Es gibt nur wenige Studien des nTOS bei jugendlichen Patienten, insbesondere fehlen Daten mit Langzeitergebnissen. Material und Methoden Bei einer retrospektiven Studie von chirurgisch behandelten nTOS-Fällen in unserer Klinik wurden zwischen 2002–2021 acht Patienten zwischen 15 und 18 Jahren eingeschlossen. Demografische Daten, Risikofaktoren, der neurologische Status, klinische Funktionstests, neurophysiologische, radiologische und intraoperative Befunde wurden ausgewertet. Die Erhebung der postoperativen Befunde erfolgte anhand eines standardisierten Fragebogens. Die Dekompression des Truncus inferior und der Nervenwurzeln C8 und Th1 erfolgte über einen supraklavikulären Zugang. Ergebnisse Die durchschnittliche Dauer der Symptome vor der Operation betrug zwei Jahre. Von den acht operierten Patienten beantworteten sechs Patienten den schriftlichen Fragebogen und konnten für die Studie ausgewertet werden. Das Follow-Up war im Mittel neun Jahre (1–18 Jahre). Nach der Operation hatten alle Patienten eine Schmerzreduktion, drei Patienten waren im Langzeitverlauf schmerzfrei und fünf Patienten benötigten keine Schmerzmedikation mehr. Die Kraft verbesserte sich bei allen Patienten, bei zwei Patienten bestanden jedoch noch leichte motorische Defizite. Die sensiblen Störungen waren bei allen Patienten rückläufig, es bestand jedoch bei fünf Patienten eine residuelle Hypästhesie. In Bezug auf die Überkopfarbeiten hatte die Hälfte der Patienten nach der Operation keine Beeinträchtigung. Alle Patienten waren zum Zeitpunkt der Durchführung des Fragebogens arbeitsfähig. Die Hälfte der Patienten ging ihren sportlichen Aktivitäten ohne Beeinträchtigung nach, während die andere Hälfte eine leichte Einschränkung angab. Schlussfolgerung Das nTOS bei Jugendlichen ist ein seltenes Kompressionssyndrom. Der supraklavikuläre Zugang mit Dekompression der unteren Anteile des Plexus brachialis, ohne Resektion der ersten Rippe, stellt eine adäquate Therapie dar. Diese retrospektive Studie ergab, dass bei allen Patienten eine deutliche Schmerzreduktion erzielt werden konnte. Bei einigen Patienten persistierten leichte sensible und motorische Störungen sowie eine gewisse Einschränkung bei Überkopfarbeiten. Die sportlichen Aktivitäten waren wieder möglich.

Cranioplasty (CP) after decompressive hemicraniectomy (DHC) is a common neurosurgical procedure with a high complication rate. The best material for the repair of large cranial defects is unclear. The aim of this study was to evaluate different implant materials regarding surgery related complications after CP. Type of materials include the autologous bone flap (ABF), polymethylmethacrylate (PMMA), calcium phosphate reinforced with titanium mesh (CaP-Ti), polyetheretherketone (PEEK) and hydroxyapatite (HA). A retrospective, descriptive, observational bicenter study was performed, medical data of all patients who underwent CP after DHC between January 1st, 2016 and December 31st, 2022 were analyzed. Follow-up was until December 31st, 2023. 139 consecutive patients with a median age of 54 years who received either PMMA (56/139; 40.3%), PEEK (35/139; 25.2%), CaP-Ti (21/139; 15.1%), ABF (25/139; 18.0%) or HA (2/139; 1.4%) cranial implant after DHC were included in the study. Median time from DHC to CP was 117 days and median follow-up period was 43 months. Surgical site infection was the most frequent surgery-related complication (13.7%; 19/139). PEEK implants were mostly affected (28.6%; 10/35), followed by ABF (20%; 5/25), CaP-Ti implants (9.5%; 2/21) and PMMA implants (1.7%, 1/56). Explantation was necessary for 9 PEEK implants (25.7%; 9/35), 6 ABFs (24.0%; 6/25), 3 CaP-Ti implants (14.3%; 3/21) and 4 PMMA implants (7.1%; 4/56). Besides infection, a postoperative hematoma was the most common cause. Median surgical time was 106 min, neither longer surgical time nor use of anticoagulation were significantly related to higher infection rates (p = 0.547; p = 0.152 respectively). Ventriculoperitoneal shunt implantation prior to CP was noted in 33.8% (47/139) and not significantly associated with surgical related complications. Perioperative lumbar drainage, due to bulging brain, inserted in 38 patients (27.3%; 38/139) before surgery was protective when it comes to explantation of the implant (p = 0.035). Based on our results, CP is still related to a relatively high number of infections and further complications. Implant material seems to have a high effect on postoperative infections, since surgical time, anticoagulation therapy and hydrocephalus did not show a statistically significant effect on postoperative complications in this study. PEEK implants and ABFs seem to possess higher risk of postoperative infection. More biocompatible implants such as CaP-Ti might be beneficial. Further, prospective studies are necessary to answer this question.

OBJECTIVE: Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in SMA syndrome, a symptom complex characterized by transient akinesia and mutism. Because the factors influencing patient functional outcomes after surgery remain elusive, the authors investigated network-based predictors in a multicentric cohort of glioma patients. METHODS: The participants were 50 patients treated for glioma located in the SMA at one of the three centers participating in the study. Postoperative functional outcomes (motor deficits, mutism) and duration of symptoms were assessed during hospitalization. Long-term outcome was assessed 3 months after surgery. MRI-based lesion-symptom mapping was performed to estimate the severity of gray matter damage and white matter disconnection. RESULTS: The median duration of acute symptoms was 3 days (range 1–42 days). Long-term deficits involving fine motor movements and speech were found at follow-up in 27 patients (54%). Disconnection of the central callosal fibers was associated with prolonged acute symptoms (p < 0.05). Postoperative mutism was significantly related to disconnection severity of the left frontopontine tract, frontal aslant tract, cingulum, and corticostriatal tract (p < 0.05). Disconnection of midposterior callosal fibers and lesion loads within the left medial Brodmann area 4 were associated with long-term motor deficits (p < 0.05). CONCLUSIONS: This study provides evidence for the pathophysiology and predictive factors of postoperative SMA syndrome by demonstrating the relation of the disconnection of callosal fibers with prolonged symptom duration (central segment) and long-term motor deficits (midposterior segment). These data may be useful for presurgical risk assessment and adequate consultation for patients prior to undergoing resection of glioma located within the SMA region.

The aim of the study was to assess the quality, accuracy and benefit of navigated 2D and 3D ultrasound for intra-axial tumor surgery in a prospective study. Patients intended for gross total resection were consecutively enrolled. Intraoperatively, a 2D and 3D iUS-based resection was performed. During surgery, the image quality, clinical benefit and navigation accuracy were recorded based on a standardized protocol using Likert’s scales. A total of 16 consecutive patients were included. Mean ratings of image quality in 2D iUS were significantly higher than in 3D iUS (p < 0.001). There was no relevant decrease in rating during the surgery in 2D and 3D iUS (p > 0.46). The benefit was rated 2.2 in 2D iUS and 2.6 in 3D iUS (p = 0.08). The benefit remained stable in 2D, while there was a slight decrease in the benefit in 3D after complete tumor resection (p = 0.09). The accuracy was similar in both (mean 2.2 p = 0.88). Seven patients had a small tumor remnant in intraoperative MRT (mean 0.98 cm³) that was not appreciated with iUS. Crucially, 3D iUS allows for an accurate intraoperative update of imaging with slightly lower image quality than 2D iUS. Our preliminary data suggest that the benefit and accuracy of 2D and 3D iUS navigation do not undergo significant variations during tumor resection.