The Extension of Traumatic Subdural Hematoma into the Interhemispheric Fissure Is Associated with Coagulation Disorders: A Retrospective Study.

BACKGROUND: This study investigates the correlation of the radiologic sign of interhemispheric subdural hematoma (iSDH) in different injury patterns with clinical coagulation disorders. It is hypothesized that the presence of iSDHs is correlated with clinical coagulation disorders in patients with traumatic brain injuries and subdural hematoma (SDH). METHODS: Between January 1, 2020 and June 30, 2022, 154 patients with SDH were identified. Coagulation disorders were assessed using chart review and patients were divided into four groups: SDH without iSDH without further injuries (SDH), SDH with iSDH without further injuries (SDH + iSDH), SDH without iSDH with further brain injuries (Combi), SDH with iSDH with further injuries (Combi + iSDH). These four groups were formed under the assumption that isolated SDHs result from a highly specific trauma mechanism (rupture of bridging veins) in predisposed elderly patients, while combined brain injuries with SDH result from a severe global traumatic brain injury combining different pathophysiologic mechanisms often in younger patients. The groups were analyzed for patient demographics, clinical presentation, and association with coagulation disorders. The significance level was set at p < 0.005. RESULTS: The presence of an iSDH was associated with a higher likelihood of concomitant coagulation disorder or anticoagulants in cases of isolated subdural hemorrhage (56.8% of the population in SDH vs. 94.7% in SDH + iSDH, p < 0.005). This effect was not significant in the cases with combined traumatic brain injuries (33.3% in Combi vs. 53.6% in Combi + iSDH, p > 0.005). CONCLUSION: Our data indicate a high positive predictive value (PPV = 94.7%) for coagulation disorders in traumatic SDH patients with iSDH without any further focal and diffuse brain injuries. We consider this a relevant finding since it hints at the presence of coagulation disorders and might be used in early hemostaseologic assessment and emergency management.

Impact of early follow-up CT in the conservative management of traumatic brain injury on surgical decision making: A retrospective, single-center analysis with special respect to coagulopathy.

INTRODUCTION: Initial management of traumatic brain injury (TBI) without immediate need for surgical therapy varies across centers. The additional value of routine repeat cranial computerized tomography (CT) to neurological monitoring is controversial. This retrospective study investigates the impact of routine follow-up CT after 6 h (CT6h) in initially conservatively managed TBI on surgical decision making. Furthermore, the impact of coagulopathy on lesion size and progression was examined. METHODS: We reviewed charts of patients admitted to our clinic in the time between 1st January 2020 and 30th June 2022 for the ICD10 diagnosis S06.3 (traumatic brain contusion), S06.4 (epidural hematoma), S06.5 (subdural hematoma), and S06.6 (traumatic subarachnoid hemorrhage). Baseline characteristics as well as timing, reason, and consequences of first and second cranial CT, clinical course, lesion size at first and second CT as well as presence and type of coagulopathy (standard laboratory testing and prior medical history) were noted among others. Significance testing was carried out using Student's t-test. The significance level was set to p < 0.005. RESULTS: A total of 213 patients were included, 78 were operated after first CT, 123 underwent clinical and imaging surveillance, and 12 patients were not treated. CT6h did not anticipate imminent neurological deterioration. Early secondary deteriorating patients (9/123, 7.3%) did so before 6 h after admission clustering between 3 and 4 h (6/9, 66.7%). CT6h changed surgical decision making in one case (1/114, < 1%). Nine out of 106 (8.5%) patients managed conservatively after CT6h showed a late secondary clinical deterioration or failure of conservative treatment, eight out of which had stable size of hemorrhage in CT6h. There was no significant difference in lesion size at first CT related to the presence of coagulopathy, antiplatelet agents, or anticoagulant drugs for SDH or contusions. In patients with radiological progression of SDH in combined brain injury (CBI), coagulopathy was associated with a higher increase of lesion size (diameter increase > 6 mm: 11.1% with vs. 2.8% without coagulopathy). This effect was not observed for contusions in CBI (volume increase > 6 ml: 17.4% with vs. 22.7% without coagulopathy). CONCLUSION: Early routine follow-up CT does neither anticipate imminent neurological deterioration nor impact surgical decision making. A substantial number of patients with initially stable follow-up imaging need delayed surgery due to conservative treatment failure. If patients can be monitored clinically, surgical decision making depends on clinical status. Patients with coagulopathy do not present with larger lesions, but show a higher ratio of drastic increase in SDH in contrast to contusions.

A Step-by-Step Dissection of Cerebral Pathologies for Neurosurgical Trainees: The Middle Cerebral Artery Bifurcation Aneurysm.

BACKGROUND: Aneurysmal subarachnoid hemorrhage remains one of the most prevalent causes of strokes in the young causing a high socioeconomic damage. Both emergent and elective treatments of intracranial aneurysms remain essential challenges for neurovascular centers. We aim to present conceptual education on clip ligation of middle cerebral artery bifurcation aneurysms in an accessible and structured way to maximize the educational takeaway of residents from aneurysm cases. METHODS: After 30 years of experience of the senior author in cerebrovascular surgery in three centers, we closely reviewed an exemplary case of elective right middle cerebral artery bifurcation aneurysm clipping and contrasted it to an alternative microneurosurgical approach to illustrate key principles of microneurosurgical clip ligation for neurosurgical trainees. RESULTS: Dissection of the sylvian fissure, subfrontal approach to the optic-carotid complex, proximal control, aneurysm dissection, dissection of kissing branches, dissection of aneurysm fundus, temporary and permanent clipping, as well as aneurysm inspection and resection are highlighted as key steps of clip ligation. This proximal-to-distal approach is contrasted to the distal-to-proximal approach. Additionally, general principles of intracranial surgery such as use of retraction, arachnoid dissection, and draining of cerebrospinal fluid are addressed. CONCLUSION: Due to a constantly decreasing case load in the era of neurointerventionalism, the paradox of facing increased complexity with decreased experience must be met with a sophisticated practical and theoretical education of neurosurgical trainees early on and with a low threshold.

Operative V2 decompression for traumatic vertebrobasilar insufficiency: illustrative case.

BACKGROUND: Blunt vertebral artery injuries after cervical trauma due to the close anatomical relationship of the vertebral artery to the cervical spine may have fatal consequences because of posterior circulation ischemia and vertebrobasilar insufficiency. While the standard of care remains medical treatment by anticoagulation or antiplatelet therapy, surgical decompression of the vertebral artery is rarely indicated. OBSERVATIONS: The authors present a case of selective decompression of a traumatically constricted vertebral artery within the transverse foramen of C2 presenting with vertebrobasilar insufficiency due to bilateral aplasia of the posterior communicating arteries and contralateral hypoplasia of the vertebral artery. LESSONS: Because of their close relationship to the cervical spine, the vertebral arteries are at risk for blunt injury, which may present asymptomatically or with symptoms of posterior circulation ischemia or vertebrobasilar insufficiency either immediately or after a latency phase. The anatomical variability of (1) the vertebral arteries, (2) collateral brainstem perfusion, and (3) the individual injury pattern demands individualized treatment strategies. If endovascular treatment of hemodynamically relevant stenosis of the V2 segment of the vertebral artery poses too high a risk for vessel injury, decompression of the transverse foramen can be performed safely and without risk to the biomechanical stability of the cervical spine.

Adult intracranial ependymoma-relevance of DNA methylation profiling for diagnosis, prognosis, and treatment.

BACKGROUND: A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas. METHODS: Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from 8 diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS). RESULTS: The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6%, and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE, and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (GTR) (P = .009) and postoperative radiotherapy (P = .007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of the prognosis within molecularly defined ependymoma classes. CONCLUSIONS: DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. GTR and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.

Percheron-like artery infarction after transsphenoidal surgery: illustrative case.

BACKGROUND: The transsphenoidal approach to the skull base has enjoyed increasing popularity for surgery of the sellar region avoiding brain retraction and causing few severe complications. While vitally important vessels in this region show a high degree of variability, some anatomical variants might be involved in characteristic complications. OBSERVATIONS: We present the case of a 40-year-old female patient with acromegaly due to a pituitary adenoma that was transsphenoidally operated. Postoperatively, the patient presented with bilateral unresponsive mydriasis, loss of consciousness and tetraparesis. An MRI showed well-circumscribed bilateral paramedian thalamic infarctions which indicated a rare Percheron-like artery. At 2-year follow-up examination the patient was dramatically improved but with a profound impact on her ability to interact with the world. LESSONS: The basilar artery or perforators might be injured during dissection of suprasellar lesions. This vascular territory is essential to interaction of the brain with the outside world. We conclude that we will approach future suprasellar adenomas strictly intracapsularly.

The genomic and transcriptional landscape of primary central nervous system lymphoma.

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.

Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity.

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

Clinical Situation, Therapy, and Follow-Up of Adult Craniopharyngioma.

CONTEXT: Craniopharyngioma is a rare neoplastic entity of the central nervous system. Childhood-onset craniopharyngioma is the subject of frequent research whereas the information on adult-onset craniopharyngioma is scarce. OBJECTIVE: The objective of this study was to examine the level of daily impairment in adult patients suffering from craniopharyngioma. DESIGN: Noninterventional patient registry indexed as PV4842 with the local ethics committee. SETTING: The study is set in a hospitalized and ambulatory setting. PATIENTS: 148 patients with adult-onset craniopharyngioma were recruited from 8 centers, 22 prospectively and 126 retrospectively. Mean follow-up was 31 months. INTERVENTIONS: No interventions performed. MAIN OUTCOME MEASURES: Complications, symptoms, body mass index (BMI), and quality of life (QoL; EORTC QLQ C30 and BN20) were recorded preoperatively and at follow-up. The hypotheses tested were generated after data collection. RESULTS: Complications were more frequent after transcranial than transsphenoidal approaches (31 % vs. 11%; P < 0.01). Preoperative obesity was present in 0% papillary and in 38% of all adamantinomatous craniopharyngiomas (P = 0.05), and diabetes insipidus was more frequent for papillary craniopharyngioma (36.8% vs. 16,7%; P < 0.05). Hormone deficits at follow-up were reduced in 16.9%, equal in 31.4%, and increased in 63.6% (P < 0.001). BMI increased from 28.7 ± 7.4 kg/m2 before surgery to 30.2 ± 7.4 kg/m2 at follow-up (P < 0.001). In QoL, a decrease of future uncertainty (62.5 vs. 36.8; P = 0.02) and visual disorders (38.9 vs. 12.0; P = 0.01) were observed in the prospective collective after surgery. CONCLUSIONS: Adult craniopharyngioma is associated with a complex sociological and psychological burden and hypothalamic dysfunction, warranting further investigation and emphasizing the need for a wider treatment approach.

Consensus on Postoperative Recommendations After Transsphenoidal Surgery.

BACKGROUND: Guidelines for patient behavior following transsphenoidal surgery do not exist. To gain generally recommendations, the German pituitary working group conducted a study among pituitary surgeons to elucidate their opinions and customs of patients' counselling. METHODS: Questions concerning daily activities, exertion of sports and work life were addressed. It was asked to provide the postoperative time interval after which specific activities can be resumed both after a routine or an extended approach. RESULTS: Fourteen pituitary surgeons returned the completed questionnaire. Following routine operations, washing the hair was allowed within one week, blowing the nose after 3, flying on an airplane and driving a car after one, lifting heavy weights after 4, playing wind instruments after 6, use of CPAP (continuous positive airway pressure) device after 3, permit leisure sports after 2 to 4 weeks (except for scuba diving). Competitive sports can be resumed after 6 weeks. Occupation with mental demands was considered feasible after 2 weeks, with physical labor after 4 weeks. After extended transsphenoidal surgery, the recommended time interval was roughly twice as long compared to the routine approach. Driving a car was allowed within the first 4 weeks after surgery by some pituitary surgeons, while others allow driving only after 3 months analogous to the regulations after craniotomy. The risk of scuba diving was considered high. CONCLUSIONS: The data of our study and the literature, and expert opinions from related scientific fields resulted in a consensus on recommendations for patients' conduct to minimize risks after transsphenoidal surgery.

Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07).

Background: Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy. Methods: The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy. Results: Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock. Conclusions: Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

Transient sacroiliac joint-related pain is a common problem following lumbar decompressive surgery without instrumentation.

OBJECTIVE: Patients with lumbar stenosis profit substantially from decompressive surgery. The change of body position and walking behaviour after successful surgery might lead to changed force effects on the entire spine and on the sacroiliac joint (SIJ). We analyzed the incidence of postoperative SIJ-related pain. METHODS: The authors analyzed the records of 100 consecutive patients from three institutions, who underwent decompressive surgery without instrumentation. The diagnosis of SIJ-related pain was confirmed by periarticular infiltration. The radiological changes of the sacroiliac joint were assessed in plain radiographs in both groups: patients with SIJ pain (group 1) and patients without SIJ pain (group 2) after surgery. RESULTS: 22 patients required medical attention due to SIJ-related pain after surgery. While the walking distance increased substantially in both groups without difference (p=0.150), the analysis of overall satisfaction favoured group 2 (p=0.047). Female patients suffered more from SIJ pain after surgery (p=0.036). Age, severity of radiological changes or number of operated segments appeared not to trigger SIJ-related pain. CONCLUSION: The adaptation of a changed body posture and gait could lead to transient overload of the SIJ and surrounding myofascial structures. The patients should be informed about this possible condition to avoid uncertainty, discontent, unnecessary diagnostics and to induce a quick, specific treatment. Non-diagnosed sacroiliac joint-related pain could be a possible, but reversible reason for the diagnosis of a "failed-back-surgery".

[Diagnostic of brain death]. / Management von Organspendern und Organempfängern - Hirntoddiagnostik.

Despite of some discussion, there is general acceptance of the brain death criterion. As for Germany, there is a quasi legal regulation (TPG §16): two physicians with a longstanding experience in the management of patients with severe brain lesions are personally responsive for the diagnostic procedure lege artis. No false positive diagnosis has been published, hitherto. Before any organ explantation, diagnosis of brain death is mandatory. Nevertheless, discussions on brain death should not be instrumentalized by circumstances of organ explantation. Brain death should be part of a good educational background, to anticipate reflections free from the emotional binding of an acute incident.