Diagnostic, clinical management, and outcomes in patients with spinal dural arteriovenous fistula.

Background: Spinal dural arteriovenous fistulas (SDAVFs) are rare spinal vascular malformations, but account for 70 to 80% of all spinal arteriovenous malformations. SDAVFs can be treated either surgically or endovascularly, with surgical treatment appearing to lead to higher closure rates. Our aim was to analyze the demographic data, diagnostic history, treatment characteristics and clinical short- and long-term outcomes. Methods: The medical records of 81 patients who underwent surgical (n = 70, 86.4%) and endovascular (n = 11, 13.6%) treatment for SDAVF at a university hospital between 2002 and 2023 were retrospectively analyzed. Results: SDAVF was observed more frequently in men than women (61, 75.3% vs. 20, 24.7%) with a mean age of 63.5 ± 12.7 years and a mean duration of symptoms to diagnosis of 12.0 ± 12.8 months. The most common first symptom was gait disturbance (36, 44.4%), followed by sensory disturbance (24, 29.6%). The location of the fistula point was most common in the lower thoracic region (36, 44.5%), followed by the lumbar region (23, 28.4%). Incomplete or failed occlusion of the fistula occurred in 8 patients (9.9%), with 6 patients (7.4%) undergoing further treatment either surgically or endovascularly. Treatment- or hospital-related complications were observed in 16 patients (19.8%). A single-level laminectomy was the most common approach (31, 44.3%), followed by single-level hemilaminectomy (28, 40.0%), and unilateral interlaminar fenestration (11, 15.7%). Back pain or radiculopathy was observed in 58% of patients (47/81) pre-treatment and had already decreased to 24.7% at hospital discharge (p < 0.001). No significant differences were observed in sensory disturbances (p = 0.681). The median of American Spinal Injury Association motor score (ASIA-MS) was 94 [82.5-100] at admission, 98 [86.5-100] at hospital discharge, 100 [90-100] at the first, second, and third follow-up (p = 0.019). The median modified Aminoff-Logue scale (mALS) was 5 [2-7] at admission, 3 [1-6] at hospital discharge, 2 [1-5] at the first follow-up, 2 [0.5-5] at the second follow-up and 2 [1-7] at the third follow-up (p = 0.006). Conclusions: SDAVF occurs predominantly in men in the 6th decade of life and can be safely and effectively treated surgically and endovascularly, improving symptoms such as pain and motor deficits, gait disturbances as well as bowel and bladder dysfunction, but not sensory disturbances.

Diagnostics, Management, and Outcomes in Patients with Pyogenic Spinal Intra- or Epidural Abscess.

BACKGROUND: Owing to the lack of evidence on the diagnostics, clinical course, treatment, and outcomes of patients with extremely rare spinal intradural abscess (SIA) and spinal epidural abscess (SEA), we retrospectively analyzed and compared a cohort of patients to determine the phenotyping of both entities. METHODS: Over a period of 20 years, we retrospectively analyzed the electronic medical records of 78 patients with SIA and SEA. RESULTS: The patients with SIA showed worse motor scores (MS scores) on admission (SIA: 20 ± 26 vs. SEA: 75 ± 34, p < 0.001), more often with an ataxic gait (SIA: 100% vs. SEA: 31.8%, p < 0.001), and more frequent bladder or bowel dysfunction (SIA: 91.7% vs. SEA: 27.3%, p < 0.001) compared to the SEA patients. Intraoperative specimens showed a higher diagnostic sensitivity in the SEA patients than the SIA patients (SIA: 66.7% vs. SEA: 95.2%, p = 0.024), but various pathogens such as Staphylococcus aureus (SIA 33.3% vs. SEA: 69.4%) and Streptococci and Enterococci (SIA 33.3% vs. SEA: 8.1%, p = 0.038) were detected in both entities. The patients with SIA developed sepsis more often (SIA: 75.0% vs. SEA: 18.2%, p < 0.001), septic embolism (SIA: 33.3% vs. SEA: 8.3%, p = 0.043), signs of meningism (SIA: 100% vs. 18.5%, p < 0.001), ventriculitis or cerebral abscesses (SIA: 41.7% vs. SEA: 3.0%, p < 0.001), and pneumonia (SIA: 58.3% vs. SEA: 13.6%, p = 0.002). The mean MS score improved in both patient groups after surgery (SIA: 20 to 35 vs. SEA: 75 to 90); however, the SIA patients showed a poorer MS score at discharge (SIA: 35 ± 44 vs. SEA: 90 ± 20, p < 0.001). C-reactive protein (CrP) (SIA: 159 to 49 vs. SEA: 189 to 27) and leukocyte count (SIA: 15 to 9 vs. SEA: 14 to 7) were reduced at discharge. The SIA patients had higher rates of disease-related mortality (SIA: 33.3% vs. SEA: 1.5%, p = 0.002), had more pleural empyema (SIA: 58.3% vs. SEA: 13.6%, p = 0.002), required more than one surgery (SIA: 33.3% vs. SEA 13.6%, p = 0.009), were treated longer with intravenous antibiotics (7 ± 4 w vs. 3 ± 2 w, p < 0.001) and antibiotics overall (12 ± 10 w vs. 7 ± 3 w, p = 0.022), and spent more time in the hospital (SIA: 58 ± 36 vs. SEA: 26 ± 20, p < 0.001) and in the intensive care unit (SIA: 14 ± 18 vs. SEA: 4 ± 8, p = 0.002). CONCLUSIONS: Our study highlighted distinct clinical phenotypes and outcomes between both entities, with SIA patients displaying a markedly less favorable disease course in terms of complications and outcomes.

Leptomeningeal Metastases in Melanoma Patients: An Update on and Future Perspectives for Diagnosis and Treatment.

Leptomeningeal disease (LMD) is a devastating complication of cancer with a particularly poor prognosis. Among solid tumours, malignant melanoma (MM) has one of the highest rates of metastasis to the leptomeninges, with approximately 10-15% of patients with advanced disease developing LMD. Tumour cells that metastasise to the brain have unique properties that allow them to cross the blood-brain barrier, evade the immune system, and survive in the brain microenvironment. Metastatic colonisation is achieved through dynamic communication between metastatic cells and the tumour microenvironment, resulting in a tumour-permissive milieu. Despite advances in treatment options, the incidence of LMD appears to be increasing and current treatment modalities have a limited impact on survival. This review provides an overview of the biology of LMD, diagnosis and current treatment approaches for MM patients with LMD, and an overview of ongoing clinical trials. Despite the still limited efficacy of current therapies, there is hope that emerging treatments will improve the outcomes for patients with LMD.

Increased relative biological effectiveness and periventricular radiosensitivity in proton therapy of glioma patients.

PURPOSE: Currently, there is an intense debate on variations in intra-cerebral radiosensitivity and relative biological effectiveness (RBE) in proton therapy of primary brain tumours. Here, both effects were retrospectively investigated using late radiation-induced brain injuries (RIBI) observed in follow-up after proton therapy of patients with diagnosed glioma. METHODS: In total, 42 WHO grade 2-3 glioma patients out of a consecutive patient cohort having received (adjuvant) proton radio(chemo)therapy between 2014 and 2017 were eligible for analysis. RIBI lesions (symptomatic or clinically asymptomatic) were diagnosed and delineated on contrast-enhanced T1-weighted magnetic resonance imaging scans obtained in the first two years of follow-up. Correlation of RIBI location and occurrence with dose (D), proton dose-averaged linear energy transfer (LET) and variable RBE dose parameters were tested in voxel- and in patient-wise logistic regression analyses. Additionally, anatomical and clinical parameters were considered. Model performance was estimated through cross-validated area-under-the-curve (AUC) values. RESULTS: In total, 64 RIBI lesions were diagnosed in 21 patients. The median time between start of proton radio(chemo)therapy and RIBI appearance was 10.2 months. Median distances of the RIBI volume centres to the cerebral ventricles and to the clinical target volume border were 2.1 mm and 1.3 mm, respectively. In voxel-wise regression, the multivariable model with D, D × LET and periventricular region (PVR) revealed the highest AUC of 0.90 (95 % confidence interval: 0.89-0.91) while the corresponding model without D × LET revealed a value of 0.84 (0.83-0.86). In patient-level analysis, the equivalent uniform dose (EUD11, a = 11) in the PVR using a variable RBE was the most prominent predictor for RIBI with an AUC of 0.63 (0.32-0.90). CONCLUSIONS: In this glioma cohort, an increased radiosensitivity within the PVR was observed as well as a spatial correlation of RIBI with an increased RBE. Both need to be considered when delivering radio(chemo)therapy using proton beams.

Surgical results of 158 petroclival meningiomas with special focus on standard craniotomies.

OBJECTIVE: The goal of this retrospective study is the evaluation of risk factors for postoperative neurological deficits after petroclival meningioma (PCM) surgery with special focus on standard craniotomies. MATERIALS AND METHODS: One-hundred-fifty-eight patients were included in the study, of which 133 patients suffered from primary and 25 from recurrent PCM. All patients were operated on and evaluated concerning age, tumor size, histology, pre- and postoperative cranial nerve (CN) deficits, morbidity, mortality, and surgical complications. Tumor-specific features-e.g., consistency, surface, arachnoid cleavage, and location-were set in a four-grade classification system that was used to evaluate the risk of CN deficits and tumor resectability. RESULTS: After primary tumor resection, new CN deficits occurred in 27.3% of patients. Preoperative ataxia improved in 25%, whereas 10% developed new ataxia. Gross total resection (GTR) was achieved in 59.4%. The morbidity rate, including hemiparesis, shunt-dependence, postop-hemorrhage, and tracheostomy was 22.6% and the mortality rate was 2.3%. In recurrent PCM surgery, CN deficits occurred in 16%. GTR could be achieved in three cases. Minor complications occurred in 20%. By applying the proposed new classification system to patients operated via standard craniotomies, the best outcome was observed in type I tumor patients (soft tumor consistency, smooth surface, plane arachnoid cleavage, and unilateral localization) with GTR in 78.7% (p < 0.001) and 11.9% new CN deficits (p = 0.006). CONCLUSION: Standard craniotomies as the retrosigmoid or subtemporal/pterional approaches are often used for the resection of PCMs. Whether these approaches are sufficient for GTR-and avoidance of new neurological deficits-depends mainly on the localization and intrinsic tumor-specific features.

Isocitrate dehydrogenase 1 mutant glioblastomas demonstrate a decreased rate of pseudoprogression: a multi-institutional experience.

BACKGROUND: Pseudoprogression (psPD) represents false radiologic evidence of tumor progression and is observed in some glioblastoma (GBM) patients after postoperative chemoradiation (CRT) with temozolomide (TMZ). The ambiguity of the psPD diagnosis confounds identification of true progression and may lead to unnecessary interventions. The association between psPD and isocitrate dehydrogenase 1 (IDH1) mutational (mut) status is understudied, and its incidence may alter clinical decision making. METHODS: We retrospectively evaluated 120 patients with IDH1-mut (n = 60) and IDH1-wild-type (IDH-WT; [n = 60]) GBMs who received postoperative CRT with TMZ at 4 academic institutions. Response Assessment in Neuro-Oncology criteria were used to identify psPD rates in routine brain MRIs performed up to 90 days after CRT completion. RESULTS: Within 90 days of completing CRT, 9 GBM patients (1 [1.7%] IDH1-mut and 8 [13.3%] IDH1-WTs) demonstrated true progression, whereas 17 patients (3 [5%] IDH1-muts and 14 [23.3%] IDH1-WTs) demonstrated psPD (P = .004). IDH1-mut GBMs had a lower probability of psPD (hazard ratio: 0.173, 95% CI, 0.047-0.638, P = .008). Among the patients with radiologic signs suggestive of progression (n = 26), psPD was found to be the cause in 3 of 4 (75.0%) of the IDH1-mut GBMs and 14 of 22 (63.6%) of the IDH1-WT GBMs (P = .496). Median overall survival for IDH1-mut and IDH1-WT GBM patients was 40.3 and 23.0 months, respectively (P < .001). CONCLUSIONS: IDH1-mut GBM patients demonstrate lower absolute rates of psPD expression. Irrespective of GBM subtype, psPD expression was more likely than true progression within 90 days of completing CRT. Continuing adjuvant treatment for IDH1-mut GBMs is suggested if radiologic progression is suspected during this time interval.

Is there pseudoprogression in secondary glioblastomas?

PURPOSE: Pseudoprogression (PP) during adjuvant treatment of glioblastoma (GBM) is frequent and is a clinically and radiologically challenging problem. While there are several reports of the frequency of PP in GBM cohorts including mainly patients with primary GBM, there are few data on the incidence of PP in patients with secondary glioblastomas (sGBM). Therefore, the goal of this study was to evaluate the frequency of PP in sGBM. METHODS AND MATERIALS: We retrospectively evaluated the incidence of PP in adult patients with sGBM treated with chemoradiation therapy (CRTx) using temozolomide (TMZ) and sought to assess if there was an association between PP and MGMT promoter methylation status, IDH mutations status, or 1p/19q codeletion. The definition of PP according to the Response Assessment in Neuro-Oncology Working Group was used. RESULTS: None of the evaluable 15 sGBM patients in our series demonstrated a PP. Of the 9 sGBM patients who received concomitant CRTx with TMZ, 6 patients had the methylated MGMT promoter, and 6 patients had IDH mutations. There also was no PP identified in sGBM patients who received sequential CRTx, irrespective of MGMT or IDH status. The median time of follow-up was 3.4 years after diagnosis of an sGBM, and the median overall survival was 18.2 months (range, 14.3-45.2 months). Three of 15 patients had previously received radiation therapy for their World Health Organization low-grade 2 glioma, while none of them had received chemotherapy at that stage. CONCLUSIONS: Based on this small series of sGBM patients treated with CRTx (concomitantly or sequentially) the frequency of PP appears to be very low in sGBM, even in those patients with methylated MGMT promoter or IDH mutations. Our results highlight the differences between primary glioblastomas and sGBM in particular as they relate to PP.

[Late distant metastases of intracranial hemangiopericytomas]. / Späte Fernmetastasierung eines intrakraniellen Hämangioperizytoms.

Hemangiopericytomas are rare tumors which arise from the pericytes of Zimmermann. They can occur anywhere, where capillaries can be found. Seldomly this primitive mensenchymal tumors are found intracranially. The current classification of the World Health Organization (WHO) lists the Hemangiopericytomas as entity of its own and they belong to the mesenchymal non-meningoendothelial tumors. These tumors are very aggressive. They have a high rate of local recurrence and also a high propensity for late distant metastases. The case presented, is an example for these special characteristics with late development of distant metastases in spite of no Local recurrence. The treatment of both, the primary tumor as well as the recurrence and the distant metastases is radical surgery. The post-operative radiation therapy improves the local control of the tumor. Within the frame of the oncological follow-up the diagnostic imaging procedures play the most important role.