Magnetic resonance imaging fingerprints of status epilepticus: A case-control study.

OBJECTIVE: Status epilepticus (SE) is frequently associated with peri-ictal magnetic resonance imaging (MRI) abnormalities (PMA). However, the anatomical distribution of these alterations has not been systematically studied. The aim of this study was to assess the localization patterns of PMA in patients with SE. METHODS: In this prospective case-control study, we compared the distribution and combinations of diffusion-restricted PMA to diffusion-restricted lesions caused by other neurological conditions. All patients of the SE group and the control group underwent MRI including a diffusion-weighted imaging sequence. Patients with SE were imaged within 48 h after its onset. RESULTS: We enrolled 201 patients (51 with SE and 150 controls). The most frequent locations of PMA in SE were cortex (25/51, 49%), followed by hippocampus (20/51, 39%) and pulvinar of thalamus (10/51, 20%). In the control group, the cortex was involved in 80 of 150 (53%), white matter in 53 of 150 (35%), and basal ganglia in 33 of 150 (22%). In the control group, the pulvinar of thalamus was never affected and hippocampal structures were rarely involved (7/150, 5%). Involvement of the pulvinar of thalamus and the hippocampus had high specificity for SE at 100% (95% confidence interval [CI] = 98-100) and 95% (95% CI = 91-98), respectively. The sensitivity, however, was low for both locations (pulvinar of thalamus: 20%, 95% CI = 10-33; hippocampus: 39%, 95% CI = 26-54). SIGNIFICANCE: Diffusion-restricted MRI lesions observed in the pulvinar of thalamus and hippocampus are strongly associated with SE. These changes may help physicians in diagnosing SE-related changes on MRI in an acute setting, especially in cases of equivocal clinical and electroencephalographic manifestations of SE.

Surgeon experience in glioblastoma surgery of the elderly-a multicenter, retrospective cohort study.

PURPOSE: To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. METHODS: GBM patients aged ≥ 65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). RESULTS: 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0-12.0); median EOR was 89.4%. Surgery-related morbidity affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P < .001); patients with surgery-related morbidity were less likely to receive adjuvant treatment (P = .002). In multivariable testing, adjuvant therapy (P < .001; HR = 0.064, 95%CI 0.028-0.144) remained the only significant predictor for improved OS. CONCLUSION: Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial for generating a treatment benefit for this cohort.

Imaging of status epilepticus: Making the invisible visible. A prospective study on 206 patients.

BACKGROUND: Peri-ictal MRI abnormalities (PMA) frequently affect the cerebral cortex, hippocampus, pulvinar of the thalamus, corpus callosum, and cerebellum. In this prospective study, we aimed to characterize the spectrum of PMA in a large cohort of patients with status epilepticus. METHODS: We prospectively recruited 206 patients with SE and an acute MRI. The MRI protocol included diffusion weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), arterial spin labeling (ASL), and T1-weighted imaging pre-and post-contrast application. Peri-ictal MRI abnormalities were stratified as either neocortical or non-neocortical. Amygdala, hippocampus, cerebellum, and corpus callosum were regarded as non-neocortical structures. RESULTS: Peri-ictal MRI abnormalities were observed in 93/206 (45%) of patients in at least one MRI sequence. Diffusion restriction was observed in 56/206 (27%) of patients, which was mainly unilateral in 42/56 (75%) affecting neocortical structures in 25/56 (45%), non-neocortical structures in 20/56 (36%) and both areas in 11/56 (19%) of patients. Cortical DWI lesions were located mostly in frontal lobes 15/25 (60%); non-neocortical diffusion restriction affected either the pulvinar of the thalamus or hippocampus 29/31 (95%). Alterations in FLAIR were observed in 37/203 (18%) of patients. They were mainly unilateral 24/37 (65%); neocortical 18/37 (49%), non-neocortical 16/37 (43%), or affecting both neocortical and non-neocortical structures 3/37 (8%). In ASL, 51/140 (37%) of patients had ictal hyperperfusion. Hyperperfused areas were located mainly in the neocortex 45/51 (88%) and were unilateral 43/51 (84%). In 39/66 (59%) of patients, PMA were reversible in one week. In 27/66 (41%), the PMA persisted and a second follow-up MRI was performed three weeks later in 24/27 (89%) patients. In 19/24 (79%) PMA were resolved. CONCLUSIONS: Almost half of the patients with SE had peri-ictal MRI abnormalities. The most prevalent PMA was ictal hyperperfusion followed by diffusion restriction and FLAIR abnormalities. Neocortex was most frequently affected especially the frontal lobes. The majority of PMAs were unilateral. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Serum Neurofilament Light Chain as Biomarker for Cladribine-Treated Multiple Sclerosis Patients in a Real-World Setting.

Serum neurofilament light chain (sNfL) is an intensely investigated biomarker in multiple sclerosis (MS). The aim of this study was to explore the impact of cladribine (CLAD) on sNfL and the potential of sNfL as a predictor of long-term treatment response. Data were gathered from a prospective, real-world CLAD cohort. We measured sNfL at baseline (BL-sNfL) and 12 months (12Mo-sNfL) after CLAD start by SIMOA. Clinical and radiological assessments determined fulfilment of "no evidence of disease activity" (NEDA-3). We evaluated BL-sNfL, 12M-sNfL and BL/12M sNfL ratio (sNfL-ratio) as predictors for treatment response. We followed 14 patients for a median of 41.5 months (range 24.0-50.0). NEDA-3 was fulfilled by 71%, 57% and 36% for a period of 12, 24 and 36 months, respectively. We observed clinical relapses in four (29%), MRI activity in six (43%) and EDSS progression in five (36%) patients. CLAD significantly reduced sNfL (BL-sNfL: mean 24.7 pg/mL (SD ± 23.8); 12Mo-sNfL: mean 8.8 pg/mL (SD ± 6.2); p = 0.0008). We found no correlation between BL-sNfL, 12Mo-sNfL and ratio-sNfL and the time until loss of NEDA-3, the occurrence of relapses, MRI activity, EDSS progression, treatment switch or sustained NEDA-3. We corroborate that CLAD decreases neuroaxonal damage in MS patients as determined by sNfL. However, sNfL at baseline and at 12 months failed to predict clinical and radiological treatment response in our real-world cohort. Long-term sNfL assessments in larger studies are essential to explore the predictive utility of sNfL in patients treated with immune reconstitution therapies.

VarioGuide® frameless neuronavigation-guided stereoelectroencephalography in adult epilepsy patients: technique, accuracy and clinical experience.

BACKGROUND: Stereoelectroencephalography (SEEG) allows the identification of deep-seated seizure foci and determination of the epileptogenic zone (EZ) in drug-resistant epilepsy (DRE) patients. We evaluated the accuracy and treatment-associated morbidity of frameless VarioGuide® (VG) neuronavigation-guided depth electrode (DE) implantations. METHODS: We retrospectively identified all consecutive adult DRE patients, who underwent VG-neuronavigation DE implantations, between March 2013 and April 2019. Clinical data were extracted from the electronic patient charts. An interdisciplinary team agreed upon all treatment decisions. We performed trajectory planning with iPlan® Cranial software and DE implantations with the VG system. Each electrode's accuracy was assessed at the entry (EP), the centre (CP) and the target point (TP). We conducted correlation analyses to identify factors associated with accuracy. RESULTS: The study population comprised 17 patients (10 women) with a median age of 32.0 years (range 21.0-54.0). In total, 220 DEs (median length 49.3 mm, range 25.1-93.8) were implanted in 21 SEEG procedures (range 3-16 DEs/surgery). Adequate signals for postoperative SEEG were detected for all but one implanted DEs (99.5%); in 15/17 (88.2%) patients, the EZ was identified and 8/17 (47.1%) eventually underwent focus resection. The mean deviations were 3.2 ± 2.4 mm for EP, 3.0 ± 2.2 mm for CP and 2.7 ± 2.0 mm for TP. One patient suffered from postoperative SEEG-associated morbidity (i.e. conservatively treated delayed bacterial meningitis). No mortality or new neurological deficits were recorded. CONCLUSIONS: The accuracy of VG-SEEG proved sufficient to identify EZ in DRE patients and associated with a good risk-profile. It is a viable and safe alternative to frame-based or robotic systems.

Carotid Calcium Volume and Stenosis after Stent Implantation.

INTRODUCTION: Internal carotid artery (ICA) stenosis could be treated with stent placement. It was hypothesized that calcium amount could be predictive of vessel stenosis after stent placement. We utilised computed tomography (CT) angiography to quantify volume of calcium material in bulbar ICA. MATERIALS AND METHODS: 28 patients with 31 treated ICA stenosis were collected and analysed using CT angiography-based calcium volume measurement. The Casper stent system (CSS) was used exclusively. Prospective data on emergent carotid stenosis were collected using serial ultrasound controls over a 12-month period. RESULTS: Median age was 76 years (interquartile range (IQR) 67.5-77.8) and the majority were men (71.4%). Plaque median calcium volume was 0.142 cm3 (IQR 0.030 - 0.227) and median average Hounsfield Units (HU) were 561.0 (414.5-675.0). We detected positive linear relationship between average HU and ICA calcium volume. Furthermore, weak positive correlation was observed between calcium volume and residual stenosis as seen on post-interventional angiography, (correlation coefficient R = 0.38, p=0.035). Stronger positive correlation emerged between plaques' average HU and residual stenosis (R = 0.42, p=0.018). Angiographic stenosis showed univariate association with late stenosis as detected 12 months after CAS. CONCLUSION: Calcium burden could be associated with residual stenosis after CSS placement. Larger studies are needed to confirm our preliminary data.

Post-hypoxic status epilepticus - A distinct subtype of status epilepticus with poor prognosis.

OBJECTIVE: To evaluate the clinical outcome of patients with possible and definitive post-hypoxic status epilepticus (SE) and to describe the SE types in patients with definitive post-hypoxic SE. METHODS: Patients with definitive or possible SE resulting from hypoxic brain injury after cardiac arrest (CA) were prospectively recruited. Intermittent EEG was used for the diagnosis of SE according to clinical practice. Two raters blinded to outcome analyzed EEGs retrospectively for possible and definitive SE patterns and background features (frequency, continuity, reactivity, and voltage). Definitive SE was classified according to semiology (ILAE). Mortality and Cerebral Performance Categories (CPC) score were evaluated 1 month after CA. RESULTS: We included 64 patients of whom 92% died. Among the survivors, only one patient had a good neurological outcome (CPC 1). No patient survived with a burst suppression pattern, low voltage, or electro-cerebral silence in any EEG. Possible or definitive SE was diagnosed in a median of 47 h (IQR 39-72 h) after CA. EEG criteria for definitive electrographic SE were fulfilled in 39% of patients; in 38% - for electroclinical SE and in 23% - for ictal-interictal continuum (IIC). The outcome did not differ significantly between the three groups. The only patient with good functional outcome belonged to the IIC group. Comatose non-convulsive SE (NCSE) without subtle motor phenomenon occurred in 20% of patients with definitive electrographic SE and outcome was similar to other types of SE. SIGNIFICANCE: Possible or definitive SE due to hypoxic brain injury is associated with poor prognosis. The outcome of patients with electrographic SE, electroclinical SE, and IIC did not differ significantly. Outcome was similar in patients with definitive electrographic SE with and without prominent motor features.

Unilateral delayed post-hypoxic leukoencephalopathy: a case report.

BACKGROUND: Delayed post-hypoxic leukoencephalopathy is a rare entity following hypoxia. Clinical and radiological signs of delayed post-hypoxic leukoencephalopathy have not previously been reported following acute ischemic stroke. CASE PRESENTATION: We report a case of an 81-year-old Central European man who presented with a dissection-related occlusion of the left carotid artery. He showed clinical improvement immediately after endovascular stroke therapy, followed by a significant clinical and especially cognitive deterioration thereafter and a clinical recovery after several weeks. The clinical course of the patient was accompanied by morphological changes on magnetic resonance imaging characteristic of delayed post-hypoxic leukoencephalopathy; that is, strictly limited and localized unilaterally to the left anterior circulation. CONCLUSION: This case demonstrates that clinical symptoms and morphological changes on magnetic resonance imaging compatible with delayed post-hypoxic leukoencephalopathy do not necessarily only occur with global hypoxia, but can also occur in patients with a large vessel occlusion in the corresponding vascular territories.

The effect of extracorporeal shock wave therapy in acute traumatic spinal cord injury on motor and sensory function within 6 months post-injury: a study protocol for a two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled clinical trial.

BACKGROUND: The pathological mechanism in acute spinal cord injury (SCI) is dual sequential: the primary mechanical lesion and the secondary injury due to a cascade of biochemical and pathological changes initiated by the primary lesion. Therapeutic approaches have focused on modulating the mechanisms of secondary injury. Despite extensive efforts in the treatment of SCI, there is yet no causal, curative treatment approach available. Extracorporeal shock wave therapy (ESWT) has been successfully implemented in clinical use. Biological responses to therapeutic shock waves include altered metabolic activity of various cell types due to direct and indirect mechanotransduction leading to improved migration, proliferation, chemotaxis, modulation of the inflammatory response, angiogenesis, and neovascularization, thus inducing rather a regeneration than repair. The aim of this clinical study is to investigate the effect of ESWT in humans within the first 48 h after an acute traumatic SCI, with the objective to intervene in the secondary injury phase in order to reduce the extent of neuronal loss. METHODS: This two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled study has been initiated in July 2020, and a total of 82 patients with acute traumatic SCI will be recruited for the first stage in 15 participating hospitals as part of a two-armed three-stage adaptive trial design. The focused ESWT (energy flux density: 0.1-0.19 mJ/mm2, frequency: 2-5 Hz) is applied once at the level of the lesion, five segments above/below, and on the plantar surface of both feet within the first 48 h after trauma. The degree of improvement in motor and sensory function after 6 months post-injury is the primary endpoint of the study. Secondary endpoints include routine blood chemistry parameters, the degree of spasticity, the ability to walk, urological function, quality of life, and the independence in everyday life. DISCUSSION: The application of ESWT activates the nervous tissue regeneration involving a multitude of various biochemical and cellular events and leads to a decreased neuronal loss. ESWT might contribute to an improvement in the treatment of acute traumatic SCI in future clinical use. TRIAL REGISTRATION: ClinicalTrials.gov NCT04474106.

A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature.

Here, we report on a patient presenting with two histopathologically distinct gliomas. At the age of 42, the patient underwent initial resection of a right temporal oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade II followed by adjuvant radiochemotherapy with temozolomide. 15 months after initial diagnosis, the patient showed right hemispheric tumor progression and an additional new left frontal contrast enhancement in the subsequent imaging. A re-resection of the right-sided tumor and resection of the left frontal tumor were conducted. Neuropathological work-up showed recurrence of the right-sided oligodendroglioma with features of an anaplastic oligodendroglioma WHO Grade III, but a glioblastoma WHO grade IV for the left frontal lesion. In depth molecular profiling revealed two independent brain tumors with distinct molecular profiles of anaplastic oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade III and glioblastoma IDH wildtype WHO grade IV. This unique and rare case of a patient with two independent brain tumors revealed by in-depth molecular work-up and epigenomic profiling emphasizes the importance of integrated work-up of brain tumors including methylome profiling for advanced patient care.

Quantitative Analysis of Diffusion-Restricted Lesions in a Differential Diagnosis of Status Epilepticus and Acute Ischemic Stroke.

Background and Purpose: Distinction between acute ischemic stroke (AIS) and status epilepticus (SE) on MRI can be challenging as restricted diffusion may occur in both conditions. In this study, we aimed to test a tool, which could help in differentiating AIS from SE when restricted diffusion was present on MRI. Materials and Methods: In diffusion weighted imaging (DWI) with a b-value of 1,000 and apparent diffusion coefficient (ADC) maps, we compared the ratios of intensities of gray values of diffusion-restricted lesions to the healthy mirror side in patients with AIS and SE. Patients were recruited prospectively between February 2019 and October 2021. All patients underwent MRI and EEG within the first 48 h of symptom onset. Results: We identified 26 patients with SE and 164 patients with AIS. All patients had diffusion-restricted lesions with a hyperintensity in DWI and ADC signal decrease. Diffusion restriction was significantly more intense in patients with AIS as compared to patients with SE. The median ratios of intensities of gray values of diffusion-restricted lesions to the healthy mirror side for DWI were 1.42 (interquartile range [IQR] 1.32-1.47) in SE and 1.67 (IQR 1.49-1.90) in AIS (p < 0.001). ADC decrease was more significant in AIS as compared to SE with median ratios of 0.80 (IQR 0.72-0.89) vs. 0.61 (IQR 0.50-0.71), respectively (p < 0.001). A cutoff value for ratios of DWI signal was 1.495 with a sensitivity of 75% and a specificity of 85%. Values lower than 1.495 were more likely to be associated with SE and higher values were with AIS. A cutoff value for ADC ratios was 0.735 with a sensitivity of 73% and a specificity of 84%. Values lower than 0.735 were more likely to be associated with AIS and higher values were with SE. Conclusion: Diffusion restriction and ADC decrease were significantly more intense in patients with AIS as compared to SE. Therefore, quantitative analysis of diffusion restriction may be a helpful tool for differentiating between AIS and SE when restricted diffusion is present on MRI.

Genotypical glioblastoma of the frontal lobe mimicking ganglioglioma: A case report and review of the literature.

This case of severe phenotype-genotype mismatch brain tumor morphologically mimicking benign ganglioglioma emphasizes the urgent need for advanced molecular profiling in brain tumor diagnosis in the era of sophisticated molecular profiling.

Tetravalent Influenza Vaccine Is Not Associated With Neuroaxonal Damage in Multiple Sclerosis Patients.

Background: Efficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS). Objective: To assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF). Methods: In this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs). The primary endpoints were responder rate of strain-specific antibody production (seroconversion or significant (4-fold) increase in influenza-antibody titers for ≥2/4 strains) at 30 days post-vaccination and changes in sNfL levels. Results: All patients treated with DMF fulfilled the responder criteria for immunization compared with 53% of the controls. However, higher proportions of HCs already had influenza-antibody titers ≥1:40 at baseline (53% vs. 41%, p = 0.174). sNfL levels were comparable among both groups at baseline and did not increase 34 days after vaccination. In addition, no clinical or radiological disease reactivation was found. Conclusion: DMF-treated patients mount an adequate humoral immune response to influenza vaccines. Within the limits of the small cohort investigated, our data suggest that influenza immunization is not associated with clinical or subclinical disease reactivation.

Non-convulsive status epilepticus with right arm apraxia: A case report.

Non-convulsive SE (NCSE) is characterized by altered consciousness with or without slight motor manifestations or other phenomena such as aphasia, sensory, auditory, emotional, gustatory or other symptoms. A 69-year-old right-handed man developed the sudden onset of apraxia in his right arm. On admission, the patient was alert and well oriented. In his past medical history, an intracerebral hematoma (ICH) in the left temporo-parietal area was noted occurred five years before the current admission. An electroencephalography (EEG) showed rhythmic theta-delta activity with fluctuating frequency between 1.5 and 5 Hz in the left centro-parieto-temporal area, which promptly responded to the intravenous injection of 2 mg clonazepam and 1000 mg levetiracetam. Apraxia resolved completely and the EEG demonstrated intermittent non-rhythmic delta-theta slowing in the left temporo-parietal area. A cranial CT scan showed residual cystic encephalomalacia in the left temporo-parietal area due to the previous ICH. An MRI exhibited an old parenchymal defect in the left temporo-parietal area with a residual hemosiderin rim on the susceptibility weighted imaging (SWI) and no diffusion restriction on the diffusion weighted image (DWI). NCSE presented with right arm apraxia in our patient with a post-hemorrhagic residual parenchymal defect in the left temporo-parietal area.

Diffuse midline glioma of the cervical spinal cord with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma: a case report and review of the literature.

Here, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4 cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensive molecular workup revealed H3F3A K27M, TERT C228T and PDGFRα Y849C mutations indicating poor prognosis. The H3F3A K27M mutation assigned the tumor to the molecular group of diffuse midline glioma (WHO Grade IV). Epigenome-wide methylation profiling confirmed the methylation class of diffuse midline glioma. Thus, this is a very rare case of malignant glioma with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma. This case emphasizes the importance of comprehensive morphological and molecular workup including methylome profiling for advanced patient care.

Influence of the circle of Willis on leptomeningeal collateral flow in anterior circulation occlusive stroke: Friend or foe?

BACKGROUND: Clinical outcome after large vessel occlusion (LVO) stroke depends on collateral integrity. We aimed to evaluate whether the completeness of the circle of Willis (CoW) and anterior temporal artery (ATA) determines the status of leptomeningeal collaterals (LC) in patients with acute LVO (internal carotid artery (ICA) and middle cerebral artery M1 (MCA) occlusion) treated with endovascular thrombectomy. PATIENTS AND METHODS: LC, cross-flow through the anterior communicating artery (ACoA), presence of the ipsilateral posterior communicating artery (IpsiPCoA) and presence of the ATA were evaluated using CT angiography. LC was graded as good when ≥50% collateral filling was noted compared to the unaffected hemisphere. RESULTS: We included 159 patients with a median age of 75 years (IQR 63-82), MCA M1 occlusion in 96 (60%) and good outcome in 68 (45.6%). The LC were good in 129 (81.1%) patients. Complete IpsiPCoA and incomplete ACoA status was inversely associated with good LC in LVO (OR 0.51 (95% CI 0.02-0.07)). A complete CoW was associated with good LC in ICA occlusions, OR 8.4 (p = .025). Good outcome (modified Rankin scale 0-2 at 3 months) was associated with good LC (OR 5.63 (95% CI 1.11-28.4)), small ischemic lesion volume (OR 0.94 (95% CI 0.97-0.98)) and absence of the ACoA and IpsiPCoA (OR 4.47 (95% CI 1.09-18.3)). CONCLUSIONS: ATA presence was associated with good leptomeningeal collaterals in LVO (OR 8.13 (95% CI 1.69-39.0)) and in MCA M1 patients (OR 7.9 (95% CI 1.7-36.4)). The effect of ATA was most pronounced in MCA M1 occlusions, and that of ACoA was most pronounced in ICA occlusions.

Extensive Leptomeningeal Intracranial and Spinal Metastases in a Patient with a Supratentorial Glioblastoma Multiforme, IDH-Wildtype.

BACKGROUND: Glioblastoma multiforme (GBM) is usually characterized by diffuse, infiltrative growth and local tumor progression. Extensive leptomeningeal metastases are rarely observed. It is unclear which GBMs are prone to this specific growth pattern and progression, and standardized salvage treatment protocols are unavailable. CASE DESCRIPTION: In a 45-year-old man without focal neurologic deficit, a right temporal GBM, IDH-wildtype (biomarkers MGMT promoter methylation negative, Ki-67 proliferation rate 70%) was diagnosed. Gross tumor resection followed by concomitant and adjuvant radiotherapy and chemotherapy with temozolomide was performed. Routine follow-up imaging 8 months later showed a right parietal meningeal tumor. Resection confirmed a distant GBM, and next-generation sequencing revealed high tumor mutational burden, high-frequency microsatellite instability, and a pharmacologically targetable KIT mutation. Complete neuraxis imaging revealed multiple contrast-enhancing tumors in the craniocervical junction and levels C7, Th8-Th11, and S1. The craniocervical tumors and the cervical spine from C1-C2 were irradiated as palliative care, and second-line combined chemotherapy and antiangiogenic therapy with irinotecan and bevacizumab was initiated, which was later changed to an immune-checkpoint blockade with pembrolizumab in combination with bevacizumab owing to tumor progression. Tumor growth was slowed, but the patient eventually developed a progressive paraparesis. Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. The patient died 13.8 months after initial diagnosis. CONCLUSIONS: High-risk genetic profiles for GBMs prone to develop extensive leptomeningeal metastases need to be identified. Guidelines on preemptive, complete neuraxis imaging in certain patients with GBM as well as treatment guidelines need to be developed.

The Casper Stent System for carotid artery stenosis.

PURPOSE: To report the results of a retrospective analysis of prospectively collected data evaluating the safety and efficacy of a double layer stent engineered for carotid artery occlusive disease. METHODS: Between January 2014 and February 2017, 138 patients (25.4% women; median age 71 years) underwent Casper stent implantation for carotid artery stenosis. Eligibility criteria included stenosis >70% of vessel diameter (or >50% diameter with ulceration) in symptomatic patients or asymptomatic patients with >80% stenosis at the carotid bifurcation or in the proximal internal carotid artery. For all procedures, a distal embolic protection device was used. The primary endpoint was the rate of 90 day major adverse neurological events, defined as minor stroke, major stroke, or death by independent neurological assessment. RESULTS: Stent deployment was completed successfully in all cases without documented technical failure. There were no adverse neurological events or mortalities within 90 days. One thromboembolic occlusion of a small distal branch of the anterior cerebral artery occurred during the procedure and resolved with systemic recombinant tissue plasminogen activator administration. New ischemic lesions, all clinically silent, were seen in 6.5% of patients on post-procedure cerebral MRI. CONCLUSION: The Casper carotid stent demonstrated safety and efficacy in the treatment of carotid stenosis, with no technical failures and no adverse neurological events seen throughout the 90 day follow-up period. Its double layer structure seems to combine adequate plaque scaffolding with high vessel adaptability.

Ventriculoatrial Shunts in Adults, Incidence of Infection, and Significant Risk Factors: A Single-Center Experience.

BACKGROUND: In recent years, the number of ventriculoatrial (VA) shunt insertions has decreased worldwide, the major cause being the risk of shunt infection. VA shunts remain as an alternative option to ventriculoperitoneal shunts. We describe our 10-year experience with VA shunts by analyzing the incidence of shunt infections and predisposing cofactors. METHODS: During a median follow-up of 15.3 months, 259 shunt insertions, performed on 255 patients, were analyzed. The infection rate was calculated and the predisposing cofactors age, gender, cause of the hydrocephalus, previous external ventricle drainage, antibiotic-impregnated catheters, the number of revisions, the educational level of the surgeons, and the duration of the operations were analyzed. Two observation times were stratified. RESULTS: We found overall infections in 18 patients (7.1%), 16 deep infections (6.3%) including 1 shunt nephritis (0.4%) and 2 superficial infections (0.8%). Wound dehiscence occurred in 17 patients (6. 6%). Analyzing follow-up time, the infection rate was 3.65% (95% confidence interval, 0.9%-5.9%) at survival time 1, 3.38% (95% confidence interval, 1.1%-6.2%) at survival time 2. In the first 6 months, 95% of patients were free of infection. Only the number of revision procedures was associated with the number of infections (P value < 0.0005). CONCLUSIONS: In our patient cohort, the infection rate related to VA shunt insertion is low; the only statistically significant risk factor was the number of revisions. If the VA shunt is applied following a standardized protocol, the infection risk does not represent an argument for reluctance towards the VA draining concept.