Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

Risk factors for the development of secondary intracranial hypertension in acute cerebral venous thrombosis.

PURPOSE: Intracranial hypertension (IH) can complicate cerebral venous thrombosis (CVT), potentially causing permanent visual loss. Current knowledge on risk factors for the development of IH following CVT is scarce. We applied a compound classifier (CSF opening pressure > 25 cmH2O, papilledema, or optic disc protrusion on MRI) as a surrogate for IH and studied the predictive value of thrombus location, the number of thrombosed segments, and thrombus volume. METHODS: We prospectively included 26 patients with acute CVT and complete MRI data. IH was defined by CSF opening pressure > 25 cmH2O, papilledema, or optic disc protrusion on MRI. Using high-resolution contrast-enhanced venography, we determined the thrombus location, number of thrombosed segments, and thrombus volume. We analyzed their association with IH by logistic regression, their predictive power by the area under the receiver operating characteristic curve, and their association with CSF opening pressure by linear regression. RESULTS: IH occurred in 46% of CVT patients and was associated with higher thrombus volume (AUC 0.759, p = 0.025) and superior sagittal sinus thrombosis both alone (OR 2.086, p = 0.049) and combined with transverse sinus thrombosis (OR 2.014, p = 0.028). Effects in patients presenting CSF opening pressure > 25 cm H2O and the compound classifier were consistent. Thrombus volume > 4 ml was the single most important predictor of higher CSF opening pressure (ß = 0.566, p = 0.035), increasing IH risk. CONCLUSION: Larger thrombus volume, dominant transverse sinus occlusion, and extensive superior sagittal combined with transverse sinus thrombosis were associated with IH. Thrombus volumetry might identify patients at risk for IH and direct further clinical evaluation.

Intracranial Vessel Segmentation in 3D High-Resolution T1 Black-Blood MRI.

We demonstrate the feasibility of intracranial vascular segmentation based on the hypointense signal in non-contrast-enhanced black-blood MR imaging using convolutional neural networks. We selected 37 cases. Qualitatively, we observed no degradation due to stent artifacts, a comparable recognition of an aneurysm recurrence with TOF-MRA, and consistent success in the differentiation of intracranial arteries and veins. False-positive and false-negative results were observed. Quantitatively, our model achieved a promising Dice similarity coefficient of 0.72.

Idiopathic intracranial hypertension - a wider spectrum than headaches and blurred vision.

BACKGROUND: The purpose of this study was to analyse less known clinical scenarios associated with idiopathic intracranial hypertension. METHODS: The study involved analysis of magnetic resonance imaging signs of idiopathic intracranial hypertension in patients with spontaneous rhinoliquorrhoea (n = 7), in patients with temporal lobe epilepsy and surgically treated antero-inferior temporal lobe meningo-encephaloceles (n = 15), and in patients who developed clinical signs of idiopathic intracranial hypertension following the treatment of spontaneous intracranial hypotension (n = 7). RESULTS: Three of six patients with spontaneous rhinoliquorrhoea and six of 15 operated patients with temporal lobe epilepsy due to temporal lobe meningo-encephaloceles showed magnetic resonance imaging signs of idiopathic intracranial hypertension and had a body mass index >30 kg/m2. Rebound high pressure headaches and sings of idiopathic intracranial hypertension occurred in seven of 44 surgically treated spontaneous intracranial hypotension patients. CONCLUSIONS: Magnetic resonance imaging findings should guide the clinician to consider (idiopathic) intracranial hypertension when patients develop spontaneous rhinoliquorrhoea, temporal lobe epilepsy secondary to temporal lobe meningoencephaloceles or high pressure headaches in spontaneous intracranial hypotension. Whether idiopathic intracranial hypertension must be regarded as a differential diagnosis or as a cause, or whether there are common pathophysiological pathways that lead to signs of idiopathic intracranial hypertension in this wider spectrum of disease is the focus of further study.

High-Resolution Gadolinium-Enhanced MR Cisternography Using Compressed-Sensing T1 SPACE Technique for Detection of Intracranial CSF Leaks.

In patients with CSF rhinorrhea, accurate identification of the CSF leakage site is crucial for surgical planning. We describe the application of a novel gadolinium-enhanced high-resolution 3D compressed-sensing T1 SPACE technique for MR cisternography and compare findings with CT cisternography and intraoperative results. In our pilot experience with 7 patients, precise detection of CSF leaks was feasible using compressed-sensing T1 SPACE, which appeared to be superior to CT cisternography.

Contrast Enhancement of Intracranial Aneurysms on 3T 3D Black-Blood MRI and Its Relationship to Aneurysm Recurrence following Endovascular Treatment.

BACKGROUND AND PURPOSE: Endovascular treatment of intracranial aneurysms aims at preventing aneurysm rupture. Contrast-enhanced black-blood MR imaging facilitates imaging of the vessel walls and the aneurysmal sac contents and is therefore suitable for studying the healing process. This study aims to describe imaging findings of aneurysmal contrast enhancement following endovascular treatment and its correlation to recurrence and elapsed time since coiling. MATERIALS AND METHODS: Patients undergoing MR imaging follow-up after endovascular treatment of an intracranial aneurysm were included. Contrast-enhanced black-blood T1WI was acquired. Aneurysm wall and intra-aneurysmal enhancement were independently assessed by 2 neuroradiologists and were related to the time elapsed since coiling and the presence of recurrence. RESULTS: Thirty aneurysms in 30 patients were included. The median time elapsed since treatment was 417 days (interquartile range, 189-1273 days). Aneurysmal contrast enhancement was seen in 24/30 (80%) aneurysms. Enhancement inside the sac in 55% (n = 17), the wall in 23% (n = 7), at the dome (n = 1), or at the base (n = 6) was observed. No statistically significant correlation between aneurysmal contrast enhancement and the elapsed time (P = .83) and presence of a recurrence (P = .184) was detected. In 28/30 patients, the images were of adequate diagnostic quality. Stent implants caused negligible image artifacts. CONCLUSIONS: Intra-aneurysmal contrast enhancement following endovascular treatment of intracranial aneurysms is a common finding and likely reflects the healing process. A long-term study to examine changes occurring with time and their association with packing density, type of coils (bare platinum versus bioactive coils), and aneurysm recurrence is underway (German Clinical Trials Register, DRKS-ID: DRKS00014644).

Melanoma-associated retinopathy.

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic autoimmune manifestation of cutaneous malignant melanoma. Patients classically present with acute onset night blindness, positive visual phenomena and visual field defects, and typically have significantly reduced quality of life as a result. Early recognition of MAR is of prognostic significance as it can precede the diagnosis of primary or metastatic malignant melanoma, and early treatment can lower the risk of irreversible immunological damage to the retinal cells with improved visual outcomes. The focus of our review article is therefore to raise awareness of MAR and present the latest evidence relating to the investigation and management of this condition.

[Mechanical thrombectomy for acute ischemic stroke : current evidence and open questions]. / Mechanische Thrombektomie beim ischämischen Schlaganfall : Studienlage und offene Fragen.

OBJECTIVE: To determine the importance of mechanical thrombectomy (MT) in the treatment of ischemic stroke. MATERIAL AND METHODS: Analysis and comparison of randomized controlled trials (RCT) of MT versus i.v. thrombolysis (IVT) considering pathophysiological and logistic aspects. RESULTS: The use of MT is more effective than IVT for internal carotid artery terminus (ICAT), M1 segment and tandem occlusions, i.e. proximal internal carotid artery (ICA) occlusion or stenosis, even in patients older than 75-80 years of age. Due to the small sample sizes this question cannot be answered for patients with M2 occlusions. It is still uncertain whether MT is needed in patients with a low National Institutes of Health stroke scale (NIHSS) score, whether IVT is needed before MT and what type of imaging should be performed. Approximately one third of eligible patients currently undergo MT in Germany. Results from RCTs with stent retrievers for patients with vertebrobasilar artery occlusions are lacking. CONCLUSION: After becoming established as a first-line therapy for patients with ICAT, M1 segment and tandem occlusions, the effectiveness of MT with stent retrievers has to proven in patients with more distal occlusions, low NIHSS scores and even vertebrobasilar artery occlusions.

An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study).

BACKGROUND: This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer. PATIENTS AND METHODS: Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3. RESULTS: Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 ≥50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders. CONCLUSIONS: Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.

High pressure synthesis and in situ Raman spectroscopy of H2 and HD clathrate hydrates.

By means of a newly constructed high pressure and low temperature optical apparatus we have measured the Raman spectra of H(2) and HD simple clathrate hydrates, synthesized in situ by the application of more than 2500 bar gas pressure on solid water. High resolution spectra of the molecular vibration have been measured at low temperature (about 20 K). In the case of HD this band is simpler than in the case of H(2), where the presence of the ortho- and para-species complicated the interpretation of the spectrum. We have determined frequency positions of the bands arising from multiple occupancy of the large cages of the sII clathrate, some of which are almost superimposed. The intensity of the bands gives information on the average and distribution of cage occupation, and of the ortho-para (o-p) ratio of H(2) molecules. Hydrogen o-p conversion rate is measured, for molecules in the small cages and in the large cages, and it is observed that these are different. A model considering both intrinsic and extrinsic conversion processes is applied to the measured data. The intrinsic conversion rate so derived is compared favorably to that measured for pure hydrogen in different situations.

Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype.

Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein expression was assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2 expression was observed in 13.4 and 5.9% of all breast cancer, respectively. Their expression was strongly associated with high histological grade, lack of steroid hormone receptor positivity (ER and PR), and expression of basal markers (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant association between CAV1 and CAV2 expression and basal-like phenotype. On univariate analysis only CAV2 had a prognostic impact on breast cancer-specific survival; however, this was not independent from other traditional markers on multivariate analysis. Our results demonstrate that both CAV1 and CAV2 are associated with basal-like phenotype. Further studies are warranted to determine whether they play an oncogenic role in basal-like/triple-negative breast cancer development or are just surrogate markers for this subgroup.

Nasal endoscopy and CT study of Pharaonic and Roman mummies.

In ancient Egypt mummifications were first carried out around 3000 BC. The visceral organs (lungs, stomach, liver and bowel) were removed from the body, cleansed, desiccated and placed in four canopic jars. The brain was removed from the body but was not preserved. Exactly how removal of the brain was accomplished is not clear. This study investigated the route of brain removal during mummification. Nasal endoscopy was carried out on 20 Pharaonic and Roman mummies. CT examination was performed on 2 mummy heads. In all mummies a communication between the cranial and nasal cavities was found passing through the posterior ethmoids and cribriform plates. The cranial cavity was empty. Our results demonstrate that brain removal during mummification was performed endonasally by trained personnel with a good knowledge of anatomy, using special instruments capable of creating a clean-cut endonasal craniotomy.