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European Stroke Journal Feb 2024Decompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral...
Swiss trial of decompressive craniectomy versus best medical treatment of spontaneous supratentorial intracerebral haemorrhage (SWITCH): an international, multicentre, randomised-controlled, two-arm, assessor-blinded trial.
RATIONALE
Decompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral haemorrhage (ICH) is unknown.
AIM
To determine whether DC without haematoma evacuation plus best medical treatment (BMT) in people with ICH decreases the risk of death or dependence at 6 months compared to BMT alone.
METHODS AND DESIGN
SWITCH is an international, multicentre, randomised (1:1), two-arm, open-label, assessor-blinded trial. Key inclusion criteria are age ⩽75 years, stroke due to basal ganglia or thalamic ICH that may extend into cerebral lobes, ventricles or subarachnoid space, Glasgow coma scale of 8-13, NIHSS score of 10-30 and ICH volume of 30-100 mL. Randomisation must be performed <66 h after onset and DC <6 h after randomisation. Both groups will receive BMT. Participants randomised to the treatment group will receive DC of at least 12 cm in diameter according to institutional standards.
SAMPLE SIZE
A sample of 300 participants randomised 1:1 to DC plus BMT versus BMT alone provides over 85% power at a two-sided alpha-level of 0.05 to detect a relative risk reduction of 33% using a chi-squared test.
OUTCOMES
The primary outcome is the composite of death or dependence, defined as modified Rankin scale score 5-6 at 6 months. Secondary outcomes include death, functional status, quality of life and complications at 180 days and 12 months.
DISCUSSION
SWITCH will inform physicians about the outcomes of DC plus BMT in people with spontaneous deep ICH, compared to BMT alone.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02258919.
PubMed: 38347736
DOI: 10.1177/23969873241231047 -
Diagnostics (Basel, Switzerland) Jan 2024Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with...
Time-Dependent Changes in Hematoma Expansion Rate after Supratentorial Intracerebral Hemorrhage and Its Relationship with Neurological Deterioration and Functional Outcome.
BACKGROUND
Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT.
METHODS
We included 567 consecutive patients with supratentorial ICH and baseline head CT within 24 h of onset. ND was defined as a ≥4-point increase on the NIH stroke scale (NIHSS) or a ≥2-point drop on the Glasgow coma scale. Poor outcome was defined as a modified Rankin score of 4 to 6 at 3-month follow-up.
RESULTS
The rate of HE was higher among those scanned within 3 h (124/304, 40.8%) versus 3 to 24 h post-ICH onset (53/263, 20.2%) ( < 0.001). However, HE was an independent predictor of ND ( < 0.001), poor outcome ( = 0.010), and mortality ( = 0.003) among those scanned within 3 h, as well as those scanned 3-24 h post-ICH ( = 0.043, = 0.037, and = 0.004, respectively). Also, in a subset of 180/567 (31.7%) patients presenting with mild symptoms (NIHSS ≤ 5), hematoma growth was an independent predictor of ND ( = 0.026), poor outcome ( = 0.037), and mortality ( = 0.027).
CONCLUSION
Despite decreasing rates over time after ICH onset, HE remains an independent predictor of ND, functional outcome, and mortality among those presenting >3 h after onset or with mild symptoms.
PubMed: 38337824
DOI: 10.3390/diagnostics14030308 -
Brain Tumor Research and Treatment Jan 2024We report a patient with whole neuroaxis dissemination of a sporadic supratentorial hemangioblastoma (HB) for more than 15 years. A 68-year-old female patient presented...
We report a patient with whole neuroaxis dissemination of a sporadic supratentorial hemangioblastoma (HB) for more than 15 years. A 68-year-old female patient presented with severe radiating pain in the right leg. Gadolinium-enhanced lumbar spine MRI showed an intradural mass (2.5 cm in diameter) at the L4 level. The patient had been severely disabled for 22 years after a previous intraventricular brain tumor resection. At that time, the diagnosis was angioblastic meningioma, which was thought to be incorrect. At 14 years after the brain surgery, gamma knife radiosurgery was performed three times for newly developed or recurred supratentorial and infratentorial tumors in the cerebrospinal fluid pathway. The patient underwent lumbar spinal surgery, and a gross total removal of the mass was performed, which confirmed the histopathological diagnosis of HB. We reexamined the old histopathological specimen of the intraventricular tumor from 20 years ago and changed the diagnosis from angioblastic meningioma to supratentorial HB. Six months after spinal surgery, the patient underwent a second spinal surgery and brain surgery, and the histopathological diagnosis was HB following both surgeries, which was the same following the first spinal surgery. Here, we report a sporadic supratentorial HB patient who showed cranial and spinal disseminations for more than two decades along with a literature review.
PubMed: 38317493
DOI: 10.14791/btrt.2023.0047 -
Brain Tumor Research and Treatment Jan 2024A 27-year-old male patient, previously diagnosed with Hodgkin lymphoma (HL), presented with gait disturbance. Brain MRI showed a 4.5 cm mass lesion in the right...
A 27-year-old male patient, previously diagnosed with Hodgkin lymphoma (HL), presented with gait disturbance. Brain MRI showed a 4.5 cm mass lesion in the right occipital lobe, suggesting either intracranial involvement of HL or a potential meningioma. Despite high-dose methotrexate and steroid treatment, the patient's symptoms persisted, and imaging showed an enlarging mass, leading to surgical intervention. Histopathological examination confirmed central nervous system (CNS) involvement of HL. Postoperatively, the patient underwent whole-brain radiotherapy and demonstrated marked clinical improvement. Our literature review from 1980 to 2023 identified only 46 cases of intracranial HL (IC-HL), underscoring its rarity. Lymphomas represent 2.2% of brain tumors, with 90%-95% being diffuse large B-cell lymphoma (DLBCL). In contrast, the incidence of CNS-HL patients is a mere 0.02%. Notably, IC-HL and intracranial DLBCL have differences in their typical locations and treatment strategies. Unlike DLBCL, which predominantly appears in the supratentorial region (87%), IC-HL is found there in 61.5% of cases. Additionally, 33.3% of IC-HL cases occur in the cerebellum, with 43.5% associated with posterior circulation regions. Furthermore, while biopsy followed by chemotherapy induction is a common strategy for DLBCL, 81.8% of IC-HL cases underwent surgical resection, and only 18.1% had a biopsy alone. The distinct characteristics of IC-HL tumors, including their larger size, attachment to the dura, and fibrotic nature with clear boundaries, might account for the preference for surgical intervention. The unique features of IC-HL compared to DLBCL highlight the need for distinct considerations in diagnosis and management.
PubMed: 38317490
DOI: 10.14791/btrt.2023.0041 -
Acta Neuropathologica Communications Jan 2024Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited... (Review)
Review
Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and a slight female predominance (female/male ratio = 1.55). Among the confirmed fusions, 25 (33.8%) featured an EWSR1::ATF1 fusion, 24 (32.4%) EWSR1::CREB1, 23 (31.1%) EWSR1::CREM, one (1.4%) FUS::CREM, and one (1.4%) EWSR1::CREB3L3. Among 66 patients with follow-up information available (median: 17 months; range: 1-158 months), 26 (39.4%) experienced progression/recurrences (median 10.5 months; range 0-120 months). Ultimately, three patients died of disease, all of whom underwent a subtotal resection for an EWSR1::ATF1 fusion-positive tumor. Outcome analysis revealed subtotal resection as an independent factor associated with a significantly shorter progression free survival (PFS; median: 12 months) compared with gross total resection (median: 60 months; p < 0.001). A younger age (< 14 years) was associated with a shorter PFS (median: 9 months) compared with an older age (median: 49 months; p < 0.05). Infratentorial location was associated with a shorter overall survival compared with supratentorial (p < 0.05). In addition, the EWSR1::ATF1 fusion appeared to be associated with a shorter overall survival compared with the other fusions (p < 0.05). In conclusion, IMT is a locally aggressive tumor with a high recurrence rate. Potential risk factors include subtotal resection, younger age, infratentorial location, and possibly EWSR1::ATF1 fusion. Larger case series are needed to better define prognostic determinants in these tumors.
Topics: Humans; Male; Female; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Meningioma; Prognosis; In Situ Hybridization, Fluorescence; Histiocytoma, Malignant Fibrous; Brain Neoplasms; Meningeal Neoplasms; Oncogene Proteins, Fusion; Biomarkers, Tumor
PubMed: 38291529
DOI: 10.1186/s40478-024-01721-2 -
Frontiers in Oncology 2023Recently, there has been growing interest in the presence and function of meningeal lymphatic vessels, with no direct evidence linking these vessels to primary brain...
Recently, there has been growing interest in the presence and function of meningeal lymphatic vessels, with no direct evidence linking these vessels to primary brain tumors. We report a unique case of recurrent ependymoma in the dura mater, showing histopathological signs of lymphatic proliferation at the tumor attachment site. The patient initially presented with a headache, and was diagnosed with fusion-positive supratentorial ependymoma, central nervous system WHO Grade 3. Following multiple dura mater recurrences and surgery, the fifth procedure revealed numerous tumors contralateral to the original site, with genetic testing confirming fusion positivity, indicating recurrent ependymoma. Immunohistochemical analysis showed D2-40 lymphatic vessel proliferation around tumor attachment sites within the dura mater. Elevated expression of , which is an epithelial-to-mesenchymal transition factor, was also observed, implicating potential involvement in the unique pathophysiology. The present case suggests a new process of metastasis through meningeal lymphatic vessels, although we were unable to visually confirm tumor cell infiltration into the lymphatic vessels. This case is the first report suggesting ependymoma metastasis through dural lymphatic vessels, underlining the need for further case accumulation and study to understand the mechanisms of this phenomenon.
PubMed: 38282673
DOI: 10.3389/fonc.2023.1340167 -
International Journal of Surgery Case... Feb 2024Medulloblastoma in adults is a rare and highly aggressive central nervous system (CNS) tumor, representing less than 1 % of all brain tumors. Supratentorial metastasis...
INTRODUCTION AND IMPORTANCE
Medulloblastoma in adults is a rare and highly aggressive central nervous system (CNS) tumor, representing less than 1 % of all brain tumors. Supratentorial metastasis is uncommon, and extra-neural metastasis occurs in approximately 5 % of cases, primarily in frontal and temporal lobes. Here, we present an exceptional case of parietal lobe metastasis in an adult with desmoplastic/nodular medulloblastoma. To explore prior cases and establish the uniqueness of our case, we conducted a thorough search on the PubMed database.
CASE PRESENTATION
A 46-year-old male, who was previously treated for medulloblastoma with surgery and adjuvant chemoradiotherapy seven years ago, presented with clinical symptoms suggestive of potential tumor recurrence. Despite two years of dedicated adjuvant chemoradiotherapy, the patient exhibited progressive right hemiparesis, ataxia, and gait disturbances. Subsequent brain magnetic resonance imaging (MRI) revealed a distinct 6 × 4 × 2 cm lesion in the left parietal lobe, which, upon post-operative histopathological examination, was identified as a supratentorial metastasis originating from desmoplastic/nodular medulloblastoma.
CLINICAL DISCUSSION
Medulloblastomas, once categorized as primitive neuroectodermal tumors (PNET), are now distinctly classified as high-grade embryonal tumors, mainly characterized by their histological features and cellular origin. Common clinical presentations include hydrocephalus, headache, unsteady gait, and truncal ataxia. Surgical intervention aims for radical excision, complemented by vital adjuvant chemoradiotherapy to minimize recurrence risk.
CONCLUSION
Considering the possibility of tumor recurrence or intracranial metastasis in patients with medulloblastoma is crucial. Therefore, regular follow-ups are strongly recommended to promptly detect any signs of reoccurrence in these atypical presentations.
PubMed: 38281381
DOI: 10.1016/j.ijscr.2024.109322 -
Cells Jan 2024Glioblastoma is characterised by extensive infiltration into the brain parenchyma, leading to inevitable tumor recurrence and therapeutic failure. Future treatments will...
BACKGROUND
Glioblastoma is characterised by extensive infiltration into the brain parenchyma, leading to inevitable tumor recurrence and therapeutic failure. Future treatments will need to target the specific biology of tumour recurrence, but our current understanding of the underlying mechanisms is limited. Significantly, there is a lack of available methods and models that are tailored to the examination of tumour recurrence.
METHODS
NOD-SCID mice were orthotopically implanted with luciferase-labelled donor U87MG or MU20 glioblastoma cells. Four days later, an unlabelled recipient tumor was implanted on the contralateral side. The mice were euthanised at a humane end-point and tissue and blood samples were collected for ex vivo analyses.
RESULTS
The ex vivo analyses of the firefly-labelled MU20 tumours displayed extensive invasion at the primary tumour margins, whereas the firefly-labelled U87MG tumours exhibited expansive phenotypes with no evident invasions at the tumour margins. Luciferase signals were detected in the contralateral unlabelled recipient tumours for both the U87MG and MU20 tumours compared to the non-implanted control brain. Remarkably, tumour cells were uniformly detected in all tissue samples of the supratentorial brain region compared to the control tissue, with single tumour cells detected in some tissue samples. Circulating tumour cells were also detected in the blood samples of most of the xenografted mice. Moreover, tumour cells were detected in the lungs of all of the mice, a probable event related to haematogenous dissemination. Similar results were obtained when the U87MG cells were alternatively labelled with gaussian luciferase.
CONCLUSIONS
These findings describe a systemic disease model for glioblastoma which can be used to investigate recurrence biology and therapeutic efficacy towards recurrence.
Topics: Mice; Animals; Glioblastoma; Neoplasm Recurrence, Local; Mice, Inbred NOD; Mice, SCID; Disease Models, Animal; Luciferases
PubMed: 38275817
DOI: 10.3390/cells13020192 -
Biomedical Reports Feb 2024The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an... (Review)
Review
The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an increasing amount of concern is developing among the universal medical community as regards the application of DC in the treatment of other causes of brain edema, such as subarachnoid hemorrhage, cerebral hemorrhage, sinus thrombosis and encephalitis. Managing stroke continues to remain challenging, and demands the aggressive and intensive consulting of a number of medical specialties. Middle cerebral artery (MCA) infarcts, which consist of 1-10% of all supratentorial infarcts, are often associated with mass effects, and high mortality and morbidity rates. Over the past three decades, a number of neurosurgical medical centers have reported their experience with the application of DC in the treatment of malignant MCA infarction with varying results. In addition, over the past decade, major efforts have been dedicated to multicenter randomized clinical trials. The present study reviews the pertinent literature to outline the use of DC in the management of malignant MCA infarction. The PubMed database was systematically searched for the following terms: 'Malignant cerebral infarction', 'surgery for stroke', 'DC for cerebral infarction', and all their combinations. Case reports were excluded from the review. The articles were categorized into a number of groups; the majority of these were human clinical studies, with a few animal experimental clinical studies. The surgical technique involved was DC, or hemicraniectomy. Other aspects that were included in the selection of articles were methodological characteristics and the number of patients. The multicenter randomized trials were promising. The mortality rate has unanimously decreased. As for the functional outcome, different scales were employed; the Glasgow Outcome Scale Extended was not sufficient; the Modified Rankin Scale and Bathel index, as well as other scales, were applied. Other aspects considered were demographics, statistics and the very interesting radiological ones. There is no doubt that DC decreases mortality rates, as shown in all clinical trials. Functional outcome appears to be the goal standard in modern-era neurosurgery, and quality of life should be further discussed among the medical community and with patient consent.
PubMed: 38273901
DOI: 10.3892/br.2024.1721 -
Acta Neuropathologica Jan 2024The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular...
The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular information. However, as the integrated approach is still novel and some molecular ependymoma subtypes are quite rare, few studies have correlated integrated pathology and clinical outcome, often focusing on small series of single molecular types. We collected data from 2023 ependymomas as classified by DNA methylation profiling, consisting of 1736 previously published and 287 unpublished methylation profiles. Methylation data and clinical information were correlated, and an integrated model was developed to predict progression-free survival. Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%, respectively. EPN-PFA harbored chromosome 1q gains and/or 6q losses as markers for worse survival. In supratentorial EPN-ZFTA, a combined loss of CDKN2A and B indicated worse survival, whereas a single loss did not. Twelve out of 200 EPN-ZFTA (6%) were located in the posterior fossa, and these tumors relapsed or progressed even earlier than supratentorial tumors with a combined loss of CDKN2A/B. Patients with MPE and PF-SE, generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 59% and 65%, respectively. For the prediction of the 5-year progression-free survival, Kaplan-Meier estimators based on the molecular subtype, a Support Vector Machine based on methylation, and an integrated model based on clinical factors, CNV data, and predicted methylation scores achieved balanced accuracies of 66%, 68%, and 73%, respectively. Excluding samples with low prediction scores resulted in balanced accuracies of over 80%. In sum, our large-scale analysis of ependymomas provides robust information about molecular features and their clinical meaning. Our data are particularly relevant for rare and hardly explored tumor subtypes and seemingly benign variants that display higher recurrence rates than previously believed.
Topics: Humans; Ependymoma; Progression-Free Survival; Protein Processing, Post-Translational
PubMed: 38265522
DOI: 10.1007/s00401-023-02674-x