ABSTRACT
Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.
Subject(s)
Brain Neoplasms , Glioblastoma , Mutation , Protein Kinase Inhibitors , Proto-Oncogene Proteins B-raf , Humans , Proto-Oncogene Proteins B-raf/genetics , Male , Adult , Glioblastoma/genetics , Glioblastoma/drug therapy , Glioblastoma/pathology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Brain Neoplasms/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/geneticsSubject(s)
Image Enhancement , Intracranial Hypotension/diagnosis , Intracranial Hypotension/therapy , Magnetic Resonance Imaging , Adult , Cerebrospinal Fluid Leak/complications , Cerebrospinal Fluid Leak/diagnosis , Cerebrospinal Fluid Leak/etiology , Combined Modality Therapy , Contrast Media , Diagnosis, Differential , Female , Headache Disorders/etiology , Humans , Intracranial Hypotension/etiology , Male , Middle Aged , Organometallic Compounds , Remission, SpontaneousABSTRACT
BACKGROUND AND PURPOSE: Detection and evaluation of ruptured aneurysms is critical for choosing an appropriate endovascular or neurosurgical intervention. Our aim was to assess whether bone-subtraction CTA is capable of guiding treatment for cerebral aneurysms in patients with acute SAH and could replace DSA. MATERIALS AND METHODS: We prospectively studied 116 consecutive patients with SAH with 16-detector row bone-subtraction CTA and DSA before intracranial aneurysm treatment. Two independent neuroradiologists reviewed the bone-subtraction CTA blinded to DSA (reference standard). We determined the accuracy of bone-subtraction CTA for aneurysm detection and the measurement of aneurysm dimensions and compared the radiation doses of the 2 imaging modalities. RESULTS: Seventy-one patients (61%) had 74 aneurysms on DSA. Bone-subtraction CTA detected 73 of these aneurysms, but it detected 1 additional aneurysm. On a per-aneurysm basis, sensitivity, specificity, and positive and negative predictive values for bone-subtraction CTA were 99%, 98%, and 99% and 98%, respectively. For aneurysms of ≤3 mm, sensitivity was 94% (95% CI, 73%-99%). Bone-subtraction CTA slightly overestimated neck and dome diameters by <0.2 mm and overestimated the dome-to-neck ratios by 2% on average. Dose-length product was 565 ± 201 mGy × cm for bone-subtraction CTA and 1609 ± 1300 mGy × cm for DSA. CONCLUSIONS: Bone-subtraction CTA is as accurate as DSA in detecting cerebral aneurysms after SAH, provides similar information about aneurysm configuration and measures, and reduces the average effective radiation dose for vascular diagnostics by 65%. Diagnostic equivalence in association with dose reduction suggests replacing DSA with bone-subtraction CTA in the diagnostic work-up of spontaneous SAH.
Subject(s)
Cerebral Angiography/methods , Intracranial Aneurysm/diagnostic imaging , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/etiology , Adult , Aged , Aged, 80 and over , Angiography, Digital Subtraction/methods , Female , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/diagnosis , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
PURPOSE: To prospectively evaluate the prognostic impact of multimodal computed tomography-based imaging in ischemic stroke patients potentially eligible for reperfusion therapy. METHODS: Anterior circulation stroke patients underwent non-contrast CT (NCCT), CT-angiography, and CT-perfusion within 12 h from symptom-onset. Patients could be treated with intravenous-tissue plasminogen activator (IV-tPA), endovascular or combined reperfusion therapies. Cerebral imaging profiles (IP) were NCCT-Alberta Stroke Program Early CT Score (ASPECTS) > 7 (IP1); NCCT-ASPECTS > 5 and proximal occlusion on CT-angiography (IP2); CT-perfusion mismatch between cerebral blood volume (CBV)-ASPECTS, and cerebral blood flow (CBF)-ASPECTS ≥ 2 (IP3). Favorable outcome was defined as modified Rankin Scale ≤ 2 at 3 months. RESULTS: Of 102 included patients, 62 (61%) received any reperfusion therapy. In IP2 and IP3, favorable outcome was more frequent in patients with reperfusion therapy than in those without; however, this did not reach statistical significance (IP2: 39% vs 15%, p = 0.26; IP3: 50% vs 17 %; p = 0.31). No difference was seen in IP1 (58% vs 58%, p = 1.0). In IP2, patients with IV-tPA alone achieved better functional outcome (50% vs 11%, p = 0.03) and lower mortality (0% vs 28%, p = 0.045) than those without. CONCLUSIONS: Our results suggest a benefit with imaging profile selection based upon the combination of a small-to-moderate-sized infarction and a visible intracranial occlusion in patients receiving IV-tPA. Reperfusion therapy may be futile in patients without proven vessel occlusion.
Subject(s)
Cerebral Angiography/methods , Multimodal Imaging/methods , Stroke/diagnostic imaging , Stroke/therapy , Tissue Plasminogen Activator/administration & dosage , Tomography, X-Ray Computed/methods , Aged , Female , Fibrinolytic Agents/administration & dosage , Humans , Injections, Intravenous , Male , Prognosis , Prospective Studies , Reperfusion/methods , Reproducibility of Results , Sensitivity and Specificity , Treatment OutcomeABSTRACT
Imaging of Graves' orbitopathy (GO) includes radiological and nuclear medicine procedures. Depending on the method used they provide information about the distribution and activity of the disease. Magnetic resonance imaging (MRI) is not only a helpful tool for making the diagnosis it also enables differentiation of the active and inactive forms of GO due to intramuscular edema. The modality is therefore appropriate to evaluate the disease activity and the course of therapy. The disease leads to the typical enlargement of the muscle bodies of the extraocular muscles. The inferior rectus, medial rectus and levator palpebrae muscles are mostly involved. Signal changes of the intraconal and extraconal fat tissue are possible and a bilateral manifestation is common. The differential diagnosis includes inflammatory diseases and tumors, of which orbital pseudotumor (idiopathic, unspecific orbital inflammation), ocular myositis and orbital lymphoma are the most important. The specific patterns (localization, involvement of orbital structures and signal changes) can be differentiated by MRI.