NCOG-35. THE LATE INTRACRANIAL ADVERSE EVENTS OCCUR MORE FREQUENTLY IN INTRACRANIAL GERMINOMAS TREATED WITH HIGH DOSE RADIOTHERAPY

OBJECTIVE The standard treatment for intracranial germinoma has been radiotherapy covering the whole ventricle together with chemotherapy. Radiotherapy is important, but it is a cause of the late brain damages. Therefore, the recent clinical trials have been planned to evaluate the reduced radiation dose. The aim of this study was to evaluate the intracranial adverse events in the patients with intracranial germinomas treated in our hospital. PATIENTS AND METHODS 65 patients were diagnosed as intracranial germinoma. Patients with hCG > 100 IU/l and/or AFP > 10 ng/ml were excluded. Patients, who were diagnosed as germinoma by imaging without histology, were included. RESULTS Follow-up time was from 2 to 467 months (median 136 months). Until 2005, 37 patients were treated with radiotherapy >30 Gy alone or with chemotherapy. After then, 23 patients received whole-ventricle radiotherapy 24-30 Gy with chemotherapy. 2 patients were treated with chemotherapy alone, 3 were unknown. 10-year PFS was 82.05% in radiotherapy >30 Gy alone, 86.36% in radiotherapy >30 Gy with chemotherapy and 100% in radiotherapy 24-30 Gy with chemotherapy. The intracranial adverse events after the initial treatment were identified, such as pituitary dysfunction: 6 (9.2%), hearing disturbance: 2 (3.1%), neurocognitive dysfunction 6 (9.2%), microbleeds 10 (15.4%), cavernous angioma 6 (9.2%), brain tumor 1 (1.5%), cerebral artery stenosis 1 (1.5%). The frequency of late adverse brain events is higher in radiotherapy >30 Gy with/without chemotherapy than 24-30 Gy (total events, 25 vs. 9, P< 0.03). CONCLUSION Patients with intracranial germinoma obtain long-term survival but suffer from the late intracranial adverse events. The late intracranial adverse events occur more frequently in intracranial germinomas treated with radiotherapy >30 Gy than 24-30 Gy. Long-term follow-up is important to promptly identify and deal with the late brain damages.

Rigid endoscopic surgery of brainstem cavernous malformation on the cerebral aqueduct. Case report

Cavernous angiomas (malformations) of the brain occur in 0.5% of the population. Most of them are asymptomatic, but due to their anatomical features, namely escape of blood into surrounding tissues, significant neurological symptoms can occur. The deep location of cavernous angiomas in the area of cerebral aqueduct makes surgical intervention difficult. Microsurgical approaches are the gold standard in removal of cavernous angiomas, but they are associated with certain surgical risks in the formation of the surgical corridor. Cavernous malformations in the cerebral aqueduct are a rare subtype. Due to anatomical localization and concomitant obstructive hydrocephalus ІІІ and lateral ventricles, they can be removed by endoscopic frontal transcortical transventricular approach. A 59-year-old patient was diagnosed with cavernous angioma of the brainstem (in the area of cerebral aqueduct) with hemorrhage and the formation of obstructive hydrocephalus ІІІ and lateral ventricles. The operation was performed: removal of the cavernous angioma in the area of cerebral aqueduct by endoscopic frontal transcortical transventricular approach on the right. Additionally, a triventriculocisternostomy was performed. Osteoplastic trepanation with centering at the Kocher’s point in size of 4 × 4 cm and the formation of a free bone flap was performed. The dura mater is cut in an H-shape. Approach to the anterior horn of the right lateral ventricle was performed. An intracerebral retractor was inserted into the anterior horn of the right lateral ventricle. Transforaminal approach to the tuber cinereum was performed - a triventriculocisternostomy was performed. Transforaminal approach to the cerebral aqueduct was performed and the cavernous angioma of the brainstem was removed. In the postoperative period, the patient had a slight deterioration in short-term memory, which regressed 2 weeks after surgery, an increase in oculomotor disorders, in particular persistent diplopia due to moderate paresis of the left oculomotor nerve. Three months after the operation, magnetic resonance imaging of the brain with intravenous contrast enhancement was performed. There are no signs of cavernous angioma. After the operation of frontal transcortical transventricular removal of cavernous angioma in the area of cerebral aqueduct, the compression of the latter was eliminated. Occlusive hydrocephalus regressed, the size of the ventricles decreased. Endoscopic frontal transcortical transventricular approach allows reaching the area of cerebral aqueduct in a less traumatic and minimally invasive manner. This technique is effective due to the low risk of surgical approach complications.

Why Me? To Be an Ultra-Responder to Antiplatelet Therapy: A Case Report

Background: Platelet function testing is a valid tool to investigate the clinical response to antiplatelet therapy in different clinical settings; in particular, it might supply helpful information in patients with cerebrovascular disease. Oral antiplatelet treatment, such as Aspirin (ASA) and Clopidogrel, is the gold standard in secondary stroke prevention of non-cardiogenic ischemic stroke; conversely, its application as a primary prevention therapy is not routinely recommended in patients with vascular risk factors. Multiple electrode platelet aggregometry (MEA) impedance aggregometer is a validated device to test platelet inhibition induced by ASA or Clopidogrel.Case Report: We report the case of a 78-year-old patient without relevant clinical history, taking ASA as primary prevention strategy, who was admitted for sudden onset of dysarthria and left facial hyposthenia during physical effort. Brain CT revealed two small subcortical bilateral spontaneous intracranial hemorrhages. Platelet aggregometry with MEA performed upon admission revealed a very strong platelet inhibition induced by ASA (result of the ASPI Test was 5 U, consistent with an ultra-responsiveness to ASA, and the cutoff value of correct responsiveness is <40 U). MRI at longitudinal follow-up revealed the presence of two small cavernous angioma underlying hemorrhagic spots.Conclusion: The evaluation of platelet reactivity in stroke patients undergoing antiplatelet therapies, not commonly performed in clinical practice, could be useful to optimize prevention strategies; the verification of the biological effectiveness of ASA or Clopidogrel could be a valid tool in the definition of each patient's risk profile, particularly in patients with cerebrovascular disease known to be at increased risk for both hemorrhagic and thrombotic complications.

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: ‘arteriovenous malformation’, ‘AVM’, and ‘BAVM’, or ‘cavernous malformation’, ‘cavernoma’, and ‘cavernous angioma’ on the one hand; and ‘microRNA’, ‘miRNA’, and ‘miR’ on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies.