by Dr. Inna Lutsenko, @inna_lutsenko

and Ahmet Gunkan, @doctorgunkan

Preventive Measurements in ICH: From Aneurysms and Beyond (joint with EAN)

This was a collaborative session with the European Academy of Neurology and emphasized the preventive measures in intracranial hemorrhage, starting from the precise patient risk stratification to detect an aneurysm and finishing with the modern methods of aneurysm embolization. 

In her talk, Ynte Ruigrok from Utrecht, Netherlands “Differences in diagnostics, screening, and treatment of aneurysmal vs non-aneurysmal subarachnoid hemorrhage” highlighted that an early diagnostic and detection of the aneurysms plays a crucial role, especially in identifying lesions on repeated imaging in non-aSAH (aneurysmal subarachnoid hemorrhage). Lesions may be initially missed due to thrombosis, small lesion size, or inadequate views without 3D reconstructions. Common types of missed lesions include arterial dissection, dural arteriovenous malformation, spinal arteriovenous malformation, and pseudoaneurysms. The work-up protocol for non-aSAH includes initial imaging with CTA and follow-up imaging in the case when initial CTA is negative with repeated CTA on days 3 and 10 and after 3 months. Additional imaging such as MRI/MRA is recommended if there is neck pain or blood flow into the occipital lobe. 

Treatment for aSAH focuses on preventing rebleeding by treating the aneurysm and avoiding hypertension, following guidelines for blood pressure targets. By preventing delayed cerebral ischemia (DCI), which occurs in 20-30% of cases, speaker recommended to follow guideline recommendations  with nimodipine and enabling the normovolemia to maintain hemodynamics. Hydrocephalus is present in 10% of SAH patients, but only 3% are symptomatic; treatment is required in 12-31% of cases. Post-admission diagnostic imaging for SAH involves checking coiling with MRA after 3-6 months and 12-24 months (up to 5 years) for aSAH. It is also essential to check for de novo aneurysms in familial aSAH, autosomal dominant polycystic kidney disease (ADPKD) patients, and young patients (<40 years). For non-aSAH, repeat CTA is recommended after 3 months, and no additional imaging is specified for PMH.

In conclusion, there are no clear guidelines for repeated imaging after non-aSAH. Different modalities and imaging schemes are suggested, with repeated imaging within the first 2 weeks and after 6 weeks seems reasonable. According to the ESO guidelines (2013) for PMH, a single CTA is sufficient, with DSA in case of uncertainty. Screening for de novo aneurysms every 5 years after aSAH may be considered in familial aSAH, ADPKD patients, and young patients (<40 years).

Justiina Huhtakangas (Finland) with her talk “Identification of Unstable Unruptured Intracranial Aneurysms” underlined that unruptured intracranial (and intradural) aneurysms can become unstable if they present signs of growth or morphological changes, which indicate a risk of rupture. These aneurysms might start to cause symptoms and can eventually rupture. Epidemiologically, in Europe, with a population of 742 million, about 15 million people (2%) have unruptured intracranial aneurysms, and approximately 60,000 people suffer from subarachnoid hemorrhage (SAH) yearly, with an incidence rate of 8 per 100,000. The main challenge is to identify those at risk of rupture rather than just detecting as many aneurysms as possible. Known risk factors for rupture include smoking, hypertension, being female (especially postmenopausal), larger aneurysm size/volume, and irregular aneurysm shape, such as the presence of blebs or secondary pouches. Degeneration of the aneurysm wall is associated with rupture, and different types of aneurysm wall degeneration were detailed: A-type (normal wall), B-type (proliferative changes), C-type (degenerated wall), and D-type (highly degenerated wall). The presence of blebs can vary, with some having thin translucent walls and others having thick atherosclerotic walls. Bleb presence has been associated with dental infection and is negatively associated with hormone replacement therapy.

SAH causes more deaths in middle-aged women than cerebral infarction or car crashes, highlighting the importance of screening. Screening for unruptured intracranial aneurysms offers early detection, more treatment options including preventive methods, and potentially reduces morbidity and mortality. However, there are cons, such as the risk of false positives, overdiagnosis, the use of invasive methods, ethical aspects, mental strain, and increased use of healthcare resources. For abdominal aortic aneurysms, a single ultrasound screening of male smokers or former smokers at the age of 60-65 is cost-effective.  For screening cerebral aneurysms a pilot study conducted by the Finnish Institute for Health and Welfare and Helsinki Biobank invited 50-60-year-old women known to be smokers for brain CTA examination. Out of 43 brain CTAs performed, 5 unruptured intracranial aneurysms were found (12%), along with one fronto-basal dural AVF as an incidental finding. Future MRA screening is being considered as an option for cerebral aneurysm screening.

In conclusion, finding patients with unstable cerebral aneurysms could allow the prevention of rupture with low-risk methods and potentially be cost-effective. Postmenopausal smoking women are identified as the group with the highest risk of aneurysm rupture. Efficient high-risk patient detection could prevent aneurysm rupture with timely intervention.

The talk “Genetic Basis and Therapies for Vascular Malformations” was presented by Prof. Miikka Vikkula (Brussels, Belgium). Vascular malformations, often categorized as rare diseases, can lead to various complications such as pain, bleeding, dysfunction (affecting standing, sitting, walking, writing, etc.), and a reduced quality of life, causing chronic health issues. These anomalies frequently result from somatic mutations, with significant progress made in understanding their genetic underpinnings. Somatic mutations in the angiopoietin receptor gene TIE2 cause both solitary and multiple sporadic venous malformations. More than 60% of venous malformations are due to a somatic gain-of-function TIE2 mutation. Various genes have been identified over the years, contributing to our understanding of these malformations. The pathophysiology of vascular anomalies involves several signaling pathways, including the RAS/MAPK/ERK pathway and the PI3K/AKT/mTOR pathway. These pathways contribute to the proliferation, cell growth, differentiation, and angiogenesis observed in these malformations.

Medical treatments for vascular anomalies include sirolimus and thalidomide. Sirolimus has demonstrated a progressive decrease in lesion size in patients with spinal vascular malformations, with significant symptomatic relief within two months of treatment initiation. Thalidomide, used as an off-label treatment for vascular malformations, has shown promising results in reducing lesion size and improving symptoms in some patients.

Robert Starke from Miami, United States in his talk “Treating AVMs after ARUBA: Is There Room for a Novel Trial” presented the results of the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) trial which has significantly influenced the management of unruptured AVMs, showing that medical management alone was superior to interventional therapy in preventing death or stroke, primarily due to the risks associated with surgical and endovascular interventions. However, these findings have sparked ongoing debate and highlighted the need for further investigation. Endovascular therapy risks analysis of ARUBA data showed a substantial risk of treatment-associated stroke, with certain patient and lesion characteristics increasing these risks. Understanding these factors is crucial for improving patient selection and treatment planning. Long-term outcomes of stereotactic radiosurgery for cerebral AVMs showed the effectiveness and safety of this treatment modality. Careful patient selection highlights the potential benefits of radiosurgery for certain AVM cases. The development and validation of grading scales for predicting outcomes after radiosurgery for AVMs were discussed. These tools help clinicians assess the risks and benefits of radiosurgery, aiding in treatment planning and decision-making. This allows for personalized treatment strategies and improved outcomes.

And the session was finished with the talk of Dominik Vollherbst from Heidelberg, Germany. In his presentation “Endovascular Treatment for Chronic Subdural Hematoma”. Chronic subdural hematoma (cSDH) is one of the most frequently treated neurosurgical conditions, with a high and increasing incidence. Standard management of cSDH includes both non-surgical and surgical interventions. Non-surgical management involves watchful waiting and the optimization of risk factors, such as managing anticoagulant therapy. Surgical management typically involves burr-hole drainage or craniotomy. However, there is a high rate of treatment failure in cSDH, with conservative non-surgical management failing in up to 50% of cases and surgical management failing in up to 15% of cases due to persistence, recurrence, or the need for re-operation. The pathophysiology of cSDH involves initial bleeding, which leads to the formation of a subdural collection, leakage of cerebrospinal fluid into the subdural space, and chronic inflammation. These factors perpetuate a cycle of bleeding and re-bleeding, complicating the condition further. Embolization of the middle meningeal artery (MMA) is a promising treatment aimed at devascularizing the meninges, decreasing or preventing recurrent micro-hemorrhages, and facilitating the physiological absorption of the subdural collection. Various embolic agents are used in these procedures, including particulate agents like microspheres, coils, and liquid embolic agents such as cyanoacrylates, copolymer-based agents, Onyx/Squid, and PHIL. A systematic review and meta-analysis by Ku et al. in 2023 compared different embolic agents for MMA embolization in cSDH treatment. The study found that Onyx had the lowest rates of radiological recurrence, re-operations, and complications, while combinations of particles and coils provided the best clinical outcomes. 

Future directions in the treatment of cSDH include the MAGIC-MT study, which aims to clarify whether MMA embolization could reduce the recurrence or progression rate of symptomatic non-acute SDH compared to conventional treatment (burr-hole drainage and conservative treatment). Follow-ups are scheduled at 30 days and one year. This study aims to provide robust evidence to guide the management of cSDH, potentially leading to new standards of care.