The vanishing of the ACoA syndrome after aneurysmal subarachnoid haemorrhage: New era, different management, fewer problems?

Historically, a specific set of symptoms has been related to the rupture and repair of anterior communicating artery (ACoA) aneurysms. These consequences were defined as the 'ACoA syndrome' and included observations of severe memory loss, confabulation and personality or behavioural changes. These observations correspond to neuropsychological impairments in memory, executive functions and social cognition. However, in more recent studies, the existence of such a distinct syndrome has been called into question. We aimed to investigate the existence of the ACoA syndrome, by combining analysis of our own data with a systematic review of the literature. Memory, executive functions and social cognition of subarachnoid haemorrhage patients with ACoA aneurysms (N = 28) were compared to patients with aneurysms in other locations (N = 66). Results showed no significant differences. Subsequently, a systematic review of the existing literature on the ACoA syndrome was performed using Embase and PubMed until October 2022. Studies that investigated cognitive functions after rupture and repair of ACoA aneurysms were included. The search yielded 847 unique entries and after screening titles and abstracts, 648 records were excluded. 199 full-text articles were assessed for eligibility and 55 articles were included. Evidence was found for the ACoA syndrome in studies between 1960 and 2000, with impairments in memory and executive problems in the majority of studies. However, the majority of studies from 2000 did not demonstrate a distinct ACoA syndrome, although neuropsychological measurements improved. This coincides with the changes in the management of ACoA aneurysms over the past decades, such as the emergence of endovascular treatment and improvement of neurointensive care. Therefore, we hypothesize that the management techniques of ACoA aneurysms until around 2000, i.e. mainly conventional clipping, could be related to the presence of symptoms of the ACoA syndrome.

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery.

BACKGROUND: Meningiomas are the most frequently occurring primary intracranial tumours in adults. Surgical removal can only be curative by complete resection; however surgical access can be challenging due to anatomical localization and local invasion of bone and soft tissues. Several intraoperative techniques have been tried to improve surgical resection, including intraoperative fluorescence guided imaging; however, no meningioma-specific (fluorescent) targeting has been developed yet. Here, we aimed to identify the most promising biomarkers for targeted intra-operative fluorescence guided meningioma surgery. METHODS: One hundred forty-eight meningioma specimens representing all meningioma grades were analysed using immunohistochemistry (IHC) on tissue microarrays (TMAs) to determine expression patterns of meningioma biomarkers epithelial membrane antigen (EMA), platelet-derived growth factor ß (PDGF-ß), vascular endothelial growth factor α (VEGF-α), and somatostatin receptor type 2 (SSTR-2). Subsequently, the most promising biomarker was selected based on TArget Selection Criteria (TASC). Marker expression was examined by IHC in 3D cell culture models generated from freshly resected tumour material. RESULTS: TMA-IHC showed strongest staining for SSTR-2. All cases were positive, with 51.4% strong/diffuse, 30.4% moderate/diffuse and only 18.2% focal/weak staining patterns. All tested biomarkers showed at least weak positivity in all meningiomas, regardless of WHO grade. TASC analysis showed that SSTR-2 was the most promising target for fluorescence guided imaging, with a total score of 21 (out of 22). SSTR-2 expression was determined on original patient tumours and 3D cultures of three established cultures. CONCLUSIONS: SSTR-2 expression was highly sensitive and specific in all 148 meningiomas, regardless of WHO grade. According to TASC analysis, SSTR-2 is the most promising receptor for meningioma targeting. After establishing in vitro meningioma models, SSTR-2 cell membrane expression was confirmed in two of three meningioma cultures as well. This indicates that specific fluorescence in an experimental setting can be performed for the further development of targeted fluorescence guided meningioma surgery and near-infrared fluorescent tracers targeting SSTR-2.