2024
Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder
Agarwal N, Frigerio G, Rizzato G, Ciceri T, Mani E, Lanteri F, Molteni M, Carare RO, Losa L and Peruzzo D
Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder
Agarwal N, Frigerio G, Rizzato G, Ciceri T, Mani E, Lanteri F, Molteni M, Carare RO, Losa L and Peruzzo D
The parasagittal dura, a tissue that lines the walls of the superior sagittal sinus, acts as an active site for immune-surveillance, promotes the reabsorption of cerebrospinal fluid, and facilitates the removal of metabolic waste products from the brain. Cerebrospinal fluid is important for the distribution of growth factors that signal immature neurons to proliferate and migrate. Autism spectrum disorder is characterized by altered cerebrospinal fluid dynamics.
Defining an Ageing-Related Pathology, Disease or Syndrome: International Consensus Statement
Short E, Adcock IM, Al-Sarireh B, Ager A, Ajjan R, Akbar N, Akeroyd MA, Alsaleh G, Al-Sharbatee G, Alavian K, Amoaku W, Andersen J, Antoniades C, Arends MJ, Astley S, Atan D, Attanoos R, Attems J, Bain S, Balaskas K, Balmus G, Bance M, Barber TM, Bardhan A, Barker K, Barnes P, Basatemur G, Bateman A, Bauer ME, Bellamy C, van Beek E, Bellantuono I, Benbow E, Bhandari S, Bhatnagar R, Bloom P, Bowdish D, Bowerman M, Burke M, Carare R, Carrington EV, Castillo-Quan JI, Clegg P, Cole J, Cota C, Chazot P, Chen C, Cheong Y, Christopher G, Church G, Clancy D, Cool P, Del Galdo F, Dalakoti M, Dasgupta S, Deane C, Dhasmana D, Dojcinov S, Di Prete M, Du H, Duggal NA, Ellmers T, Emanueli C, Emberton M, Erusalimsky JD, Feldmeyer L, Fleming A, Forbes K, Foster TC, Frasca D, Frayling I, Freedman D, Fülöp T, Ellison-Hughes G, Gazzard G, George C, Gil J, Glassock R, Goldin R, Green J, Guymer R, Haboubi H, Harries L, Hart S, Hartley D, Hasaballa S, Henein C, Helliwell M, Henderson E, Heer R, Holte K, Idris I, Isenburg D, Jylhävä J, Iqbal A, Jones SW, Kalaria R, Kanamarlapudi V, Kempf W, Kermack AJ, Kerns J, Koulman A, Khan AH, Kinross J, Klaucane K, Krishna Y, Gill HS, Lakatta E, Laconi E, Lazar A, Leeuwenburgh C, Leung S, Li X, van der Linde I, Lopes LV, Lorenzini A, Lotery A, Machado P, Mackie S, Madeddu P, Maier A, Mukkanna K, Manousou P, Markey O, Mauro C, McDonnell B, Medina RJ, Meran S, Metzler-Baddeley C, Meglinksi I, Milman N, Mitteldorf C, Montgomery R, Morris AC, Mühleisen B, Mukherkee A, Murray A, Nelson S, Nicolaou A, Nirenberg A, Noble S, Nolan LS, Nus M, Van On C, Osei-Lah V, Peffers M, Palmer A, Palmer D, Palmer L, Parry-Smith W, Pawelec G, Peleg S, Perera R, Pitsillides A, Plack CJ, Progatzsky F, Pyott S, Rajput K, Rashid S, Ratnayaka JA, Ratnayake SAB, Rodriguez-Justo M, Rosa AC, Rule A, Sanger GJ, Sayers I, Saykin A, Selvarajah D, Sethi J, Shanahan C, Shen-Orr S, Sheridan C, Shiels P, Sidlauskas K, Sivaprasad S, Sluimer J, Small G, Smith P, Smith R, Snelling S, Spyridopoulos I, Srinivasa Raghavan R, Steel D, Steel KP, Stewart C, Stone K, Subbarayan S, Sussman M, Svensson J, Tadanki V, Tan AL, Tanzi RE, Tatler A, Tavares AAS, Tengku Mohd TAM, Tiganescu A, Timmons J, Tree J, Trivedi D, Tsochatzis EA, Tsimpida D, Vinke EJ, Whittaker A, Vallabh NA, Veighey K, Venables ZC, Reddy V, Vernooij MW, Verschoor C, Vinciguerra M, Vukanovic V, Vyazovskiy V, Walker J, Wakefield R, Watkins AJ, Webster A, Weight C, Weinberger B, Whitney SL, Willis R, Witkowski JM, Yeo LLL, Chung TY, Yu E, Zemel M, Calimport SRG and Bentley BL
Defining an Ageing-Related Pathology, Disease or Syndrome: International Consensus Statement
Short E, Adcock IM, Al-Sarireh B, Ager A, Ajjan R, Akbar N, Akeroyd MA, Alsaleh G, Al-Sharbatee G, Alavian K, Amoaku W, Andersen J, Antoniades C, Arends MJ, Astley S, Atan D, Attanoos R, Attems J, Bain S, Balaskas K, Balmus G, Bance M, Barber TM, Bardhan A, Barker K, Barnes P, Basatemur G, Bateman A, Bauer ME, Bellamy C, van Beek E, Bellantuono I, Benbow E, Bhandari S, Bhatnagar R, Bloom P, Bowdish D, Bowerman M, Burke M, Carare R, Carrington EV, Castillo-Quan JI, Clegg P, Cole J, Cota C, Chazot P, Chen C, Cheong Y, Christopher G, Church G, Clancy D, Cool P, Del Galdo F, Dalakoti M, Dasgupta S, Deane C, Dhasmana D, Dojcinov S, Di Prete M, Du H, Duggal NA, Ellmers T, Emanueli C, Emberton M, Erusalimsky JD, Feldmeyer L, Fleming A, Forbes K, Foster TC, Frasca D, Frayling I, Freedman D, Fülöp T, Ellison-Hughes G, Gazzard G, George C, Gil J, Glassock R, Goldin R, Green J, Guymer R, Haboubi H, Harries L, Hart S, Hartley D, Hasaballa S, Henein C, Helliwell M, Henderson E, Heer R, Holte K, Idris I, Isenburg D, Jylhävä J, Iqbal A, Jones SW, Kalaria R, Kanamarlapudi V, Kempf W, Kermack AJ, Kerns J, Koulman A, Khan AH, Kinross J, Klaucane K, Krishna Y, Gill HS, Lakatta E, Laconi E, Lazar A, Leeuwenburgh C, Leung S, Li X, van der Linde I, Lopes LV, Lorenzini A, Lotery A, Machado P, Mackie S, Madeddu P, Maier A, Mukkanna K, Manousou P, Markey O, Mauro C, McDonnell B, Medina RJ, Meran S, Metzler-Baddeley C, Meglinksi I, Milman N, Mitteldorf C, Montgomery R, Morris AC, Mühleisen B, Mukherkee A, Murray A, Nelson S, Nicolaou A, Nirenberg A, Noble S, Nolan LS, Nus M, Van On C, Osei-Lah V, Peffers M, Palmer A, Palmer D, Palmer L, Parry-Smith W, Pawelec G, Peleg S, Perera R, Pitsillides A, Plack CJ, Progatzsky F, Pyott S, Rajput K, Rashid S, Ratnayaka JA, Ratnayake SAB, Rodriguez-Justo M, Rosa AC, Rule A, Sanger GJ, Sayers I, Saykin A, Selvarajah D, Sethi J, Shanahan C, Shen-Orr S, Sheridan C, Shiels P, Sidlauskas K, Sivaprasad S, Sluimer J, Small G, Smith P, Smith R, Snelling S, Spyridopoulos I, Srinivasa Raghavan R, Steel D, Steel KP, Stewart C, Stone K, Subbarayan S, Sussman M, Svensson J, Tadanki V, Tan AL, Tanzi RE, Tatler A, Tavares AAS, Tengku Mohd TAM, Tiganescu A, Timmons J, Tree J, Trivedi D, Tsochatzis EA, Tsimpida D, Vinke EJ, Whittaker A, Vallabh NA, Veighey K, Venables ZC, Reddy V, Vernooij MW, Verschoor C, Vinciguerra M, Vukanovic V, Vyazovskiy V, Walker J, Wakefield R, Watkins AJ, Webster A, Weight C, Weinberger B, Whitney SL, Willis R, Witkowski JM, Yeo LLL, Chung TY, Yu E, Zemel M, Calimport SRG and Bentley BL
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased healthspan. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand, and meet the healthcare, workforce, wellbeing, and socioeconomic needs of ageing populations, while supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies.
Alzheimer's disease pathophysiology in the Retina
Gaire BP, Koronyo Y, Fuchs DT, Shi H, Rentsendorj A, Danziger R, Vit JP, Mirzaei N, Doustar J, Sheyn J, Hampel H, Vergallo A, Davis MR, Jallow O, Baldacci F, Verdooner SR, Barron E, Mirzaei M, Gupta VK, Graham SL, Tayebi M, Carare RO, Sadun AA, Miller CA, Dumitrascu OM, Lahiri S, Gao L, Black KL and Koronyo-Hamaoui M
Alzheimer's disease pathophysiology in the Retina
Gaire BP, Koronyo Y, Fuchs DT, Shi H, Rentsendorj A, Danziger R, Vit JP, Mirzaei N, Doustar J, Sheyn J, Hampel H, Vergallo A, Davis MR, Jallow O, Baldacci F, Verdooner SR, Barron E, Mirzaei M, Gupta VK, Graham SL, Tayebi M, Carare RO, Sadun AA, Miller CA, Dumitrascu OM, Lahiri S, Gao L, Black KL and Koronyo-Hamaoui M
The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.
Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial
Dumitrascu OM, Doustar J, Fuchs DT, Koronyo Y, Sherman DS, Miller MS, Johnson KO, Carare RO, Verdooner SR, Lyden PD, Schneider JA, Black KL and Koronyo-Hamaoui M
Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial
Dumitrascu OM, Doustar J, Fuchs DT, Koronyo Y, Sherman DS, Miller MS, Johnson KO, Carare RO, Verdooner SR, Lyden PD, Schneider JA, Black KL and Koronyo-Hamaoui M
The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.
Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies
van Veluw SJ, Benveniste H, Bakker ENTP, Carare RO, Greenberg SM, Iliff JJ, Lorthois S, Van Nostrand WE, Petzold GC, Shih AY and van Osch MJP
Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies
van Veluw SJ, Benveniste H, Bakker ENTP, Carare RO, Greenberg SM, Iliff JJ, Lorthois S, Van Nostrand WE, Petzold GC, Shih AY and van Osch MJP
The brain's network of perivascular channels for clearance of excess fluids and waste plays a critical role in the pathogenesis of several neurodegenerative diseases including cerebral amyloid angiopathy (CAA). CAA is the main cause of hemorrhagic stroke in the elderly, the most common vascular comorbidity in Alzheimer's disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid β-a key culprit in CAA-from the brain to draining lymphatics and systemic circulation remains poorly understood. This knowledge gap is critically important to bridge for understanding the pathophysiology of CAA and accelerate development of targeted therapeutics. The authors of this review recently converged their diverse expertise in the field of perivascular physiology to specifically address this problem within the framework of a Leducq Foundation Transatlantic Network of Excellence on Brain Clearance. This review discusses the overarching goal of the consortium and explores the evidence supporting or refuting the role of impaired perivascular clearance in the pathophysiology of CAA with a focus on translating observations from rodents to humans. We also discuss the anatomical features of perivascular channels as well as the biophysical characteristics of fluid and solute transport.
[1-C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects
Mehta NH, Wang X, Keil SA, Xi K, Zhou L, Lee K, Tan W, Spector E, Goldan A, Kelly J, Karakatsanis NA, Mozley PD, Nehmeh S, Chazen JL, Morin S, Babich J, Ivanidze J, Pahlajani S, Tanzi EB, Saint-Louis L, Butler T, Chen K, Rusinek H, Carare RO, Li Y, Chiang GC and de Leon MJ
[1-C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects
Mehta NH, Wang X, Keil SA, Xi K, Zhou L, Lee K, Tan W, Spector E, Goldan A, Kelly J, Karakatsanis NA, Mozley PD, Nehmeh S, Chazen JL, Morin S, Babich J, Ivanidze J, Pahlajani S, Tanzi EB, Saint-Louis L, Butler T, Chen K, Rusinek H, Carare RO, Li Y, Chiang GC and de Leon MJ
Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer's disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.
Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome
Agarwal N, Lewis LD, Hirschler L, Rivera LR, Naganawa S, Levendovszky SR, Ringstad G, Klarica M, Wardlaw J, Iadecola C, Hawkes C, Carare RO, Wells J, Bakker ENTP, Kurtcuoglu V, Bilston L, Nedergaard M, Mori Y, Stoodley M, Alperin N, de Leon M and van Osch MJP
Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome
Agarwal N, Lewis LD, Hirschler L, Rivera LR, Naganawa S, Levendovszky SR, Ringstad G, Klarica M, Wardlaw J, Iadecola C, Hawkes C, Carare RO, Wells J, Bakker ENTP, Kurtcuoglu V, Bilston L, Nedergaard M, Mori Y, Stoodley M, Alperin N, de Leon M and van Osch MJP
Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3.
Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy
Kelly L, Brown C, Michalik D, Hawkes CA, Aldea R, Agarwal N, Salib R, Alzetani A, Ethell DW, Counts SE, de Leon M, Fossati S, Koronyo-Hamaoui M, Piazza F, Rich SA, Wolters FJ, Snyder H, Ismail O, Elahi F, Proulx ST, Verma A, Wunderlich H, Haack M, Dodart JC, Mazer N and Carare RO
Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy
Kelly L, Brown C, Michalik D, Hawkes CA, Aldea R, Agarwal N, Salib R, Alzetani A, Ethell DW, Counts SE, de Leon M, Fossati S, Koronyo-Hamaoui M, Piazza F, Rich SA, Wolters FJ, Snyder H, Ismail O, Elahi F, Proulx ST, Verma A, Wunderlich H, Haack M, Dodart JC, Mazer N and Carare RO
This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.
Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance
Dumitrascu OM, Doustar J, Fuchs DT, Koronyo Y, Sherman DS, Miller MS, Johnson KO, Carare RO, Verdooner SR, Lyden PD, Schneider JA, Black KL and Koronyo-Hamaoui M
Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance
Dumitrascu OM, Doustar J, Fuchs DT, Koronyo Y, Sherman DS, Miller MS, Johnson KO, Carare RO, Verdooner SR, Lyden PD, Schneider JA, Black KL and Koronyo-Hamaoui M
The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition.
A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging
Digpal R, Arkill KP, Doherty R, Yates J, Milne LK, Broomes N, Katsamenis OL, Macdonald J, Ditchfield A, Narata AP, Darekar A, Carare RO, Fabian M, Galea I and Bulters D
A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging
Digpal R, Arkill KP, Doherty R, Yates J, Milne LK, Broomes N, Katsamenis OL, Macdonald J, Ditchfield A, Narata AP, Darekar A, Carare RO, Fabian M, Galea I and Bulters D
Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, = 0.001 and = 0.002), endothelial cell markers (CD34 and CD31, = 0.007 and = 0.003), glycans (Alcian blue, = 0.003) and wall thickness ( = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.