Evaluation of the cerebrovascular reactivity in patients with Moyamoya Angiopathy by use of breath-hold fMRI: investigation of voxel-wise hemodynamic delay correction in comparison to [15^{15}O]water PET

PURPOSE: Patients with Moyamoya Angiopathy (MMA) require hemodynamic assessment to evaluate the risk of stroke. Hemodynamic evaluation by use of breath-hold-triggered fMRI (bh-fMRI) was proposed as a readily available alternative to the diagnostic standard [$^{15}$O]water PET. Recent studies suggest voxel-wise hemodynamic delay correction in hypercapnia-triggered fMRI. The aim of this study was to evaluate the effect of delay correction of bh-fMRI in patients with MMA and to compare the results with [$^{15}$O]water PET. METHODS: bh-fMRI data sets of 22 patients with MMA were evaluated without and with voxel-wise delay correction within different shift ranges and compared to the corresponding [$^{15}$O]water PET data sets. The effects were evaluated combined and in subgroups of data sets with most severely impaired CVR (apparent steal phenomenon), data sets with territorial time delay, and data sets with neither steal phenomenon nor delay between vascular territories. RESULTS: The study revealed a high mean cross-correlation (r = 0.79, p < 0.001) between bh-fMRI and [$^{15}$O]water PET. The correlation was strongly dependent on the choice of the shift range. Overall, no shift range revealed a significantly improved correlation between bh-fMRI and [$^{15}$O]water PET compared to the correlation without delay correction. Delay correction within shift ranges with positive high high cutoff revealed a lower agreement between bh-fMRI and PET overall and in all subgroups. CONCLUSION: Voxel-wise delay correction, in particular with shift ranges with high cutoff, should be used critically as it can lead to false-negative results in regions with impaired CVR and a lower correlation to the diagnostic standard [$^{15}$O]water PET

Quality of life impairment in adult Moyamoya patients—preoperative neuropsychological assessment and correlation to MRI and H215O PET findings

Moyamoya angiopathy (MMA) related cerebral perfusion deficits or infarctions might influence quality of life (QoL). This study examines preoperative QoL in adult patients with MMA and correlates these with findings obtained via diagnostic imaging. Sixty-seven adult Moyamoya patients underwent preoperative neuropsychological testing including questionnaires to determine QoL, as well as psychiatric and depressive symptoms. The results were checked for correlation with territorial hypoperfusions seen in H215O PET with acetazolamide (ACZ) challenge (cerebrovascular reserve) and infarction patterns observed in MRI. Each vascular territory was analyzed separately and correlated with QoL. Physical role function was restricted in 41.0% of cases and emotional role function in 34.4% of cases (SF-36). Obsessive–compulsive disorder (39.3%) (SCL-90-R), psychoticism (34.4%) (SCL-90-R), and depression (32.7%) (BDI-II) were also very common. Psychoticism was significantly more frequent in cases where perfusion deficits in PET CT were observed in both MCA territories (left p = 0.0124, right p = 0.0145) and infarctions in MRI were present in the right MCA territory (p = 0.0232). Depression was significantly associated with infarctions in the right MCA territory (SCL-90-R p = 0.0174, BDI-II p = 0.0246). Women were affected more frequently by depression (BDI-II, p = 0.0234). Physical role function impairment was significantly associated with perfusion deficits in the left MCA territory (p = 0.0178) and infarctions in the right MCA territory (p = 0.0428). MMA leads to impairments in different areas of QoL. Approximately one-third of all adult MMA patients suffered from depression, with women being most affected. In addition to depression, presence of executive dysfunctions and mental disorders such as psychoticism, obsessive–compulsive disorder, and impaired physical and emotional role function affected QoL. These patients showed significantly more often infarctions and perfusion deficits in the right MCA territory. Long-term studies with follow-up results are necessary to clarify a possible beneficial impact of early surgical revascularization on QoL and depression in adult MMA patients

PrImary decompressive Craniectomy in AneurySmal Subarachnoid hemOrrhage (PICASSO) trial: study protocol for a randomized controlled trial

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear. METHODS: PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4–5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0–4) and unfavorable (mRS 5–6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC. DISCUSSION: This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients. TRIAL REGISTRATION: DRKS DRKS00017650. Registered on 09 June 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06969-4

Gemeinsame genetische Polymorphismen von Moyamoya und atherosklerotischen Erkrankungen

The Moyamoya Disease (MMD) is an uncommon cerebrovascular disease with a very poor outcome if untreated. The etiology of this disease is still unknown; however genetics seem to be the most promising approach to understand the reason for the pathologic changes. In our study we genotyped seventeen SNPs in 40 affected patients and 68 healthy controls from central Europe. The SNPs were chosen based on publications describing histopathological changes in the walls of vessels affected by MMD as being in some aspects similar with those in atherosclerosis. The results of our study revealed a significant association for the SNP rs599839 [A/G] (p=0.0136, OR = 2.17, CI95%=1.17-4.05, risk allele G), and a strong tendency towards significance for the SNP rs501120 [A/G] (p=0.0994, OR = 2.00, CI 95% = 0.87-4.64, risk allele G). In conclusion we found a new association between MMD and rs599839 and a strong tendency towards significant association for rs501120 in a central European cohort. For both SNPs an association with coronary artery disease was proven by Samani et al. [113] in a European cohort, underlining our assumptions of common pathways in the genesis of MMD and atherosclerotic disease. Because of the limited amount of MMD samples and strong genetic variability between different ethnicities, further studies with larger cohorts from different ethnical groups are needed to verify our findings for a better understanding of the Moyamoya disease.Die Moyamoya Erkrankung ist eine in nicht-asiatischen Ländern äußerst seltene Erkrankung zerebraler Blutgefäße. Per definitionem beschreibt der Begriff „Moyamoya Erkrankung“ die bilaterale Stenose großer zerebraler Gefäße, insbesondere der arteria carotis interna, mit begleitenden feinen arteriellen Kollateralen. Diese Veränderungen können zu einer Minderversorgung und/oder Einblutung wichtiger Hirnareale führen, was die hohe Morbidität und Mortalität dieser Erkrankung erklärt. Auf Grund zahlreicher genetischer Vorstudien aus asiatischen Ländern und der Beschreibung familiärer Häufungen haben wir 40 DNA Proben von Moyamoya Patienten aus Mitteleuropa gesammelt, analysiert und die Ergebnisse mit 68 gesunden Kontrollprobanden verglichen. Es wurden 17 SNPs (Single Nucleotide Polymorphism), welche in vorherigen Studien als mit Atherosklerose, koronarer Herzkrankheit, intrakraniellen Aneurysmen, sowie Moyamoya assoziiert beschrieben wurden, durch Sequenzierungen genotypisiert. Das Studiendesign beruht auf Gemeinsamkeiten in der Beschreibung histopathologischer Veränderungen von Gefäßen von Patienten mit Atherosklerose, koronarer Herzkrankheit sowie intrakraniellen Aneurysmen und der Moyamoya Erkrankung. Es konnte gezeigt werden, dass für den SNP rs599839 das G Allel mit der Moyamoya Erkrankung assoziiert ist und die Wahrscheinlichkeit des Erkrankungseintritts um das 2.17 fache gesteigert wird (p=0.0236, OR=2.17, CI95%=1.17-4.05). rs599839 liegt auf Chromosom 1p13.3 und es wurde bereits mehrfach eine Assoziation mit erhöhten LDL Cholesterinwerten beschrieben. Weiterhin konnte gezeigt werden, dass für den SNP rs501120 das G Allel die Tendenz eines Risikoallels zeigt (p=0.0994, OR=2.00, CI95%=0.87-4.64). Dieser SNP liegt auf Chromosom 10q11.21 nahe dem CXCL12 Gen. Dieses Gen ist dafür bekannt, dass es Prozesse der Angiogenese und Stenose, aufgrund überschießender Reparaturmechanismen nach vaskulären Verletzungen und in ischämischen Geweben, beeinflussen kann. Dies könnte die zwei wichtigsten Prozesse bei der Entstehung der Moyamoya Erkrankung erklären: Die Verengung der Gefäße und die starke Kollateralisierung. Zusammenfassend wurde ein mit der Moyamoya Erkrankung assoziierter SNP (rs599839), sowie ein SNP (rs501120) mit starker Tendenz für eine signifikante Assoziation gefunden. Die stärkste Limitierung dieser Arbeit besteht in der äußerst geringen verfügbaren Fallzahl an Patienten mit der Moyamoya Erkrankung in Europa