Background and purpose
Occlusive cerebrovascular moyamoya disease (MMD) is rare and has been characterized mainly in Asian countries, so far. In recent years, MMD has been increasingly reported ...worldwide, raising the question whether its clinical presentation would vary amongst different ethnic backgrounds. Here, a homogeneous series of 153 patients with MMD are reported and the specific clinical features of this rare disease amongst European Caucasians are highlighted.
Methods
A total of 153 European Caucasians with MMD who were treated in our institution between 1997 and 2014 were retrospectively identified. Demographic data, clinical symptoms, angiographic characteristics and functional hemodynamic studies were analyzed.
Results
Moyamoya disease presented with a female predominance of 2,9:1.,78% presented with a typical MMD, 17% with a unilateral MMD and 5% with an atypical MMD. 16% of our patients belonged to the pediatric population. Overall, 81% and 8.5% of our cohort presented initially with ischaemic and hemorrhagic manifestation, respectively. The rate of hemorrhagic manifestation of MMD amongst the pediatric group was slightly higher (12%). Angiographic analysis revealed steno‐occlusive involvement of the posterior circulation in 34% with a higher involvement in pediatric patients (64%) compared to adults (28%).
Conclusions
The characterization of our homogeneous European Caucasian cohort reveals several significant differences compared to Asian cohorts. In contrast, MMD presents similarly amongst European and North American cohorts, suggesting that non‐Asian MMD is characterized by distinct clinical features.
The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the ...hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown.
The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated.
Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.
The extra domain A (ED A) of fibronectin has been identified as a tumor vessel specific neovascular marker in glioma. Antibody based vascular targeting against ED A of fibronectin allows precise ...accumulation of photosensitizer in glioma microvasculature and thereby promises to overcome drawbacks of current photodynamic therapy (PDT) for glioma treatment. Our aim was to characterize microcirculatory consequences of F8-small immunoprotein (SIP) mediated PDT by intravital microscopy (IVM) and to analyze the effects on glioma growth. For IVM SF126 glioma cells were implanted into dorsal skinfold-chamber of nude mice. PDT was performed after intravenous injection of photosensitizer (PS)-coupled F8-SIP or PBS (n = 4). IVM was performed before and after PDT for 4 days. Analysis included total and functional (TVD, FVD) vessel densities, perfusion index (PI), microvascular permeability and blood flow rate (Q). To assess tumor growth SF126 glioma cells were implanted subcutaneously. PDT was performed as a single and repetitive treatment after PS-F8-SIP injection (n = 5). Subcutaneous tumors were treated after uncoupled F8-SIP injection as control group (n = 5). PDT induced microvascular stasis and thrombosis with reduced FVD (24 h: 115.98 ± 0.7 vs. 200.8 ± 61.9 cm/cm
2
) and PI (39 ± 11 vs. 70 ± 10 %), whereas TVD was not altered (298 ± 39.2 vs. 278.2 ± 51 cm/cm
2
). Microvascular dysfunction recovered 4 days after treatment. Microvascular dysfunction led to a temporary reduction of glioma growth in the first 48 h after treatment with complete recovery 5 days after treatment. Repetitive PDT resulted in sustained reduction of tumor growth. F8-SIP mediated PDT leads to microvascular dysfunction and reduced glioma growth in a preclinical glioma model with recovery of microcirculation 4 days after treatment. Repetitive application of PDT overcomes microvascular recovery and leads to prolonged antiglioma effects.
Highlights • The influence of sacropelvic fixation on postoperative SIJ pain in patients undergoing multilevel stabilisation was evaluated. • An additional fixation of the SIJ with iliac screws or ...iliosacral plate did not have an influence on the SIJ pain. • The patientś BMI is the only preoperative factor that correlated with a higher incidence to develop postoperative SIJ pain.
The Berlin Grading System assesses clinical severity of moyamoya angiopathy (MMA) by combining MRI, DSA, and cerebrovascular reserve capacity (CVRC). Our aim was to validate this grading system using ...
15
OH
2
O PET for CVRC. We retrospectively identified bilateral MMA patients who underwent
15
OH
2
O PET examination and were treated surgically at our department. Each hemisphere was classified using the Suzuki and Berlin Grading System. Preoperative symptoms and perioperative ischemias were collected, and a logistic regression analysis was performed. A total of 100 hemispheres in 50 MMA patients (36 women, 14 men) were included. Using the Berlin Grading System, 2 (2.8%) of 71 symptomatic hemispheres were categorized as grade I, 14 (19.7%) as grade II, and 55 (77.5%) as grade III. The 29 asymptomatic hemispheres were characterized as grade I in 7 (24.1%) hemispheres, grade II in 12 (41.4%), and grade III in 10 (34.5%) hemispheres. Berlin grades were independent factors for identifying hemispheres as symptomatic and higher grades correlated with increasing proportion of symptomatic hemispheres (
p
< 0.01). The Suzuki grading did not correlate with preoperative symptoms (
p
= 0.26). Perioperative ischemic complications occurred in 8 of 88 operated hemispheres. Overall, complications did not occur in any of the grade I hemispheres, but in 9.1% (
n
= 2 of 22) and 9.8% (
n
= 6 of 61) of grade II and III hemispheres, respectively. In this study, we validated the Berlin Grading System with the use of
15
OH
2
O PET for CVRC as it could stratify preoperative symptomatology. Furthermore, we highlighted its relevance for predicting perioperative ischemic complications.
Study design
Retrospective study.
Objective
For successful multilevel correction and stabilization of degenerative spinal deformities, a rigid basal construct to the sacrum is indispensable. The ...primary objective of this study was to compare the results of two different sacropelvic fixation techniques to conventional stabilization to the sacrum in patients with multilevel degenerative spine disease.
Methods
A total of 69 patients with multisegmental fusion surgery (mean number of stabilized functional spinal units: 7.0 ± 3.3) with a minimum of 1-year follow-up were included. 32 patients received fixation to the sacrum (S1), 23 patients received S1 and iliac screw fixation (iliac) and 14 patients were treated with iliosacral plate fixation (plate). Primary outcome parameters were radiographic outcome concerning fusion in the segment L5–S1, rate of screw loosening, back and buttock pain reduction numeric rating scale for pain evaluation: 0 indicating no pain, 10 indicating the worst pain, overall extent of disability after surgery (Oswestry Disability Index) and the number of complications.
Results
The three groups did not differ in body mass index, ASA score, the number of stabilized functional spinal units, duration of surgery, the number of previous spine surgeries, or postoperative complication rate. The incidence of L5–S1 pseudarthrosis after 1 year in the S1, iliac, and plate groups was 19, 0, and 29 %, respectively (
p
< 0.05 iliac vs. plate). The incidence of screw loosening after 1 year in the S1, iliac, and plate groups was 22, 4, and 43 %, respectively (
p
< 0.05 iliac vs. plate). Average Oswestry scores after 1 year in the S1, iliac, and plate groups were 40 ± 18, 42 ± 20, and 58 ± 18, respectively (
p
< 0.05 both S1 and iliac vs. plate).
Conclusion
The surgical treatment of multilevel degenerative spine disease carries a significant risk for pseudarthrosis and screw loosening, mandating a rigid sacropelvic fixation. The use of an iliosacral plate resulted in an inferior surgical and clinical outcome when compared to iliac screws.
Background
Moyamoya disease (MMD) may be graded based on DSA, the presence of ischemia in MRI and cerebrovascular reserve capacity allowing the prediction of ischemic symptoms in patients. Cerebral ...ischemia represents a severe complication in revascularization surgery. Focusing on different clinical features of hemodynamic impairment, MMD grading may allow prediction of ischemic complications. It was the aim to analyze whether MMD grading stratifies for ischemic complications in revascularization surgery for MMD.
Method
In 37 MMD patients a bilateral, standardized, one-staged revascularization approach consisting of STA-MCA bypass/encephalomyosynangiosis (EMS) and single EMS on the contralateral hemisphere was performed. Clinical data including DSA, MRI and rCBF (Xenon-CT) studies were assessed and used for grading MMD. All patients were observed on the ICU for at least 24 h and received CT imaging on the first postoperative day and in case of neurological deterioration. Ischemic complications were analyzed until the day of discharge and at 6-month follow-up.
Results
Grading of MMD revealed 11 hemispheres (15 %) as grade I, 33 hemispheres (44 %) as grade II and 30 hemispheres (41 %) as grade III. Eight ischemic complications were observed (11 %). MMD grading demonstrated a significant correlation with ischemic complications: 0 complications in grade I, 3 in grade II (9 %) and 5 in grade III hemispheres (16 %;
p
< 0.05, Fisher’s exact test).
Conclusions
The proposed grading system allows to stratify for ischemic complications in MMD patients that receive bilateral, one-staged revascularization surgery. Future studies will have to investigate its use for predicting ischemic complications in other revascularization strategies for MMD.
The best revascularization strategy for moyamoya disease (MMD) remains unknown. Our aim was to characterize angiographic revascularization effects of a bilateral standardized revascularization ...approach, consisting of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass and encephalomyosynangiosis (EMS) on one hemisphere and single EMS on the contralateral hemisphere of each patient, and to compare the effects of both revascularization strategies on cerebral hemodynamics.
In 30 patients (18 females/12 males, age 8-63 years), standardized revascularization was performed. Digital subtraction angiography was performed preoperatively and at 7 days, 6 months and 12 months postoperatively. STA-MCA and EMS functions were graded I (poor), II (medium) or III (extensive) according to angiographic aspects. In 20 patients, cerebrovascular reserve capacity (CVRC) was assessed pre- and postoperatively (at 12 months) using xenon CT.
After 12 months, STA-MCA/EMS function was grade 1 in 40/40%, grade 2 in 27/26%, and grade 3 in 27/10% of hemispheres, respectively. Twelve months after surgery, single EMS showed grade I in 37%, grade II in 27%, and grade III in 20% of hemispheres. Combined revascularization improved CVRC significantly compared to preoperative measurement (preoperative: 16.5 ± 34.6% vs. postoperative: 60.8 ± 64.22%; p < 0.05). Single EMS did not improve CVRC significantly (preoperative: 21.8 ± 35.9% vs. postoperative: 34.8 ± 63.0%; p < 0.05).
Combined and indirect revascularization may be successfully applied in a bilateral standardized approach. STA-MCA/EMS is superior to single EMS in restoring CVRC in adult MMD patients.
Antiangiogenic therapies could be limited by various escape mechanisms including bone marrow-derived myeloid cell-induced vasculogenesis. The recruitment of vascular accessory cells (VACs) to the ...tumor neovasculature is as a multistep process. However, the recruitment process of these cells during antiangiogenic treatment remains unknown. The aim of our study was to characterize the recruitment of VACs during antiangiogenic therapy using sunitinib.
C6 glioma cells were implanted into dorsal skinfold chambers. Animals received antiangiogenic therapy intraperitoneally for 5 days prior to VAC application intra-arterially. Intravital microscopy was performed during VAC injection and 1 and 48 h after injection. Analyses included total (TVD) and functional vessel densities (FVD), the perfusion index (PI), microvascular permeability, blood flow rate (Q), microvascular diameter (D), red blood cell velocity (RBCV), wall shear rate (γ), wall shear stress (τ), first and firm adhesions of VACs, and accumulation in the perivascular niche.
Antiangiogenic therapy resulted in a significant reduction in TVD (365 ± 47 cm/cm(2) vs. 183 ± 37 cm/cm(2)) and FVD (227 ± 65 cm/cm(2) vs. 147 ± 25 cm/cm(2)) and an increase in PI, Q, D, and RBCV. γ and τ remained unaltered. Initial adhesion and firm adhesion were unaffected by antiangiogenic therapy; however, the accumulation in the perivascular niche was significantly diminished in treated tumors (53.7 ± 8% vs. 24.0 ± 17%).
Antiangiogenic treatment inhibits the accumulation of VACs in the perivascular niche and therefore interferes with consecutive neovascularization.
There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of
isocitrate dehydrogenase 1
, codeletion of 1p/19q and promoter hypermethylation of
O
6
...-methylguanine
-
DNA
-
methyltransferase
. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (
P
= 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.
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