Fungal Planet description sheets: 1436-1477.

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilaxglyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes. Citation: Tan YP, Bishop-Hurley SL, Shivas RG, et al. 2022. Fungal Planet description sheets: 1436-1477. Persoonia 49: 261-350. https://doi.org/10.3767/persoonia.2022.49.08.

Novel collophorina-like genera and species from Prunus trees and vineyards in Germany.

Strains with a yeast-like appearance were frequently collected in two surveys on the biodiversity of fungi in Germany, either associated with necroses in wood of Prunus trees in orchards in Saxony, Lower Saxony and Baden-Württemberg or captured in spore traps mounted on grapevine shoots in a vineyard in Rhineland-Palatinate. The morphology of the strains was reminiscent of the genus Collophorina: all strains produced aseptate conidia on integrated conidiogenous cells directly on hyphae, on discrete phialides, adelophialides and by microcyclic conidiation, while in some strains additionally endoconidia or conidia in conidiomata were observed. Blastn searches with the ITS region placed the strains in the Leotiomycetes close to Collophorina spp. Analyses based on morphological and multi-locus sequence data (LSU, ITS, EF-1α, GAPDH) revealed that the 152 isolates from wood of Prunus spp. belong to five species including C. paarla, C. africana and three new species. A further ten isolates from spore traps belonged to seven new species, of which one was isolated from Prunus wood as well. However, a comparison with both LSU and ITS sequence data of these collophorina-like species with reference sequences from further Leotiomycetes revealed the genus Collophorina to be polyphyletic and the strains to pertain to several genera within the Phacidiales. Collophorina paarla and C. euphorbiae are transferred to the newly erected genera Pallidophorina and Ramoconidiophora, respectively. The new genera Capturomyces, Variabilispora and Vexillomyces are erected to accommodate five new species isolated from spore traps. In total nine species were recognised as new to science and described as Collophorina badensis, C. germanica, C. neorubra, Capturomyces funiculosus, Ca. luteus, Tympanis inflata, Variabilispora flava, Vexillomyces palatinus and V. verruculosus.

Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.

OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population. SUBJECTS: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models. RESULTS: We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10-7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue. CONCLUSION: Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Prospective evaluation of reliability of cone-beam computed tomography in detecting different position of vibroplasty middle ear implants.

OBJECTIVES: This study had the following objectives: (i) to determine the accuracy of determination of Vibrant Soundbridge position in the spectrum of typically implanted sites in the middle ear, (ii) to assess interobserver agreement between three observers with different levels of radiology experience and (iii) to determine the suitability of cone-beam computed tomography (CT) to be used as the baseline radiological assessment post implantation, confirm ferromagnetic transducer (FMT) position. DESIGN: Prospective research study. Using four fresh human cadaveric heads, different types of vibroplasty were performed. After each step, cone-beam CT was performed for each of the four cadaveric heads. SETTING: University hospital (ENT and Neuroradiology). PARTICIPANTS: Four fresh cadaveric heads of human donors were operated and analysed by radiological imaging. MAIN OUTCOME MEASURES: There are different ways of coupling an ferromagnetic transducer to the anatomical structures of the middle and inner ear. Possibilities of differentiation between these coupling variants should be presented. RESULTS: The individual reconstruction view was significantly different from a standardised view for each observer (observer 1: P = 0.003; observer 2: P = 0.001; observer 3: P = 0.002) for all coupling variants combined as well as for each individual coupling variant (overall correct diagnosis: 100% versus 60%). Regarding the frequency of correct diagnosis, no significant differences were found between the three observers (P > 0.500) for each individual coupling variant as well as for all coupling variants combined. The worst rates of correct diagnosis were found in the standardised view for incus (42%), stapes (0%) and TORP (17%) vibroplasty. CONCLUSION: Cone-beam CT as a radiological control for Vibrant Soundbridge is safe and adequately sensitive and reliable and is therefore suitable for clinical investigation. The position of the ferromagnetic transducer in the middle ear and the presence or absence of an additional coupler could be determined in this study. Therefore, cone-beam-CT is useful for the assessment of device failure when there has been gross displacement of the ferromagnetic transducer (or smaller displacements in case of a baseline postoperative cone-beam CT). Regarding the quality of imaging, cone-beam CT produced accurate results with different observers with widely varying radiological experience.

Regulation of interferon-inducible proteins by doxorubicin via interferon γ-Janus tyrosine kinase-signal transducer and activator of transcription signaling in tumor cells.

Activation of the immune system is a way for host tissue to defend itself against tumor growth. Hence, treatment strategies that are based on immunomodulation are on the rise. Conventional cytostatic drugs such as the anthracycline doxorubicin can also activate immune cell functions of macrophages and natural killer cells. In addition, cytotoxicity of doxorubicin can be enhanced by combining this drug with the cytokine interferon-γ (IFNγ). Although doxorubicin is one of the most applied cytostatics, the molecular mechanisms of its immunomodulation ability have not been investigated thoroughly. In microarray analyses of HeLa cells, a set of 19 genes related to interferon signaling was significantly over-represented among genes regulated by doxorubicin exposure, including signal transducer and activator of transcription (STAT) 1 and 2, interferon regulatory factor 9, N-myc and STAT interactor, and caspase 1. Regulation of these genes by doxorubicin was verified with real-time polymerase chain reaction and immunoblotting. An enhanced secretion of IFNγ was observed when HeLa cells were exposed to doxorubicin compared with untreated cells. IFNγ-neutralizing antibodies and inhibition of Janus tyrosine kinase (JAK)-STAT signaling [aurintricarboxylic acid (ATA), (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), STAT1 small interfering RNA] significantly abolished doxorubicin-stimulated expression of interferon signaling-related genes. Furthermore, inhibition of JAK-STAT signaling significantly reduced doxorubicin-induced caspase 3 activation and desensitized HeLa cells to doxorubicin cytotoxicity. In conclusion, we demonstrate that doxorubicin induces interferon-responsive genes via IFNγ-JAK-STAT1 signaling and that this pathway is relevant for doxorubicin's cytotoxicity in HeLa cells. Immunomodulation is a promising strategy in anticancer treatment, so this novel mode of action of doxorubicin may help to further improve the use of this drug among different types of anticancer treatment strategies.

Artifacts of the electrode in cochlea implantation and limits in analysis of deep insertion in cone beam tomography (CBT).

Until now more than 250,000 cochlea implantations have been performed worldwide. The surgical procedure is well standardized. A discussion about the kind of postoperative radiological control has started since cone beam tomography (CBT) has been established in ENT and hearing preservation operations have come more into the focus. Further research has been concentrated on the role of CBT and the insertion of the basal turn. The aim of this study was to look for the possibilities of CBT and deep insertion. The second aim was to analyze the artifacts of cochlea implants in CBT. Three human cadaver ears were implanted with a flex soft electrode of MedEl© in a standard operation procedure with round window insertion and a full insertion. Afterwards 72 CBT sets per ear were performed with different X-ray-tube currents (2-10 mA), voltages (72-90 kV), and exposure times (9 and 17 s). On each data set, the radiological diameter of the electrode 9 (basal), electrode 2 (apical), the diameter of the cable next to the electrodes 9 and 2, and the associated diameter of the cochlea next to the electrodes 9 and 2 were evaluated. Additionally, a comparison to the real diameter was done. The mean radiological diameters of the measure point at electrode 9 were: electrode = 1.19 mm; cable = 0.65 mm; cochlea = 1.77 mm. Results for measure point at electrode 2 were: electrode = 0.98 mm; cable = 0.48 mm; cochlea = 1.21 mm. The real diameters were at electrode 9 in lateral view 0.58 mm and in top view 0.63 mm and at electrode 2 in lateral view 0.36 mm and in top view 0.50 mm. Differences between the diameters of the electrode 9 and 2 were highly significant. Interestingly, the real diameter of the electrode is half in comparison to the radiological one. Also in comparison to the diameter of the cable and the associated electrode is nearly half. Nearly 50% artifact exists on radiologic evaluation of the diameter of the electrode. Varying the X-ray adjustments did not lead to optimized results. The difficulties in evaluating a cochlea electrode with CBT could be shown. The high rate of artifacts (50%) makes it extremely difficult to predict the inserted scale, especially when evaluating the intracochlear position in the medial and apical turn of the cochlea. In conclusion, until now CBT allows a relatively safe evaluation of the electrode in the basal turn, whereas in deep insertion it is not really a useful tool to answer the question of insertion trauma, implanted scale, or scale displacements.

[Intracochlear electrode position: evaluation after deep insertion using cone beam computed tomography]. / Intracochleäre Elektrodenlage : Beurteilung mittels "cone beam computed tomography" nach tiefer Insertion.

INTRODUCTION: Due to the increasing number of cochlear implantations (CI), postoperative radiological verification of the electrode position, e.g., with respect to quality control, plays a central role. The aim of this study was to evaluate the intracochlear position of deep inserted electrodes by cone beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT data sets (Accu-I-tomo, Morita, Kyoto, Japan) of 22 patients (28 ears operated between 2008 and 2011) were retrospectively analyzed. All patients underwent a CI (round window approach) with deep insertion of the electrode (Flex soft or standard electrode from MedEl©). CBCT data were analyzed for intracochlear position of the electrode (scala vestibuli, scala tympani, malposition between the scalae) and the certainty of this evaluation. RESULTS: All ears could be evaluated with the status certain or relatively certain in the basal turn of the cochlea. Thereby, the electrode array was inserted into the scala tympani in 93% (n = 26). Primary insertion into the scala vestibuli and the scala media was observed in 3.5% of the ears, respectively. In the apical part of the cochlea, only 32% (n = 9 ears) could be evaluated with relative certainty. The remaining 68% of cases could not be evaluated. Of the 32% interpretable cases in the apical part of the cochlea, 25% (n = 7) were inserted into the scala tympani, 3.5% (n = 1) into the scala vestibuli, and 3.5% (n = 1) were malpositioned between the scalae. CONCLUSION: The exact evaluation of the intracochlear position of the electrode by CBCT is only possible in the basal turn of the cochlea. In deep insertion, determination of the position in the medial and apical parts of the cochlea by CBCT is still not possible. Furthermore, the round window approach allows reliable implantation into the scala tympani.

Paradoxical embolization of brachiocephalic and pulmonary arteries in a case of persistent foramen ovale: a case report.

Paradoxical embolism is the result of systemic arterial embolism and pulmonary embolism. It indicates the presence of an intracardial defect in the area of the atrial or ventricular septum. The most frequent cause of an intracardiac defect associated with paradoxical embolism is a patent foramen ovale (PFO). In the case presented here, the symptoms, diagnostics and surgical therapy are discussed.

Radiological examinations of the anatomy of the inferior turbinate using digital volume tomography (DVT).

BACKGROUND: Since the last 120 years there were only few descriptions of the anatomical sizes of the inferior turbinate in the literature. On this background the current study should evaluate the radiological dimensions of the inferior turbinate and the septum using DVT. METHODS: The latest generation of the Accu-I-tomo was used. The data of 100 adult patients have been evaluated. RESULTS: The bony length was found to be 38.9 mm, the mucosal length 51.0 mm. The findings of the total mucosal thickness at different measuring points were between 8.1 mm and 10.9 mm, those of the bony thickness were between 0.9 mm and 2.3 mm and those of the bony height were between 3.9 mm and 20.8 mm. CONCLUSION: The results of this radiological study are able to point out the importance of preoperative anatomical evaluation of radiological images. The preoperative focus on the individual anatomy is very important because of the choice of an adequate surgical treatment. Today new radiological techniques can help to find out whether the reason for hypertrophied turbinates is caused by bone, mucosa or both. This knowledge enables a concerted treatment concept.

Wyburn-Mason syndrome: a case report.

OBJECTIVE: Wyburn-Mason syndrome is a rare disease associated with multiple arteriovenous malformations of the brain, orbit, and face resulting from an insult occurring during embryonic development. CASE REPORT: We present the clinical and radiological features of a 47-year-old-man with Wyburn-Mason syndrome who suffered from recurrent bleeding episodes primarily at the nasal corner of the left orbit. After radiotherapy and several angioembolisations, surgical reduction with exenteration of the left orbit was performed and resulted in reduced bleeding. Two years later the patient presented with maxillary sinus empyema. Due to massive endonasal bleeding, endoscopy could not be performed and the maxillary empyema was treated via a transorbital approach. CONCLUSION: Although close observation represents the standard of care in Wyburn-Mason syndrome, patient-specific management decisions are required in the presence of symptoms or complications. In the presented case, surgical intervention proved to be successful.

New species of Phaeomoniellales from a German vineyard and their potential threat to grapevine (Vitis vinifera) health.

Recently, the order Phaeomoniellales was established that includes fungi closely related to Phaeomoniella chlamydospora, a phytopathogen assumed to be the main causal agent of the two most destructive grapevine trunk diseases, Petri disease and esca. Other species of this order are reported as pathogens of other economically important crops, like olive, peach, apricot, cherry, plum, rambutan, lichee or langsat. However, they are rarely isolated and hence, little is known about their ecological traits and pathogenicity. During a 1-yr period of spore trapping in a German vineyard divided in minimally and intensively pruned grapevines, 23 fungal strains of the Phaeomoniellales were collected. Based on morphological and molecular (ITS, LSU and tub2) analyses the isolated strains were assigned to eight different species. Two species were identified as P. chlamydospora and Neophaeomoniella zymoides, respectively. The remaining six species displayed morphological and molecular differences to known species of the Phaeomoniellales and are newly described, namely Aequabiliella palatina, Minutiella simplex, Moristroma germanicum, Mo. palatinum, Neophaeomoniella constricta and N. ossiformis. A pathogenicity test conducted in the greenhouse revealed that except for P. chlamydospora, none of the species of the Phaeomoniellales isolated from spore traps is able to induce lesions in grapevine wood.

Subcentimetre thyroid nodules: Sonographic features associated with malignancy.

INTRODUCTION: The aim of this study was to identify the ultrasound features which are associated with malignancy in subcentimetre thyroid nodules. METHODS: This retrospective study included 454 thyroid nodules <10 mm in size in 413 patients from 2012 to 2016, which were subjected to fine needle aspiration cytology. Each nodule was classified according to the ultrasound patterns of the 2015 American Thyroid Association guidelines and the high suspicion ultrasound features (solid, hypo-echogenicity, irregular margins, microcalcifications, taller-than-wide, interrupted rim calcifications, and extrathyroidal extension) were identified for evaluation of their diagnostic performance. RESULTS: Of the American Thyroid Association high suspicion ultrasound features, univariate analysis showed that hypo-echogenicity (sensitivity 81.6% (95% CI 65.7-92.3%), specificity 50.0% (95% CI 43.4-56.6%)), irregular margins (sensitivity 34.2% (95% CI 19.6-51.4%), specificity 92.2% (95% CI 88.0-95.3%)), microcalcifications (sensitivity 23.7% (95% CI 11.4-40.2%), specificity 91.0% (95% CI 86.5-94.3%)), and taller-than-wide (sensitivity 23.7% (95% CI 11.4-40.2%), specificity 92.2% (95% CI 88.0-95.3%)) were significantly associated with a malignant diagnosis. Amongst the above features, subsequent multivariate analysis identified a combination of hypo-echogenicity and irregular margins as significantly associated with malignancy. Our malignancy rates based on American Thyroid Association ultrasound patterns from benign to high suspicion were 0.0, 8.3, 3.9, 15.7, and 40.4%, respectively. The American Thyroid Association high suspicion ultrasound pattern had a sensitivity of 50.0% (95% CI 33.4-66.7%) and specificity of 84.5% (95% CI 79.2-88.9%). CONCLUSION: The presence of both hypo-echogenicity and irregular margins was significantly associated with malignancy in subcentimetre thyroid nodules in our study. Hence, subcentimetre nodules which are hypoechoic with irregular margins may warrant further follow-up.

Digital volume tomography in the diagnosis of nasal bone fractures.

Digital volume tomography (DVT) is a kind of cone beam computed tomography and enables high quality 3D images of osseous structures. It is a well-established diagnostic tool in dentistry. High detail resolution is reached with a reduced exposition of radiation dose in comparison to conventional computed tomography. The data volume can be analysed in three orthogonal plains, which can be changed in angle arbitrarily. The aim of the study was to evaluate, if and in which performance DVT is able to detect discrete nasal bone fractures that cannot be seen in conventional radiography occasionally. DVT was performed in sixty-five patients with suspected nasal bone fracture. Five of these patients underwent lateral radiographs of the nasal bones in other departments which failed to show any radiologic signs of a nasal bone fracture, whereas DVT showed clear fracture lines. DVT-findings were also used to classify fractures according to their dimensions. Additionally DVT enabled the reconstruction of three-dimensional volume images. With this technique it is possible to get an image of the extent of the nasal bone fracture and the dislocation of the fragments. Because of these facts as well as its high resolution and low radiation dose, DVT can be recommended as the routine radiological examination in suspected nasal bone fractures.

Catecholamine secreting glomus tumor detected by iodine-123-MIBG scintigraphy.

We report the case of a 41-yr-old woman who presented with arterial hypertension and tinnitus in the right ear synchronous with pulse. She had previously undergone surgery for suspected pheochromocytoma without positive therapeutic effect. CT and MRI revealed a homogenous tumor with contrast enhancement in the right hypotympanon and foramen jugulare, and [123I]metaiodobenzylguanidine (MIBG) scintigraphy demonstrated strong tracer uptake in the same area. Selective venous sampling of catecholamines in the ipsilateral jugular vein confirmed the tumor to have originated from hormone production.

Endovascular occlusion of vertebral arteries in the treatment of unclippable vertebrobasilar aneurysms.

Twenty-one patients with aneurysms of the vertebrobasilar circulation underwent unilateral or bilateral endovascular occlusion of the vertebral artery. Six patients presented with subarachnoid hemorrhage (SAH), 10 with mass effect, four with mass effect and SAH, and one with ischemic symptoms. Thirteen patients had good outcomes with complete clinical and angiographic cure. Six patients had partial thrombosis of their aneurysms. There was one death and one treatment failure. One patient suffered transient stroke. It is concluded that endovascular occlusion of the vertebral artery following test occlusion is a safe and effective treatment for proximal aneurysms of the vertebrobasilar circulation.

Endovascular occlusion of intracranial vessels for curative treatment of unclippable aneurysms: report of 16 cases.

Among 121 intracerebral aneurysms presenting at one institution between 1984 and 1989, 16 were treated by endovascular means. All 16 lesions were intradural and intracranial, and had failed either surgical or endovascular attempts at selective exclusion with parent vessel preservation. The lesions included four giant middle cerebral artery (MCA) aneurysms, one giant anterior communicating artery aneurysm, six giant posterior cerebral artery aneurysms, one posterior inferior cerebellar artery aneurysm, one giant mid-basilar artery aneurysm, two giant fusiform basilar artery aneurysms, and one dissecting vertebral artery aneurysm. One of the 16 patients failed an MCA test occlusion and was approached surgically after attempted endovascular selective occlusion. Treatment involved pretreatment evaluation of cerebral blood flow followed by a preliminary parent vessel test occlusion under neuroleptic analgesia with vigilant neurological monitoring. If the test occlusion was tolerated, it was immediately followed by permanent occlusion of the parent vessel with either detachable or nondetachable balloon or coils. The follow-up period ranged from 1 to 8 years. Excellent outcomes were obtained in 12 cases with complete angiographic obliteration of the aneurysm and no new neurological deficits and/or improvement of the preembolization symptoms. Four patients died: two related to the procedure, one secondary to rupture of another untreated aneurysm, and the fourth from a postoperative MCA thrombosis after having failed endovascular test occlusion. The angiographic, clinical, and cerebral blood flow criteria for occlusion tolerance are discussed.

Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations.

OBJECT: To date, both arteriovenous malformations (AVMs) and cavernomas have been considered to be congenital malformations. A recent survey of the literature has shown the potential for de novo generation of both familial and sporadic cavernomas as well as AVMs. Therefore, it was of interest to determine the biological behavior of these lesions in detail. METHODS: The proliferative and angiogenic capacities of the endothelium of 13 cavernomas and 25 AVMs obtained in patients recently treated (1997-1998) at one institution were studied. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), MIB-1, and vascular endothelial growth factor (VEGF) and its receptor Flk-1 was performed using standard staining procedures. Positive immunostaining of the nuclei of endothelial cells was observed in specimens of both AVMs and cavernomas for PCNA (80% of AVMs and 85% of cavernomas), and Flk-1 (80% of AVMs and 31% of cavernomas). Endothelial expression of VEGF in the 18 incompletely embolized AVMs was found in 72% of cases but only in 28% of the seven cases in which patients did not undergo endovascular treatment: it was found in 38% of cavernomas. Endothelial expression of MIB-1 was found in 12% of AVMs but in no cavernomas. CONCLUSIONS: These results indicate that there is endothelial proliferation as well as neoangiogenesis in cerebral cavernomas and AVMs. The increased level of angiogenesis in only partially obliterated AVMs underscores the need for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.

Haemodynamic changes in arteriovenous malformations induced by superselective embolization: transcranial Doppler evaluation.

To reduce the intraoperative and postoperative complications in patients who suffer intracerebral arteriovenous malformations (AVM's), the slow reduction of the shunt flow to a brain perfusion flow has been tried by the use of several methods: microsurgical techniques, selective and superselective embolization, intraoperative embolization, staged operation. The risk of re-bleeding and intraoperative oedema increases in AVM's with two or more feeders. Our policy was to exclude such AVM's by primary superselective embolization. If there was only a small residual angioma, we tried to remove this by microsurgical techniques. The haemodynamics in AVM's could be examined by measuring the blood flow velocities in the feeding arteries and in the other parts of the circle of Willis by transcranial Doppler sonography (TCD). Signs of haemodynamic effective embolization could be measured by the reduction of flow velocities. After exclusion of an AVM the velocities in the brain and feeding arteries decreased to below normal values in the first days after the operation. In the feeding arteries this was due to the fact that the arteries were enlarged so that the velocity must be decreased when there was normal volume flow. The combination of superselective angiography and microsurgical resection of the residual angioma seemed to be the best way to treat AVM's which are fed by more than two arteries and which are 3 or more cm in diameter. TCD investigations were used to measure the haemodynamic changes before and after angioma superselective embolization and microsurgical operation.