The management of arteriovenous malformations.

Arteriovenous malformations (AVM) can occur in the entire central nervous system with a predilection of the supratentorial intracranial compartment. Intracerebral hemorrhage is the most common clinical presentation of AVM and associated with a high morbidity and mortality rate. Correct management of these lesions is therefore of utmost importance. In this review, the authors present actual diagnostic and interdisciplinary treatment modalities based on their experience in a major neurovascular center and taking into consideration actual literature data. Different treatment strategies are discussed.

Is Histologic Thrombus Composition in Acute Stroke Linked to Stroke Etiology or to Interventional Parameters?

BACKGROUND AND PURPOSE: Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results. MATERIALS AND METHODS: Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate. RESULTS: Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis (P = .021 and .003) or the embolic stroke of undetermined source (P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval (P = .021) and were associated with an increased number of retrieving maneuvers (P = .001), longer procedural times (P = .001), and a higher lymphocyte content (P = .035). CONCLUSIONS: We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi.

Endovascular treatment resolves non-hemorrhagic brainstem dysfunction due to tentorial dural AV fistula.

Tentorial dural arteriovenous fistulas (tDAVF) clinically present usually with subarachnoid and/or intraparenchymal hemorrhage. Reported rates range from 58% to 92% and neurological deficits occur in 79% to 92% of patients. This is due to venous congestion resulting from retrograde leptomeningeal venous drainage, which rarely, can be clinically silent. A 69-year-old woman presented with vertigo, double vision and gait instability. Cerebral digital subtraction angiography revealed a tDAVF with retrograde cerebellar venous drainage directed through the vein of Galen into the straight sinus. MRI showed extensive cerebellar edema due to venous congestion. Clinical manifestations of cerebellar and brainstem dysfunction resolved completely after transarterial embolization with N-butylcyanoacrylate.

[Embolization of life-threatening intercostal hemorrhaging in a severely injured patient: a rarity in trauma care]. / Embolisation einer lebensbedrohlichen Interkostalblutung bei einem Schwerstverletzten : Eine Rarität in der Traumaversorgung.

Transarterial embolization of ruptured intercostal arteries due to massive bleeding represents an infrequent indication in severely injured patients. The current literature shows isolated case descriptions but no clinical trials exist. In the case depicted here embolization is represented as a form of therapy after haemorrhagic shock caused by a ruptured intercostal artery. The embolization carried out led to an immediate cessation of bleeding. The vital signs returned to normal immediately after the procedure and surgical intervention could be avoided. The course of the disease represented in the following shows the effectiveness of this type of treatment not only for bleeding due to pelvic fractures and abdominal injuries, but also for isolated arterial bleeding in other body regions.

[Endovascular treatment of epistaxis of the internal carotid artery. Vessel occlusion and vessel preservation]. / Endovaskuläre Therapie bei Epistaxis aus der A. carotis interna: Gefässrekonstruktive und gefässverschliessende Verfahren.

Epistaxis can become an ENT emergency situation. In most patients the bleeding source are branches of the external carotid artery. Hemorrhage of the internal carotid artery is very rare and can be due to inflammatory disease, trauma, or iatrogenic laceration of the ICA during endonasal surgery. Depiction of the bleeding source with radiological methods (computed tomography with contrast enhancement and conventional angiography) is crucial to avoid fatal complications. We report three cases with life-threatening epistaxis in whom bleeding was stopped with endovascular treatment alone.

[Cerebral MRI in neurological asymptomatic patients with malignant melanoma]. / Zerebrales MRT bei neurologisch asymptomatischen Patienten mit malignem Melanom.

PURPOSE: Detection of metastasis in the whole body is important for sufficient the staging of malignant melanoma. Sufficient imaging of the brain is particularly important. Although there is evidence that clinical examination is not sufficient for prediction of cerebral metastasis, MRI scan is not always regarded as reasonable in neurological asymptomatic patients. Therefore, we explored the incidence of cerebral metastasis in our patient population in relation to the stage of disease to estimate the reasonability of this examination. MATERIALS AND METHODS: 120 consecutive patients with malignant melanoma were retrospectively evaluated. All patients were neurologically without pathological findings and received routine staging by cranial MRI. The incidence of brain metastasis was evaluated. The examination protocol consisted of an axial orientated flair and a T 1 sequence. Ten minutes after administration of contrast agent, a T 1 sequence in axial and coronal orientation was performed using the magnetization transfer technique. The type of melanoma, the thickness of the tumor, the Clark level, the location of the primary tumor, and the clinical stage were recorded from the clinical records. RESULTS: 15 (12.5 %) of the 120 patients (clinical stage I: 27 patients, stage II: 29 patients, stage III: 25 patients, stage IV: 39 patients) had cerebral metastasis in MRI. 14 patients were in stage III or IV at this time. Consequently 21.8 % of the patients in stage III and IV had cerebral metastasis. Only one patient in stage IIc had cerebral metastasis. CONCLUSION: Cranial MRI of neurologically asymptomatic patients seems to be an important factor in the staging of melanoma especially in the advanced stage of this disease and in patients with a thick primary tumor.

Rapid intracranial clot removal with a new device: the alligator retriever.

BACKGROUND AND PURPOSE: Despite availability of an approved drug to treat acute cerebral ischemia, most patients with stroke do not realize a good outcome. A method that would rapidly increase or restore cerebral perfusion before irreversible cell death should improve patient outcomes. MATERIALS AND METHODS: We recently had the opportunity to treat 6 middle-aged-to-elderly patients who presented with signs and symptoms of acute cerebral ischemia, by mechanically removing their (predominantly) middle cerebral artery clots by using a new retrieval device that had been previously approved by the US Food and Drug Administration for intravascular retrieval of foreign bodies. During a 2-month period, the 6 patients were treated in 5 separate institutions. No patient had an unsuccessful attempt at clot removal. The cases were collected by personal communication with each operator. RESULTS: In all instances, use of the device resulted in rapid clot removal. Each patient had a large improvement in National Institutes of Health Stroke Scale score. Two of the 6 patients had experienced failure of another clot retrieval device, and 3 patients required no systemic thrombolytics, reducing the likelihood of one of the most feared complications of stroke therapy, intracranial hemorrhage. SUMMARY: We believe that use of this device may result in improved outcomes for patients with acute ischemic stroke. In our limited experience, it provided a rapid, safe, and effective means for achieving revascularization.

[Bleeding risk of intracranial vascular malformations]. / Das Risiko intrazerebraler Gefässmissbildungen.

In general, intracranial vascular malformations are divided into pial AVM, dural AV fistula, cavernoma and capillary telangiectasias. Developmental venous anomalies are sometimes thought to be vascular malformations. In fact, they are just a variant of venous drainage. In general, pial AVMs have a high risk of intracerebral bleeding. In dural AV fistulas, the individual bleeding risk can be effectively estimated by analyzing the venous drainage. Cavernomas have a low bleeding risk and the bleeding is rarely life-threatening. DVAs do not have any bleeding risk but 30 % are associated with cavernomas. Capillary telangiectasias also have no bleeding risk. Therefore, a radiological finding of an intracranial vascular malformation should not automatically elicit the reaction "time bomb in your head with a bleeding risk" but should be subjected to an analysis of the bleeding risk for the individual patient.

Endovascular treatment of middle cerebral artery aneurysms with electrolytically detachable coils.

BACKGROUND AND PURPOSE: Middle cerebral artery (MCA) aneurysms often have an unfavorable aneurysm geometry that might limit endovascular therapy. Our purpose was to analyze the feasibility, safety, and efficacy of coil embolization in a consecutive series of MCA aneurysms chosen for endovascular treatment. PATIENTS AND TECHNIQUES: Of 235 MCA aneurysms seen at our institution during the past 5 years, 36 patients harboring 38 MCA aneurysms were primarily selected for coil embolization: 18 patients had an acute subarachnoid hemorrhage (SAH), 16 of which were due to a ruptured MCA aneurysm. SAH was classified according to Hunt and Hess grade: I (5), II (7), III (5), IV (0), and V (1). RESULTS: Complete occlusion could be achieved in 33 of 38 aneurysms. In 5 aneurysms, coil embolization was not performed because of an unfavorable aneurysm geometry with a wide neck or incorporation of adjacent branches (3) or failed because of insecure coil placement (1) or severe vasospasm (1). Procedural complications included coil protrusion into the parent artery (1), and thromboembolic M2 occlusion (5), with recanalization in 4 of 5 cases. Of 8 aneurysms with initial subtotal occlusion, 3 progressed to total occlusion during follow-up. Three aneurysms had to be retreated, and no patient rebled. Glasgow Outcome Scale at 6 months for the patients with SAH (17/18) was good recovery (12), moderate disability (4), severe disability (0), persistent vegetative state (0), and death (1); outcomes for patients with an incidental aneurysm (17/18) were good recovery (16) and moderate disability (1). CONCLUSION: Endovascular coil embolization can be performed safely and effectively in selected MCA aneurysms. Initial subtotal aneurysm occlusion might progress to total occlusion.

[Reducing radiation exposure for patient and staff during interventional radiology demonstrated for coil embolisation]. / Reduzierung der Strahlenexposition für Patienten und Personal bei radiologischen Interventionen am Beispiel der Coilembolisation.

PURPOSE: Coil embolization of intracranial aneurysms is a radiographic interventional procedure associated with relatively high radiation exposure for the patient and staff. Modern angiographic fluoroscopy systems have a high potential for reducing radiation exposure of a wide bandwidth (e. g. automatic beam filtering, pulsed fluoroscopy, characteristic curve selection). The purpose of this study was to determine how those features could be implemented in the daily routine. MATERIAL AND METHODS: The radiation exposure for the patient and staff was measured during 60 coiling procedures and compared to the mean values before changing the parameters. RESULTS: Implementation of those dose-reducing features during complex radiographic procedures is limited for various reasons. A 35 % dose reduction during coil embolization was able to be achieved in our trial. CONCLUSIONS: From an economic point of view, some resources implemented by the manufacturer and included in the prime cost of the system are not being fully utilized. With some effort, instruction and further education of the staff could lead to a further reduction in radiation exposure without losing too much image quality.

Phlorizin or vanadate treatment reverses impaired expression of albumin and hepatocyte nuclear factor 1 in diabetic rats.

Diabetes decreases transcription of the albumin gene. The role of hyperglycemia in mediating this suppression of albumin gene activity is unclear. To study the effect of glucose in vivo, we treated diabetic rats with phlorizin or vanadate, two agents that ameliorate hyperglycemia without increasing the levels of circulating insulin. When glucose was normalized in diabetic rats with either agent, the hepatic levels of albumin mRNA became indistinguishable from those in nondiabetic animals. In light of our previous observation that diabetes decreases the abundance of hepatocyte nuclear factor 1 (HNF1), the predominant factor increasing albumin gene transcription, we wondered whether glucose normalization in diabetes would alter HNF1. Both the levels and DNA binding activity of HNF1 were restored to control values when phlorizin or vanadate was administered to diabetic rats. These findings suggest that hyperglycemia is integrally involved in mediating the suppression of albumin gene expression in diabetes. The effect of hyperglycemia on HNF1 suggests that glucose affects albumin expression at the level of transcription.

[Stenting plus coiling: dangerous or helpful?]. / Stenting plus Coiling bei akut rupturierten intrakraniellen Aneurysmen.

PURPOSE: The purpose of this study was to evaluate the procedural risk of treating acute ruptured aneurysms with a stent-coil combination. MATERIAL AND METHODS: Between August 2001 and January 2004 we treated nine acute subarachnoid hemorrhage (SAH) patients with a combination of stents and platinum coils. RESULTS: Six aneurysms were 100% eliminated; the residual three aneurysms had a 95% to 99% occlusion. A transient thrombosis in the stent in one patient could be recanalized by intravenous application of ReoPro. In another patient an occlusive vasospasm at the distal end of the stent was successfully treated with intraarterial Nimotop. Neurological complications occurred in none of the patients. CONCLUSION: In broad-based aneurysms which cannot be clipped or in which any neurosurgical treatment presents an unacceptably high risk (posterior circulation and paraophthalmic aneurysms), treatment using a combination of stent and platinum coils might be an option even in the acute phase of an SAH. Platelet aggregation can be treated with Aspirin and Plavix after placement of the first coil, vasospasms with intraarterial Nimotop, and acute stent thrombosis with GP IIa/IIIb-antagonists.

Evolution of purely infratentorial PML under HAART--negative outcome under rapid immune reconstitution.

Progressive multifocal leukoencephalopathy (PML) caused by the polyomavirus JC is a well-recognised complication of AIDS. Purely infratentorial manifestations are rare. Introduction of highly active antiretroviral therapy (HAART) has been associated with a reduction in morbidity and an improvement in overall survival among HIV-infected individuals. Recently, several reports have described adverse events in patients with PML who begin HAART and show evidence for immune reconstitution. We describe the clinical course of two patients with PML with purely infratentorial manifestation, whose clinical course deteriorated despite the successful introduction of HAART. Possible underlying immunological mechanisms are discussed.

Basal ganglia infarction mimicking glioblastoma.

Modern brain imaging techniques usually allow a very good differential diagnosis of intracerebral lesions, but in some cases the differential diagnosis is difficult. We report the case of a 52 year old male with acute brachiofacial paresis and a hyperintense lesion with mass effect and ring-enhancement in basal ganglia suspiciously to a tumor. The neurosurgeons recommend stereotactical brain biopsy for diagnosis, but the patient recovered in following time gradually and in repeated computer tomographic images contrast enhancement disappeared and a hypodense zone in the basal ganglia remains. Our case demonstrates that brain infarctions can mimick glioblastoma in taking cystic appearance and contrast enhancement. Stereotactic biopsy would have been a precipitated invasive procedure in this case.

The Dural AV-Fistula (DAVF), the Most Frequent Acquired Vascular Malformation of the Central Nervous System (CNS).

Acquired arteriovenous malformations, such as is the case with dural arteriovenous fistulae (DAVF), are the consequence of a pathological new arterial ingrowth into venous spaces that reaches directly the venous lumen, without interposition of a capillary network, thereby creating an AV-shunt.The following concise text will provide elements in regards to diagnosis, indication for treatment discussion and choice of endovascular treatment (EVT) method.

Benefit of second catheter angiography in patients with nontraumatic subarachnoidal hemorrhage.

PURPOSE: This study aimed to determine the yield of repetitive catheter angiography (digital subtraction angiography (DSA)) for the detection of causative vascular lesions in patients with nontraumatic subarachnoidal hemorrhage (SAH) and negative initial DSA. We hypothesize that a second DSA might be helpful to detect an initially occult bleeding source. METHODS: We retrospectively evaluated 649 patients with acute SAH and invasive catheter angiographies between 2004 and 2012. In 90 SAH patients initial imaging was negative concerning a causative bleeding source. A total of 113 repetitive DSA were performed. Two neuroradiologists reanalyzed the initial imaging and the result of the reangiography independently. RESULTS: In 4/90 patients (4.5 %) bleeding source was first detected in the second or third DSA. In all other patients, no causative vascular lesion was found. Reasons for the initially false negative diagnostics were one dissecting aneurysm and thrombosis of three aneurysms within the acute phase of SAH. CONCLUSIONS: Repetitive DSA revealed the cause of SAH in 4.5 % of the cases. These findings have a therapeutic and prognostic impact. We think that at least a second DSA should be part of diagnostic work-up in patients with SAH and missing bleeding source, even considering the risk of an additional invasive angiography itself.

Hormonal and dietary regulation of a mammalian gene introduced into rat liver by direct injection.

The difficulty of introducing foreign genes into a target tissue such as liver prompted us to explore the method of direct injection of DNA into this organ. In this article we examine whether direct hepatic injection of DNA enables the liver to express a transgene controlled by a mammalian promoter. The construct pS14CAT, composed of the rat S14 gene promoter coupled to CAT, was directly injected into rat liver. Hepatic expression of the pS14CAT transgene mimicked expression of the endogenous S14 gene, characterized by a low level of basal expression that increased markedly after exposure to thyroid hormone or a high sucrose diet. This effect was specific, since similar treatments had no effect on activity of a control transgene, pSV2CAT, which is under the direction of the viral SV40 promoter/enhancer. Dexamethasone treatment enhanced the activity of both pS14CAT or pSV2CAT transgenes, an effect likely mediated by both transcriptional and nontranscriptional pathways. In summary, our study demonstrates the feasibility of using direct DNA injection to study transcriptional regulation of hepatic gene promoters in vivo.

Receptors for vasoactive intestinal peptide in rat anterior pituitary glands: localization of binding to lactotropes.

Vasoactive intestinal peptide (VIP) has been implicated as a physiological PRL-releasing factor; however, characterization of VIP receptors on normal pituitaries using radioligand-binding methods has been problematic. In this study we demonstrated specific receptors for VIP in anterior pituitary glands of female rats using HPLC-purified monoiodinated [Tyr(125I)10]VIP. Binding of VIP was reversible, saturable to receptor and radioligand, regulated by guanine nucleotides, and dependent on time and temperature. Scatchard analysis of competitive binding studies indicated high and low affinity binding sites, with equilibrium dissociation constants (Kd) of 0.19 +/- 0.03 and 28 +/- 16 nM, respectively. The corresponding maximum numbers of binding sites were 158 +/- 34 fmol/mg and 11.7 +/- 6.9 pmol/mg. Binding was specific, as peptides with structural homology to VIP were less than 100th as potent as VIP. The rank order of potency of the peptides tested was VIP greater than rat (r) peptide histidine isoleucine = human (h) PHI greater than rGRF greater than bovine GRF = porcine PHI = VIP-(10-28) greater than hGRF greater than secretin greater than apamin greater than glucagon. Radioligand binding was associated primarily with lactotrope-enriched fractions prepared by unit gravity sedimentation of dispersed anterior pituitary cells. VIP stimulated PRL release from cultured rat anterior pituitary cells, with an ED50 of 1 nM. These results, comprising the first identification of specific VIP receptors in normal rat anterior pituitary tissue using radioligand-binding methods, provide additional support for a biological role of VIP in lactotrope function.

Developmental and lactational changes in the rat anterior pituitary VIP receptor.

The regulation of female rat anterior pituitary vasoactive intestinal peptide (VIP) receptors was examined during postnatal development and lactation. VIP receptor binding to anterior pituitary membranes from 1- to 60-week-old rats and lactating rats was examined using HPLC purified [Tyr(125I)10]VIP. Nonlinear regression of competitive binding studies indicated the presence of 2 VIP binding sites in 3-week and older animals, whereas only 1 site was identified in 1- and 2-week-old rats. The single site did not differ significantly in affinity or number when compared to the low affinity site of older animals. The guanine nucleotide, GTP-gamma-S, decreased the specific binding of VIP by 60-80% in 3-week and older animals, but not in younger animals. Compared with adult nonlactating animals, the number of high affinity binding sites decreased significantly during lactation, with no change in receptor binding affinity.

Selective effect of castration on the anterior pituitary VIP receptor of male rats.

We investigated the effect of surgical castration of male rats on the binding of [Tyr(125I)10]VIP to receptors on the anterior pituitary gland, superior mesenteric artery, brain, liver, and prostate gland. In anterior pituitary membranes the maximum number of VIP binding sites was increased whereas binding affinity was decreased 24 hours following castration. In particular, the high affinity equilibrium dissociation constant (KD) increased from 0.13 +/- 0.02 nM (mean +/- SEM) to 0.67 +/- 0.07 nM and the maximum number of high affinity binding sites (Bmax) increased from 71 +/- 9 to 470 +/- 112 fmol/mg protein. No significant change was observed in the other tissues. Anesthesia or sham operation did not alter the anterior pituitary VIP receptor binding parameters. The changes in the VIP receptor 24 hours after castration were prevented by prior injection of testosterone. These findings demonstrate tissue-selective alterations to the anterior pituitary VIP receptor by castration that are likely mediated by withdrawal of testosterone.