Subarachnoid haemorrhage from the rupture of two intracranial aneurysms in the same day: a rare occurrence, not a myth.

The incidence of intracranial aneurysms is approximately 6% throughout the world, although it can be more prevalent in some populations than others. Subarachnoid haemorrhage from a single aneurysm rupture can be devastating, with approximately 35% of patients not regaining consciousness after the initial bleed. In some cases, patients will have two or more aneurysms at presentation, and only one of them will have bled. Having two or more aneurysms that have bled within a few minutes or few hours of one another, is almost unheard of. Our case report is based on a patient who presented with subarachnoid haemorrhage from two ruptured aneurysms, confirmed intraoperatively and corroborated by the available, preoperative, standard head CT scan, which can be performed in any hospital with CT scanning facilities, and CT angiogram.

[RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT INTERNATIONAL TRENDS]. / AZ INTRACEREBRALIS CAVERNOMÁK SUGÁRSEBÉSZETE--HOL TART MA A VILÁG?

Although still a controversial management option, radio-surgery of intracranial cavernomas has become increasingly popular world-wide during the last decade. Microsurgery is a safe and effective treatment for symptomatic hemispheric cavernomas. However, the indication for microsurgical resection of deep eloquent cavernomas is relatively limited even in experienced hands. The importance of radiosurgery has recently been appreciated in parallel with increasing positive experiences both in terms of effectiveness and safety, especially for cases high risk for surgical resection, in the brainstem, thalamus and basal ganglia. While radiosurgery was earlier indicated mainly for surgically inaccessible lesions that had bled multiple times, a more proactive policy has recently become more accepted. In our opinion preventive treatment with the low morbidity radiosurgery serves the patients' interest especially for deep eloquent lesions that had bled not more than once, due to the cumulative morbidity of repeated hemorrhages. Despite our increasing knowledge on natural history, there is currently no available treatment algorithm for cavernomas. Arguments for all three treatment modalities (observation, microsurgery and radiosurgery) are established, but their indication criteria are yet to be defined. It is time to organize a prospective population based data collection in Hungary, which appears to be the most realistic way to clarify indication criteria.

[Tailored cranioplasty using CAD-CAM technology]. / Személyre szabott koponyacsontpótlások CAD-CAM technológia felhasználásával.

OBJECTIVE: The majority of cranial defects are results of surgical intervention. The defect must be covered within resonable period of time usually after 4-6 week given the fact that the replacement of bone improve the brain circulation. Number of surgical techniques and materials are available to perform cranioplasty. Due to favorable properties we chosed ultra high molecular weight polyethylene as material. In this paper the authors show a procedure which allows tailored artificial bone replacement using state of art medical and engineering techniques. METHODS: between 2004 and 2012, 19 patients were operated on cranial bone defect and a total of 22 3D custom-designed implants were implanted. The average age of patients was 35.4 years. In 12 patients we performed primary cranioplasty, while seven patients had the replacement at least once. Later the implants had to be removed due to infection or other causes (bone necrosis, fracture). All patients had native and bone-windowed 1 mm resolution CT. The 3D design was made using the original CT images and with design program. Computer controlled lathe was used to prepare a precise-fitting model. During surgery, the defect was exposed and the implant was fixed to normal bone using mini titanium plates and screws. All of our patients had control CT at 3, 6 and 12 months after surgery and at the same time neurological examination. RESULTS: Twenty-one polyethylene and one titanium implants were inserted. The average follow-up of the patients was 21.5 months, ranged from two to 96 months. We follow 12 patients (63.15%) more than one year. No intraoperative implant modifications had to be made. Each of the 22 implant exactly matched the bone defect proved by CT scan. No one of our patients reported aesthetic problems and we did not notice any kind of aesthetic complication. We had short term complication in three cases due to cranioplasty, subdural, epidural haemorrhage and skin defect. CONCLUSION: Polyethylene is in all respects suitable for primary and secondary cranioplasty. Combined with 3D CAD- CAM method excellent aesthetic and functional result was achieved. In our study no case of infection occured. Proper preoperative preparation is important.

Morphological observations in brain arteriovenous malformations after gamma knife radiosurgery.

Morphological studies after Gamma Knife radiosurgery (GKRS) revealed endothelial destruction followed by spindle-shaped cell proliferation in the subendothelial region and in the connective tissue stroma of arteriovenous malformation (AVM) vessels. Histological, immunohistochemical and ultrastructural characteristics of this spindle-shaped cell population in the irradiated AVMs were reminiscent of those described as myofibroblasts in wound healing processes and pathological fibromatoses. These modified fibroblasts have contractile capacity, therefore this might contribute to the vessel occlusion, shrinking process and final volume reduction of AVMs after GKRS. Similar histopathological changes were observed in a cavernous malformation following high-dose irradiation.

Stereotactic radiosurgery for arteriovenous malformations located in deep critical regions.

BACKGROUND: Radiosurgery is widely used to treat deep eloquent arteriovenous malformations (AVMs). OBJECTIVE: To evaluate how anatomic location, AVM size, and treatment parameters define outcome. METHODS: Retrospective analysis of 356 thalamic/basal ganglia and 160 brainstem AVMs treated with gamma knife radiosurgery. RESULTS: Median volume was 2 cm (range, 0.02-50) for supratentorial and 0.5 cm (range, 0.01-40) for brainstem AVMs; the marginal treatment doses were 17.5 to 25 Gy. After single treatment, obliteration was achieved in 65% of the brainstem, in 69% of the supratentorial, and 40% of the peritectal AVMs. Obliteration of lesions <4 cm was better in the brainstem (70%) and in the supratentorium (80%), but not in the peritectal region (40%). Complications were rare (6%-15%) and mild (≤ modified Rankin scale [MRS] 2). Rebleed rate increased with size, but was not higher than before treatment. AVMs >4 cm in the brainstem were treated with unacceptable morbidity and low cure rate. Obliteration of large supratentorial AVMs was 65% to 47% with more complications ≥ MRS3. Repeat radiosurgical treatment led to obliteration in 66% of the cases with minor morbidity. CONCLUSION: Deep eloquent AVMs <4 cm can be treated safely and effectively with radiosurgery. Obliteration of peritectal AVMs is significantly lower after a single treatment. However, morbidity is low, and repeat treatment leads to good obliteration. Radiosurgical treatment >4 cm in the brainstem is not recommended. Supratentorial deep AVMs >8 cm can be treated with radiosurgery with higher risk and lower obliteration rate. However, these lesions are difficult to treat with other treatment modalities, and a 50% success rate makes radiosurgery a good alternative even in this challenging group.

Pathological considerations to irradiation of cavernous malformations.

Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous malformations (CVMs). Systematic pathological studies of irradiated specimens probably could help to resolve the controversy. Light microscopic investigation of a surgically resected thalamic CVM 1 year after 40-Gy irradiation revealed endothelial cell destruction in the cavernous channels, and marked fibrosis with scar tissue formation in the connective stroma of the lesion. These histopathological findings were similar to those described in arteriovenous malformations after Gamma Knife surgery, and suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CVMs as well.

Physiological and pathological observations on rat middle cerebral arteries and human AVM tissue cultures following single high-dose gamma irradiation.

In vitro isometric myograph and histopathological studies were performed on rat middle cerebral arteries (MCAs) to explore changes in contractile capacity following experimental Gamma Knife radiosurgery. Right MCAs were treated with 25 Gy and 50 Gy at the 50% isodose line, while contralateral vessels received 15 Gy and 20 Gy at the 20% isodose region. Survival period varied from 3 to 18 months. Reduction in contractile capacity of irradiated normal rat MCAs was detected but their lumina remained patent. In another study, we investigated human AVM tissue cultures in order to detect genetic and phenotypic modifications contributing to vessel occlusion after irradiation. In culture, the proliferation index decreased considerably following 15-, 20-, 25- or 50-Gy irradiation at the 5th posttreatment day and remained depressed during the observation period of 14 days. P53, p21Waf-1 and mdm-2 mRNA contents were elevated significantly after irradiation, indicating enhanced apoptosis. Immunohistochemistry revealed vigorous vimentin positivity in the nonirradiated control AVM cultures, which gradually decreased by the time in the irradiated specimens. Smooth muscle alpha-actin positivity was prominent in the irradiated cultivated samples, suggesting transformation of resting fibroblasts onto activated myofibroblastic elements with contractile capacity. This transformation process was confirmed by the appearance of TGF-Beta in the irradiated AVM cell lines also. These data support the hypothesis that one of the contributing factors to AVM shrinkage and obliteration after radiosurgery might be fibrocyte-myofibroblastic cell transformation in the vessel wall.

Radiosurgery of isolated cerebral vessels following administration of paclitaxel in the rat.

OBJECT: Progressive obliteration occurs in arteriovenous malformations (AVMs) after radiosurgery; however, the risk of hemorrhage remains until the obliteration process is complete. The authors sought to enhance the radiation effect and reduce the risk of hemorrhage by facilitating faster vessel obliteration. To that end, a combination of a lower radiation dose with the addition of a radiosensitizing agent was compared with the effect of a higher radiation dose alone. METHODS: Using a method described by Mulvany and Halpern, isometric myography measurements were made on isolated rat middle cerebral artery specimens. The vessels were treated with 200 Gy, 80 Gy, 50 Gy, 25 Gy, 20 Gy, or 15 Gy by using Gamma Knife surgery. Taxol (paclitaxel 3 mg/kg/body weight) was administered intravenously to the animals. Survival times posttreatment were 24 hours, 6 weeks, 12 weeks, 12 months, or 18 months. After dissection, the middle cerebral arteries were mounted on a small-vessel myograph, and contraction and relaxation studies were performed. In a second series of experiments these results were validated in human fibroblast culture. When the cultures were 75 to 80% colonized, the samples were treated in vitro with 60Co gamma radiation in similar doses with or without paclitaxel. CONCLUSIONS: Constriction responses were generally decreased in the paclitaxel-treated vessels. Differences were significant at 6 weeks (p < 0.05) and at 1 year (p < 0.05). After 1 year, in the paclitaxel-treated groups vascular reactivity was completely abolished in vessels receiving 50 Gy. In comparison, it took 6 months longer (18 months) for this reaction to be abolished in vessels without paclitaxel treatment. In tissue cultures Giemsa staining and immunohistochemical reactions for p53, Ki-67, CD-34, and SMA antigens revealed marked fibroblast hypertrophy in all of the paclitaxel-treated groups. Paclitaxel-treated vessels demonstrated decreased reactivity at significantly earlier stages than vessels that had not been treated. It would appear that paclitaxel causes acceleration in the time course of the late biological effect of gamma radiation. This beneficial effect could be used in Gamma Knife surgery in patients with AVMs, thus reducing the risk of posttreatment hemorrhage.

Histopathological findings in a surgically resected thalamic cavernous hemangioma 1 year after 40-Gy irradiation.

Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous hemangiomas (CHs), and results vary from center to center. Even the interpretation of treatment failure is controversial. It is suggested that the systematic pathological investigation of irradiated specimens could help to resolve the controversy. A hemorrhagic lesion in the posterior part of the thalamus had been diagnosed as a tumor and was treated with 40-Gy fractionated radiotherapy. One year after this treatment the case was reconsidered based on new imaging evidence, and the lesion was removed by conventional craniotomy. Histopathological examination revealed a CH with postirradiation changes. Compared with nonirradiated control CH tissue samples, there was endothelial cell destruction and marked fibrosis with scar tissue formation in the stroma of the treated lesion. The histopathological findings in this specimen were similar to those described in arteriovenous malformations after gamma knife surgery. The results of light microscopic investigations suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CHs as well.

Ultrastructural changes in arteriovenous malformations after gamma knife surgery: an electron microscopic study.

OBJECT: The authors analyzed morphological alterations at the subcellular level by undertaking transmission electron microscopy in arteriovenous malformations (AVMs) after gamma knife surgery (GKS). METHODS: Histological, immunohistochemical, and electron microscopic investigations were performed in a series of pathological specimens obtained in seven patients. The patients harbored cerebral AVMs that had been previously treated with GKS and had suffered subsequent bleeding 10 to 52 months after treatment. Histological studies revealed spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. Electron microscopy demonstrated different ultrastructural characteristics of this spindle cell population. There were cells with a smooth-edged oval nuclei surrounded by massive bundles of collagen fibers in the extracellular matrix. Other cells with the same nuclear morphology contained abundant intracytoplasmic filaments. Nuclear deformation was connected to a fibrillary system developed within the cytoplasm, and peripheral attachment sites were related to an extracellular layer of basement membrane-like material arranged parallel to the cell border. Also present were cells containing well-developed cisterns of rough endoplasmic reticulum and dense bodies at the periphery of the cytoplasm with folded, irregular nuclei. CONCLUSIONS: The ultrastructural and histological characteristics of the spindle cell population in the GKS-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Because similar cell modifications have not been demonstrated in control nonirradiated AVM specimens, these myofibroblasts may contribute to the shrinking process and final occlusion of AVMs after radiosurgery.

[Effectiveness and safety of intraventricular fibrinolysis in secondary intraventricular hemorrhages (a prospective, randomized study)]. / Az agykamrába töro vérzések lokális fibrinolízisének biztonságossága és hatékonysága (prospektív, randomizált vizsgálat).

BACKGROUND AND PURPOSE: Intraventricular clot secondary to brain hemorrhage has still one of the worst prognosis among all stroke subtypes, regardless of conservative therapy or surgical interventions. The rapid clot resolution with thrombolytic agents could improve the outcome by restoring the impaired cerebrospinal fluid circulation, for this reason, the authors examined the safety and efficacy of Urokinase therapy in a randomized, controlled study. METHODS: They enrolled 27 patients with severe intraventricular hemorrhage between 1998 and 2002. All patients had supratentorial intracerebral hemorrhage caused by hypertension, with IVH, moreover clinically worsening course due to the obstructive hydrocephalus confirmed by CT. Eleven persons were treated with ventriculostomy alone and 16 received adjunctive intraventricular urokinase. The authors examined the early, 30-day and 1-year mortality, furthermore the neurological (Scandinavian Stroke Scale) and functional outcome (Barthel Scale). The mean age was 60 +/- 9.5. The initial Scandinavian Stroke Scale was 7.51 +/- 8.64, Glasgow Coma Scale was 6.85 +/- 2.52, intracerebral hemorrhage volume was 22.44 +/- 18.14 ml. RESULTS: The 1 year survival rate was significant higher in the urokinase treated group (p = 0.014), This tendency in the mortality (31.3% vs. 54.5%) and in the neurological/functional condition (SSS, p = 0.078/Barthel, p = 0.119) at 30th day have been also documented. No hemorrhagic complications due to urokinase were observed. Two meningitis (7.4%) and two intraparenchymal hemorrhages (7.4%) related to drain insertion were detected (p = 0.009). The probability of pulmonary infection was roughly two times higher in the group without clot lysis (RR = 1.870; 95% CI: 1.004-3.482). CONCLUSIONS: In the authors experience, urokinase treatment reveals to be safe in the intraventricular clot lysis. This therapy allows earlier mobilization and rehabilitation, and decreases the number of infections, which are favorable to the long-term survival rate.

[New methods of intensive therapy in stroke: hemicraniectomy in patients with complete middle cerebral artery infarction and treatment of intracerebral and intraventricular hemorrhage with urokinase]. / Uj módszerek a stroke intenzív terápiájában: hemicraniectomia ischaemiás stroke-ban, valamint az intracerebralis és az intraventricularis vérzés kezelése urokinázzal.

Life-threatening, complete middle cerebral artery infarction occurs in up to 10% of all stroke patients. The "malignant media occlusion" is an infarction occupying more than 50% of middle cerebral artery territory. The malignant, space-occupying supratentorial ischemic stroke is characterised by a mortality rate of up to 80%. Several reports indicate, that hemicraniectomy in this situation can be life-saving. Hemicraniectomy increases cerebral perfusion pressure and optimises retrograde perfusion via the leptomeningeal collateral vessels. A case of a patient is presented, having progressive neurological deterioration due to massive cerebral infarctions. The patient rehabilitation was successful. Decompressive surgery is life saving and can also give acceptable functional recovery. Hemorrhagic stroke is due to stroke in 15% of cases and in 10%, it is "spontaneous" intracerebral hematoma. The intracerebral and intraventricular hemorrhage represents one of the most devastating types of stroke associated with high morbidity and mortality. The 30-day mortality rate is 35% to 50% and most survivors are left with a neurological disability. The value of surgical therapy is debatable. The aspiration and urokinase therapy of the hematoma of intracerebral hemorrhage could improve final neurological outcome. Spontaneous, nontraumatic intraventricular hemorrhage frequently carries a grave prognosis. A large part of morbidity after intraventricular hemorrhage is related to intracranial hypertension from hydrocephalus. One patient presented had intracerebral hemorrhage and another had intraventricular hemorrhage treated with urokinase. Rapid and extensive reduction in the amount of intracerebral and intraventricular blood occurred. Urokinase lysis is safe and can be a potentially beneficial intervention in intracerebral and intraventricular hemorrhage. By performing decompressive craniectomy, the neurologists of stroke departments and intensive care units with the neurosurgeons will have to play major role in the management of stroke patients.

Experimental stereotactic gamma knife radiosurgery. Vascular contractility studies of the rat middle cerebral artery after chronic survival.

In vitro isometric small vessel myograph experiments and pathological investigations were performed on rat middle cerebral arteries. Thirty-four animals provided 68 normal vessels, six further rats had the endothelial layer mechanically removed from their 12 arteries. Eighteen animals received gamma knife irradiation to the middle cerebral arteries. Fifteen of these received 50 Gray, and three 25 Gray dose to the 50% isodose and the contralateral vessels offered 20 Gray and 15 Gray irradiated specimens. Survival times varied from 12 weeks to 18 months. In the acute stage, abolition of potassium-induced relaxation occurred as early as 24 h after irradiation whilst in one year this reaction seemed to recover and remained active to 18 months. The contraction response to prostaglandin F2 alpha was diminished at six weeks in the 50 Gray-irradiated vessels. However, from one year further reduction was seen and by 18 months this response was totally abolished. We demonstrated reduction of contractile capability of the irradiated normal vessels while the vessels remained patent. When using low irradiation dose there were no pathological changes even at 18 months, but marked physiological changes could be demonstrated. Different vessel wall functions appear to have different radiosensitivity, time course and capability for regeneration.

Effect of a single high-dose gamma irradiation on cultured cells in human cerebral arteriovenous malformation.

OBJECT: The purpose of this study was to analyze the effect of single high-dose gamma irradiation at a cellular biological level on tissue cultures obtained in patients who underwent surgery for cerebral arteriovenous malformation (AVM). METHODS: The cell proliferation indices and changes in activation of p53, p21Waf-1, and mdm-2 were determined. Additionally, immunohistochemical investigations for vimentin, desmin, alpha-smooth muscle actin (alpha-SMA), glial fibrillary acidic protein, Factor VIII-related antigen (F-VIII), cytokeratin, S100, and transforming growth factor-beta (TGFbeta) were performed on cultured AVM cells after a single high-dose irradiation. Normal human brain microvessel endothelial (HBE) cells and aortic smooth muscle cells served as controls. The proliferation index decreased on the 5th day after irradiation and remained depressed over the observation period in the irradiated AVM cultures. The p53, p21Waf-1, and mdm-2 messenger RNA measurements showed considerable elevation both in AVM cultures and HBE cells after 15-Gy irradiation, which indicated apoptosis. Immunohistochemistry revealed strong vimentin positivity in the nonirradiated cultures, which gradually decreased in the irradiated cultures. Transforming growth factor-beta positivity was demonstrated in the irradiated specimens, indicating transformation of fibroblastic cells into activated myofibroblastic elements. This transformation was confirmed by demonstrating elevated SMA expression as well in the radiation-treated fibroblasts. CONCLUSIONS: The presence of TGFbeta and alpha-SMA activity in the irradiated AVM cells suggests that along with the genetically confirmed apoptotic activity, fibroblast transformation into myofibroblasts might be one of the mechanisms leading to shrinkage and obliteration of AVMs after single high-dose gamma irradiation.