Endovascular glue embolization of a radiation-induced lenticulostriate artery pseudoaneurysm in a pediatric patient with optic pathway glioma: Case report and review of literature.

Radiation-associated vascular changes most commonly present in the form of stenosis, thrombosis and occlusion. However, development of intracranial aneurysms secondary to radiation is far less common and often manifests with rupture. These aneurysms are difficult to treat and associated with high morbidity and mortality when ruptured compared with saccular aneurysms unrelated to radiation treatment. Both surgical and endovascular options are available for treatment of these aneurysms. We present a young patient with a radiation-induced intracranial pseudoaneurysm arising from the lenticulostriate branch of the left middle cerebral artery (MCA); this developed 1 year 4 months after 59.4 Gy of focused radiation to the suprasellar pilomyxoid astrocytoma. The patient successfully underwent endovascular glue embolization of the aneurysm and occlusion of the lenticulostriate artery after unsuccessful trapping of the aneurysm and occlusion of the parent artery using coils. She developed transient hemiparesis of the right side following the procedure, which was managed conservatively. We performed a complete review of the literature dealing with the radiation-induced intracranial aneurysms, their presentation, treatment and outcome.

A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN) were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT) and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs), internal carotid arteries (ICAs) and basal artery (BA) were estimated through Transcranial Color Doppler (TCD). The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05). IMT had positive correlation with post radiation interval (p = 0.049). Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001). Plaques were more common in patients with TLN than patients without TLN (p = 0.038). In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001). Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001). CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

Lacunar stroke attributable to radiation-induced intracranial arteriopathy.

We report the rare presentation of lacunar stroke syndrome secondary to single perforator mouth occlusion from radiation-induced middle cerebral artery (MCA) stem arteriopathy. A 30-year-old female had acute-onset right-sided ataxic hemiparesis and dysarthria. As a child, she had a medulloblastoma of the posterior fossa and had surgery followed by cranial radiotherapy. She had no significant vascular risk factors. Acute CT showed extensive bilateral basal ganglia and left thalamic calcification; DWI showed a left internal capsule lacunar infarct; and MRA and CTA showed a 50% stenosis of the proximal left MCA.

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.

Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice.

Recent advances in genetical engineering of the mouse have highlighted the importance of reproducible and less invasive models of cerebral ischemia in mice. In this paper, we developed minimally invasive and reproducible model of distal middle cerebral artery (MCA) occlusion in mice using krypton (Kr) laser-induced photothrombosis. C57BL/6 or BALB mice (n=8 each) were anesthetized with halothane. The skin was cut, the temporal muscle was retracted, and the right distal MCA was observed through the skull. A Kr laser beam of wavelength 568 nm was focused onto the MCA over the intact skull. Upon laser irradiation, intravenous administration of a rose bengal solution was begun. After 4 min of irradiation, the laser beam was refocused on the MCA just proximal to the first spot, and another 4-min irradiation was performed. Then, the right common carotid artery (CCA) was ligated. Three days later, the brain was removed, and infarct volume was determined. Infarction confined almost solely to the cortical area was produced in each mouse. Mean infarct volume in C57BL/6 mice was 25.2+/-13.7 mm3. The BALB mice group showed significantly larger and more reproducible infarction (44.1+/-5.2 mm3; the coefficient of variation was 12%) than did C57BL/6 mice (P<0.005). Our photothrombosis model of stroke in mice can be performed without craniectomy, and its reproducibility is satisfactory when using BALB mice.

Cerebral hemorrhagic infarction after radiation for pituitary adenoma.

We report a case of cerebral hemorrhagic infarction after radiation for pituitary adenoma. A 55-year-old woman was hospitalized to check for aldosteronism, post-operative pituitary function, and recurrence of thyroid cancer. She had short-term memory disturbance beginning two months prior to admission. Brain MRI showed a T1 and T2 high intensity lesion of her left anterolateral thalamus. Brain MRA revealed a narrowing in her left middle cerebral artery. The abnormal brain lesion was diagnosed as cerebral hemorrhagic infarction. She had received radiation therapy for pituitary adenoma 20 years earlier. It was considered that her cerebral hemorrhagic infarction was caused by radiation therapy.

Treatment of experimentally induced transient cerebral ischemia with low energy laser inhibits nitric oxide synthase activity and up-regulates the expression of transforming growth factor-beta 1.

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been shown to be neurotoxic while transforming growth factor-beta 1 (TGF-beta1) is neuroprotective in the stroke model. The present study investigates the effects of low energy laser on nitric oxide synthase (NOS) and TGF-beta1 activities after cerebral ischemia and reperfusion injury. STUDY DESIGN/MATERIALS AND METHODS: Cerebral ischemia was induced for 1 hour in male adult Sprague-Dawley (S.D.) rats with unilateral occlusion of middle cerebral artery (MCAO). Low energy laser irradiation was then applied to the cerebrum at different durations (1, 5, or 10 minutes). The activity of NOS and the expression of TGF-beta1 were evaluated in groups with different durations of laser irradiation. RESULTS: After ischemia, the activity of NOS was gradually increased from day 3, became significantly higher from day 4 to 6 (P < 0.001), but returned to the normal level after day 7. The activity and expression of the three isoforms of NOS were significantly suppressed (P < 0.001) to different extents after laser irradiation. In addition, laser irradiation was shown to trigger the expression of TGF-beta1 (P < 0.001). CONCLUSIONS: Low energy laser could suppress the activity of NOS and up-regulate the expression of TGF-beta1 after stroke in rats.

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.

Prospective value of perfusion and X-ray attenuation imaging with single-photon emission and transmission computed tomography in acute cerebral ischemia.

BACKGROUND AND PURPOSE: The aim of the present study was to test the hypothesis that perfusion single-photon emission computed tomography (SPECT), carried out in addition to transmission computed tomography (TCT), improves the predictive value of brain imaging within the therapeutically relevant time window after acute cerebral ischemia. METHODS: Using TCT and [(99m)Tc]ethyl cysteinate dimer (ECD)-SPECT within 6 hours after symptom onset, we examined 108 patients (44 women, 64 men; mean age 65+/-13 years) with acute ischemic stroke attributed to the territory of the middle cerebral artery (MCA). In each case, 3 experts prospectively evaluated the early SPECT and TCT images. We correlated these ratings with follow-up TCT findings for the final infarction as well as with clinical outcome (Scandinavian Stroke Scale, Barthel Index, Modified Rankin Scale) after 30 and 90 days. RESULTS: Severe activity deficits on SPECT, not caused by local atrophy on TCT, were the best predictors (positive predictive value [PPV ]94%, 95% CI 89% to 99%; negative predictive value [NPV] 90%, 95% CI 78% to 100%; P<0.001) for evolving cerebral infarction. Complete MCA infarctions were predicted with significantly higher accuracy with early SPECT (area under receiver operating characteristic curve [AUC] index 0.91) compared with early TCT (AUC index 0.77) and clinical parameters (AUC index 0.73, P<0.05). Logistic regression analysis revealed 1 independent predictor for completed MCA territory infarction: SPECT activity deficits in the corresponding areas (PPV 88%, 95% CI 65% to 100%; NPV 96%, 95% CI 92% to 100%; P<0.001). Furthermore, death after stroke was optimally predicted by [(99m)Tc]ECD-SPECT. Clinical outcome up to 90 days after the stroke event best correlated with the degree of activity deficits in early SPECT (r=0.53, P<0.001). CONCLUSIONS: [(99m)Tc]ECD brain perfusion SPECT that completes TCT definitely improves the predictive value of brain imaging after acute cerebral ischemia. Thus, the combined imaging of brain edema and of cerebral perfusion early after stroke is recommended for clinical use.

Radiation-induced cerebrovasculopathy of the distal middle cerebral artery and distal posterior cerebral artery--case report.

A 15-year-old girl underwent partial removal of a pituitary adenoma followed by local irradiation of the brain with a total of 70 Gy through two lateral opposing ports. Twenty years later, she experienced frequent transient ischemic attacks with left sensory disturbance. Cerebral angiography revealed stenoses of the right distal middle cerebral artery (MCA) and the right distal posterior cerebral artery without net-like vessels. There was a severe decrease of vasoreactivity in the right hemisphere. Right superficial temporal artery (STA)-MCA anastomosis was performed. Her neurological deficits were resolved and perfusion reserve capacity had markedly improved 6 months later. We recommend STA-MCA anastomosis in such cases.