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The authors present a case of atlantoaxial instability associated with C1-C2 inflammatory tissue leading to subarachnoid hemorrhage. A 65-year-old male patient arrived in June 2011 to the emergency unit for cervical pain and fever. Imaging studies documented periodontoid pseudotumor at C1-C2 level. Infective disease was suspected; the patient was therefore hospitalized and treated with antibiotics. Subsequent computed tomographic (CT) scans revealed C1-C2 instability. In August, the patient showed acute neurological deterioration and coma. Urgent brain CT revealed a hemorrhagic lesion which caused compression on the medulla oblongata, subarachnoid hemorrhage, and ventricular dilatation. An external ventricular drainage was positioned. Angio-CT and angiography did not show any vascular abnormalities. Cervical magnetic resonance imaging documented a solid tissue lesion between the atlas arch and axis. The lesion was associated with an epidural and subdural hematoma, exerting compression on brainstem. The patient underwent posterior decompression and C1-C2 fusion according to Harms technique in October, with significant clinical improvement. The authors present a case of atlantoaxial instability associated with a periodontoid pseudotumor at C1-C2 level determining dural sac compression. The patient showed an acute neurological deterioration caused by bleeding of the solid component of the cervical lesion. Hemorrhage of the solid component of periodontoid masses linked to atlantoaxial instability has not yet been reported in literature. To the best of our knowledge, this is the first case of C1-C2 instability with periodontoid pseudotumor leading to subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper is to report the results of our review of the literature of published cases of intracranial aneurysms appearing after radiotherapy, and to present our case to add it to the current literature, in order to discuss the role of inflammation., Methods: We searched the PubMed database using combinations of the following MeSH terms: intracranial aneurysm, radiosurgery, radiotherapy, inflammatory changes in aneurysmal walls from 1967 to 2019., Results: 51 studies, for a total cohort of 60 patients, are described. The median latency between the radiation treatment and the diagnosis was 9,83 years, ranging from a minimum of 0,33 to a maximum of 33. The modality of rays' administration was variable, and the dosage ranged from a minimum of 12 grays to a maximum of 177,2 grays. The anterior circulation appeared to be more frequently involved, and the most compromised vessel was the internal carotid artery. Radiation-induced vascular diseases have already been described in literature as well as RT-induced cellular and structural changes such as necrosis, macrophage or mononuclear cell infiltration, and several data support the role of inflammation in the development and remodelling of intracranial aneurysms, that, on one hand, favours them and, on the other, is necessary to their healing after endovascular treatment., Conclusions: Our team suggested a new insight in the management of these vascular lesions, which corresponds to a lower threshold when deciding whether or not to treat, and a longer and stricter follow-up.

The systemic administration of endogenous inhibitors significantly reduced the growth of human glioma in vivo, but required the production of a large amount of biologically active protein. In this study we reduced the amount of protein needed and optimized the therapeutical response by delivering the endogenous inhibitors locally into the brain by osmotic minipumps. Human hemopexin fragment of MMP-2 or COOH-terminal fragment of platelet factor-4 were delivered locally and continuously into the brain of mice implanted intracranially with glioma cells, by osmotic minipumps connected to an intracranial catheter. Local delivery of human hemopexin fragment of MMP-2 and COOH-terminal fragment of platelet factor-4 significantly inhibited the growth of well-established malignant glioma in nude and BALB/C mice. When the inhibitors were given at the same concentration, the efficacy of the local delivery was much higher than that reached with the systemic administration, both when the inhibitor was administered daily or continuously by s.c. minipumps. Moreover, the local delivery reduced the amount of protein needed to reach a significant therapeutic response. Intracerebral delivery maintained a long-term control of glioma growth and inhibited glioma recurrence in a surgical resection model. Treatment showed no side effects. Histochemical analysis of tumors showed that the tumor growth inhibition was the result of a decrease in tumor vasculature and a change in tumor vessel morphology. Our data demonstrate that local intracerebral delivery of endogenous inhibitors effectively inhibits malignant glioma growth and reduces the amount of protein needed to reach a therapeutical response.

A few peptide residues in structurally important locations often determine biological functions of proteins implicated in the regulation of angiogenesis. We have shown recently that the short COOH-terminal segment PF-4(47-70) derived from platelet factor 4 (PF-4) is the smallest sequence that conserves potent antiangiogenic activity in vitro and in vivo. Here we show that modified COOH-terminal PF-4 peptides containing the sequence ELR (or related DLR), a critical domain present in proangiogenic chemokines, surprisingly elicit several times greater antiangiogenic potential than the original peptide. The modified peptides inhibit binding of iodinated vascular endothelial growth factor and fibroblast growth factor 2 to endothelial cell receptors, endothelial cell proliferation, migration, and microvessel assembly in the rat aortic ring model at lower doses than PF-4(47-70). On the differentiated chick chorioallantoic membrane, topical application of 40 micro g of modified peptides potently reduces capillary angiogenesis induced by vascular endothelial growth factor(165), a dose where peptide PF-4(47-70) was inactive. Established intracranial glioma in nude mice decreased significantly in size when treated locally with a total dose of 250 micro g of peptide PF-4(47-70)DLR (n = 10) compared with the same dose of the original PF-4(47-70) peptide (n = 10) or controls (n = 30). Tailored PF-4 peptides represent a new class of antiangiogenic agents with a defined mode of action and a strong in vivo activity.

Glioma recurrences develop at the borders of the surgical cavity and are the main cause of their poor prognosis. There are no therapeutic advances to reduce the incidence of recurrence or animal models that closely mimic the clinical scenario to evaluate novel therapeutics. This work investigates the efficacy of endogenous inhibitors, in preventing the recurrence of human malignant gliomas, in a newly developed animal model of glioma surgical resection. We developed a nude mice model in which human glioma xenografts were microsurgically removed. After surgery, small islets of tumor cells persisted in the normal brain parenchyma, grew, and formed a recurrence. As inhibitors we used PEX and a fragment of platelet factor 4 (PF-4/CTF), which were administered systemically on a daily basis or in metronomic combination with chemotherapy for 120 days. Treatment was started 1 or 15 days after tumor removal. PEX or PF-4/CTF produced a significant improvement in survival, and delayed the appearance of glioma recurrence. Survival of animals that received daily PEX or PF-4/CTF was similar to that of animals that received metronomic PEX or PF-4/CTF and chemotherapy, respectively. The effect of treatment was dependent on the time at which the treatment was initiated. The highest level of inhibition was observed when the treatment was administered 1 day after surgical resection and when PEX was used as the inhibitor (120 days versus 35 days of the control). Tumors treated with PEX or PF-4/CTF were small and well delineated, with few vessels. Postsurgical administration of PEX or PF-4/CTF significantly reduces the incidence human malignant glioma recurrences for a long period of time.