Eradication of LIG4-deficient glioblastoma cells by the combination of PARP inhibitor and alkylating agent.

Cancer cells often accumulate spontaneous and treatment-induced DNA damage i.e. potentially lethal DNA double strand breaks (DSBs). Targeting DSB repair mechanisms with specific inhibitors could potentially sensitize cancer cells to the toxic effect of DSBs. Current treatment for glioblastoma includes tumor resection followed by radiotherapy and/or temozolomide (TMZ) - an alkylating agent inducing DNA damage. We hypothesize that combination of PARP inhibitor (PARPi) with TMZ in glioblastoma cells displaying downregulation of DSB repair genes could trigger synthetic lethality. In our study, we observed that PARP inhibitor (BMN673) was able to specifically sensitize DNA ligase 4 (LIG4)-deprived glioblastoma cells to TMZ while normal astrocytes were not affected. LIG4 downregulation resulting in low effectiveness of DNA-PK-mediated non-homologous end-joining (D-NHEJ), which in combination with BMN673 and TMZ resulted in accumulation of lethal DSBs and specific eradication of glioblastoma cells. Restoration of the LIG4 expression caused loss of sensitivity to BMN673+TMZ. In conclusion, PARP inhibitor combined with DNA damage inducing agents can be utilized in patients with glioblastoma displaying defects in D-NHEJ.

Primary spinal cord melanoma - a case report.

Authors present a case of a 57-year-old woman with primary spinal cord malignant melanoma. Intramedullary localization of primary melanoma is extremely rare. The patient presented neurological deficits such as lower limbs paresis and sensory loss. MRI examination showed intramedullar tumor located on the Th10 vertebra level. Surgical treatment with total removal of tumor was performed. Histopathological study confirmed melanoma. Subsequent chemotherapy was given. Tumor was successfully treated by neurosurgery; radio- and chemotherapy with disease free follow up of 9 months. Surgical treatment of melanoma in this location is extremely important as it leads to regression of neurological symptoms and improvement of the quality of life.

Treatment of giant paraclinoid aneurysms. Own experience.

OBJECTIVES: The incidence of giant aneurysms in the paraclinoid section of the internal carotid artery (ICA) is low. They manifest their occurrence by subarachnoid haemorrhage and neurological and hormonal symptoms, resulting from compression on either the nervous structures or on the pituitary. The treatment of these aneurysms is a challenge for the surgeon, due to a difficult access, high operational risk and when the size of operated malformations is large. MATERIAL AND METHODS: Between the years 1994 and 2001, twenty (20) patients with giant paraclinoid aneurysms of the carotid artery were submitted to: endovascular treatment - 7 patients and to microsurgery - 13 patients. The treatment, following the access to the aneurysm and consisting in short-time (temporary) endovascular occlusion of ICA, was applied in some cases, while trapping was the method of choice in other cases. RESULTS: Good results of the endovascular treatment were obtained in 6 patients and, in one (1) case, satisfactory result was observed. Regarding the whole study group, hormonal symptoms (amenorrhoea) occurred in one case only. Four aneurysms were totally embolized, 1 - almost totally and 2 - partially. Recanalisation was observed in one case after 2 years. In the surgical method, good and very good results were obtained in 10 patients and satisfactory results - in 3 patients. CONCLUSION: Application of either the endovascular method or of the microsurgical method - or of both these methods - used individually in case of a given aneurysm, increases the chances for an effective occlusion with a lower operative risk.

Herpes simplex encephalitis: a case report.

BACKGROUND: Despite advances in antiviral therapy over the past 2 decades, herpes simplex encephalitis (HSE) remains a serious illness with significant risk of morbidity and death. HSE is the most common cause of sporadic viral encephalitis, with a predilection for the temporal lobes and a range of clinical presentations, from aseptic meningitis and fever to a severe rapidly progressive form involving altered consciousness. Clinical features of HSE include fever with mental status changes (depressed level of consciousness, confusion, disorientation, personality changes) sometimes with seizures (focal or generalized), dysphagia, or other focal neurological signs. Symptoms vary in intensity early in the disease, but tend to progress rapidly. CT and MRI can play an important role in determining the diagnosis and extent of the disease. CASE REPORT: This case report refers to a 17-year-old girl, previously diagnosed with herpes encephalitis, and presents the outcome of rehabilitation on the patient's mental state during a 7-year follow-up period. CONCLUSIONS: The prognosis for patients with HSE has been dramatically improved by the availability of specific antiviral therapy; sequelae in surviving patients may include severe neurological deficits, seizures, and/or neuropsychological dysfunctions that greatly impair quality of life. To improve the prognosis for patients with HSE, acyclovir treatment should be initiated as soon as HSE is suspected. After discharge, rehabilitation should be provided, in the effort to improve the patient's self-reliance in everyday life.

Coexistence of diffuse large B-cell lymphoma within pontocerebellar angle schwannoma.

We present an unusual case of diffuse large B-cell lymphoma within pontocerebellar angle schwannoma in 62-year-old woman. The patient suffered for 5 months with V, VII and VIII nerves paresis and with cerebellar ataxia. CT scan demonstrated large hyperdensive mass in cerebellopontine angle translocating cerebellar hemisphere and cerebral trunk. The patient was subjected to surgery and the tumour was removed totally by suboccipital retromastoidal right craniectomy approach. Histopathological examination revealed schwannoma infiltrated with high grade B-cell lymphoma. The patient did well following surgery without any other lymphoma manifestations, and she died from a heart attack 20 months later. Solitary lymphoma of pontocerebellar angle coexisting with schwannoma is an unusual finding, thus our case is the first report.

[Embolization of supratentorial angiomas. Own experience]. / Embolizacja naczyniaków nadnamiotowych mózgu. Doswiadczenia wlasne.

UNLABELLED: Embolization of intracerebral angiomas has been performed in our Center since 1995. Main criteria for the treatment include bleeding into the central nervous system (CNS), epilepsy, and other neurological symptoms. METHOD: CNS angiography and angioma location were performed using the Seldinger technique. A highly selective microcatheterization of particular angioma feeders was carried out then in the DVM system. After a radiological confirmation of the precise location of the catheter end in the angioma, embolization of the angioma feeders and nidus was performed with the Histoacryl-Lipiodol mixture. RESULTS: One hundred endovascular treatment procedures were performed in 58 patients with cerebral angiomas of IV and V grade according to the Spetzler-Martin scale. The total angioma occlusion was attained in 35 patients (63.3%), and partial--in 18 (31.8%) cases. There were four early deaths (6.8%) and one late (1.8%), not related to the surgical procedure. CONCLUSION: Embolization is a new and effective method of treatment of extensive supratentorial angiomas.

[Combined treatment of cerebral aneurysm and angioma. A case report]. / Tetniak i naczyniak mózgu--leczenie skojarzone. Opis przypadku.

The paper presents a case of co-existent cerebral aneurysm and angioma, as well as the treatment method used. Although in the authors' Center over 600 patients were submitted to aneurysm surgery and in about 250 cases endovascular procedures were performed during the past decade, it is for the first time that the co-existence of both aneurysm and angioma has been found. Successive stages of the diagnostic process, therapeutic procedures in the order of their application, as well as the treatment outcome are discussed. "Combined" treatment including both microsurgery and endovascular techniques can be regarded as effective in the treatment of mixed vascular malformations in the brain, making a full recovery possible.