Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the coagulation system due to steroids and asparaginase during treatment for acute lymphoblastic leukemia (ALL) are well known side effects and may cause bleeding or thrombosis. We report the case history of a 7-year old girl who developed thrombosis of the sinus sagittalis superior during ALL-treatment. Diagnosis was made by computed tomography and magnetic resonance imaging after the child became symptomatic with seizure. Until this event the girl had been treated already for two weeks with prednisone and E. coli-asparaginase (4 infusions). This medication caused distinct hypofibrinogenemia (Fibrinogen 53 mg/dl), prothrombin time expressed as percent of normal values of 58% was also pathological, activated partial thromboplastin time of 35 sec, antithrombin III 120% and thrombocyte count 178 G/l were in normal range. We were not successful in the attempt to adjust the imbalance in the coagulation system by transfusion of fresh frozen plasma (FFP)--seizure happened during FFP-infusion, fibrinogen blood level could be elevated only slightly. Our patient stayed consequently asymptomatic, the clinical recovery was confirmed radiologically.
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PMID:[Venous thrombosis of cranial sinuses in asparaginase therapy. A case report]. 796 36

During or immediately following L-asparaginase (L-asp) therapy especially intracranial thromboembolic or hemorrhagic complications due to hemostatic imbalance have been observed. We report about 6 children who had intracranial thrombosis or hemorrhage after 3 to 8 doses of L-asp. Initial symptoms of the cerebral events were similar--seizure, coma, hemiparesis and disorientation. All patients were examined by cerebral computerized tomography (CT) or/and magnetic resonance imaging (MRI). Three patients had a dural sinus thrombosis, one had an intracranial hemorrhage and two a hemorrhagic infarction with typical findings in the cerebral CT or MRI. Two other patients were interpreted as having peripheral thrombosis. They showed nontypical hypodense cortical and subcortical areas without any contrast medium enhancement in CT and hyperintense areas in T2-weighted MRI scan. All patients recovered from neurological symptoms, and showed obvious regression of CT and MRI findings which correlate with the good prognosis of these complications. Both CT and MRI are useful in diagnosis and follow-up of cerebrovascular complications of L-asp therapy. The CT and MRI findings of the reported cases seem to reflect different appearances of the same entity, i.e. thrombosis of venous vessels of different size with or without congestive edema and hemorrhagic complication.
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PMID:[Imaging methods in diagnosis of cerebrovascular complications with L-asparaginase therapy]. 796 35

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.
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PMID:Dural sinus thrombosis in children with cancer. 1211 89

L-Asparaginase is the major induction-phase agent for treatment of acute lymphoblastic leukemia (ALL) and an important adjuvant in treatment of non-Hodgkin's lymphoma (NHL). However, L-asparaginase-induced disturbances of clotting homeostasis may result in thrombosis or hemorrhage. Thrombotic occlusion of small cerebral veins has been reported in patients with ALL treated with this agent, but have not been described in NHL patients or those treated with the long-acting synthetic congener, pegaspargase. We report a 16-year-old boy with NHL who developed a focal motor seizure 15 min after receiving intravenous pegaspargase. MRI of the brain demonstrated multiple cortical and subcortical lesions that most likely represented focal brain edema due to thrombotic venous occlusion, which improved remarkably within 3 days and completely resolved within 3 weeks without specific intervention or permanent clinical consequences. This process must be considered when such changes are detected in NHL patients.
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PMID:Reversible MRI lesions due to pegaspargase treatment of non-Hodgkin's lymphoma. 936 5

Cerebral sinus thrombosis associated with acquired free protein S deficiency is very rare. We report the case of an adult patient with acute lymphoblastic leukemia who presented with repeated transient ischemic attacks followed by a seizure during consolidation treatment with L-asparaginase. Magnetic resonance of the brain showed a small cortical hemorrhagic infarct. Superior sagittal sinus thrombosis was demonstrated by cerebral angiogram. A marked decrease of the free form of protein S was documented. One month later, when the patient was free of symptoms, the follow-up free protein S antigen level was restored to the normal range. We suggest that the sagittal sinus thrombosis in this patient was caused by acquired, transient free protein S deficiency. This case also extends the clinical spectrum of cerebral sinus thrombosis to include recurrent transient ischemic attacks alternating with seizures.
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PMID:Sagittal sinus thrombosis associated with transient free protein S deficiency after L-asparaginase treatment: case report and review of the literature. 1071 1

Two patients with cerebral sinus thrombosis were successfully treated with neuroradiological intervention procedures, one with local thrombolysis and the other with mechanical thrombosuction using a hydrolyser catheter. The first patient, a 20-year-old woman, was treated with asparaginase for acute lymphatic leukaemia. She lapsed into coma with extensor posturing due to superior sagittal and right transverse sinus thrombosis. She recovered completely after local thrombolysis with 2,940,000 units urokinase, administered over a period of 40 hours. The second patient was a 29-year-old man who presented with clinical deterioration after seizures due to superior sagittal, left transverse and straight sinus thrombosis. A CT-scan demonstrated bilateral haemorrhagic cerebral infarctions. Since the risk of haemorrhage during thrombolysis with urokinase was considered to be high, mechanical thrombosuction with a hydrolyser catheter was performed. This procedure took only 4 hours. The patient recovered completely in two weeks. These cases add further evidence to the effectiveness of thrombolysis and thrombosuction in selected patients with severe cerebral sinus thrombosis.
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PMID:[Neuroradiologic intervention in two patients with cerebral sinus thrombosis]. 1115 59

Patients treated with L-asparaginase may present with hemorrhagic and thrombotic cerebrovascular events. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Complications appear to result from depletion of plasma proteins involved in coagulation and fibrinolysis. Seizures are uncommon symptoms, and are always caused by cerebrovascular events. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events.
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PMID:L-asparaginase-provoked seizures as singular expression of central nervous toxicity. 1103 May 30

Recent studies have shown that angiogenesis, which is induced by VEGF, may be involved in the pathogenesis of hematopoietic malignancies. A human leukemia model consisting of T-lymphoblastic CEM/0, 7 monoclonal refractory clones resistant to both cytosine arabinoside (ara-C) and L-asparaginase (ASNase), Jurkat/E6-1 and U937, representing the leukemic blasts from relapsed patients with leukemias was investigated for secretion of VEGF before and after treatment with various agents. The T-lymphoblastic cell line, Jurkat/E6-1, was used as the negative control, which has been characterized as not expressing mRNA nor the VEGF protein, and did not secrete VEGF. With no treatment, U937, the positive control, secreted the highest VEGF concentration of 1612.7 pg/ml. The CEM/O wild type cell line and 5 other drug-resistant clones secreted VEGF at levels ranging from 180.9 to 414.2 pg/ml. Two CEM drug-resistant clones, CEM/ara-C/G/ASNase-0.5-1 and CEM/ara-C/G/ASNase-1-1, lacked VEGF production. Docetaxel (Taxotere, TXR), Vincristine (VCR), ASNase, and the Fit-1/Fc chimera, a specific inhibitor of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, were tested for inhibition of VEGF secretion. Treatment of the leukemic cell lines with 2 microg/ml Flt-1/Fc chimera for 24 hours completely inhibited VEGF secretion to the detection limit of the assay (<10pg/ml). After 24 hours incubation with Flt-1/Fc chimera, the leukemic cells appeared to be undergoing apoptosis, based on microphotography examination, suggesting that VEGF could be used in an autocrine loop to promote cell survival by the leukemic cells. Treatment with 0.5, 1, and 2 microg/ml Flt-1/FC chimera for 48 hours demonstrated a 15-25% growth inhibition by MTT assay. Strong inhibition of VEGF secretion in the culture media was observed after 10 microM TXR or 0.1 microM VCR for 24 hours in the wild-type and drug-resistant clones, except CEM/ara-C/I, in comparison with controls. In contrast, treatment with 1 IU/ml ASNase, a specific T-cell protein inhibitor, in 5 cell lines for 24 hours demonstrated no inhibition of VEGF in CEM/0 3 drug-resistant clones and the myeloid U937 line. We conclude that the leukemia cell lines actively secrete VEGF, in vitro. TXR and VCR, but not ASNase, strongly inhibit the VEGF production, suggesting that inhibition of this growth factor may be a mechanism of antileukemic activity. Moreover, the leukemic cell lines examined here may constitute a useful model to study antiangiogenic drugs, alone or in combination with established drug regimens used against refractory leukemias.
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PMID:Taxotere and vincristine inhibit the secretion of the angiogenesis inducing vascular endothelial growth factor (VEGF) by wild-type and drug-resistant human leukemia T-cell lines. 1172 83

Reversible posterior leukoencephalopathy syndrome (RPLS) is being increasingly described with various etiologies even in the absence of hypertension. We present an 11-year-old patient with acute lymphoblastic leukemia who presented with seizures while on treatment with L-asparaginase. MRI showed bilaterally symmetrical nonenhancing occipital lesions characteristic of RPLS. L-Asparaginase-induced RPLS is a rare cause of neurological symptoms in patients on induction chemotherapy.
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PMID:L-asparaginase-induced reversible posterior leukoencephalopathy syndrome in a child with acute lymphoblastic leukemia. 1237 14

Coagulation disorders are common in cancer patients. In patients with solid tumors, a low-grade activated coagulation can result in systemic and cerebral arterial or venous thrombosis. Cancer treatments may also contribute to this coagulopathy, which usually, but not exclusively, occurs in the setting of advanced malignant disease. There may be TIAs or cerebral infarctions. Because of the widespread distribution of cerebral thromboses, there may be a superimposed encephalopathy; sometimes this is the only sign. Concurrent systemic thrombosis is present in many patients and is a useful clue to the diagnosis. In cerebral venous occlusion, the initial symptom is usually a headache. Except for cerebral intravascular coagulation that is unassociated with NBTE, neuriomaging studies usually demonstrate one or more parenchymal infarctions. MRI or MRV may demonstrate venous thrombosis. The laboratory evidence of coagulopathy is difficult to distinguish from the asymptomatic coagulopathy that often accompanies advanced cancer, and the test results must be interpreted cautiously. NBTE can be diagnosed by transesophageal echocardiography. There is no established treatment for the thrombotic coagulopathy associated with cancer, but anticoagulation should be considered. In leukemia and lymphoma, the coagulopathy is typically acute DIC that can lead to systemic and brain hemorrhages. It is especially common in acute myelogenous leukemias. The clinical signs of cerebral hemorrhage are fulminant and may be fatal. The bleeding usually occurs in the brain or subdural compartment, and rarely in the subarachnoid space. The diagnosis can be suspected by the clinical setting and by systemic thrombosis or hemorrhage. It can be established by examination of the peripheral smear, the platelet count, and tests of coagulation function. Therapy of acute DIC is controversial and should be individualized for the clinical setting. Cerebrovascular disorders can complicate metastatic or primary tumor in the brain, skull, dura, or leptomeninges. The clinical signs of infarction are indistinguishable from other causes of stroke, except that tumor-related venous occlusion will usually first produce signs of increased intracranial pressure. The diagnosis of tumor-related infarction can usually be established by neuroimaging studies that show infarction and may show extracerebral sites of tumor. CSF examination is useful in diagnosing leptomeningeal metastasis. A search for lung or cardiac tumor should be performed when embolic tumor infarction is suspected. Primary or metastatic tumors in the brain or dura may hemorrhage, producing the initial clinical signs of the brain tumor or a change in chronic signs induced by the tumor. There are helpful clues to a neoplastic hemorrhage on brain CT or MRI scans. The brain hemorrhage may require evacuation and the underlying tumor will usually require additional antineoplastic treatment. Hyperleukocytosis (extreme elevation of the cell count) in acute myelogenous leukemia is a less common cause of brain hemorrhage in recent years because of improved methods to lower the cell count. Cerebral arterial or venous thrombosis is sometimes the result of cancer therapy. The attribution of thrombosis to chemotherapy in many published cases is only speculative, because carefully conducted prospective studies that include investigation for other thrombotic causes are not available. The best-known associations with thrombosis are L-asparaginase, which is typically used in the induction therapy of acute lymphocytic leukemia, and combination hormonal therapy and chemotherapy for breast cancer. Radiation to the head and neck, typically administered for head and neck epithelial cancers or lymphoma, may result in delayed carotid atherosclerosis. The distribution of stenosis or occlusion is within the radiation portal and is typically more extensive than is atherosclerosis that develops in the absence of radiation. Small clinical series suggest that surgical treatment is equally effective as in nonirradiated carotid atherosclerosis. In children, the cerebral vessels can be affected by brain radiation resulting in stenosis or occlusion. Brain hemorrhages can result from chemotherapy effects on the hemostatic system or a microangiopathic anemia. Hemorrhages from radiation-induced vascular abnormalities are rare. Opportunistic infections, especially fungal infections, can complicate cancer or its treatment. Septic cerebral emboli may result in focal cerebral signs, seizures, or encephalopathy. Sometimes there is an associated hemorrhagic vasculitis or cerebritis. Rarely, mycotic aneurysms may bleed. A high index of suspicion is needed to diagnose fungal infection because of the difficulty in culturing the organism from the blood or CSF. A clinician can usually establish the cause of stroke in the cancer patient by performing a careful review of the clinical setting--including the type and extent of cancer and the type of antineoplastic therapy--in which the stroke occurred. Systemic thrombosis, embolism, or hemorrhage can be a clue to the cause, and appropriate neuroimaging and coagulation studies to aid in the diagnosis are available. Therapy may ameliorate symptoms or prevent further episodes. The identification of one of these unusual stroke syndromes that leads to the diagnosis of an occult and treatable cancer can be particularly rewarding.
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PMID:Cerebrovascular complications in cancer patients. 1269 Jun 49


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