Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-asparaginase is frequently used in combination therapy for the treatment of lymphoid malignancies. We report 5 children aged between 8 and 14 years with neurologic complications presenting with headache and seizures during the first three weeks of L-asparaginase treatment. Three patients had venous thrombosis, one presented a parenchymal hemorrhage, and one showed a peculiar encephalopathy with extended cortical and subcortical lesions suggesting a neurotoxic reaction. Decreased fibrinogen and antithrombin III levels were found. Early MRI is critical even in cases with mild neurologic symptoms. Diagnosis should be followed by early cessation of l-asparaginase application.
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PMID:Cerebrovascular complications of L-asparaginase in the therapy of acute lymphoblastic leukemia. 1279 28

A 10-year, retrospective review of the etiology, outcome, and complications of ischemic stroke in children from a nonurban population was conducted. Twenty-seven children were identified (14 boys, 13 girls), ages 1.25 to 17 years (mean 7.7 years). Etiologies included undetermined (22%), arterial dissection (19%), coagulopathy (15%), embolism (15%), moyamoya disease (11%), sickle cell disease (11%), isolated angiitis of the central nervous system or vasculitis (11%), or other known source (11%; two fibromuscular dysplasia, one L-asparaginase). More than one risk factor was present in five children. Seventeen (65%) children were anticoagulated, with no adverse events occurring. Nine children were anticoagulated initially with low-molecular-weight heparin. Other treatments included corticosteroids; physical, occupational, and speech therapy; and anticonvulsants for concomitant seizures. Follow-up ranged from 3 to 60 months (mean 17 months) and was as follows: 6 (22%) were normal, 9 (33%) had mild impairment, and 12 (44%) had moderate to severe deficits. There were no deaths. Neurologic complications included seizure (two), behavioral problems (two), and hemorrhagic conversion (one). In this population, the outcome from ischemic stroke was similar to that of other studies, with the majority of children demonstrating persistent neurologic deficits. Etiology could be determined for the majority of patients, with 19% having more than one risk factor.
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PMID:Childhood ischemic stroke in a nonurban population. 1583 8

A 46-year-old male with refractory biphenotypic acute leukemia was treated with doxorubicin (days 1-3, 15-17), vincristine (days 1, 8, 15, 22), prednisolone (days 1-28), and L-asparaginase (L-ASP: days 15-28) as reinduction therapy. Physical examination revealed normotensive state and normal consciousness. On the 27th day, systemic seizures developed with mild hypertension (BP 151/98 mmHg). Computed tomography (CT) imaging of the brain showed areas of hypodensity in the bilateral white matter, and in the occipital and posterior parietal areas. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) showed some high intensity area involving the white matter, but also involving the cortex in the same area. Because the patient's condition progressed into unconsciousness and apnea from recurrent seizures, a respirator and anticonvulsants were needed. Four days later, the patient's general condition dramatically improved. There were no abnormal findings on MRI, and we diagnosed the cause of the seizures as reversible posterior leukoencephalopathy syndrome (RPLS). In adults, RPLS caused by chemotherapy is rare, especially L-ASP. Our patient did not have any previous history of convulsion up to the LAdVP, which brought on the seizures. It was considered that the RPLS might be caused by L-ASP, which had been given to this patient for the first time and was being given to him at the time of developing the seizures. RPLS is one of the causes of neurologic complications by L-ASP.
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PMID:[Reversible posterior leukoencephalopathy syndrome probably caused by L-asparaginase]. 1686 82

L-asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. The purpose of this article is to present the first case-series of posterior reversible encephalopathy syndrome (PRES) associated with L-asparaginase treatment. We report 3 cases of children with acute lymphoblastic leukemia who developed seizures and altered sensorium after L-asparaginase therapy. MRI showed increased T(2) signal intensity predominant in the posterior regions of the brain suggestive of PRES. Two of our patients developed septic shock and deteriorated whereas one patient improved and recovered completely.
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PMID:L-asparaginase-induced posterior reversible encephalopathy syndrome during acute lymphoblastic leukemia treatment in children. 1850 83

Reversible posterior leukoencephalopathy syndrome (RPLS) is recently described disorder with typical radiological findings in the posterior regions of the cerebral hemisphere and cerebellum. Its clinical symptoms include headache, decreased alertness, mental abnormalities, such as confusion, diminished spontaneity of speech, and changed behavior ranging from drowsiness to stupor, seizures, vomiting and abnormalities of visual perception like cortical blindness. RPLS is caused by various heterogeneous factors, the commonest being hypertension, followed by non-hypertensive causes such as eclampsia, renal diseases and immunosuppressive therapy. We presented nine patients with RPLS who had primary diagnoses such as acute post-streptococcal glomerulonephritis, idiopathic hypertension, the performing of intravenous immunoglobulin for infection with crescentic glomerulonephritis, erythrocyte transfusion for severe iron deficiency, L: -asparaginase treatment for acute lymphoblastic leukemia and performing of granulocyte-colony stimulating factor for ulcerative colitis due to neutropenia. Early recognition of RPLS as complication during different diseases and therapy in childhood may facilitate precise diagnosis and appropriate treatment.
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PMID:Reversible posterior leukoencephalopathy syndrome in childhood: report of nine cases and review of the literature. 1980 87

Cerebral Sinovenous Thrombosis (CSVT) is a serious complication of L-asparaginase chemotherapy for leukemia in children. Clinical features of headache, altered consciousness, focal neurological deficit, and seizures developing during or immediately after treatment with L-asparaginase should alert the treating physician to the possibility of CSVT. Immediate imaging of the brain should be done using CT and MRI and the veins should be visualized noninvasively by CT and MR venography. We report two children on induction therapy for acute leukemia who presented with seizures, headache, and altered consciousness. Venous infarcts with and without hemorrhage were seen on CT in one patient and the empty delta sign was seen after contrast injection; however, the early changes were missed by CT. MRI detected dural sinus thrombosis relatively earlier in another patient, while the CT findings were equivocal; in this patient, contrast-enhanced MRI showed the empty delta sign and MR venography confirmed absent flow in the superior sagittal sinus, which was diagnostic of sinus thrombosis. Rapid anticoagulation was started with heparin and maintained with warfarin. The child with a unilateral small nonhemorrhagic infarct made a complete recovery while the other, with bilateral hemorrhagic infarcts, did not survive. We stress the importance of early diagnosis of CSVT using CT and MRI in children with leukemia being treated with L-asparaginase; this will permit timely treatment.
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PMID:Sagittal sinus thrombosis due to L-asparaginase. 2104 5

We report the case of a 4-year-old boy with acute lymphoblastic leukemia in high-risk group who suffered from generalized tonic-colonic seizure evolving into status epilepticus, and subsequent left hemiparesis during his first reinduction chemotherapy, consisting of dexamethasone, vincristine, l-asparaginase, and epirubicin. Superior sagittal sinus and cerebral venous thrombosis, predominantly in right side, were proved by brain magnetic resonance imaging. After aggressive treatment with low-molecular weight heparin (LMWH), left hemiparesis improved in 1 week. And he was fully ambulatory 3 weeks later. The second cycle of reinduction chemotherapy was conducted smoothly with the concomitant use of LMWH. This case illustrates the strong correlation of the rare thrombotic complication, superior sagittal sinus thrombosis, and hypercoagulable status secondary to combination use of l-asparaginase and corticosteroid. Early and vigilant recognition of superior sagittal sinus thrombosis and prompt anticoagulation with LMWH may prevent further neurological damage.
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PMID:A rare complication in a child undergoing chemotherapy for acute lymphoblastic leukemia: superior sagittal sinus thrombosis. 2146 50

The authors describe a case of L-asparaginase induced intracranial thrombosis and subsequent haemorrhage in a newly diagnosed 30-year-old man with acute lymphoblastic leukaemia who was successfully managed by surgical intervention. At presentation, he had a Glasgow Coma Score of 7/15, was aphasic and had dense right hemiplegia. Neuroimaging revealed an acute anterior left middle cerebral artery infarct with parenchymal haemorrhagic conversion, mass effect and subfalcine herniation. He subsequently underwent left frontal craniotomy and evacuation of large frontal haematoma and decompressive craniectomy for cerebral oedema. Six months postoperatively he underwent titanium cranioplasty. He had made good clinical recovery and is currently mobilising independently with mild occasional episodes of expressive dysphasia, difficulty with fine motor movement on the right side, and has remained seizure free. This is the first documented case of L-asparaginase induced haemorrhagic stroke managed by neurosurgical intervention. The authors emphasise the possible role of surgery in managing chemotherapy induced intracranial complications.
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PMID:Neurosurgical management of L-asparaginase induced haemorrhagic stroke. 2260 98

Sinovenous thrombosis (SVT) is a well-recognized and serious complication in children treated for acute leukemia. This frequently occurs during or immediately upon completion of induction therapy and is commonly attributed to asparaginase therapy.Headache is the first and most common clinical symptom to occur during the early development of SVT. With advancement of the thrombosis, the clinical symptoms can progress to increased sleepiness, focal neurological deficit, seizures, and altered consciousness. We report the case of a 4-year-old girl who presented after several days of headaches and anorexia, which then progressed to seizures, left-sided weakness, and altered consciousness. She was later found to have a widespread and occlusive SVT with right cerebral hemorrhagic infarction. This case is notable for the extensive nature of the cerebral SVT and the child's complete clinical recovery from the neurological event. The report discusses the relation of the thrombosis and leukemia and also emphasizes the importance of early recognition and prompt management, while incorporating a collaborative multidisciplinary approach to prevent long-term consequences.
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PMID:Extensive sinovenous thrombosis and hemorrhagic infarction during therapy for T-cell acute lymphoblastic leukemia. 2328 76

Superior sagittal sinus thrombosis (SSST) is a very rare but life-threatening complication in leukemia patients. SSST is very rare in acute myeloid leukemia (AML). In leukemia patients, several risk factors for SSST have been reported such as administration of L-asparaginase, disseminated intravascular coagulation, congenital thrombophilia, meningeal leukemia, and intrathecal chemotherapy (IT). Lumbar puncture itself and corticosteroid administration have also been acknowledged as risk factors. We describe herein our clinical experience with SSST in a 29-year-old Japanese man suffering from AML with t(8;21)(q22;q22), who presented with abrupt onset of loss of consciousness, left hemiplegia, and seizure soon after IT and high-dose cytarabine (HD-AraC) with dexamethasone for post remission consolidation. Despite the presence of intracranial hemorrhage (ICH) due to SSST rupture, we conducted anticoagulant therapy with heparin. Although ICH worsened temporarily, his clinical condition gradually improved with resolution of the SSST, and he eventually became fully ambulatory. There were no deficiencies of natural anticoagulants. Three additional cycles of HD-AraC without IT therapy were conducted, but no neurological complications recurred with the concomitant use of warfarin. He was discharged free of neurological deficits. In our case, there is a possibility that IT and the administration of corticosteroids along with HD-AraC triggered SSST.
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PMID:[Superior sagittal sinus thrombosis after intrathecal chemotherapy and intravenous high-dose cytarabine in an acute myeloid leukemia case with t(8;21)(q22;q22)]. 2716 54


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