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)

Approximately 10% of children treated with contemporary therapy for acute lymphoblastic leukemia (ALL) will experience an isolated relapse in the central nervous system (CNS). From 5 to 25% of this group will become long-term survivors, but only after additional, more aggressive therapy. A review of the limited number of studies of children surviving treatment for CNS relapse disclosed a strikingly higher incidence of intellectual impairment than was found in similarly treated patients who remain in complete remission. Specific risk factors for this complication included the number of courses of cranial irradiation, a young age at treatment, increasing time since treatment, neuropathological changes apparent on abnormal computed tomography scans of the brain, and seizures. The methodological problems inherent in neurobehavioral research in childhood acute lymphoblastic leukemia are critically reviewed and suggestions for future studies are offered. Children with a CNS relapse should be serially evaluated for psychoeducational performance to facilitate early intervention in cases of learning difficulties.
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PMID:Neuropsychological status of children with acute lymphoblastic leukemia treated for central nervous system relapse. 265 77

An 8-year-old child with acute lymphoblastic leukemia (ALL) developed seizures associated with bilateral lucencies on CT scan during standard induction therapy with vincristine and prednisone. Because of the progressive nature of her symptoms, a brain biopsy was performed and revealed neurotubular dissociation, which, in experimental animal models, is characteristic of vincristine toxicity. All other causes of encephalopathy have been ruled out. The drug was withheld and the clinical symptoms and findings resolved. The occurrence of unusual and severe neurologic side effects during the course of conventional induction therapy for childhood ALL warrants careful evaluation for evidence of vincristine toxicity.
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PMID:Reversible encephalopathy and seizures as a result of conventional vincristine administration. 232 68

L-Asparaginase therapy for childhood acute lymphoblastic leukemia causes deficiencies of plasma hemostatic proteins, especially antithrombin, plasminogen, and fibrinogen. Severe thromboses and hemorrhages occurred in 18 children receiving vincristine, prednisone, and asparaginase therapy for ALL. Thirteen children had intracranial thrombosis or hemorrhage, four had extremity thrombosis, and one had both an intracranial hemorrhage and an extremity thrombosis. These events occur characteristically in the third and fourth weeks of therapy during or just after a three-week course of L-asparaginase. Symptoms of headache, obtundation, hemiparesis, and seizure were common for the intracranial events: local pain, swelling, and discoloration were common for the extremity thromboses. These complications have been recognized in 1 to 2% of children undergoing induction therapy which includes asparaginase.
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PMID:A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia. 695 21

We reviewed the records of 127 consecutive pediatric patients with acute lymphoblastic leukemia (ALL) to determine the incidence, timing, etiologies, and recurrence rate of seizures in this population. Patients with ALL and seizures were identified retrospectively by review of the records of all pediatric ALL patients who were diagnosed and treated during the years 1983 through March 1993 in a large tertiary-care hospital. Seventeen patients (13%) developed one or more seizures. In 16 patients, seizures occurred during antileukemic treatment, and in almost all of them seizures were related to intrathecal methotrexate (IT MTX) or subcutaneous L-asparaginase treatment. One patient who developed a seizure while not receiving chemotherapy had a history of cerebral infarctions. In 8 patients, (47%), the initial seizure episode was associated with a cerebral lesion. One or more seizures recurred in 6 patients. Four of these patients had an isolated recurrence, in 3 patients < or = 3 months and in 1 patient < or = 6 months after the initial event. Two patients (12%) with static encephalopathy and neurological deficits developed a chronic seizure disorder. There is a significant risk of acute symptomatic seizures in pediatric ALL patients. Most seizures in these patients occur during the acute treatment phase and are most frequently related to side effects of chemotherapy. The long-term recurrence risk is low; recurrence occurs most often in patients with evidence of cerebral structural lesions and neurological deficits. Long-term antiepileptic drug (AED) therapy should be restricted to such patients.
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PMID:Prognosis and treatment of seizures in children with acute lymphoblastic leukemia. 763 3

As survival rates for childhood acute lymphoblastic leukemia have increased, concerns over improved quality-of-life have also increased. Although 3-10% of children may experience acute transient neurotoxicity during induction chemotherapy, they are felt to be at low risk for late sequelae. We report three previously healthy boys with newly-diagnosed acute lymphoblastic leukemia who presented with obtundation and severe seizures during late induction with a standard four drug chemotherapy regimen. While all three are disease-free survivors, they unexpectedly have persistent and medically intractable partial complex seizures, broad-based neuropsychological impairment and striking neuroimaging abnormalities. These findings suggest that children with leukemia who develop an acute encephalopathy during induction chemotherapy are at risk for long-term neurological and neuropsychological sequelae, despite the cessation of further potentially neurotoxic therapy.
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PMID:Severe permanent encephalopathy in acute lymphoblastic leukemia. 822 83

Lymphomatoid granulomatosis, a rare condition in children, affects the lungs primarily but may have significant extrapulmonary manifestations, especially in the central nervous system. We report a case of lymphomatoid granulomatosis with onset after the completion of chemotherapy for childhood acute lymphoblastic leukemia. Two months after treatment ended, the 7-year-old girl developed splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary infiltrates. She improved on cefotaxime but experienced a seizure 1 month later. A computed tomography scan of the head was normal, but her pulmonary infiltrates had become nodular. A computed tomography-guided biopsy of 1 of the nodules revealed cellular interstitial pneumonitis. One month later, she had persistent pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance imaging of the head revealed cerebral nodules. Itraconazole was begun, and the pulmonary infiltrates resolved. Five months after her initial symptoms, she developed tonic pupil and a decreased level of consciousness. Dexamethasone was initiated. Needle biopsies of the brain were carried out, yielding the diagnosis of severe chronic inflammatory changes focally consistent with granuloma. The child redeveloped splenomegaly and fever, and then suffered an acute decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open-lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was initiated, and the patient had complete resolution of pulmonary and cerebral nodules 5 months later. No intrathecal chemotherapy was administered, and radiation therapy was not necessary. Neuropsychological testing obtained after completion of therapy revealed an improvement in attention, coordination, and fine motor speed over time. She is now in good health and attending school.
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PMID:Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: report of effective therapy. 1133 32

We report a case of primitive neuroectodermal tumor (PNET) arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. A 15-year-old boy with a history of acute lymphoblastic leukemia, at the age of 7, underwent chemotherapy and 14Gy of radiotherapy to the whole brain. He was admitted to our department due to the development of aphasia, right hemiparesis and generalized convulsive seizure. MRI showed an irregularly enhanced mass in the left frontal lobe. A gross total removal of the tumor was performed and histological examination showed it to be PNET. Postoperatively, the patient underwent 20Gy of radiotherapy to the whole brain and 42Gy of local radiotherapy. Follow-up MRI showed no evidence of recurrent tumor 4 months after the radiotherapy. This tumor was thought to be a secondary brain tumor arising in this survivor of childhood acute lymphoblastic leukemia and it is a rare complication of successful leukemia treatment.
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PMID:[Primitive neuroectodermal tumor arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia: case report]. 1600 13

Pathogenetic roles of human herpesvirus (HHV)-6 in lymphoproliferative diseases have been of continued interest. Many molecular studies have tried to establish a pathogenic role for HHV-6 in lymphoid malignancies. However, whether HHV-6 plays a role in these pathologies remains unclear, as positive polymerase chain reaction results for HHV-6 in those studies may reflect latent infection or reactivation rather than presence of HHV-6 in neoplastic cells. A small number of studies have investigated HHV-6 antigen expression in pathologic specimens. As a result, the lack of HHV-6 antigen expression on neoplastic cells argues against any major pathogenic role of HHV-6. The role of HHV-6 in childhood acute lymphoblastic leukemia (ALL) has also been of interest but remains controversial, with 2 studies documenting higher levels of HHV-6 antibody in ALL patients, and another 2 large-scale studies finding no significant differences in HHV-6 seroprevalences between ALL patients and controls. Alternatively, HHV-6 is increasingly recognized as an important opportunistic pathogen. HHV-6 reactivation is common among recipients of allogeneic stem cell transplantation (SCT), and is linked to various clinical manifestations. In particular, HHV-6 encephalitis appears to be significant, life-threatening complication. Most HHV-6 encephalitis develops in patients receiving transplant from an unrelated donor, particularly cord blood, typically around the time of engraftment. Symptoms are characterized by short-term memory loss and seizures. Magnetic resonance imaging typically shows limbic encephalitis. Prognosis for HHV-6 encephalitis is poor, but appropriate prophylactic measures have not been established. Establishment of preventive strategies against HHV-6 encephalitis represents an important challenge for physicians involved with SCT.
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PMID:Human herpesvirus 6 in hematological malignancies. 1990 10

Asparagine synthetase (ASNS) converts aspartate and glutamine to asparagine and glutamate in an ATP-dependent reaction. ASNS is present in most, if not all, mammalian organs, but varies widely in basal expression. Human ASNS activity is highly responsive to cellular stress, primarily by increased transcription from a single gene located on chromosome 7. Elevated ASNS protein expression is associated with resistance to asparaginase therapy in childhood acute lymphoblastic leukemia. There is evidence that ASNS expression levels may also be inversely correlated with asparaginase efficacy in certain solid tumors as well. Children with mutations in the ASNS gene exhibit developmental delays, intellectual disability, microcephaly, intractable seizures, and progressive brain atrophy. Thus far, 15 unique mutations in the ASNS gene have been clinically associated with asparagine synthetase deficiency (ASD). Molecular modeling using the Escherichia coli ASNS-B structure has revealed that most of the reported ASD substitutions are located near catalytic sites or within highly conserved regions of the protein. For some ASD patients, fibroblast cell culture studies have eliminated protein and mRNA synthesis or stability as the basis for decreased proliferation.
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PMID:Asparagine synthetase: Function, structure, and role in disease. 2908 49