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)

A 34-year-old man with refractory acute myelogenous leukemia underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sibling. Engraftment was prompt and no acute GVHD developed. However, high fever persisted even after engraftment, and the patient developed headache, diplopia, vertigo and nuchal rigidity on day 20 posttransplant. Cerebrospinal fluid (CSF) showed pleocytosis with no detectable microorganisms. Despite therapy with broad-spectrum antibiotics, antifungal agents and antituberculous drugs, he developed rapid mental deterioration with seizures and died on day 40. Just prior to his death, trichomonads were isolated from both CSF and urine. Scanning electron microscopic examination identified the trichomonad as Trichomonas foetus. At autopsy, trichomonads were detected histopathologically in an area involving meningoencephalitis. To our knowledge, this is the first case of T. foetus meningoencephalitis in a recipient of allogeneic PBSCT and, more importantly, the first human case of T. foetus infection.
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PMID:Trichomonas foetus meningoencephalitis after allogeneic peripheral blood stem cell transplantation. 948 1

Vascular endothelial growth factor (VEGF) and placental derived growth factor (PlGF) stimulate cell proliferation and differentiation by binding to their specific receptors, Flk-1/KDR and Flt-1 respectively. Flk-1/KDR-deficient murine embryos manifest failure of blood-island formation and vasculogenesis. The aim of this study was to directly evaluate the importance of VEGF, PlGF/Flt-1 and Flk-1/KDR receptor ligand interactions in regulating normal and malignant human haemopoiesis. Addition of VEGF and PlGF failed to enhance survival or cloning efficiency of human haemopoietic progenitors isolated from adult bone marrows, fetal livers or cord blood samples. This finding may be explained by the apparent absence of mRNA encoding Flt-1 and Flk-1/KDR receptors on stem cell rich CD34+ c-kit-R+ Rh123(low) cells. Further studies revealed that Fit-1 R mRNA, but not Flk-1/KDR mRNA was first detectable in the more mature cells isolated from haemopoietic colonies. Accordingly, VEGF receptors are either absent, or expressed at very low level, on human haemopoietic stem/progenitor cells. Of interest, normal and malignant human haemopoietic cells appeared to secrete VEGF protein. However, in contrast to normal haemopoietic progenitors, VEGF co-stimulated HEL cell proliferation as well as CFU-GM colony formation from approximately 15% of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) patients studied. Therefore, although VEGF appeared to have minimal effects on normal haemopoietic cell growth it would appear to drive malignant haemopoietic cell proliferation to some degree. Of more importance, however, we speculate that VEGF may play an very important role in leukaemogenesis by stimulating growth of vascular endothelium, thereby providing a sufficient blood supply to feed the growing haematological tumour.
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PMID:Role of vascular endothelial growth factor (VEGF) and placenta-derived growth factor (PlGF) in regulating human haemopoietic cell growth. 988 8

We report a case of reversible encephalopathy syndrome in a 16-year-old girl with acute myelogenous leukemia (AML), who is undergoing during consolidation chemotherapy composed of BH-AC (N4-behenoyl-1-beta-D-arabinofuranosyl cytosine) and idarubicin. On the 6th day of chemotherapy, she was in a drowsy state following generalized tonic clonic seizure lasting 20 minutes. MR images revealed extensive cortical and subcortical white matter brain edema. Alertness returned over the 24 hr following by the discontinuation of BH-AC and intravenous administration of diphenylhydantoin, although she complained of intermittent headaches and visual disturbance. She gradually recovered from these symptoms during subsequent 7 days. Previously noted abnormal signal intensities have nearly disappreared on follow-up MRI obtained on the 22nd day after the first seizure. She was discharged without any neurologic sequela. This case suggests that BH-AC, a derivative of cytosine arabinoside (1-beta-D-arabinofuranosylcytosine) could be a cause of reversible encephalopathy syndrome.
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PMID:Behenoyl cytarabine-associated reversible encephalopathy in a patient with acute myelogenous leukemia. 1010 31

In October 1996, a 26-year-old woman was given a diagnosis of acute myeloblastic leukemia, FAB subtype M1. Treatment with combined chemotherapy achieved a complete remission (CR). In May 1997, the patient received an allogenic bone marrow transplant (BMT) from an HLA-identical sibling donor. Cyclosporine (CsA) and short-term methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment was obtained and signs of acute or chronic GVHD never developed. Five months after BMT, the patient experienced low-grade fever and blurred vision. Retinal examination demonstrated intraretinal hemorrhages, cotton-wool spots, and retinal detachments, which were presumably attributable to multiple thrombosis of retinal microvessels. The patient also exhibited hemolytic anemia with red cell fragmentation, thrombocytopenia, elevated lactate dehydrogenase, and renal impairment, and was thus given a diagnosis of BMT-associated thrombotic microangiopathy (BMT-TM). Discontinuation of CsA and administration of ticlopidine and prednisolone induced successful recovery from BMT-TM. Three months after the onset of BMT-TM, however, the patient experienced generalized clonic-tonic seizures with consciousness loss. Single-photon-emission computed tomography revealed blood-flow disturbances in the brain, suggesting the recurrence of microthrombosis. Accordingly, multiple transfusions of fresh frozen plasma were administered together with dipyridamole and aspirin. The patient gradually recovered and remained asymptomatic through the following 13 months. Currently, early diagnosis of BMT-TM is considered to be difficult. We suggest that careful examination of the ocular base may be useful for the early detection of BMT-TM.
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PMID:[Bone marrow transplantation-associated thrombotic microangiopathy manifested by visual disturbance]. 1069 95

Cyclosporine (CSP) is the most frequently used immunosuppressive agent for prevention of graft versus host disease (GVHD) in allogeneic bone marrow transplantation (BMT). Some adverse effects such as hepatic and renal toxicity have been frequently encountered, but central nervous system (CNS) toxicity caused by CSP is rare. We report an adult male patient with acute myeloid leukemia who developed CSP-induced encephalopathy under treatment for allogeneic BMT from an unrelated donor. Methotrexate and CSP were used for GVHD prophylaxis. Leukocyte and platelet engraftment were successfully achieved on days 21 and 24 after BMT, respectively. Abrupt onset of mental confusion and disorientation occurred on day 25, followed by a generalized tonic clonic seizure and consciousness disturbance. The whole blood CSP level was 160.65 ng/mL. Magnetic resonance (MR) imaging revealed high signal intensities in the bilateral occipital lobes with predominant involvement of the cortical areas. The patient recovered from the CNS toxicity, but with slight memory impairment, 6 days after CSP was discontinued. When patients receiving CSP treatment for allogeneic BMT develop mental confusion, consciousness disturbance, or seizure, CSP-induced CNS toxicity should be taken into consideration.
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PMID:Cyclosporine-induced encephalopathy in a patient with relapsed acute myeloid leukemia treated with unrelated allogeneic bone marrow transplantation. 1082 Sep 59

A 10-year-old girl with M2 acute myeloid leukemia underwent an unrelated cord blood transplantation in refractory first relapse. On day +13, after 48 hours with fever, she showed a measles-like rash, and on day +15, she began experiencing neurologic symptoms (headache, tremors, weakness, nystagmus, mild confusion, speaking, taste, and behavior disturbances, and focal seizures). She also had amnesia for recent events with disability to learn, mimicking Wernicke-Korsakoff syndrome. Computed tomography of the brain and cerebrospinal fluid (CSF) and electroencephalogram were nonspecific. We found human herpesvirus 6 (HHV-6) DNA in CSF and cytomegalovirus in bronchoalveolar lavage using polymerase chain reaction techniques. Treatment with ganciclovir and foscarnet was effective, with total resolution of symptoms.
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PMID:Herpesvirus-6 encephalitis complicated by Wernicke-Korsakoff syndrome in a pediatric recipient of unrelated cord blood transplantation. 1190 11

Glycogen storage disease (GSD) is a rare autosomal-recessive disorder characterized by hypoglycemia, hepatosplenomegaly, seizures, and failure to thrive in infants. Neutropenia and/or neutrophil dysfunction develops in GSD1b, but not in other types. GSD1b results from a deficiency of the glucose-6-phosphate translocase enzyme and the genetic defect maps to chromosome 11q23. Patients with GSD1b are susceptible to recurrent bacterial infections, commonly involving the perirectal area, ears, skin, and urinary tract, although life-threatening infections, such as septicemia, pneumonia, and meningitis occur less frequently. Although the exact mechanism of neutropenia in patients with GSD1b is not known, treatment with recombinant human granulocyte colony-stimulating factor (G-CSF) has reduced the incidence of infections and has improved the quality of life of these patients. Defects in neutrophil chemotaxis and intracellular bacterial killing have been described and appear to be corrected by the use of G-CSF. To date, no cases of myelodysplasia or acute myeloid leukemia have been observed in patients with GSD1b treated with G-CSF. A significant complication of cytokine therapy is the development of hypersplenism, requiring either a reduction in the dosage of G-CSF or splenectomy.
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PMID:Glycogen storage disease. 1195 92

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

The single-stranded DNA- and RNA-binding protein, Puralpha, has been implicated in many biological processes, including control of transcription of multiple genes, initiation of DNA replication, and RNA transport and translation. Deletions of the PURA gene are frequent in acute myeloid leukemia. Mice with targeted disruption of the PURA gene in both alleles appear normal at birth, but at 2 weeks of age, they develop neurological problems manifest by severe tremor and spontaneous seizures and they die by 4 weeks. There are severely lower numbers of neurons in regions of the hippocampus and cerebellum of PURA(-/-) mice versus those of age-matched +/+ littermates, and lamination of these regions is aberrant at time of death. Immunohistochemical analysis of MCM7, a protein marker for DNA replication, reveals a lack of proliferation of precursor cells in these regions in the PURA(-/-) mice. Levels of proliferation were also absent or low in several other tissues of the PURA(-/-) mice, including those of myeloid lineage, whereas those of PURA(+/-) mice were intermediate. Evaluation of brain sections indicates a reduction in myelin and glial fibrillary acidic protein labeling in oligodendrocytes and astrocytes, respectively, indicating pathological development of these cells. At postnatal day 5, a critical time for cerebellar development, Puralpha and Cdk5 were both at peak levels in bodies and dendrites of Purkinje cells of PURA(+/+) mice, but both were absent in dendrites of PURA(-/-) mice. Puralpha and Cdk5 can be coimmunoprecipitated from brain lysates of PURA(+/+) mice. Immunohistochemical studies reveal a dramatic reduction in the level of both phosphorylated and nonphosphorylated neurofilaments in dendrites of the Purkinje cell layer and of synapse formation in the hippocampus. Overall results are consistent with a role for Puralpha in developmentally timed DNA replication in specific cell types and also point to a newly emerging role in compartmentalized RNA transport and translation in neuronal dendrites.
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PMID:Puralpha is essential for postnatal brain development and developmentally coupled cellular proliferation as revealed by genetic inactivation in the mouse. 1297 5

Interictal hypometabolism is commonly found in mesio-temporal lobe epilepsy (MTLE), but its pathophysiology remains incompletely understood. We hypothesized that metabolic changes reflect the preferential networks involved by ictal discharges. We analysed the topography of interictal hypometabolism according to electro-clinical patterns in 50 patients with unilateral hippocampal sclerosis (HS) and consistent features of MTLE. Based on electro-clinical correlations, we identified four groups: (i) mesial group (13 cases) characterized by mesial seizure onset without evidence of early spread beyond the temporal lobe; (ii) anterior mesio-lateral group (AML; 18 cases) with early anterior spread involving the anterior lateral temporal cortex and insulo-fronto-opercular areas; (iii) widespread mesio-lateral group (WML; 15 cases) with wide spread (involving both anterior and posterior lateral temporal and perisylvian areas); and (iv) bitemporal (BT) group (four cases) with early contralateral temporal spread. Results of [18F]fluorodeoxyglucose-PET imaging in each group were compared with those of 10 control subjects using statistical parametric mapping software (SPM99). MRI data and surgical outcome in each group were compared with metabolic findings. Hypometabolism was limited to hippocampal gyrus, temporal pole and insula in the mesial group. Gradual involvement of lateral temporal cortex, insula and perisylvian areas was observed in the AML and WML groups. The BT group differed from the others with mild bitemporal involvement, bilateral insular hypometabolism and longer epilepsy duration. MRI structural abnormalities outside of the mesial formations were detected in 65% of the cases. Neither the severity of HS nor temporal atrophy appeared related to the topography of hypometabolism. However, temporal hypometabolism was more extended when temporo-polar signal changes were detected. Among operated patients (n = 43), seizure-free outcome was obtained in 82%. Surgical outcome appeared more favourable in the mesial group. However, the difference between the four groups was not significant. Our results suggest that hypometabolism in MTLE may be related to ictal discharge generation and spread pathways, even if structural changes and epilepsy duration may also play a role.
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PMID:Metabolic changes and electro-clinical patterns in mesio-temporal lobe epilepsy: a correlative study. 1453 61


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