Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma may be extremely difficult to recognize, particularly when the tumor presents as a primary central nervous system disease. Central nervous system involvement may be considered as primary intracerebral neuroblastoma, metastases to the cranium from an occult primary, primary intraorbital neuroblastoma originating in the ciliary ganglion, metastatic intraorbital neuroblastoma from an occult primary, primary intraspinal neuroblastoma originating in dorsal root ganglia, intraspinal metastatic disease, and distant effects such as myoclonic encephalopathy. Primary neuroblastoma within the ciliary ganglion and primary intraspinal neuroblastoma are extremely rare entities. Illustrative cases the demonstrate the broad spectrum of neurologic presentations are offered. The second known report of neuroblastoma in association with primary pulmonary hypoventilation (Ondine curse) is included.
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PMID:Neuroblastoma presenting as central nervous system disease. 681 38

The clinical characteristics of 43 patients (pts) and the biological features of their non-stage 4 neuroblastoma (11, 3, 15, 7 and 7 with stages 1, 2A, 2B, 3 and 4S, respectively) all managed initially without cytotoxic therapy at Memorial Sloan-Kettering Cancer Center are summarised. We staged patients by the International Neuroblastoma Staging System and measured their urine and serum tumour markers. Tumour MYCN copy number, chromosomal ploidy, chromosome 1p deletion, Shimada histopathology, trk-A and CD44 expression were analysed. Among patients with localised tumour (n = 36), 13 had residual disease after initial surgery, 19 had regional lymph node invasion and 6 had epidural involvement (2 of 6 being paraplegic). All 7 stage 4S patients had liver tumours, 3 had bone marrow involvement and 3 had lymph node involvement. The most common adverse biological markers were unfavourable histopathology (9/40 evaluable tumours) and diploidy (7/39 tumours tested). At a median follow-up of 50+ months, 42 patients are alive and well (5 with evidence of disease), and 1 patient in remission died of encephalopathy. Progressive/recurrent disease occurred in 12 patients, 1 stage 2A, 2 stage 2B, 4 stage 3 and 5 stage 4S. Chemotherapy was eventually used in 4 patients: a 3-year-old stage 2B patient who developed stage 4; a 2-year-old whose recurrent tumour had poor-risk biological markers; a 1-year-old whose recurrent stage 3 disease infiltrated a vertebral body and a stage 4S infant with respiratory impairment from progressive hepatomegaly. Three of the treated patients had diploid tumours. We conclude that non-stage 4 is of itself a strong predictor of a favourable outcome. Diploidy, unfavourable histopathology and unresectable tumours were associated with disease progression. However, evolution of local-regional tumour into distant metastatic stage 4 disease is not typical of neuroblastoma.
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PMID:Survival from non-stage 4 neuroblastoma without cytotoxic therapy: an analysis of clinical and biological markers. 951 65

Aluminum is highly oxophilic and its minerals are usually found surrounded by six oxygen atoms. A role for the metal has been established in dialysis encephalopathy and Al-induced osteomalacia. The metal has been implicated in Alzheimer's disease but the issue is at present controversial. Human cell lines of neural origin were utilized to study the effect of lipophilic aluminum acetylacetonate and non-lipophilic aluminum sulfate on cell proliferation and viability. Although analysis of Al species in the cell culture media demonstrated that there are positively charged Al species present in solutions prepared with both Al salts, only the aluminum acetylacetonate salt caused changes in cell proliferation and viability. Therefore, the lipophilic nature of the organic Al salt is a critical determinant of toxicity. The effect of aluminum acetylacetonate was dose-dependent and time-dependent. Neuroblastoma (SK-N-SH) cells were more susceptible to decreased cell proliferation although the lipophilic Al salt was more toxic to the glioblastoma (T98G) cells. While the toxicity of aluminum acetylacetonate was inhibited in the T98G cells by the addition of phosphate, the same treatment did not reverse cell death in the SK-N-SH cells. Thus, the mechanism of Al toxicity appears to be different in the two cell lines. It is possible that the principal neurotoxic target of the metal is glial and when these cells are in a compromised state, this may secondarily impact the neuronal population and thus eventually lead to neurodegeneration.
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PMID:Differential toxicity of aluminum salts in human cell lines of neural origin: implications for neurodegeneration. 1130 52

Neuroblastoma (NB) is a frequent embryonal tumor of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harboring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes.
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PMID:Germline gain-of-function mutations of ALK disrupt central nervous system development. 2197 13