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 family had a dominantly inherited amyloid angiopathy that involved the meninges of the brain and spinal cord, retina, vitreous humor, peripheral nerves, and systemic organs. Clinical features included hemiplegic migraine, periodic obtundation, psychosis, seizures, intracerebral hemorrhage, myelopathy, visual impairment, deafness, and peripheral neuropathy. Pathological findings consisted of amyloid deposition in the leptomeningeal and retinal vessels, in the vitreous humor, and in perivascular tissue throughout the body. Evaluation of the amyloid showed it to be a transthyretin (prealbumin). A brief course of plasmapheresis produced a short-lived decrease concentration in circulating transthyretin.
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PMID:Familial oculoleptomeningeal amyloidosis. Report of a new family with unusual features. 317 32

Familial transthyretin (TTR) amyloidosis commonly presents with peripheral neuropathy and involvement of visceral organs. In contrast, signs of central nervous system (CNS) involvement are exceptional. We report that members of a kindred affected by a slowly progressive dementia, seizures, ataxia, hemiparesis, and decreased vision without neuropathy have TTR amyloid deposits in the leptomeninges, the brain parenchyma, and the eye. This condition, previously labeled oculoleptomeningeal amyloidosis, is linked to a mutation at codon 30 of TTR gene, resulting in the substitution of valine with glycine in this family, TTR amyloid deposits were present in the leptomeninges, especially the leptomeningeal vessels, and in the subependymal regions of the ventricular system where they disrupted the ependymal lining and resulted in amyloid-glial formations protruding into and narrowing the ventricular system. Hydrocephalus and atrophy and infarction of cerebral and cerebellar cortexes were also present. Review of the literature shows that amyloid deposition in the leptomeninges is not uncommon in TTR amyloidoses clinically characterized by peripheral neuropathy and lack of CNS signs. The present kindred, which presented exclusively with signs of CNS involvement, expands the phenotype of TTR amyloidosis and raises questions concerning the mechanisms determining phenotypic expression in TTR familial amyloidosis.
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PMID:Transthyretin amyloidosis: a new mutation associated with dementia. 906 51

We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR. Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and periods of decreased consciousness. MRI showed a marked enhancement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy. The simultaneous presence of extensive visceral amyloid and clinically significant deposits affecting both the peripheral and central nervous system extends the spectrum of amyloid-related disease associated with TTR mutations. The unusual association of severe peripheral neuropathy with symptoms of leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy.
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PMID:Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis. 1007 Oct 47

CNS involvement is rare in systemic amyloidoses due to transthyretin (TTR) mutation and manifests as a combination of dementia, seizures, and myelopathy. The authors report two French siblings who experienced recurrent subarachnoid hemorrhages as the main clinical feature. Brain specimens showed that the leptomeningeal vessels walls were thickened by amyloid deposits, and sequencing of the TTR exons showed a heterozygous single base-pair transition from G to A (codon 53), resulting in a glycine for glutamic acid substitution (G53E).
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PMID:Recurrent subarachnoid hemorrhage associated with a new transthyretin variant (Gly53Glu). 1144 44

SePP (selenoprotein P) is central for selenium transport and distribution. Targeted inactivation of the Sepp gene in mice leads to reduced selenium content in plasma, kidney, testis and brain. Accordingly, activities of selenoenzymes are reduced in Sepp(-/-) organs. Male Sepp(-/-) mice are infertile. Unlike selenium deficiency, Sepp deficiency leads to neurological impairment with ataxia and seizures. Hepatocyte-specific inactivation of selenoprotein biosynthesis reduces plasma and kidney selenium levels similarly to Sepp(-/-) mice, but does not result in neurological impairment, suggesting a physiological role of locally expressed SePP in the brain. In an attempt to define the role of liver-derived circulating SePP in contrast with locally expressed SePP, we generated Sepp(-/-) mice with transgenic expression of human SePP under control of a hepatocyte-specific transthyretin promoter. Secreted human SePP was immunologically detectable in serum from SEPP1-transgenic mice. Selenium content and selenoenzyme activities in serum, kidney, testis and brain of Sepp(-/-;SEPP1) (SEPP1-transgenic Sepp(-/-)) mice were increased compared with Sepp(-/-) controls. When a selenium-adequate diet (0.16-0.2 mg/kg of body weight) was fed to the mice, liver-specific expression of SEPP1 rescued the neurological defects of Sepp(-/-) mice and rendered Sepp(-/-) males fertile. When fed on a low-selenium diet (0.06 mg/kg of body weight), Sepp(-/-;SEPP1) mice survived 4 weeks longer than Sepp(-/-) mice, but ultimately developed the neurodegenerative phenotype. These results indicate that plasma SePP derived from hepatocytes is the main transport form of selenium supporting the kidney, testis and brain. Nevertheless, local Sepp expression is required to maintain selenium content in selenium-privileged tissues such as brain and testis during dietary selenium restriction.
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PMID:Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. 1796 Nov 24

Cobalt focus is a seizure focus model in which cerebral neurons exhibit long-lasting severe spike discharges, followed by neuronal death. However, the neuronal death is prevented when peony root extract (PR) is administered prior to cobalt application. We tested the hypothesis that PR modulates the expression of neuroprotective proteins in the cerebrum of mouse cobalt focus by proteomic analysis using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry to screen for differentially expressed proteins. Analyses revealed that transthyretin, a carrier protein for thyroid hormones and retinoids, and the brain form of phosphoglycerate mutase, a glycolytic enzyme, were upregulated in the cobalt-treated mouse cerebrum and further increased by PR administration in association with upregulation of neurogranin/RC3, a target of the transcriptional activation by thyroid hormones and retinoids. These findings suggest that PR-induced protection of mouse cerebral neurons involves neurotrophic events caused by thyroid hormones and/or retinoids and enhanced glycolysis.
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PMID:Peony root extract upregulates transthyretin and phosphoglycerate mutase in mouse cobalt focus seizure. 1844 67

We report three non-inbred patients with Val 107 transthyretin (TTR) amyloidosis. Clinical features were remarkable by the combination of peripheral polyneuropathy, carpal tunnel syndrome, cardiomyopathy, and epilepsy. Pathologic examination disclosed unusual striking systemic amyloid angiopathy in all studied tissues including nerve, muscle, gut, lung, salivary glands, and synovial membrane. It appears that the rare TTR Val 107 variant causes a peculiar familial amyloid syndrome characterized by both widespread systemic TTR amyloidosis and central nervous system deposition sufficient to cause seizures, pointing out the extent of TTR amyloidosis phenotypic heterogeneity.
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PMID:Marked systemic amyloid angiopathy in patients with val 107 transthyretin mutation. 1907 58

The number of amyloidogenic transthyretin (TTR) mutations described in the literature is more than 100. However, for several mutations, the phenotype has been described in a few individuals only; thus, the knowledge of the clinical course and the outcome after therapeutical interventions such as liver transplantation is limited. We describe the phenotype associated with five rare amyloidogenic TTR mutations that lately were discovered in Sweden: ATTR Val30Leu, Ala45Ser, Leu55Gln, Gly57Arg and Tyr69His of which ATTR Gly57Arg is previously unknown. The symptoms at onset differed, but cardiomyopathy and peripheral neuropathy were observed in all except the ATTR Tyr69His mutation. Likewise, carpal tunnel syndrome was found or had been present in all cases except the case with the ATTR Val30Leu mutation. The phenotype of the ATTR Tyr69His mutation was characterised by oculo-meningeal symptoms with seizures and a steadily progressing dementia, symptoms rarely found in ATTR amyloidosis, but similar to those previously described for this mutation, where all cases appear to originate from one Swedish family. Two patients with the ATTR Leu55Gln and Ala45Ser mutations have been subjected to liver transplantation, but echocardiographic examination has revealed an increasing cardiomyopathy after transplantation in both cases, the ATTR Leu55Gln patient succumbed 2 years after transplantation from progressive disease.
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PMID:Report of five rare or previously unknown amyloidogenic transthyretin mutations disclosed in Sweden. 1992 32

Intracerebral amyloidoma (ICA) is a type of monoclonal immunoglobulin deposition disease (MIDD) which is accompanied by an overexpression and fibrillary assembly of monoclonal light chains, ultimately leading to nodular deposits of light chains in the form of amyloid light chain (AL-amyloid). The diagnosis is made by the histological demonstration of intracerebral masses harboring the classical staining and birefringence features of amyloid. We aim to report a case of ICA and review histological features of previous cases. A 51-year-old man with epilepsy and cognitive decline was admitted for epileptic seizures. A brain magnetic resonance imaging (MRI) disclosed periventricular enhancing lesions, hypointense on T1 and heterogeneous on T2-weighted images. A brain stereotactic biopsy was performed. The neuropathological examination revealed several congophilic nodules, allowing the diagnosis of ICA. The immunohistochemical study was positive for transthyretin (TTR), and both lambda and kappa immunoglobulin light chains. No inflammatory infiltrates were seen. Although a plasma cell clone may play a major role in the etiopathogeny of ICA, plasma cells were scarce or even absent when reviewing histological reports. ICA has a poorly understood patgogenesis. ICA may simulate malignant neoplasms, hence the need for a definite histological diagnosis.
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PMID:Intracerebral amyloidoma: case report and review of the literature. 2056 71

There is increasing evidence that depression derives from the impact of environmental pressure on genetically susceptible individuals. We analyzed the effects of chronic mild stress (CMS) on prefrontal cortex transcriptome of two strains of mice bred for high (HA)and low (LA) swim stress-induced analgesia that differ in basal transcriptomic profiles and depression-like behaviors. We found that CMS affected 96 and 92 genes in HA and LA mice, respectively. Among genes with the same expression pattern in both strains after CMS, we observed robust upregulation of Ttr gene coding transthyretin involved in amyloidosis, seizures, stroke-like episodes, or dementia. Strain-specific HA transcriptome affected by CMS was associated with deregulation of genes involved in insulin secretion (Acvr1c, Nnat, and Pfkm), neuropeptide hormone activity (Nts and Trh), and dopamine receptor mediated signaling pathway (Clic6, Drd1a, and Ppp1r1b). LA transcriptome affected by CMS was associated with genes involved in behavioral response to stimulus (Fcer1g, Rasd2, S100a8, S100a9, Crhr1, Grm5, and Prkcc), immune effector processes (Fcer1g, Mpo, and Igh-VJ558), diacylglycerol binding (Rasgrp1, Dgke, Dgkg, and Prkcc), and long-term depression (Crhr1, Grm5, and Prkcc) and/or coding elements of dendrites (Crmp1, Cntnap4, and Prkcc) and myelin proteins (Gpm6a, Mal, and Mog). The results indicate significant contribution of genetic background to differences in stress response gene expression in the mouse prefrontal cortex.
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PMID:Effects of chronic stress on prefrontal cortex transcriptome in mice displaying different genetic backgrounds. 2283 82


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