Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We retrospectively reviewed the findings in 655 consecutive young patients who underwent contrast-enhanced MR examinations (1.5T) of the head or spine. Their ages ranged from 4 months to 20 years (mean 10 years). There was a 1.7% incidence of minor adverse reactions to gadolinium (Gd)-DTPA, none of which required treatment; no serious adverse reactions were encountered. Based on the radiologic diagnosis the patients were divided into three groups: (1) normal, (2) CNS neoplasm, (3) abnormal but not neoplasm. There were 178 patients thought to have CNS neoplasms and of these 156 (88%) enhanced. Of 124 histologically confirmed neoplasms 115 (93%) showed enhancement after Gd-DTPA. Eight children had histologically confirmed spinal neoplasms; 5 of 6 neurofibromas and 2 ependymomas enhanced. In the 216 patients with abnormalities thought not to be neoplastic, the enhancement rate was 11%; most of the enhancing lesions were vascular malformations. There were very few examples of inflammatory disease, acute trauma or stroke among our patients.
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PMID:Diagnostic role of gadolinium-DTPA in pediatric neuroradiology. A retrospective review of 655 cases. 160 9

We report a unique case of histologically confirmed meningeal fibrosis in a child who had progressive ischemic neurologic symptoms before the delayed diagnosis of an intracranial primitive neuroectodermal tumor (PNET) was made > 1 year after initial presentation. This pathology has previously been described after neurosurgical procedures, subarachnoid hemorrhage, cranial irradiation, and with no known etiology, but has never been reported in association with a central nervous system neoplasm. In a 6-year-old boy with headaches of several months' duration MRI demonstrated hydrocephalus, a right cerebellopontine angle cyst, and dural enhancement. Biopsies of the thickened meninges taken when the cyst was surgically fenestrated demonstrated only fibrosis with no evidence of infection, hemorrhage, or neoplasm. In the next 6 months, the child had two acute stroke-like episodes with alternating hemiparesis that gradually improved. There were ischemic changes in the diencephalon on MRI. Repeat dural biopsies were unchanged. One year after the initial operation, a left hemiparesis recurred and MRI demonstrated multiple intracranial masses in the cerebral cortex, cerebellum, suprasellar area, and cauda equina. After surgical resection, the cortical mass was found to be a PNET. All the lesions regressed after treatment with radiation and chemotherapy. We hypothesize that the meningeal fibrosis represented a "desmoplastic" reaction to an occult PNET, similar to the fibrous proliferation with cerebellar desmoplastic medulloblastoma except for the extent of the meningeal involvement and the long undetected parenchymal tumor. The mechanism of the ischemic brain injury was most likely vascular involvement by the fibrotic process, either directly or by predisposition to vasoconstriction.
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PMID:Leptomeningeal fibrosis and the delayed diagnosis of a central nervous system neoplasm (primitive neuroectodermal tumor). 904 9

Different vector systems that have been used and/or specifically developed for central nervous system (CNS) gene transfer studies are briefly discussed along with their advantages and disadvantages with respect to potential clinical application. These include retroviruses, recombinant herpes simplex virus, adenoviruses, adenoassociated viruses, encapsulation of plasmid deoxyribonucleic acid into cationic liposomes, and neural and oliogodendroglial stem cells. Particular attention has been paid to relate the modality of a specific CNS gene therapy to the strategy for adequate delivery of genetic material to the brain for either global or localized CNS neurodegenerative chronic disorder, as well as for CNS tumors and stroke. Techniques to circumvent the "impermeable" blood-brain barrier and how to breach the more versatile blood-brain-tumor barrier to deliver the genetic material to the target CNS cells are reviewed and include the following: 1) local stereotactic CNS injection/infusion of viral vectors, administration of vector producer cells, or cell replacement; 2) local administration of genetic material into the cerebrospinal fluid ventriculocisternal system; 3) osmotic opening of the blood-brain barrier; 4) local intra-arterial infusion; and 5) administration of blood-brain-tumor barrier permeabilizers, such as a bradykinin B2 agonist RMP-7. It is concluded that gene therapy for several brain disorders holds great potential, as suggested mainly by in vitro experiments and, to some extent, by a limited number of animal experiments. However, several drawbacks currently hamper the application of gene therapy under the clinical setting. The problems associated with gene therapy that still present major obstacles are as follows: 1) inefficient transfection of host cells by viral vectors; 2) restricted delivery of genetic material across vascular barriers of the CNS and brain tumors; 3) nonselective expression of the transgene; and 4) in situ CNS regulation of the transgene expression in a therapeutically controlled manner, as imposed by the course and phenotype of the CNS disease.
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PMID:Cellular and molecular neurosurgery: pathways from concept to reality--part II: vector systems and delivery methodologies for gene therapy of the central nervous system. 909 54

The transgenic technique allows specific genetic alterations to be made in all cells of an animal and this has greatly improved our understanding of how the embryonic and adult central nervous system (CNS) develop. The CNS originates from the neuroectoderm in the neural plate on the dorsal side of the embryo and after closure of the neural tube the cells of the neuroepithelium, i.e. the CNS stem cells, transiently proliferate to generate neurons and glial cells. Here we review our attempts to gain insights into the control of CNS development. We have identified a gene, nestin, which is predominantly expressed in embryonic and adult CNS stem cells. In addition to its normal expression in the CNS stem cells, nestin is reexpressed in CNS tumors and in the adult spinal cord and brain after CNS injury. By using the lacZ reporter gene assay in transgenic mice, we have identified regulatory regions (enhancer) in the nestin gene required for expression in embryonic CNS stem cells and in the adult spinal cord after injury. In a second project, we have cloned and characterized the Notch gene family (the Notch 1, 2 and 3 genes) in mouse and man. These genes encode trans-membrane receptors, which appear to be key regulatory molecules for proliferation and differentiation both in the developing CNS and in other tissues. Expression of an activated form of the Notch 3 receptor from the nestin promoter in transgenic mice leads to a lethal, exencephaly-like phenotype in the embryo, probably as a result of excess proliferation of the CNS stem cells. The recent finding that the Notch 3 gene is the genetic cause for familial stroke is discussed in the context of current models for Notch function.
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PMID:Transgenic analysis of central nervous system development and regeneration. 924 56

Levels of DARP in the cerebrospinal fluid (CSF) of patients having a wide variety of neurological disorders were determined. Neurological disorders were categorized as degenerative, demyelinating, epilepsy, trauma, hydrocephalia, inflammatory, A-V malformation, CNS neoplasia, parasitic and stroke. DARP levels were determined by an enzyme-linked immunoabsorbent assay (ELISA) using monoclonal anti-DARP antibodies. A synthetic peptide corresponding to the first 36 aa of the N-terminal of DARP was used as standard. A total of 7 non-neurological patients and 73 patients with neurological disorders were tested. The relative concentrations of DARP decreased in patients with Parkinson's diseases vs. patients with non-neurological diseases and increased in other neuropathologies such as demyelinating, hydrocephalia and A-V malformations. Data obtained suggest that changes in the percentage and concentration of DARP may correlate with certain neurological disorders, showing particularly low levels in Parkinson's disease patients.
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PMID:Determination of dopamine-releasing protein (DARP) in cerebrospinal fluid of patients with neurological disorders. 942 87

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is often difficult, since the clinical presentation varies between patients and is often uncharacteristic. Therefore, CJD is often not suspected until late in the disease process, due to the rapid progress of the disease. Suspected CJD is, however, frequent in routine clinical practice, in the investigation of patients with rapidly progressing dementia and/or uncharacteristic neurological symptoms. We present results from cerebrospinal fluid (CSF) analyses in CJD, focusing on the two neuron-specific proteins 14-3-3 and tau. Analysis of 14-3-3 protein is performed by Western blotting, in which 14-3-3 is either detectable in CSF or not, while CSF-tau is analyzed using quantitative ELISA methodology, in which a markedly increased CSF level of tau (< 1500 pg/mL) is indicative of CJD. Tau and 14-3-3 findings show comparable sensitivity and specificity, higher than the presence of spike and wave complexes on an EEG. The increase in CSF-tau in CJD is substantially higher than in Alzheimer's disease, with low overlap between the disorders. Instead, false positive results are found in disorders with massive acute neuronal damage (encephalitis, stroke and CNS tumors). In cases in which these disorders cannot be differentiated from CJD on clinical grounds, they can often be identified by MRT or by the finding of blood-brain barrier damage or signs of inflammation upon CSF analysis. CSF-tau is increasingly used in the routine diagnosis of Alzheimer's disease, and the analysis also seems to be of use in the clinical diagnosis of CJD. We also present three cases from routine clinical practice, all with a marked increase in CSF-tau, which was the only positive objective sign in two of the cases.
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PMID:[CSF-analyses in clinical diagnosis of Creutzfeldt-Jakob disease. A literature review and three cases from routine clinical practice]. 1143 75

Toll-like receptors (TLRs) are a family of evolutionarily conserved molecules that directly detect pathogen invasion or tissue damage and initiate a biological response. TLRs can signal through two primary intracellular pathways and as such can induce either immuno-stimulatory or immuno-modulatory molecules. Both sides of this twin-edged sword are being examined for their therapeutic potential in combating neurological disease. The immuno-stimulatory properties of TLRs are being used to generate tumor-specific immune responses to CNS tumors while the immuno-modulatory properties are being used to suppress damaging inflammatory responses to stroke. Recently, a third component of TLR signaling has begun to emerge--that of direct neuroprotection. Hence, the TLRs offer novel targets for the treatment of neurological disease.
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PMID:Toll-like receptors: novel pharmacological targets for the treatment of neurological diseases. 1797 78

Notch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin-1 (the enzymatic component of the gamma-secretase complex) resulting in the release of a notch intracellular domain which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. Notch is also present in post-mitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory. Recent findings suggest that notch signaling in neurons, glia, and NSCs may be involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Studies of animal models suggest the potential of agents that target notch signaling as therapeutic interventions for several different CNS disorders.
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PMID:Notch: from neural development to neurological disorders. 1909 54

The median nerve is one of the most commonly affected peripheral nerves in various pathologies such as entrapment syndromes or transections. The diagnostic procedures applied in these situations are electromyography, physical examination methods, ultrasonography, and magnetic resonance imaging. Diffusion tensor imaging (DTI) has been used mostly in imaging the central nervous system (CNS) to visualize white matter tracts. Several studies have shown the clinical applications of DTI in neuronal disorders such as stroke, epilepsy, and CNS tumors. Recently, peripheral nerves have been visualized with DTI. Also, in several pathologies such as carpal tunnel syndrome and transection of the median nerve, on postoperative follow-up anisotropy indexes were shown to be affected. However, new studies with larger series are needed.
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PMID:Tractography of the median nerve. 1923 68

Musculoskeletal deficits remain significant impediments to the function and independence of children and adolescents following successful treatment of Central Nervous System Tumors (CNS) tumors. The sequelae often impair the function of the upper and lower extremities and manifest themselves as difficulties in gross and fine motor skills, which encompasses self care and walking. Overall, the five-year survival rate for children younger than 15 years with brain tumors is between 60 to 90 percent. Approximately two-thirds of survivors have long term neurological deficits. These neurologic deficits often manifest themselves as musculoskeletal abnormalities. It is essential to recognize the potential consequences of a CNS tumor and its associated treatments in an effort to prevent disability. Following the initial neurosurgical and oncologic treatment, the acute and chronic stages of the orthopaedic care for these patients differ significantly. Many of the rehabilitation and treatment principles for brain tumor patients have evolved from the principles used in stroke and traumatic brain injury. Orthopaedic treatment specifically includes preventing, identifying, and treating spasticity, contractures, bony and spinal deformities, and gait abnormalities.
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PMID:Orthopaedic issues in children and adolescents with central nervous system tumors. 2175 12


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