Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this paper was to investigate the role of deferoxamine (DFO) scavenging of hydroxyl radical (.OH) on disruption of the blood-brain barrier (BBB) and demyelination in experimental optic neuritis. Eighteen strain-13 guinea pigs were sensitized for experimental allergic encephalomyelitis. Nine animals received 100 mg/kg of hydroxyethyl starch-conjugated (HES) DFO by daily intraperitoneal injection commencing the day of antigenic sensitization. Nine paired litter mates received daily IP injections of HES. Serial fat-suppressed magnetic resonance imaging of the optic nerves was obtained with a T2 weighting (T2w) to evaluate demyelination and after intravascular administration of Gd-DTPA to evaluate BBB disruption. The intensity of Gd-DTPA enhancement and T2w signal of the optic nerves was quantitated 3, 7, 10 and 14 days after antigenic sensitization. Animals were then sacrificed and the optic nerves processed for light and transmission electron microscopy with ultracytochemical localization of endogenous hydrogen peroxide (H2O2) and immunogold colocalization of extravasated serum albumin. The area of the optic nerve head, intensity of toluidine blue staining, and the cellular infiltrate were digitized and quantitated. Administration of HES-DFO significantly reduced the intensity of Gd-DTPA enhancement in the optic nerves of HES-DFO-treated animals compared to paired control HES animals (p = 0.0236), with the mean difference between control and treated animals of 19.39. The difference in T2w signal was not significant (p = 0.39), with a mean difference between control and treated animals of -5.51. The intensity of toluidine blue staining of optic nerve specimens was slightly less with HES-DFO compared to untreated animals (mean pair difference 2.48), and the inflammatory infiltrate was reduced with HES-DFO compared to untreated animals (mean pair difference = 61.57); these differences were not statistically significant. In the optic nerve specimens of both groups cerium perhydroxide-derived H2O2 reaction product was evident in a predominantly perivascular and perineural distribution. Immunogold-labeled serum albumin showed extravasation at foci of perivascular inflammation in both the presence and absence of H2O2-derived reaction product. Conjugated DFO reduces disruption of the BBB, as measured by Gd-DTPA enhancement, suggesting the .OH radical generated from perivascular H2O2 may play a role in alterations of vascular permeability in experimental optic neuritis.
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PMID:Conjugated deferoxamine reduces blood-brain barrier disruption in experimental optic neuritis. 753 78

The clinical and pathological characteristics of acute disseminated encephalomyelitis are briefly outlined. The possible relation between acute disseminated encephalomyelitis and other isolated monophasic inflammatory demyelinating episodes in the central nervous system, such as acute optic neuritis, transverse myelitis or brainstem lesions, is noted and the risk of progression to multiple sclerosis is examined. The surprising results of a clinical trial of corticosteroids in optic neuritis are of particular interest in this regard, and we speculate on an explanation in terms of a spread of antimyelin T cell receptor gene usage over time. Finally, the risk factors for the progression of demyelinating ther than optic neuritis to multiple sclerosis are explored. Further work to elucidate better the relationships between these pathological entities is suggested.
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PMID:Acute disseminated encephalomyelitis and isolated central nervous system demyelinative syndromes. 755 Nov 23

Two children with a recent history of viral illness developed visual loss secondary to optic neuritis. Clinical findings and neuroimaging were consistent with acute disseminated encephalomyelitis (ADEM). Markedly elevated opening pressures were noted on lumbar puncture. The patients demonstrated an initial favorable response to high-dose corticosteroid administration. Both had recurrence of symptoms after being tapered off oral corticosteroids. High-dose corticosteroids were reinstituted and a bilateral optic nerve sheath decompression was performed on one patient who developed profound visual loss. A second patient underwent a lumboperitoneal shunt. Both children had resolution of their symptoms and had a recovery of normal visual acuity.
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PMID:Medical and surgical management of acute disseminated encephalomyelitis. 788 25

Clinically, the Schumacher Panel criteria remain the best set of diagnostic criteria. Two subsets therein are definable, i.e., exacerbating-remitting (ER) and chronic progressive (CP), with the latter subdivided into progressive from onset and secondarily progressive. A clinically stable stage can also be recognized. It has been customary in treatment trials to separate ER and CP patients. End point for the latter is a comparison of neurologic status at the end of the trial with that entry. A similar assessment can be made for ER patients. With this criterion both types could be included in a single study. One could also, though, treat the exacerbation in an acute study or assess whether exacerbations can be prevented in a long-term trial. Most clinicians no longer consider monophasic disease as multiple sclerosis (MS). Depending on clinical extent, such patients are divisible into acute disseminated encephalomyelitis, Devic disease, transverse myelopathy, or optic neuritis. Each subgroup could be studied as with an acute exacerbation or in long term as to whether future and different neurologic insults can be prevented. One measure of neurologic status is the Disability Status Scale (DSS), which grades clinical impairment due to MS on a 0 (normal) to 10 (death due to MS) basis. The expanded DSS (EDSS) subdivides each step 1 through 9 into two. Type and severity of neurologic impairment is defined by graded involvement in the following eight functional systems (FS): pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. Frequency and severity of each FS correlates strongly with DSS scores.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical definition for multiple sclerosis treatment trials. 801 92

A retrospective analysis of CT and MRI studies in 12 patients with a clinical diagnosis of acute disseminated encephalomyelitis (ADEM) was performed. MRI was the definitive modality for the assessment of the lesions of ADEM: all patients had abnormalities consistent with the clinical diagnosis. Ten had abnormalities in the brain, three spinal cord lesions, and three showed evidence of optic neuritis. CT was normal in 6 of the 7 patients in which it was performed.
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PMID:MRI in acute disseminated encephalomyelitis. 804 43

In the LEW/N rat model, a decreased hypothalamic-pituitary-adrenal (HPA) axis response to inflammatory and immune mediators confers susceptibility to the development of a variety of inflammatory and immune diseases, including experimental allergic encephalomyelitis. In humans with optic neuritis, early intervention with steroids is associated with a decrease in the number of patients who go on to develop multiple sclerosis (MS). The current study was designed to determine whether patients with MS show evidence of a hypoactive HPA axis. Thirteen patients with MS were studied at baseline and with provocative tests of HPA axis function [ovine CRH, arginine vasopressin (AVP), and ACTH stimulation]. Compared to matched controls, patients with MS had significantly higher plasma cortisol levels at baseline. Despite this hypercortisolism and in contrast to patients with depression who had similar elevations in plasma cortisol levels, patients with MS showed normal, rather than blunted, plasma ACTH responses to ovine CRH, suggesting that the pathophysiology of hypercortisolism in MS is different from that in depression. Patients with MS also showed blunted ACTH responses to AVP stimulation and normal cortisol responses to high and low dose ACTH stimulation. Taken together, these findings are compatible with data from studies of experimental animals exposed to chronic inflammatory stress, which showed mild increased activation of the HPA axis with increased relative activity of AVP in the regulation of the pituitary-adrenal axis. These data do not support a role for hypocortisolism in MS once the disease is established.
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PMID:Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function. 807 72

Two children developed mental status alteration and bilateral profound visual loss secondary to optic neuritis. The clinical picture was consistent with parainfectious encephalomyelitis. Magnetic resonance imaging showed bilateral involvement of the thalamus in both cases. In one case the thalamic involvement was solitary and was suspected initially to represent a primary thalamic neoplasm. This was ruled out by a stereotactic biopsy of the thalamus, which showed perivascular inflammation consistent with parainfectious encephalomyelitis. The clinical and neuroimaging findings improved significantly following corticosteroid administration. Several relapses occurred upon initial attempts at corticosteroid cessation.
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PMID:Parainfectious optic neuritis and encephalomyelitis. A report of two cases with thalamic involvement. 809 89

We report a 76-year-old man who developed blurred vision and dementia. He was apparently well until April 4, 1990 (70-year-old at that time) when he had a sudden onset of bilateral loss of vision. Corrected vision was 0.1 (right) and 0.09 (left). He was admitted to the ophthalmology service of our hospital on April 9, 1990, and neurological consultation was asked on April 11. Neurologic examination revealed alert and oriented man without dementia. Higher cerebral functions were intact. He had bilateral large visual field defects with loss of vision; he was only able to count the digit number with his right eye and to recognize hand movement with his left eye. Otherwise neurologic examination was unremarkable. General physical examination was also unremarkable; he had no hypertension. Cranial CT scan was normal on April 11; lumber spinal fluid contained 1 cell/microliter, 63 mg/dl of sugar, and 97 mg/dl of protein; myelin basic protein was detected, however, oligoclonal bands were absent. He was treated with methylprednisolone pulse therapy and oral steroid, however, no improvement was noted in his vision. He started to show gaze paresis to left, ideomotor apraxia, agnosia of the body, and dementia. Cranial CT scan on June 11 revealed a low density area in the deep left parietal white matter facing the trigonal area of the lateral ventricle. He was discharged on July 2, 1990. Hasegawa dementia scale was 2/32.5 upon discharge. In the subsequent course, he showed improvement in his mental capacity and Hasegawa dementia scale was 22.5/32.5 in 1991, however, no improvement was noted in his vision. In 1994, he started to show mental decline in that he became disoriented, and showed delusional ideation of self persecution and depersonalization with occasional confusional state. He also showed unsteady gait. Cranial MRI on February 13, 1996 revealed a T2-high signal intensity lesion on each side of the parietal deep white matter more on the left and another T2-high signal intensity lesion in the left pons as well as in the right thalamus. He complained of right hypochondrial pain and was admitted to another hospital on April 22, 1996. He was markedly confused and demented. He continued to show bilateral loss of vision, but no motor palsy was noted. Cranial CT scan on April 23, 1996 revealed diffuse cortical atrophy and ventricular dilatation in addition to the low density areas in both parietal deep white matter. He developed jaundice in the middle of May. Abdominal CT scan revealed multiple low-to iso-density areas in the liver and marked iso-to high-density swelling of the right kidney. The patient expired on June 9th, 1996. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had had a carcinomatous limbic encephalitis with optic neuropathy and a choleduct carcinoma. Other opinions entertained included acute disseminated encephalomyelitis with optic neuritis, and granulomatous angiitis of the central nervous system. Some participants thought the primary site of the carcinoma was the right kidney with metastasis to the liver. Post mortem examination revealed a mixed type carcinoma in the right kidney with liver metastases. Neuropathologic examination revealed an incomplete softening in the optic chiasm and the left optic nerve, and in the left parieto-occipital areas. (The right hemisphere was frozen for future biochemical assay.) One of the adjacent cortical arteries had an organized thrombus. Other arteries and arterioles also showed sclerotic changes. Some of the leptomeningeal arteries were positive for Congored staining as well as for beta-amyloid immunostaining. Many senile plaques were seen diffusely in the cerebral cortex and neurofibrillary tangles were seen in the CA1 area and the parahippocampal gylus. No cellular infiltrations or demyelinated foci were seen. The neuropathologic features were consistent with circulatory disturbance based on the amyloid angiopa
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PMID:[A 76-year-old man with loss of vision and dementia]. 928 74

Since calcium activated neutral proteinase (calpain) is present in the central nervous system (CNS) and degrades myelin proteins, this endopeptidase has been suggested to play a role in myelin destruction in demyelinating diseases such as multiple sclerosis (MS). In the present study, calpain immunocytochemical expression was examined in Lewis rats with acute experimental allergic encephalomyelitis (EAE), an animal model for MS and optic neuritis. To identify cells expressing calpain, we labeled rat optic nerve sections for calpain with a polyclonal myelin calpain antibody and with monoclonal antibodies for glial (GFAP, OX42) and inflammatory (CD2, ED2, ED1, IFN-gamma) cell-specific markers. The results showed increased calpain expression in microglia (OX42) and infiltrating macrophages (ED1,2) in EAE compared to normal controls. Astrocytes constitutively expressed calpain in controls and acute EAE. Reactive astrocytes in EAE located in or near inflammatory foci, exhibited markedly increased calpain expression. Most T cells in acute EAE showed low level calpain expression while activated IFN-gamma-producing lymphocytes in inflammatory foci exhibited elevated levels of calpain expression. Thus, our results demonstrate increased calpain expression (at transcriptional and/or translational levels) in a rat model of optic neuritis. A role for calpain in myelin destruction during optic neuritis may be relevant to the pathogenesis of this disorder.
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PMID:Increased calpain expression in experimental demyelinating optic neuritis: an immunocytochemical study. 951 58

The encephalitogenicity of optic nerve tissue was demonstrated in Biozzi ABH (H-2(dq1)) mice. Acute experimental allergic encephalomyelitis (EAE) occurred in 11/14 animals and 4/5 exhibited relapse. The involvement of the optic nerve in spinal cord homogenate induced chronic relapsing EAE (CREAE) was demonstrated by mononuclear cell infiltration and myelin degradation in the optic nerve prior to and during clinical disease. During the relapse phase gross pathological assessment revealed swollen and translucent plaques on the optic nerves. Advanced lesions showed widespread demyelination, astrocytic gliosis and fibrotic changes of the blood vessels. Physiologically, the fast axonal transport of proteins from the retina to the optic nerve and superior colliculus was significantly decreased during relapse. The association of inflammation and demyelination with physiological deficit in the optic nerve highlights the usefulness of this model in the study of multiple sclerosis in which acute monosymptomatic unilateral optic neuritis is a common manifestation. Furthermore, the novel induction of CREAE with optic nerve homogenate suggests that optic neuritis is a common significant role in the pathophysiology and progression of neurological disease in CREAE which may be relevant to studies of optic neuritis in multiple sclerosis.
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PMID:Optic neuritis in chronic relapsing experimental allergic encephalomyelitis in Biozzi ABH mice: demyelination and fast axonal transport changes in disease. 958 18


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