Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-six normal subjects and 34 patients with retrobulbar neuritis were studied with use of the technique of macrophage migration inhibition factor assay and myelin basic protein as antigen. Serial studies were carried out when possible. Normal subjects gave a mean migration index of 100.9+/-9. Eleven patients with retrobulbar neuritis alone gave a mean migration index of 55+/-16 in the first 3 weeks of illness, 89+/-17.3 during the fourth to the twenty-fourth weeks, and 100.9+/-9.0 after the twenty-fourth week. Ten multiple sclerosis patients with retrobulbar neuritis gave values of 61+/-21 in the first 3 weeks of an attack and 92+/-22.8 during the fourth to the twenty-fourth weeks, and 12 other multiple sclerosis patients 24 weeks or longer after an attack gave a value of 101.9+/-12.6. In a mean follow-up period of 1.9 years, only two patients presenting with retrobulbar neuritis alone have had a diagnosis of multiple sclerosis established; three others have weakness and reflex change in one limb only; and four have minor psychiatric problems. One retrobulbar neuritis patient has a family history of multiple sclerosis, but has no neurologic abnormalities. Comparison of these studies in both groups shows no statistical differences and supports the concept that cell-mediated hypersensitization to central nervous system myelin basic protein, however initiated, is a factor in the pathogenesis of retrobulbar neuritis.
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PMID:Retrobulbar neuritis. In vitro evidence of sensitization to myelin basic protein in patients without multiple sclerosis. 55 64

A 31-year-old woman with a history of suspected optic neuritis was admitted with weakness of right-sided extremities and confusion. On admission general physical examination revealed no abnormality. Neurological examination revealed central facial palsy, mild hemiparesis and hemisensory deficit on the right side. Cerebrospinal fluid analysis showed monocytosis of 29 cells, protein of 82 mg/dl, glucose of 62 mg/dl and myelin basic protein of 6.8 ng/ml. No oligoclonal bands were seen. X-ray computed tomographic (CT) scans showed multiple homogeneous contrast-enhancing lesions in the white matter of bilateral parietal lobes without distinct edema or mass effect. Follow-up CT scans showed ring-enhanced lesions. Magnetic resonance image (MRI) showed multiple Gadolinium-enhanced lesions. Additionally, 123I-IMP SPECT [Gamma view-SPCT 2000 H-20 (Hitachi Co.)] was performed at 30 minutes and 5 hours after intravenous administration of IMP (3 mCi). It showed high IMP uptake corresponding to the CT and MRI lesions. Cerebral angiography was considered to be normal. Other laboratory findings were within normal limits. A biopsy was performed. Histological examination showed spongiosis, gliosis and perivascular cuffing. The histological diagnosis was acute demyelinating disease. After therapy with methylprednisolone, she improved gradually. Enhanced lesions in CT and MRI may correspond to active demyelination at acute MS. High uptake of SPECT may also appear in acute stage, although it has not been reported. We should perform neuro-imaging studies including SPECT on acute MS.
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PMID:[A case of acute multiple sclerosis mimicking tumor on the neuro-imaging studies]. 130 32

Cycloleucine (CL), an inhibitor of methionine adenosyltransferase, has previously been used to produce an experimental model of subacute combined degeneration of the spinal cord. A re-investigation of its effects on the morphology of the nervous system and on brain concentrations of methionine and S-adenosylmethionine (SAM) was undertaken. Cycloleucine was administered as a single dose intraperitoneally (2 mg/g body weight) to young mice aged 21 d and adults aged 6 or 10 wks. The 21-day-old mice showed clinical evidence of toxicity within 24 h and thereafter developed progressive muscle weakness and ataxia. Animals did not survive longer than 1 wk. Light and electron microscopic examination of the central and peripheral nervous systems showed that intramyelinic vacuolation developed in the white matter of brain and cord within 12 h. The intramyelinic vacuolation in the white matter of brain and cord became more severe with longer survival, vacuoles coalescing and secondary axonal degeneration becoming evident. There was no myelin vacuolation in peripheral nerves. Axonal lesions occurred in the distal parts of motor nerves within 12-24 h resulting in degeneration of intramuscular nerve fibres and terminals. Later there was evidence of axonal degeneration in tibial and sciatic nerves. Many dorsal root ganglion cells became vacuolated or necrotic and numerous degenerated fibres were noted in the white matter of the spinal cord, particularly in the gracile funiculus. The optic nerves were not affected at any stage. In adult mice the pathology consisted of distal motor axonal degeneration which developed at 1-2 d. Little or no intramyelinic vacuolation in white matter was noted. Brain concentrations of SAM were reduced and levels of methionine became greatly elevated. The morphological effects of CL are considered to be the result of SAM deficiency impairing transmethylation processes known to be important in the formation and stabilization of myelin through the methylation of myelin basic protein. The immature developing central nervous system is much more vulnerable than the fully myelinated adult brain and spinal cord. The distal, predominantly motor axonopathy is a new observation and may be a reflection of the importance of transmethylation processes in the maintenance of axonal terminal membranes and the mechanisms of release of acetylcholine at the neuromuscular junction.
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PMID:Distal motor axonopathy and central nervous system myelin vacuolation caused by cycloleucine, an inhibitor of methionine adenosyltransferase. 162 9

Selective depletion of central nervous system norepinephrine (NE) by the neurotoxin 6-hydroxydopamine (6-OHDA) in rats subsequently inoculated with myelin basic protein (MBP) and complete Freund's adjuvant (CFA) produced experimental autoimmune encephalomyelitis (EAE) without the usual expected degree of weakness. The preservation of strength occurred in spite of continued weight loss. Post-decapitation myoclonic convulsive kick latency and kick number, which are known to depend on spinal cord NE, agreed well with the degree of weakness through the clinical disease course. The only difference between EAE groups was that the stronger 6-OHDA pretreated EAE animals did not have an elevated pons-medulla NE compared to saline intracisternal-ventricular (i.c.v.) pretreated controls. We conclude that 6-OHDA can influence the clinical course of weakness by interfering with central noradrenergic activity independent of other features associated with disease in EAE. This effect of 6-OHDA may be exerted through alteration of the blood-spinal cord barrier function and/or central nervous system blood flow.
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PMID:Suppression of clinical weakness in experimental autoimmune encephalomyelitis associated with weight changes, and post-decapitation convulsions after intracisternal-ventricular administration of 6-hydroxydopamine. 168 41

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.
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PMID:[Multiple sclerosis with higher cerebral dysfunction: a case report]. 199 97

Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi-convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter.
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PMID:[A case of herpes simplex encephalitis with cerebral white matter lesion after acyclovir administration]. 222 88

The effect of age on the ability of motor neurons to develop and maintain an enlarged total axonal and synaptic volume was compared in soleus muscles of 5-8-month and 25-30-month mice, 30-120 d after partial denervation. Before and after partial denervation (transection of the L5 root), the total number of muscle fibers was the same in all muscles. However, in young animals, there was only some transient atrophy and hypertrophy mostly receded by 120 d, whereas in old muscle, a more prominent early atrophy was followed by persistent hypertrophy. Ectopic endplates were not found. In zinc-iodide-osmium (ZIO) stained preparations, muscle fibers with small nerve terminals were present at 60 d and were still present in old muscle at 120 d. Fluorescent staining of nerve terminals and acetylcholine receptors revealed that in young muscle, postsynaptic sites were nearly or completely reoccupied by 60 d. In old muscle, about 22% of former junctions were denervated, with the remainder minimally to fully reinnervated. At 60 d and thereafter, collateral sprouts originated from nodes of Ranvier in both young and old muscle and were remyelinated in young but mainly unmyelinated and remarkably tortuous in old animals. These results, confirmed with immunofluorescent strains for myelin basic protein and neurofilaments, account for many of the physiological findings (Jacob and Robbins, 1990). Motor unit size expanded 2.5 times in young and 2 times in old muscle at 60 d after partial denervation. However, the increment in total quantal output and nerve terminal volume per motor neuron was 60-100% greater than control in young but only 20-25% greater in old muscle, with little further recovery. This inability of the motor neuron in old mice to expand the field of innervation may reflect a limitation imposed by reduced axonal transport. The present findings may elucidate the muscle weakness in postpolio syndrome and amyotrophic lateral sclerosis.
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PMID:Age differences in morphology of reinnervation of partially denervated mouse muscle. 233 95

In a hospital-based study of 400 patients with multiple sclerosis (MS), 42 per cent of patients who had had MS for 10 years or more had benign disease. Early age of onset and a long first remission were significantly associated with a good prognosis. There was a suggestion that initial presentation with paraesthesiae and possibly optic neuritis were associated with a benign prognosis, but the only significant finding was the association between limb weakness and a poor outcome (p less than 0.05). Fewer patients with benign disease had a progressive element to their disease than those in the more disabled group (p less than 0.001). The only laboratory test which was associated with a benign prognosis was the absence of CSF myelin basic protein in remission. Abnormalities of visual evoked response, CSF IgG and peripheral blood T lymphocytes appeared to have no value in assessing prognosis in the patients studied.
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PMID:A clinical and laboratory study of benign multiple sclerosis. 242 74

Region 65-102 of the myelin basic protein (MBP) houses a number of antigenic determinants known to induce delayed-type hypersensitivity, experimental allergic encephalomyelitis (EAE), suppressor cell function, and antibodies. In this report we describe the biological activity of synthetic peptides S53, S55, and S49 with sequence homology to region 69-84 of the rat, guinea pig, and bovine MBP. Peptide S53-A, defined by residues 75-84 of the guinea pig (SQRSQDEN) and of the rat (SQRTQDEN) MBP induced clinical signs of disease in Lewis rats. These included weight loss, flaccid tail, "muscle wasting," and hind-leg weakness. Histological examination of brain, spinal cord, and sciatic nerve sections of diseased rats revealed the complete absence of focal and perivascular lymphocytic infiltrates characteristics of demyelinating EAE lesions. Elongation of peptide S53 by three or six residues to residue sequences naturally found at its N-terminal end gave rise to peptides S55S (PQKSQRSQDEN) and S49S (GSLPQKSQRSDQDEN), respectively. Lewis rats challenged with either S55S or S49S developed classical clinical and histological signs of EAE. Severe hind-leg paralysis was accompanied by incontinence and sometimes death. Injected in the form of carrier-free peptide, S53 was a meager B cell immunogen. S53 conjugated with methylated-bovine serum albumin was also a potent immunogen and produced clinical signs of disease without CNS pathology. By comparison, carrier-free S55S and S49S were potent immunogens giving rise to antibodies that cross reacted completely and competitively with S55S but considerably less so with S53. The results show that the sequence of S53 defines an epitope responsible for the formation of anti-S53 antibodies. Elongation of the S53 sequence at its N-terminal end generated an additional epitope which induced cell-mediated immunity responsible for the concomitant development of pathological signs of EAE. It may be concluded that the induction of classical signs of EAE requires specific and defined sequences capable of expressing both B cell and T cell functions.
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PMID:Biological activity of region 65-102 of the myelin basic protein. 243 Jan 4

Histological and electrophysiological studies were performed on Lewis rats with acute experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea-pig myelin basic protein (MBP) and Freund's adjuvant. The histological studies showed demyelination in the lumbar, sacral and coccygeal dorsal and ventral spinal roots and to a lesser extent in the spinal cord, including the dorsal root entry and ventral root exit zones. The electrophysiological studies demonstrated reduced conduction velocities between the lumbar ventral roots and sciatic nerve. Conduction block was demonstrated at the ventral root exit zone of the lumbar spinal cord but was less severe than in rats with whole spinal cord-induced acute EAE. Recordings of the M wave and H reflex elicited in a hindfoot muscle by sciatic nerve stimulation showed a normal M wave, indicating normal peripheral nerve motor conduction, but a markedly reduced H reflex. The reduction in the H reflex is accounted for by demyelination-induced nerve conduction block in the dorsal and ventral spinal roots, intramedullary ventral roots and at the dorsal root entry and ventral root exit zones of the spinal cord. Demyelination and nerve conduction abnormalities were well established in the relevant lumbar segments on the day of onset of hindlimb weakness. It is concluded that demyelination in the lumbar ventral roots and to a lesser extent in the lumbar spinal cord, including the ventral root exit zone, is an important cause of hindlimb weakness in myelin basic protein-induced acute EAE in the Lewis rat.
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PMID:The pathophysiology of myelin basic protein-induced acute experimental allergic encephalomyelitis in the Lewis rat. 246 69


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