Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DEMYELINATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1987

Demyelinating disease of corpus callosum presenting as glioma on magnetic resonance scan: a case documented with pathological findings.

Magnetic resonance imaging (MRI) has improved the diagnosis of several pathological entities of the brain. MRI especially has been credited with distinguishing demyelinating diseases of the central nervous system from other diseases. The presence of a mass effect in a demyelinating disorder, however, makes difficult the distinction between tumor and a demyelinating disease. We report a case of a demyelinating disorder simulating an infiltrating glioma of the corpus callosum on MRI scan, resulting in surgical intervention. To our knowledge, this is the first case to be reported with MRI and documented pathological findings.

Adult↗
PubMed2006

Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher.

Prostaglandin (PG) D2 is well known as a mediator of inflammation. Hematopoietic PGD synthase (HPGDS) is responsible for the production of PGD2 involved in inflammatory responses. Microglial activation and astrogliosis are commonly observed during neuroinflammation, including that which occurs during demyelination. Using the genetic demyelination mouse twitcher, a model of human Krabbe's disease, we discovered that activated microglia expressed HPGDS and activated astrocytes expressed the DP1 receptor for PGD2 in the brain of these mice. Cultured microglia actively produced PGD2 by the action of HPGDS. Cultured astrocytes expressed two types of PGD2 receptor, DP1 and DP2, and showed enhanced GFAP production after stimulation of either receptor with its respective agonist. These results suggest that PGD2 plays an important role in microglia/astrocyte interaction. We demonstrated that the blockade of the HPGDS/PGD2/DP signaling pathway using HPGDS- or DP1-null twitcher mice, and twitcher mice treated with an HPGDS inhibitor, HQL-79 (4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine), resulted in remarkable suppression of astrogliosis and demyelination, as well as a reduction in twitching and spasticity. Furthermore, we found that the degree of oligodendroglial apoptosis was also reduced in HPGDS-null and HQL-79-treated twitcher mice. These results suggest that PGD2 is the key neuroinflammatory molecule that heightens the pathological response to demyelination in twitcher mice.

Animals↗
PubMed1996

Biology of the repair of central nervous system demyelinated lesions: an appraisal.

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

Animals↗
PubMed1997

Lack of a correlation between demyelinating plaques on MRI scan and clinical recovery in multiple sclerosis by treatment with electromagnetic fields.

A 50 year-old woman presented in January of 1995 with a prolonged history of symptoms of multiple sclerosis (MS) and was classified at the time with a remitting-progressive course. Her chief symptoms included slurring of speech, impairment of vision with intermittent diplopia, difficulties with gait and balance with spastic-ataxic gait, mental depression, insomnia, fatigue, impaired cognitive functions notably poor short term memory and recurrent urinary tract and sinus infections. An MRI scan showed multiple nodular demyelinating lesions scattered in the subcortical white matter and periventricularly of both cerebral hemispheres. Over the following 18 months, while receiving three treatment sessions per week with picotesla electro-magnetic fields (EMFs) which were applied extracranially, she showed a significant recovery in both physical and mental symptoms and additionally experienced decreased susceptibility to infections. In addition, the course of her disease appeared to have stabilized as opposed to the preceding 5 years during which time she experienced insidious, steady deterioration in her functioning. Despite this remarkable clinical recovery through the application of EMFs, and MRI scan obtained at the same diagnostic center 18 months after initiation of treatment with EMFs showed no changes in the number and size of the demyelinating plaques. These findings demonstrate lack of a correlation between recovery of symptoms and the number and extent of demyelinating plaques on MRI scan. It has been known since the days of Charcot in the latter half of the 19th century that in MS there is a great disparity between the histopathological changes of the disease and neurologic deficits. This report enhances the notion that demyelination may reflect an epiphenomenon of the disease.

Brain↗
PubMed1995

H-2 Dd transgene suppresses Theiler's virus-induced demyelination in susceptible strains of mice.

Theiler's murine encephalomyelitis virus is a picornavirus which induces chronic immune-mediated central nervous system demyelination and virus persistence in susceptible strains of mice. Using murine strains with congeneic recombinant haplotypes, the H-2D region within the class I major histocompatibility complex has been shown to be important in determining susceptibility/resistance to chronic Theiler's murine encephalomyelitis virus infection. We examined the role of H-2D in demyelinating disease with the use of transgenic D8 mice (H-2Dd, resistant haplotype) crossed to susceptible B10.Q (H-2q) and B10.S (H-2s) mice. Expression of the H-2Dd transgene dramatically suppressed demyelination and reduced the number of virus-antigen positive cells in the spinal cord 45 days following infection. More complete protection was observed in transgenic B10.Q (D8+) mice than in transgenic B10.S (D8+) mice. These experiments support the hypothesis that the immunologic basis of resistance by H-2D is determined by effective antigen presentation which prevents virus persistence and subsequent demyelination.

Animals↗
PubMed1980

Abnormal impulse generation in focally demyelinated trigeminal roots.

In 12 cats and two Macaca mulatta monkeys, areas of chronic focal injury were induced in the trigeminal root by implantation of a chromic suture in the nerve near its entry into the brain stem. Experimental lesions were examined histologically and electrophysiologically at 1 week, 3 weeks, and 6 weeks after surgery. At 3 weeks following implantation, lesioned nerves showed areas of focal inflammation surrounding implanted sutures with prominent demyelination of adjacent axons. A total of 497 trigeminal units were studied, 304 of which had associated demyelination of the root. In these 304 cells, two types of abnormal impulse generation from areas of focal demyelination were recorded. Reflected orthodromic action potentials and prolonged high-frequency after-discharges following short priming trains of orthodromic stimuli were observed in 23% and 4% of cells, respectively. Ectopic spike initiation from areas of focal demyelination was not dependent upon anatomical continuity of the nerve with the brain stem, was augmented by hyperventilation, and could be eliminated by the intravenous administration of diphenylhydantoin sodium. The relevance of these findings to the pathophysiological mechanisms of pain syndromes involving peripheral nerves in general and the trigeminal system in particular is discussed.

Action Potentials↗
PubMed2004

Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-beta plus vitamin B12: treatment to modify notch-1/sonic hedgehog balance.

Interferon-beta is a mainstay therapy of demyelinating diseases, but its effects are incomplete in human multiple sclerosis and several of its animal models. In this study, we demonstrate dramatic improvements of clinical, histological, and laboratory parameters in in vivo mouse models of demyelinating disease through combination therapy with IFN-beta plus vitamin B(12) cyanocobalamin (B(12)CN) in nonautoimmune primary demyelinating ND4 (DM20) transgenics, and in acute and chronic experimental autoimmune encephalomyelitis in SJL mice. Clinical improvement (p values <0.0001) was paralleled by near normal motor function, reduced astrocytosis, and reduced demyelination. IFN-beta plus B(12)CN enhanced in vivo and in vitro oligodendrocyte maturation. In vivo and in vitro altered expression patterns of reduced Notch-1 and enhanced expression of sonic hedgehog and its receptor were consistent with oligodendrocyte maturation and remyelination. IFN-beta-B(12)CN combination therapy may be promising for the treatment of multiple sclerosis.

Acute Disease↗
PubMed1995

Treatment of stable chronic demyelinating polyneuropathy with 3,4-diaminopyridine.

OBJECTIVE: To determine whether 3,4-diaminopyridine (3,4-DAP) would improve clinical or electrophysiologic function in patients with stable chronic demyelinating polyneuropathy. DESIGN: We conducted a prospective, randomized, placebo-controlled, blinded, crossover study of 3,4-DAP in 34 patients with demyelinating polyneuropathy. MATERIAL AND METHODS: Of the 17 men and 17 women, who were 21 to 80 years of age, 27 had hereditary motor and sensory neuropathy type I and 7 had acquired demyelinating polyneuropathy. Treatment consisted of stepped doses of 3,4-DAP (increasing to 20 mg four times daily) or placebo for 4 days. Pretreatment and posttreatment determination of the Neurologic Disability Score (NDS); isometric muscle strength testing; median, ulnar, and peroneal nerve conduction studies; and measurement of serum 3,4-DAP were performed. Quantitative computer-assisted sensory examinations were done in five patients. RESULTS: The results for the final day of treatment with 3,4-DAP or placebo and the differences between pretreatment and posttreatment findings for total NDS, sensory NDS, isometric muscle strength testing, compound muscle action potential amplitude, sensory nerve action potential amplitude, motor and sensory conduction velocities, and vibration and cold detection thresholds did not vary significantly. A small improvement of 4 points in the motor NDS (P < 0.05) was found. Five patients with electrophysiologic conduction block had no significant reduction in the degree of block. CONCLUSION: Because no improvement was noted in most measurements of neurologic function, despite use of high doses of drug, 3,4-DAP is unlikely to be beneficial in the treatment of stable chronic demyelinating polyneuropathy.

4-Aminopyridine↗
PubMed1999

[Childhood multiple sclerosis and allied demyelinative diseases].

We report five cases of multiple sclerosis (MS) and three cases of allied demyelinative diseases starting during childhood. Three of the MS patients presented with atypical initial symptoms, such as acute encephalitis or myelitis, making an early clinical diagnosis difficult. Ophthalmologic symptoms were noted in four of MS children, and in two with allied demyelinative diseases. Therefore, if a child shows ophthalmologic symptoms (i.e. optic neuritis, ophthalmoplegia), brain magnetic resonance imaging (MRI) should be conducted for the differential diagnosis of MS and other demyelinative diseases. Cerebrospinal fluid analysis is not useful for the initial diagnosis of MS, because pleocytosis and increase of oligoclonal IgG band in cerebrospinal fluid are seen in both MS and other demyelinative disorders. However, neuron specific enolase (NSE) is slightly higher in the latter than in the former. T2-weighted MRI of multiple sclerosis showed multiple high intensity areas in the white matter of the cerebrum and cerebellum, capsula interna, and crus cerebri etc. Most of these lesions were clinically silent, being characteristic of MS. In two MS cases, however, initial MRI revealed no abnormal findings. Thus, the diagnosis of MS can not be made by initial MRI only.

Biomarkers↗
PubMed1998

Osmotic demyelination syndrome with two-phase movement disorders: case report.

Osmotic demyelination syndrome (ODS) is characterized by regions of demyelination throughout the brain, which are most prominent in the pons. This demyelinating disease is associated with electrolyte disturbances and typically occurs in patients who are alcoholic or malnourished. Movement disorders are not frequently recognized in patients with ODS. This report describes a 22-year-old woman with ODS after correction of profound hyponatremia. The main neurologic symptom was two-phase movement disorder. First, she had acute onset dystonia, then the movement disorder transformed to generalized rigidity and tremors in the delayed second phase. Magnetic resonance imaging in the first phase revealed demyelinating lesions in the central pons, bilateral thalami and basal ganglia. In the second phase, the previous myelinolysis had been partially resolved. The clinical course of the two-phase movement disorder did not correlate with the resolving feature of neuroradiologic findings. During the second-phase movement disorder, the patient had a good response to propranolol and trihexyphenidyl.

Adult↗
PubMedDate not supplied

Chronic steadily progressive central and peripheral predominantly motor demyelination, involving the cranial nerves, responsive to immunoglobulins.

The association of central and peripheral demyelination was reported previously. Most of the cases refer to central chronic relapsing demyelination with clinical criteria for multiple sclerosis associated with later signs of peripheral nerve involvement. Other authors, described central lesions in patients with chronic inflammatory demyelinating polyneuropathy and in Guillain-Barré syndrome, as a seldom occurrence. We report a patient in which a chronic steadily progressive central and peripheral predominantly motor nervous system demyelination, involving the cranial nerves, was identified. The patient improved after intravenous immunoglobulin suggesting an immune-mediated mechanism. To our knowledge this presentation was not described before.

Adult↗
PubMed2000

Current perception threshold: an adjunctive test for detection of acquired demyelinating polyneuropathies.

Current Perception Threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of three sensory fiber subtypes: A-beta (2,000 Hz), A-delta (250 Hz) and C fibers (5 Hz). Demyelinating polyneuropathies tend to affect larger myelinated fibers before smaller unmyelinated fibers, and they usually begin at the proximal nerve roots or terminal axons, due to relative weakness of the blood-nerve barrier in these locations. Axonal polyneuropathies tend to affect smaller fibers before larger fibers, in a distal to proximal gradient. Ten patients with demyelinating polyneuropathy and ten patients with axonal polyneuropathy underwent CPT testing. CPT comparisons were made with regard to side-to-side asymmetries, fiber type involvement, and the ratio of fiber types involved. The C2, lateral antebrachial cutaneous, and sural distributions were examined bilaterally. Demyelinating polyneuropathies were detected with 50% sensitivity and 100% specificity. This diagnostic sensitivity is similar to that of published criteria based upon motor nerve conduction. CPT testing can distinguish demyelinating from axonal polyneuropathies. It may be particularly helpful in patients with predominantly sensory symptoms in whom EMG/NCS data may be equivocal, or in patients who decline EMG/NCS studies.

Action Potentials↗
PubMed2003

Inflammatory demyelinating disease mimicking malignant glioma.

UNLABELLED: The differential diagnosis between inflammatory demyelinating disease and malignant glioma is difficult based only on neuroimaging methods. METHODS: Four patients with inflammatory demyelinating disease who presented with clinical and neuroimaging findings strongly suggestive of malignant glioma were examined. RESULTS: MRI showed a mass lesion with prolonged T1 and T2 values and gadolinium enhancement in all cases. Proton MR spectroscopy and (201)Tl SPECT showed findings supportive of the diagnosis of malignant glioma in all cases. However, surgical biopsy revealed inflammatory demyelinating disease. After the diagnosis, 2 patients were treated by steroid administration and 2 were just observed. The gadolinium enhancement of all lesions decreased and finally disappeared. CONCLUSION: Such cases illustrate the importance of considering a demyelinating lesion in the differential diagnosis of a mass lesion. The difficulties encountered in establishing the correct diagnosis of inflammatory disease are related to the variations in the radiologic appearance, which require exclusion of gliomas or other brain tumors by surgical biopsy before the therapeutic strategy can be selected.

Adult↗
PubMed2002

Systematic reviews of treatment for chronic inflammatory demyelinating neuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathies include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraprotein-associated demyelinating neuropathy. This review summarises the evidence from randomised controlled trials (RCTs) for the treatment of these conditions. It leads to the conclusions that: 1) steroids are beneficial in CIDP but not MMN and their efficacy in paraproteinaemic demyelinating neuropathy (PDN) is uncertain; 2) intravenous immunoglobulin (IVIg) produces short-term benefit in CIDP, MMN and IgM PDN. Its effect in IgG or IgA PDN has not been tested in RCTs; 3) plasma exchange (PE) also produces short-term benefit in CIDP and IgG or IgA PDN but probably not in MMN; 4) there is almost no information from RCTs concerning the possible benefits of immunosuppressive agents; and 5) volunteers are needed to write Cochrane systematic reviews of IVIg for MMN and of interventions for PDN associated with IgG and IgA.

Humans↗
PubMed2003

[Sensitive chronic inflammatory demyelinating polyradiculoneuropathy in Schnitzler's syndrome].

BACKGROUND: Schnitzler's syndrome is a rare etiology of chronic urticaria. The disease is characterized by the association of chronic urticaria, intermittent chronic fever, bone pain, osteosclerotic bone lesions and IgM monoclonal gammapathy. More than fifty patients with this syndrome have been reported since Schnitzler reported the first case in 1974, but neuropathies are seen only in a few cases. CASE REPORT: Our patient developed, eight years after the diagnosis of Schnitzler'syndrome, a peripheral sensitive neuropathy. Anti-myelin-associated glycoprotein antibodies were not significant. A nerve biopsy specimen has revealed aspecific demyelinization. Direct and indirect immunofluorescence were negative. We conclused is that our patient presented chronic inflammatory demyelinating polyneuropathy. DISCUSSION: We found one published case of Schnitzler's syndrome and myelin-associated glycoprotein reactive peripheral neuropathy. The diagnosis of chronic inflammatory demyelinating polyneuropathy is a diagnosis of elimination. It is not the most common neuropathy associated with monoclonal gammapathy. To the best of our knowledge, it is the first case of Schnitzler's syndrome with this type of neuropathy. But there are some descriptions of chronic inflammatory demyelinating polyneuropathy presenting autoantibody activity against a myelin component, up to two years after the diagnosis of IgM monoclonal gammapathy.

Aged↗
PubMed2004

[Osmotic demyelination syndrome--can we avoid it?].

Osmotic demyelination syndrome is an iatrogenic disease related to inappropriately rapid correction of plasma osmolar disorders. The precise mechanism of injury is still unknown. Focal demyelination may appear in pontine (central pontine myelinosis, CPM) and extrapontine locations (extrapontine myelinosis, EPM), determining clinical manifestations of the disease. Modern techniques of radiological imaging like MRI play important role in demyelination syndrome diagnosis. The knowledge of conditions associated with an increased risk of osmotic demyelination syndrome and careful management of osmotic disturbances according to current standards may contribute to improved prognosis in this disease.

Demyelinating Diseases↗
PubMed2005

[Alteration of the auditory function and auditory nerve pathology in Guinea pigs with peripheral nerve demyelination].

OBJECTIVE: To study the auditory function and auditory nerve pathological changes of the experimental allergic neuritis (EAN) animal model in Guinea pigs. METHOD: To establish the animal model of EAN, heterologous myelin basic protein (MBP) of peripheral nerve was used to the immunize Guinea pigs. Serum anti-MBP-IgG levels, sciatic nerve conduction velocity (NCV), hearing thresholds and wave latencies, and pathological changes in auditory nerve, sciatic nerve and cochlea were observed. The immune lesions in inner ear were examined with immunohistochemistry. Auditory brainstem response (ABR) and compound action potential (CAP) were assayed weekly before and after immunization for a period of seven weeks. In the control group, antigen was replaced by the 0.9% saline. RESULT: Serum anti-MBP-IgG levels increased significantly in experimental group comparing with the control group (P < 0.01). Seiatic nerve conduction velocity decreased after immunization, as comparing with the control group (P < 0.01). Sciatic nerve and auditory nerve showed the existence of demyelination. There was significant increase of ABR and CAP thresholds and the latencies of wave I, III, V and N1 in experimental group when compared to the controls (P < 0.01), but no significant changes in inter-peak latencies of I-III, III-V were found( P > 0.05). In addition, there were 4 Guinea pigs (8 ears) in which only appeared lengthened wave latencies with normal hearing thresholds. Immunohistochemistry indicated that antibodies to inner ear from the MBP-sensitized animals distributed in cochlear nerve, neurofiber of inner ear and spiral ganglion cells. Cochlear scanning electron microscopy showed the pathology of inner hair cell with stereociliary disorder and cytoplasmic protrusions. CONCLUSION: The results suggest that auditory nerve demyelination are involved in this experimental allergic neuritis animal model and sciatic nerve demyelination as well, and the auditory abnormalities are elicited. This animal model seems to be a promising one of auditory dysfunction due to demyelination disorders.

Action Potentials↗
PubMed2006

Roles of an extracellular matrix (ECM) receptor and ECM processing enzymes in demyelinating canine distemper encephalitis.

Canine distemper virus (CDV) belongs to the genus Morbillivirus of the Paramyxoviridae family. Due to the central nervous system (CNS) tropism of the virus and associated neuropathological changes, demyelinating canine distemper encephalitis (CDE) represents a relevant model for human demyelinating diseases like multiple sclerosis. The present review decribes the role of CD44 antigen (CD44), the principle cell surface receptor for hyaluronate and extracellular matrix (ECM) processing enzymes (matrix metalloproteinases [MMPs]) and their inhibitors (TIMPs) in the pathogenesis of demyelination. In acute and subacute CDE, a plaque-associated CD44 up-regulation is found that parallels astrocyte activation. Likewise, MMPs and TIMPs are prominently up-regulated in these lesions and are expressed mostly by astrocytes and microglia. In chronic lesions, CD44 expression declines together with the number of glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, in this plaque type, CD44 is expressed on the cell membrane of perivascular mononuclear cells. In this phase, a decrease of MMP and TIMP expressions apart from MMP-11, -12, and -13 is obvious. In summary, CD44 and MMPs might be associated with the onset of demyelination and may interact to initiate ECM disturbances. Ligation of CD44 in the early phase may induce chemokines and cytokines and hence initiate and perpetuate the inflammatory process. In the chronic phase, it is conceivable that a MMP-TIMP imbalance may be the motor for lesion progression with a simultaneous influx of CD44-positive activated immune cells.

Animals↗