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)

Paraneoplastic neurological anti-Hu syndrome is one of the most frequent remote effects of cancer and usually manifests as encephalomyelitis combined with peripheral neuropathy. Subacute sensory neuronopathy, which results from the inflammatory destruction of sensory neurone cell bodies in the dorsal root ganglia, is thought to be the principal presentation of peripheral neuropathy. In addition to sensory involvement, evidence of motor nerve involvement is frequently found. The mechanisms of motor involvement remain largely unclear and there have been only a limited number of pathological studies. We present an autopsy case study of anti-Hu paraneoplastic encephalomyelitis/sensory-motor neuropathy, which confirms an inflammatory paraneoplastic destruction of sensory neuron cell bodies in the dorsal root ganglia and lower motor neurons in the spinal cord, as a cause of clinically rapidly progressive peripheral sensory-motor neuropathy.
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PMID:Paraneoplastic encephalomyelitis/sensory motor peripheral neuropathy - an autopsy case study. 1601 14

Neurologic complications, including meningoencephalitis, transverse myelitis, and peripheral neuropathy, have been reported in patients with acute infectious mononucleosis. Chronic active Epstein-Barr virus and human immunodeficiency virus infections occasionally induce central nervous system lymphoma. On the other hand, central nervous system disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. A 15-year-old girl who developed acute disseminated encephalomyelitis-like disease presenting fever, anuresis, diplopia, and muscle weakness is described here. Clinical and neuroimaging studies led to the diagnosis of encephalomyelitis. Despite the absence of infectious mononucleosis-like symptoms, anti-Epstein-Barr virus antibody titers in serum and cerebrospinal fluid showed the virus reactivation. The copy number of Epstein-Barr virus DNA increased in cerebrospinal fluid but not in peripheral blood. Ganciclovir and repeated methyl-prednisolone pulse therapy resulted in complete resolution. Central nervous system disease on the limited intrathecal reactivation of Epstein-Barr virus in immunocompetent children should be differentiated from acute disseminated encephalomyelitis.
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PMID:Epstein-Barr virus-associated meningoencephalomyelitis: intrathecal reactivation of the virus in an immunocompetent child. 1882 73

Glutamate neurotransmission is highly regulated, largely by glutamate transporters. In the spinal cord, the glutamate transporter GLT-1 is primarily responsible for glutamate clearance. Downregulation of GLT-1 can occur in activated astrocytes, and is associated with increased extracellular glutamate and neuroexcitation. Among other conditions, astrocyte activation occurs following repeated opioids and in models of chronic pain. If GLT-1 downregulation occurs in these states, GLT-1 could be a pharmacological target for improving opioid efficacy and controlling chronic pain. The present studies explored whether daily intrathecal treatment of rats with ceftriaxone, a beta-lactam antibiotic that upregulates GLT-1 expression, could prevent development of hyperalgesia and allodynia following repeated morphine, reverse pain arising from central or peripheral neuropathy, and reduce glial activation in these models. Ceftriaxone pre-treatment attenuated the development of hyperalgesia and allodynia in response to repeated morphine, and prevented associated astrocyte activation. In a model of multiple sclerosis (experimental autoimmune encephalomyelitis; EAE), ceftriaxone reversed tactile allodynia and halted the progression of motor weakness and paralysis. Similarly, ceftriaxone reversed tactile allodynia induced by chronic constriction nerve injury (CCI). EAE and CCI each significantly reduced the expression of membrane-bound, dimerized GLT-1 protein in lumbar spinal cord, an effect normalized by ceftriaxone. Lastly, ceftriaxone normalized CCI- and EAE-induced astrocyte activation in lumbar spinal cord. Together, these data indicate that increasing spinal GLT-1 expression attenuates opioid-induced paradoxical pain, alleviates neuropathic pain, and suppresses associated glial activation. GLT-1 therefore may be a therapeutic target that could improve available treatment options for patients with chronic pain.
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PMID:Spinal upregulation of glutamate transporter GLT-1 by ceftriaxone: therapeutic efficacy in a range of experimental nervous system disorders. 2054 13

The literature for evidence of autoimmunity in multiple sclerosis (MS) is analysed critically. In contrast to the accepted theory, the human counterpart of the animal model experimental autoimmune demyelinating disease, experimental allergic encephalomyelitis (EAE), is not MS but a different demyelinating disorder, i.e. acute disseminated encephalomyelitis and acute haemorrhagic leucoencephalitis. Extrapolation of EAE research to MS has been guided largely by faith and a blind acceptance rather than sound, scientific rationale. No specific or sensitive immunological test exists that is diagnostic of MS despite the extensive application of modern technology. Immunosuppression has failed to have any consistent effect on prognosis or disease progression. The available data on MS immunotherapy are conflicting, at times contradictory and are based on findings in animals with EAE. They show predominantly a 30% effect in relapsing/remitting MS which suggests powerful placebo effect. Critical analysis of the epidemiological data shows no association with any specific autoimmune diseases, but does suggest that geographic factors and age at development posit an early onset possibly dependent on environmental influences. Certain neurological diseases are, however, found in association with MS, namely hypertrophic peripheral neuropathy, neurofibromatosis-1, cerebral glioma, glioblastoma multiforme and certain familial forms of narcolepsy. These share a common genetic influence possibly from genes on chromosome 17 affecting cell proliferation. A significant number of these disorders are of neural crest origin, the classical example being abnormalities of the Schwann cell. These and other data allow us to propose that MS is a developmental neural crest disorder, i.e. a cristopathy, implicating glial cell dysfunction with diffuse blood-brain barrier breakdown. The data on transcription factor SOX10 mutations in animals may explain these bizarre clinical associations with MS and the phenotypic variability of such alterations (Cossais et al. 2010). Research directed to the area of neural crest associations is likely to be rewarding.
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PMID:The sad plight of multiple sclerosis research (low on fact, high on fiction): critical data to support it being a neurocristopathy. 2104 69

Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection, other neurologic complications may occur, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panicc attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome. We describe here a patient with a triad of unusual symptoms in chronic LNB including tremor, seizures and psychosis. Standardized medical interview, neurologic examination, neuroimaging, serum and CSF serology as well as EEG and EMNG evaluation were performed. The patient was treated with intravenous ceftriaxone and doxycycline and responded with rapid clinical and functional improvement.Newertheless, he suffered from multiple systemic and neurologic sequelas that influenced his daily activities in post treatment period. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating diagnosis, early treatment and the uncertainties concerning the sequelae after treatment. In patients with non-specific long lasting symptoms in the absence of overt clinical signs suggesting CNS involvement, routine treatment with i.v. ceftriaxone is not to be encouraged.
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PMID:Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB). 2164 54

The representative areas for examination of the mouse peripheral nervous system are the spinal cord, containing central components of the peripheral nervous system that needs to be examined at least at cervical and lumbar level, the sciatic and the tibial nerve. Skeletal muscle samples should include the soleus muscle and the quadriceps femoris or long digital extensor, as well as the medial gastrocnemius. Examination can be extended to the thoracic spinal cord, lumbar dorsal root ganglia and spinal nerve roots, as well as the plantar nerve, and other areas of interest. Perfusion fixation is considered optimal for the nervous system; however, immersion fixation allows producing microscopic sections of excellent quality as well. Paraffin-embedded, hematoxylin and eosin-stained sections can be made from all areas, save for small nerves such as the tibial or plantar nerve, which are examined with advantage in hard plastic sections. It is possible to produce hard plastic sections also of the vertebral column, including the spinal cord, dorsal root ganglia and nerve roots. For special investigations, mice can be fixed in toto, decalcified, embedded and sectioned to reveal the areas of interest. In the mouse peripheral nerves, myelination progresses until the adult age. In aging peripheral nerves there is axonal atrophy, degeneration, nerve fiber loss, increase of collagen and sporadic demyelination, especially radiculoneuropathy. The dorsal root ganglia of untreated control animals show frequent cytoplasmic vacuolation. Axonal degeneration is distally, primary demyelination proximally accentuated. Mouse is not very sensitive to peripheral neurotoxicity: to induce toxic peripheral neuropathy mostly parenteral administration and/or newborn animals are used. Naturally occurring infection affecting the spinal cord and peripheral nerves is Theiler's encephalomyelitis virus inducing acute poliomyelitis or chronic demyelination. Any experimental results are to be assessed taking into account spontaneous, age-related, background changes.
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PMID:Experience with examination of the spinal cord and peripheral nervous system (PNS) in mice: A brief overview. 2486 73

Hepatitis C virus (HCV) infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease. Among the extrahepatic manifestations, neuropsychiatric disorders have been reported in up to 50% of chronic HCV infected patients. Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations. Main HCV-associated neurological conditions include cerebrovascular events, encephalopathy, myelitis, encephalomyelitis, and cognitive impairment, whereas "brain fog", depression, anxiety, and fatigue are at the top of the list of psychiatric disorders. Moreover, HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia, and has also been recently recognized as an independent risk factor for stroke. These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy. The brain is a suitable site for HCV replication, where the virus may directly exert neurotoxicity; other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells, alterations in neurotransmitter circuits, autoimmune disorders, and cerebral or systemic inflammation. A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment; however, further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.
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PMID:Chronic hepatitis C virus infection and neurological and psychiatric disorders: an overview. 2574 Nov 33

X-linked Charcot-Marie-Tooth disease (CMTX1) results from numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32) and is one of the commonest forms of inherited neuropathy. Owing to the expression of Cx32 not only in Schwann cells but also in oligodendrocytes, a subset of CMT1X patients develops central nervous system (CNS) clinical manifestations in addition to peripheral neuropathy. While most GJB1 mutations appear to cause peripheral neuropathy through loss of Cx32 function, the cellular mechanisms underlying the CNS manifestations remain controversial. A novel start codon GJB1 mutation (p.Met1Ile) has been found in a CMT1X patient presenting with recurrent episodes of transient encephalomyelitis without apparent signs of peripheral neuropathy. In order to clarify the functional consequences of this mutation, we examined the cellular expression of two different constructs cloned from genomic DNA including the mutated start codon. None of the cloned constructs resulted in detectable expression of Cx32 by immunocytochemistry or immunoblot, although mRNA was produced at normal levels. Furthermore, co-expression with the other major oligodendrocyte connexin, Cx47, had no negative effect on GJ formation by Cx47. Finally, lysosomal and proteasomal inhibition in cells expressing the start codon mutant constructs failed to recover any detection of Cx32 as a result of impaired protein degradation. Our results indicate that the Cx32 start codon mutation is equivalent to a complete loss of the protein with failure of translation, although transcription is not impaired. Thus, complete loss of Cx32 function is sufficient to produce CNS dysfunction with clinical manifestations.
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PMID:A start codon CMT1X mutation associated with transient encephalomyelitis causes complete loss of Cx32. 2577 9

Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2) in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.
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PMID:Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models. 2583 19

Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain. Elicited pain levels were as high in Asic1a-/-, Asic2-/- and Asic3-/- mice as wild-type mice even though only Asic1a-/- mice showed reduced EAE disease severity, which indicates that pain in EAE was independent of disease severity. We thus adopted an EAE model without pertussis toxin (EAEnp) to restrain activated immunity in the periphery and evaluate the PNS contribution to pain. Both EAE and EAEnp mice showed similar pain behaviors and peripheral neuropathy in nerve fibers and DRG neurons. Moreover, pregabalin significantly reduced neuropathic pain in both EAE and EAEnp mice. Our findings highlight the essential role of the PNS in neuropathic pain in EAE and pave the way for future development of analgesics without side effects in the CNS.
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PMID:Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis. 2818 61


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