Delayed effects of radiation on the human central nervous system
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Abstract : Two cases of delayed effects of radiation on the central nervous system of man are reported. One demonstrates the rare early delayed reaction which occurs approximately three months after radiation. The lesions resemble most closely the plaques of acute multiple sclerosis and are not associated with degenerative vascular changes. This patient probably represents an extreme of the early delayed reaction reported by Scholz in dogs. There is clinical evidence suggesting that some degree of damage of this type occurs more frequently than has been suspected. The other patient had the late delayed reaction in which there are marked degenerative vascular alternations and severe destruction of the white matter with little cortical involvement. This patient is an extreme example of the well-documented late delayed effects of radiation and is presented for contrast with the patient in case 1. The presence of hypertrophic neurons in the irradiated cortex is a new and unexplained finding. (Author)Peripheral Nervous System
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OBJECTIVE: To determine if CNS infection with Herpes simplex 1 (HSV-1) results in 9spontaneous molecular reactivation9 without the development of recurrent immune mediated CNS demyelination
BACKGROUND: The nature of the initial trigger in MS - cytodegenertion (inside-out) or primary autoimmune attack (outside-in) remains controversial. Recently, Stys and colleagues argued in favour of a primary cytodegenerative mechanism as the initiating event with a convolution between progressive cytodegeneration and a variably primed immune system explaining the differences in clinical presentation (Nat Rev Neuro 2012). Previously, we provided evidence that viral infection in the CNS could act as the initiating event with recurrent immune mediated CNS demyelination resulting from acute and spontaneous molecular reactivation of HSV-1 in the CNS combined with an anti-viral T-cell immune response in the periphery of EAE susceptible mouse strains.
DESIGN/METHODS: To determine if HSV-1 DNA is present in the brains of BALB/c mice, a strain not developing recurrent demyelination after infection, solution phase PCR was performed during the intermediate (week 10) and late (week 25) stages of infection. Immunohistochemistry studies were performed to identify latently infected CNS cells expressing viral proteins without the development of infectious virus - spontaneous molecular reactivation.
RESULTS: Using solution phase PCR, HSV-1 DNA was identified in the brains of BALB/c mice at week 10 and 25 PI. CNS cells, stained with anti-HSV antibody, were identified in BALB/c mice during the intermediate stage of infection and when infectious virus could not be identified - consistent with spontaneous molecular reactivation.
CONCLUSIONS: This study provides support for 9spontaneous molecular reactivation9 of HSV-1 in BALB/c mice without associated immune mediated CNS demyelination. The results raise the possibility that latent viral infections of the CNS could fulfill the role of a primary cytodegenerative mechanism in an inside-out model of MS.
Study Supported by: Disclosure: Dr. Kastrukoff has nothing to disclose. Dr. Lau has nothing to disclose. Dr. Thomas has nothing to disclose.
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Demyelinating Disorder
Demyelinating disease
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Background: There is a growing need for biomarkers that can help in early diagnosis of multiple sclerosis (MS) and in recognizing patients with MS activity.Moreover, many studies are recently focusing on biomarkers that may help in diagnosis of the transition from relapsing remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS).Circulating microRNAs (miRNAs) are now considered promising biomarkers.Objectives: Studying the role of plasma miRNA-145 and miRNA-484 in the diagnosis of MS, disease activity and in diagnosing the transition from RRMS to SPMS.Patients and Methods: Forty-six subjects of both sexes were included, 31 patients with MS )21 with RRMS, 8 with SPMS and Two patients with primary progressive multiple sclerosis (PPMS)) and 15 healthy controls.Expression analysis of plasma miRNAs; miR-145 and miR-484 were assessed by real-time quantitative polymerase chain reaction (PCR) after miRNA extraction.Results: MicroRNAs 145 and 484 could significantly discriminate between MS cases and controls, with best cut-off values > 0.6 and > 1.7 respectively.They could also significantly discriminate between active and inactive MS cases, with best cut-off values > 0.8 and > 2 respectively.Plasma miRNA-145 could discriminate between RRMS and SPMS cases, with best cut-off value ≤1.4.Conclusion: Plasma miRNAs 145 and 484 might be used as promising biomarkers for early diagnosis of MS and in diagnosis of disease activity.Plasma miRNA-145 could be also helpful in diagnosis of the transition from RRMS to SPMS.
Relapsing remitting
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The pathological effects of multiple sclerosis are not confined to lesions; tissues that appear normal on conventional magnetic resonance imaging scans are also affected, albeit subtly. One imaging technique that has proven sensitive to such effects is T1-relaxation time measurement, with previous work demonstrating abnormalities in normal-appearing white matter and grey matter. In this work we investigated the evolution of T1-relaxation time changes in normal-appearing white matter and grey matter in relapsing—remitting multiple sclerosis. Three- and five-year follow-up data from 35 people with clinically early (a mean of 1.6 years from first clinical event) relapsing—remitting multiple sclerosis and 15 healthy controls were analysed. T1-relaxation time histograms were extracted from normal-appearing white matter and grey matter, and mean, peak height and peak location values were estimated. T1-relaxation time peak height declined in the multiple sclerosis normal-appearing white matter and grey matter, but not the control group (rate difference p = 0.024 in normal-appearing white matter, in normal-appearing grey matter p = 0.038); other T1-relaxation time changes were not significantly different between groups. Changes in T1-relaxation time measures did not correlate with increases in brain T2-weighted lesion loads or Expanded Disability Status Scale scores. These results suggest that the processes underlying changes in normal-appearing white matter and grey matter T1-relaxation times are not immediately linked to white matter lesion formation, and may represent more diffuse but progressive sub-clinical pathology in relapsing—remitting multiple sclerosis.
Relapsing remitting
Clinically isolated syndrome
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Clinically isolated syndrome
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Abstract Multiple sclerosis (MS) is the most common inflammatory central nervous system (CNS) disease. Yet, clinicians should be cognizant of other demyelinating and nondemyelinating CNS inflammatory diseases, some of which mimic MS. This chapter reviews the spectrum of non-MS CNS inflammatory diseases and MS mimics.
Demyelinating disease
Demyelinating Disorder
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Introduction Multiple Sclerosis (MS) is a chronic, inflammatory and nervous autoimmune disease which influences central nervous system (CNS). MS attacks axons with Myelin in the central nervous system and this attack damages Myelin and axons. The commonest type of MS observed in 85% of those affl
Demyelinating disease
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