scholarly journals Glial and Axonal Pathology in Multiple Sclerosis

Author(s):  
Maria de los Angeles Robinson-Agramonte ◽  
Alina Gonzlez-Quevedo ◽  
Carlos Alberto
2015 ◽  
Vol 21 (10) ◽  
pp. 1280-1290 ◽  
Author(s):  
V Popescu ◽  
R Klaver ◽  
P Voorn ◽  
Y Galis-de Graaf ◽  
DL Knol ◽  
...  

Background: Cortical atrophy, assessed with magnetic resonance imaging (MRI), is an important outcome measure in multiple sclerosis (MS) studies. However, the underlying histopathology of cortical volume measures is unknown. Objective: We investigated the histopathological substrate of MRI-measured cortical volume in MS using combined post-mortem imaging and histopathology. Methods: MS brain donors underwent post-mortem whole-brain in-situ MRI imaging. After MRI, tissue blocks were systematically sampled from the superior and inferior frontal gyrus, anterior cingulate gyrus, inferior parietal lobule, and superior temporal gyrus. Histopathological markers included neuronal, axonal, synapse, astrocyte, dendrite, myelin, and oligodendrocyte densities. Matched cortical volumes from the aforementioned anatomical regions were measured on the MRI, and used as outcomes in a nested prediction model. Results: Forty-five tissue blocks were sampled from 11 MS brain donors. Mean age at death was 68±12 years, post-mortem interval 4±1 hours, and disease duration 35±15 years. MRI-measured regional cortical volumes varied depending on anatomical region. Neuronal density, neuronal size, and axonal density were significant predictors of GM volume. Conclusions: In patients with long-standing disease, neuronal and axonal pathology are the predominant pathological substrates of MRI-measured cortical volume in chronic MS.


2010 ◽  
pp. no-no ◽  
Author(s):  
Tomasz Dziedzic ◽  
Imke Metz ◽  
Tobias Dallenga ◽  
Fatima Barbara König ◽  
Sven Müller ◽  
...  

2000 ◽  
Vol 2 (2) ◽  
pp. 2-8
Author(s):  
Richard Ransohoff

Abstract The last decade has been an era of unprecedented progress in our understanding of multiple sclerosis (MS). MS is now considered a destructive process of the central nervous system, initiated by inflammatory demyelination but including prominent axonal pathology. This new knowledge has been acquired from new imaging techniques and traditional histopathologic study. New mechanisms of myelin destruction have been uncovered, and hypothetical new therapies for MS include neuroprotectants. Serial gadolinium-enhanced magnetic resonance imaging (MRI) scans reveal MS as a continuously active process. Brain and spinal cord atrophy, defined by MRI, correlate closely with clinical state. MR imaging techniques therefore are considered the standard tools for monitoring disease activity and severity. These efforts have produced improved therapy for patients with MS. Two classes of agents, interferon beta and glatiramer acetate, have been approved by the US Food and Drug Administration for use. A major challenge for clinicians is to provide early diagnosis and determine appropriate treatment. New neuroprotective and anti-inflammatory drugs are on the horizon.


2011 ◽  
pp. 150-164 ◽  
Author(s):  
Sridar Narayanan ◽  
Zografos Caramanos ◽  
Paul M. Matthews ◽  
Douglas L. Arnold

1999 ◽  
Vol 9 (4) ◽  
pp. 651-656 ◽  
Author(s):  
Barbara Kornek ◽  
Hans Lassmann

2004 ◽  
Vol 10 (6) ◽  
pp. 601-606 ◽  
Author(s):  
R Ehling ◽  
A Lutterotti ◽  
J Wanschitz ◽  
M Khalil ◽  
C Gneiss ◽  
...  

We investigated whether serum and cerebrospinal fluid (CSF) antibodies to the light subunit of the NF protein (NF-L), a main component of the axonal cytoskeleton, may serve as biological markers for axonal pathology and/or disease progression in multiple sclerosis (MS). IgG to NF-L was measured in sera and CSF of MS patients, patients with inflammatory demyelinating diseases of the PNS, with acute inflammatory neurological diseases (including bacterial and viral meningitis), with neurodegenerative diseases, with acute noninflammatory neurological diseases (including stroke, headache and backache) and healthy controls by enzyme-linked immunosorbent assay. We found that serum anti-NF-L IgG antibodies were significantly elevated in MS patients with primary progressive disease course and we provide evidence for an intrathecal production of these antibodies. Our findings support the use of serum antibodies to NF-L as a marker for axonal destruction.


2010 ◽  
Vol 16 (4) ◽  
pp. 406-411 ◽  
Author(s):  
Emma C Tallantyre ◽  
Lars Bø ◽  
Omar Al-Rawashdeh ◽  
Trudy Owens ◽  
Chris H Polman ◽  
...  

Growing evidence suggests that axonal degeneration rather than demyelination is the pathological substrate underlying chronic, irreversible disability in multiple sclerosis. However, direct evidence linking clinical disability measured in vivo with corresponding post-mortem measures of axonal pathology is lacking. Our objective in this study was to investigate the relationship between motor disability accumulated by patients with multiple sclerosis during life and the degree of axonal loss observed in their descending motor tracts after death. Human spinal cord derived at autopsy from 45 patients with multiple sclerosis was investigated. The medical records of each patient were reviewed by a multiple sclerosis neurologist to determine the degree of motor disability reached before death. Spinal cord sections were stained immunohistochemically. The degree of demyelination and the number of surviving corticospinal tract axons were measured in each patient. Patients who had accumulated higher levels of motor disability prior to death demonstrated fewer surviving corticospinal axons. Motor disability did not correlate with degree of demyelination. This study provides for the first time, direct clinico-pathological evidence that axonal loss is the pathological substrate of established disability in multiple sclerosis.


1999 ◽  
Vol 12 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Bruce D. Trapp ◽  
Richard Ransohoff ◽  
Richard Rudick

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