DeMyelination And Axonal Damage In A Non-Human Primate Model Of Multiple Sclerosis
Mancardi G, Hart B, Roccatagliata L, Brok H, Giunti D, Bontrop R, Massacesi L, Capello E, Uccelli A
J Neurol Sci 2001 Feb 15;184(1):41-49
Univ of Genoa, Dept of Neurological Sciences and Vision, Via De Toni 5, 16132, Genoa, Italy
The DeMyelinating plaque is the paradigmatic lesion of Multiple Sclerosis (MS), but only recently attention has been given to Axonal Damage and to its role in the pathophysiology of disease.
Albeit the possible relevance of Axonal loss in MS and its experimental models, the amount and timing of Axonal sufferance has been addressed only in Experimental AutoImmune EncephaloMyelitis (EAE) of rodents.
In this report we observed that, in the marmoset model of EAE, Axonal damage occurs early during the DeMyelinating process as assessed by ImmunoReactivity for Amyloid Precursor Protein (APP).
And NonPhosphorylated NeuroFilaments (SMI-32 positive) detected mostly in early active lesions compared to late active and Normal-Appearing White Matter.
The rare occurrence of Morphological features of Axonal transection, such as APP or SMI-32 positive spheroids and swellings, as well as an increase of NeuroFilament density in the DeMyelinated Axons.
Without accumulation of electron dense Organelles or Osmiophilic bodies, at electron microscopy, suggests that early Axonal damage may be, at least in part, a reversible process.
These findings are of relevance for the development of therapies, which can protect Axons and enhance their function and survival.
The Oligodendrocyte Precursor Cell In Health And Disease
Levine JM, Reynolds R, Fawcett JW
Trends NeuroSci 2001 Jan 1;24(1):39-47
SUNY, Dept of NeuroBiology and Behavior, 11794, Stony Brook, NY, USA
Adult Oligodendrocyte Precursor Cells (OPCs) make up around 5-8% of the Glial Cell population in the CNS.
Their function in the undamaged CNS is largely unknown, but their processes are in contact with Nodes of Ranvier and Synapses, suggesting a regulatory role at these structures.
The cells divide slowly, and constitute approximately 70% of cells labelled following a pulse injection of BromodeoXyuridine.
In the injured CNS the cells form a reactive Glial population that undergoes hypertrophy and mitosis, probably driven by a variety of growth factors and Cytokines.
In response to DeMyelination they divide and are thought to differentiate to provide new Oligodendrocytes to replace those that have been lost.
However, ReMyelination fails during the later stages of Multiple Sclerosis, and it is not clear whether this is as a result of a depletion of adult OPCs, inhibition within the Glial scar, or damage to the Axons that prevents Myelination.
Adult OPCs are also activated and proliferate following other forms of CNS damage, such as mechanical injury, ExcitoToxicity and Viral infection. The cells produce several of the Chondroitin Sulphate Proteoglycans that might inhibit Axon regeneration.
Comparison Of Memory Performance In Relapsing/Remitting, Primary/Progressive And Secondary/Progressive Multiple Sclerosis
Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ
NeuroPsychiatry NeuroPsychol Behav Neurol 2001 Jan;14(1):32-44
Kessler Medical Rehabilitation Research and Education Corp., West Orange, New Jersey 07052, USA
PMID# 11234907; UI# 21129559
The current investigation was designed to examine the influence of disease course on the specific patterns of Acquisition and Retrieval Impairments in Multiple Sclerosis (MS).
Recent investigations of Learning and Memory in MS have shown that many subjects have Impaired Verbal and Visual New Learning Abilities, but normal long-term recall and recognition.
However, heterogeneity in the Learning and Memory abilities of subjects has been documented. Some evidence in the literature suggests that this heterogeneity may be in part attributable to clinical variables, such as disease course.
Verbal and Visual learning and Memory tests, modified to equate MS groups with healthy controls on initial acquisition of information, were administered to
- 64 individuals with Clinically Definite MS:
- Relapse/Remitting = 21
- Primary/Progressive = 18
- Secondary/Progressive = 25
- 20 healthy control participants
Recall and recognition performance then was evaluated at 30 minutes, at 90 minutes, and at 1 week for the verbal learning task, and at 30 minutes and at 90 minutes for the Visual learning task.
Results indicate that the two Progressive forms of MS result in significantly greater deficits in regard to the acquisition of New Verbal information, with the Secondary/Progressive group showing a significantly higher failure rate in regard to meeting the learning criterion.
Performance for recognition measures was not significantly different among groups, whereas Recall Performance of the Primary/Progressive group was significantly below that of the control group and of the Secondary/Progressive group.
When testing new learning with VisuoSpatial information, individuals with Relapsing/Remitting MS and Secondary/Progressive MS required more trials than control participants to learn the same amount of Visual information.
Visual Recall and Recognition performance did not differ between groups. No group differences in rates of forgetting for VisuoSpatial material was observed after equating for acquisition.
Results of the current study indicate that the primary problem in MS with regard to Memory functioning is in the acquisition of new information.
Our findings support previous research showing Verbal Memory Deficits with a Progressive disease course and VisuoSpatial Memory Deficits in Relapsing/Remitting MS.
However, the detailed analysis of new learning and memory performed in the current study, indicated that the Primary/Progressive group, may be showing difficulty in their ability to use newly learned information.
The pattern of new learning deficits observed between MS disease subtypes in the current study was determined to be unrelated to the duration of MS and to the physical severity of the disease.
The degree of physical disability observed in patients with MS, does not appear to be related to the degree of Cognitive decline.
Because of the distinct patterns and severity of Memory Dysfunction noted within each disease type, independent of physical disability.
Ge Y, Grossman RI, Udupa JK, Babb JS, Kolson DL, McGowan JC
AJNR Am J NeuroRadiol 2001 Mar;22(3):470-475
Fox Chase Cancer Center, Depts of, Radiology (Y.G., R.I.G., J.K.U., J.C.M.) and Neurology (D.L.K.), Hospital of the Univ of Pennsylvania, and Dept of Biostatistics (J.S.B.), Philadelphia, PA
PMID# 11237968; UI# 21133865
Background And Purpose
Gray Matter may be affected by Multiple Sclerosis (MS), a White Matter disease. Magnetization Transfer Ratio (MTR) is a sensitive and quantitative marker for structural abnormalities, and has been used frequently in the imaging of MS.
In this study, we evaluated the amount of MTR of Gray Matter among patients with Relapsing/Remitting MS and healthy control subjects as well as the correlation between Gray Matter MTR abnormality and Neurologic disability associated with Relapsing/Remitting MS.
We obtained fast Spin-Echo dual-echo and Magnetization Transfer (with and without MT saturation pulses) images from eighteen patients with Relapsing/Remitting MS and 18 age-matched healthy control subjects.
Gray Matter was segmented using a semiautomated system. Gray Matter MTR Histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS), total T2 lesion volume, and Gray Matter volumes were obtained for statistical analysis.
A significant difference was found in Gray Matter MTR between patients with Relapsing/Remitting MS and healthy subjects (mean and median).
Gray Matter MTR Histogram normalized peak heights in patients inversely correlated with EDSS (r = -0.65, P: =.01). There was also an inverse correlation between mean MTR of Gray Matter and total T2 lesion volume.
The MTR of Gray Matter significantly differed between patients with Relapsing/Remitting MS and healthy control subjects, suggesting that MS is a more diffuse disease affecting the whole Brain, and Neuronal damage accumulates in step with T2 lesion volume.
Our finding of the relationship between Gray Matter MTR and EDSS indicates that measurement of Gray Matter abnormality may be a potentially useful tool for assessing clinical disability in MS.