Abstract Details

Title Decreased Microglial Activation Precedes Stabilization of Disability in Multiple Sclerosis Patients Treated with Natalizumab

Topic MS and Related Diseases

Presentation(s) S21 - (-)

Poster/Presentation
Number 004

Objective

Background Our baseline data (Politis et al., 2012 Neurology) have demonstrated pathological increases of microglial activation in the cortex of MS patients and particularly in the precentral and postcentral gyrus that correlated with measures of clinical disability.

Design/Methods 10 MS patients (8F; 8 relapsing and 2 secondary progressive; EDSS range: 3.5-6.5) received a second 11C-PK11195 PET scan (a marker of microglial activation) one-year following treatment with natalizumab and were followed up clinically (with EDSS) six months before the first PET scan to 18 months after the second PET scan (total of 36 months). We used optimized modeling and segmentation procedures for the quantification of 11C-PK11195 binding.

Results The eight MS patients who completed the natalizumab infusions showed decreased 11C-PK11195 binding in the cortex (30%; p=0.0027), in the precentral (34%; p=0.0099) and postcentral (67%; p=0.0051) gyrus, following one-year treatment with natalizumab. Two MS patients had intermittent infusions or withdrew from therapy. The MS patient with intermittent infusions showed milder decreases in 11C-PK11195 binding ([sim]18%) whereas the MS patient who withdrew from treatment had an average of 23% increases in 11C-PK11195 binding. The correlations between 11C-PK11195 binding in cortex, precentral and postcentral gyrus and EDSS scores observed at baseline were not present following one-year treatment with natalizumab (p>0.1). The progressive increase of EDSS scores before initiation of tysabri (4.9% per six months) were slowed down 12 months following natalizumab until the end of the observation period with a borderline statistical EDSS improvement at 18 months (p=0.064).

Conclusions One-year treatment with natalizumab was associated with decreases of cortical microglial activation that could be relevant to the stabilization of physical disability.

Authors/Disclosures
Marios Politis, MD (Neurodegeneration Imaging Group) PRESENTER	No disclosure on file
Paolo Giannetti	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Richard S. Nicholas, FRCP (Imperial College Healthcare Trust)	Dr. Nicholas has nothing to disclose.
Paola Piccini, MD (Hammersmith Hospital)	No disclosure on file
Jan Claassen, MD, PhD (Columbia University College of Physicians & Surgeons)	Dr. Claassen has stock in iCE Neurosystems. The institution of Dr. Claassen has received research support from NINDS. The institution of Dr. Claassen has received research support from McDonnel Foundation. Dr. Claassen has received publishing royalties from a publication relating to health care. Dr. Claassen has received publishing royalties from a publication relating to health care.

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