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Increased PK11195 PET binding in the cortex of patients with MS correlates with disability.
Neurology 2012; 79(6):523-30Neur

Abstract

OBJECTIVE

Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability.

METHODS

Using PET and optimized modeling and segmentation procedures, we investigated cortical (11)C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29).

RESULTS

Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS.

CONCLUSIONS

Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM.

Authors+Show Affiliations

Centre for Neuroscience, Hammersmith Hospital, Imperial College London, London. marios.politis@imperial.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22764258

Citation

Politis, Marios, et al. "Increased PK11195 PET Binding in the Cortex of Patients With MS Correlates With Disability." Neurology, vol. 79, no. 6, 2012, pp. 523-30.
Politis M, Giannetti P, Su P, et al. Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology. 2012;79(6):523-30.
Politis, M., Giannetti, P., Su, P., Turkheimer, F., Keihaninejad, S., Wu, K., ... Piccini, P. (2012). Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology, 79(6), pp. 523-30. doi:10.1212/WNL.0b013e3182635645.
Politis M, et al. Increased PK11195 PET Binding in the Cortex of Patients With MS Correlates With Disability. Neurology. 2012 Aug 7;79(6):523-30. PubMed PMID: 22764258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. AU - Politis,Marios, AU - Giannetti,Paolo, AU - Su,Paul, AU - Turkheimer,Federico, AU - Keihaninejad,Shiva, AU - Wu,Kit, AU - Waldman,Adam, AU - Malik,Omar, AU - Matthews,Paul M, AU - Reynolds,Richard, AU - Nicholas,Richard, AU - Piccini,Paola, Y1 - 2012/07/03/ PY - 2012/7/6/entrez PY - 2012/7/6/pubmed PY - 2012/10/16/medline SP - 523 EP - 30 JF - Neurology JO - Neurology VL - 79 IS - 6 N2 - OBJECTIVE: Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability. METHODS: Using PET and optimized modeling and segmentation procedures, we investigated cortical (11)C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29). RESULTS: Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS. CONCLUSIONS: Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/22764258/Increased_PK11195_PET_binding_in_the_cortex_of_patients_with_MS_correlates_with_disability_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=22764258 DB - PRIME DP - Unbound Medicine ER -