Neurofilaments Highly specific neuronal proteins present in axons

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Neurofilaments • Highly specific neuronal proteins present in axons • Levels correlate with degree

Neurofilaments • Highly specific neuronal proteins present in axons • Levels correlate with degree of neuronal injury independent of causality • Are higher in CSF at all stages of MS, including CIS • In CSF and blood, are highly correlated • Essential for • Radial growth of axons during development • Maintaining caliber of axons • Regulation of velocity of nerve conduction • 3 types • Light chain: Nf. L – most soluble • Intermediate chain • Heavy chain: Nf. H CONTENT NO LONGER AVAILABLE • Nf. L and Nf. H have been examined most in MS Garcia ML, et al. J Cell Bio. 2003; 163: 1011 -1020. The journal of cell biology by ROCKEFELLER UNIVERSITY PRESS. Reproduced with permission of ROCKEFELLER UNIVERSITY PRESS in the format Other Published Product via Copyright Clearance Center.

Intrathecal Ig in MS Background • Intrathecal immunoglobulin synthesis • Is present in >90%

Intrathecal Ig in MS Background • Intrathecal immunoglobulin synthesis • Is present in >90% patients with MS and CIS • Likely reflects humoral immune response in the CNS • Correlations between unfavorable disease course and • Number of Ig. G OCB • Presence of Ig. M OCB • Increased Ig. G index • Available standard tests of CSF • Ig. G synthesis rate • Ig. G OCBs • Ig. G index CONTENT NO LONGER AVAILABLE Simo-Castello M, et al. Ann Neurosci. 2015; 22: 54. Gasperi C, et al. ECTRIMS 2017. Poster P 643.

Predicting MS Disease Progression From Placebo Arms Results • Progression in 434 (27. 4%)

Predicting MS Disease Progression From Placebo Arms Results • Progression in 434 (27. 4%) of subjects • Most important factors associated with progression* • PASAT • SF-36 PCS • VFT CONTENT NO LONGER AVAILABLE *No ranking of factors for prognostic importance. Copetti M, et al. ECTRIMS 2017 [Poster] P 324. Reproduced with permission from Dr. Massimiliano Copetti.

PPMS Misdiagnosis in 5 EU and U. S. Results Top 3 Presenting Symptoms •

PPMS Misdiagnosis in 5 EU and U. S. Results Top 3 Presenting Symptoms • Stiffness or weakness in the legs • Worsening bowel or bladder function • Sexual dysfunction Parameter 5 EU US Charts, no. 278 99 Male, % 56. 1 62. 6 Mean age, y 48. 7 51. 3 Initial misdiagnosis, % 16. 5 37. 4 Top 6 Misdiagnoses on Initial Presentation CONTENT NO LONGER AVAILABLE Shah-Manek B, et al. ECTRIMS 2017. [Poster] P 835. Reproduced with permission from Ipsos Healthcare.

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