title: Disability in multiple sclerosis: when synaptic long-term potentiation fails.
abstract: Clinical expression of brain damage varies over time and among individuals. This is particularly evident in Multiple Sclerosis (MS) where the expression clinico-radiological paradox has been coined to indicate the weak association between common neuroradiological markers of MS and clinical disability. Here we will review available data suggesting a possible role of adaptive synaptic long-term potentiation (LTP) in the clinical course of MS. We propose that the capacity of the brain to potentiate synaptic excitability in a long-lasting way is the brain's core adaptive property to bridge neuronal damage and clinical expression in multiple sclerosis. LTP, in fact, consists in the strengthening of synaptic communication between two connected neurons, and is virtually able therefore to restore membrane excitability of neurons that have lost part of their synaptic inputs. Recent studies have shown that cortical LTP reserve, explored through transcranial magnetic stimulation (TMS), contrasts disability progression in MS. Furthermore, promotion of cortical LTP through TMS induces acute cortical remapping and ameliorates motor symptoms in MS and in other neurological disorders.
authors.affiliation: Neurology Clinic, Department of Systems Medicine, University of Tor Vergata, Via Montpellier 1, 00133 Roma, Italy; IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Roma, Italy. Electronic address: sagit.weiss@googlemail.com.
authors.forename: Sagit
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Neurology Clinic, Department of Systems Medicine, University of Tor Vergata, Via Montpellier 1, 00133 Roma, Italy; IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Roma, Italy. Electronic address: francesco808@virgilio.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mori
authors.affiliation: Neurology Clinic, Department of Systems Medicine, University of Tor Vergata, Via Montpellier 1, 00133 Roma, Italy; IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Roma, Italy. Electronic address: silvia.rossi@uniroma2.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Neurology Clinic, Department of Systems Medicine, University of Tor Vergata, Via Montpellier 1, 00133 Roma, Italy; IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Roma, Italy. Electronic address: centonze@uniroma2.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods
keywords: Clinico-radiological paradox; Cortical remapping; Disability; Long term potentiation; Recovery; Synaptic plasticity; Transcranial magnetic stimulation