title: Preliminary Results on Long-Term Potentiation-Like Cortical Plasticity and Cholinergic Dysfunction After Miglustat Treatment in Niemann-Pick Disease Type C.
abstract: Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder, which manifests clinically with a wide range of neurological signs and symptoms. We assessed multiple neurological, neuropsychological and neurophysiological biomarkers using a transcranial magnetic stimulation (TMS) multi-paradigm approach in two patients with NPC carrying a homozygous mutation in the NPC1 gene, and in two heterozygous family members.We assessed short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), long-interval intracortical inhibition (LICI), short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity with a paired associative stimulation (PAS) protocol.Baseline SAI and LTP-like plasticity were impaired in both patients with NPC and in the symptomatic heterozygous NPC1 gene mutation carrier. Only a limited decrease in SICI and ICF was observed, while LICI was within normal range in all subjects at baseline. After 12 months of treatment with miglustat, a considerable improvement in SAI and LTP-like plasticity was observed in both patients with NPC. In conclusion, these biomarkers could help to confirm the diagnosis of NPC, and may give an indication of prognostic outcomes in pharmacological trials.
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Piazzale Spedali Civili 1, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Benussi
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Cotelli
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Piazzale Spedali Civili 1, Brescia, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Cosseddu
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertasi
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Turla
authors.affiliation: Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Salsano
authors.affiliation: University Hospital "Santa Maria della Misericordia", Udine, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Piazzale Spedali Civili 1, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Piazzale Spedali Civili 1, Brescia, Italy. bborroni@inwind.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
keywords: Long-term potentiation-like cortical plasticity; Miglustat; Niemann-Pick disease type C; Short latency afferent inhibition; Transcranial magnetic stimulation