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Preliminary Results on Long-Term Potentiation-Like Cortical Plasticity and Cholinergic Dysfunction After Miglustat Treatment in Niemann-Pick Disease Type C

  • Alberto Benussi
  • Maria Sofia Cotelli
  • Maura Cosseddu
  • Valeria Bertasi
  • Marinella Turla
  • Ettore Salsano
  • Andrea Dardis
  • Alessandro Padovani
  • Barbara BorroniEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)

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.

Keywords

Long-term potentiation-like cortical plasticity Miglustat Niemann-Pick disease type C Short latency afferent inhibition Transcranial magnetic stimulation 

Supplementary material

459230_1_En_33_MOESM1_ESM.pdf (200 kb)
Supplementary Figure. SAI and LTP-like cortical plasticity in patients and HCs. (a) SAI at different ISIs. Data are plotted as a ratio to the unconditioned MEP amplitude. (b) PAS effect on corticospinal excitability, as measured by change in 1 mV MEP amplitude at various time points. HC healthy controls, ISI inter-stimulus interval, MEP motor evoked potential, P1/2/3/4 Patient 1/2/3/4, PAS paired associative stimulation, Pre pre-PAS baseline, SAI short-latency afferent inhibition (PDF 200 kb)

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Alberto Benussi
    • 1
  • Maria Sofia Cotelli
    • 2
  • Maura Cosseddu
    • 1
  • Valeria Bertasi
    • 2
  • Marinella Turla
    • 2
  • Ettore Salsano
    • 3
  • Andrea Dardis
    • 4
  • Alessandro Padovani
    • 1
  • Barbara Borroni
    • 1
    Email author
  1. 1.Centre for Ageing Brain and Neurodegenerative Disorders, Neurology UnitUniversity of BresciaBresciaItaly
  2. 2.Neurology UnitValle Camonica HospitalBresciaItaly
  3. 3.Department of Clinical NeurosciencesFondazione IRCCS Istituto Neurologico “Carlo Besta”MilanItaly
  4. 4.University Hospital “Santa Maria della Misericordia”UdineItaly

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