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.
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Communicated by: Robin Lachmann, PhD FRCP
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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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Author Contributions
Conception and design of the study: AB, AP and BB. Acquisition and analysis of data: AB, MSC, MC, VB, MT, ES, AD, AP and BB. Drafting the manuscript and figures: AB, ES, AP and BB.
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AB, MSC, MC, VB, MT, ES, AD, AP, BB declare that they have no conflict of interest.
Ethical Standards
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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Benussi, A. et al. (2017). Preliminary Results on Long-Term Potentiation-Like Cortical Plasticity and Cholinergic Dysfunction After Miglustat Treatment in Niemann-Pick Disease Type C. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 36. JIMD Reports, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_33
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DOI: https://doi.org/10.1007/8904_2016_33
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