Alteration of cortical excitability and its modulation by Miglustat in Niemann-Pick disease type C

摘要

Highlights ? New insights into pathophysiological mechanisms in patients with NP-C are provided. ? Impairment of cerebellar inhibition suggests Purkinje cell affection in NP-C. ? Affection of glutamatergic and cholinergic networks may be improved by Miglustat. ? TMS may be useful as biomarker of NP-C severity and Miglustat response. Abstract Niemann-Pick type C (NP-C) is a rare, neurodegenerative, lysosomal storage disease. Cortical excitability using different transcranial magnetic stimulation (TMS) protocols together with clinical and neuropsychological testing was longitudinally assessed in a patient with NP-C. Cerebellar inhibition, a measure for the integrity of the cerebello-thalamo-cortical network, was impaired. Short-latency afferent inhibition, a measure for cholinergic transmission, and cognitive functions were also impaired and improved under Miglustat treatment. Short interval intracortical facilitation, a marker for glutamatergic neurotransmission, was absent initially but increased after treatment with Miglustat. Our results provide new insights into pathophysiological mechanisms of NP-C and the response to Miglustat treatment.