Author(s):
Bernardino, Inês ; Dionísio, Ana ; Castelo Branco, Miguel
Date: 2022
Persistent ID: https://hdl.handle.net/10316/101310
Origin: Estudo Geral - Universidade de Coimbra
Project/scholarship:
info:eu-repo/grantAgreement/FCT/3599-PPCDT/DSAIPA/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/PT;
Subject(s): Adult; Humans; Lovastatin; Neural Inhibition; Transcranial Magnetic Stimulation; Evoked Potentials, Motor; Neurofibromatosis 1
Description
Neurofibromatosis type 1 (NF1) is associated with GABAergic dysfunction which has been suggested as the underlying cause of cognitive impairments. Previous intervention trials investigated the statins' effects using cognitive outcome measures. However, available outcome measures have led to inconclusive results and there is a need to identify other options. Here, we aimed at investigating alternative outcome measures in a feasibility trial targeting cortical inhibition mechanisms known to be altered in NF1. We explored the neurochemical and physiological changes elicited by lovastatin, with magnetic resonance spectroscopy and transcranial magnetic stimulation (TMS). Fifteen NF1 adults participated in this randomized, triple-blind, placebo-controlled crossover trial (Clinicaltrials.gov NCT03826940) composed of one baseline and two reassessment visits after lovastatin/placebo intake (60 mg/day, 3-days). Motor cortex GABA+ and Glx concentrations were measured using HERMES and PRESS sequences, respectively. Cortical inhibition was investigated by paired-pulse, input-output curve, and cortical silent period (CSP) TMS protocols. CSP ratios were significantly increased by lovastatin (relative: p = 0.027; absolute: p = 0.034) but not by placebo. CSP durations showed a negative correlation with the LICI 50 ms amplitude ratio. Lovastatin was able to modulate cortical inhibition in NF1, as assessed by TMS CSP ratios. The link between this modulation of cortical inhibition and clinical improvements should be addressed by future large-scale studies.
