TMS for staging and predicting functional decline in frontotemporal dementia

Abstract

a b s t r a c tObjective: To evaluate if transcranial magnetic stimulation (TMS) measures correlate with disease severity and predict functional decline in frontotemporal dementia (FTD) phenotypes. Methods: Paired-pulse TMS was used to investigate the activity of different intracortical circuits in 171 FTD patients (122 bvFTD, 31 avPPA, 18 svPPA) and 74 healthy controls. Pearson's correlations were used to analyze the association between TMS measures and disease severity, while multiple regression analysis was used to identify the best clinical or neurophysiological measure to predict functional decline at 12 months. Results: We observed significant strong correlations between TMS measures [short interval intracortical inhibition-facilitation (SICI-ICF) and long interval intracortical inhibition (LICI)], and disease severity (evaluated with the FTLD-CDR) (all r > 0.5, p < 0.005). SICI-ICF, short interval intracortical facilitation (SICF) and LICI were also significant predictors of functional decline, evaluated as the change in FTLD-CDR scores at 12 months (all p < 0.005), while at the stepwise multiple regression analysis, SICI was the best predictor of disease progression, accounting for 72.5% of the variation in FTLD-CDR scores at 12 months (adjusted R 2 ¼ 0.72, p < 0.001). Conclusions:The present study has shown that the dysfunction of inhibitory and facilitatory intracortical circuits, evaluated with TMS, correlates with disease severity and progression, accurately predicting functional decline at 12 months, better than any other investigated marker.

Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

“…We also observed an association between serum GFAP concentration and indirect measures of GABAergic neurotransmission, which have been demonstrated to be impaired in FTLD (Benussi et al, 2019aPadovani et al, 2018), and reflect disease severity and progression (Benussi et al, 2020b(Benussi et al, , 2020a. We observed that the higher the serum GFAP concentration, the greater was the impairment in LICI, which is considered to reflect short-lasting postsynaptic inhibition mediated through the GABAB receptors at the level of local interneurons (Rossini et al, 2015;Ziemann et al, 2015).…”

Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

“…Cortex hyperexcitability as highlighted by a lower RMT, in fact, is a key feature of both ALS and FTD [ 116 ]. Same findings were replicated in a larger cohort of FTD patients using the Mini Mental State Examination test [ 117 ].…”

On the Use of TMS to Investigate the Pathophysiology of Neurodegenerative Diseases

“…SAI is not different in patients with FTD compared to healthy subjects; this is to be expected given that SAI reflects cholinergic transmission, which is not typically involved in FTD. As well as being correlated with the FTLD-CDR (a clinical rating scale to measure FTD severity), it was found that less SICI is associated with greater clinical progression of FTD (120). The interpretation was that, rather than reflecting impairments of a specific interneuron circuit, these abnormalities reflect an inability to integrate two, closely timed pulses.…”

“…Early studies of CSE in patients with FTD showed no changes compared to healthy subjects (103,118). However, a series of studies by Benussi et al have investigated intracortical circuits in a large number of FTD patients, finding that both intracortical facilitation (ICF and SICF) and inhibition (SICI and LICI) are lower in FTD than in healthy controls (119)(120)(121).…”