Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation for Post-stroke Vascular Cognitive Impairment: A Prospective Pilot Study

Abstract

ObjectivePost-stroke cognitive impairment (PSCI) is resistant to treatment. Recent studies have widely applied repetitive transcranial magnetic stimulation (rTMS) to treat various brain dysfunctions, such as post-stroke syndromes. Nonetheless, a protocol for PSCI has not been established. Therefore, this study is aimed to evaluate the therapeutic effect of our high-frequency rTMS protocol for PSCI during the chronic phase of stroke.MethodsIn this prospective study, ten patients with PSCI were enrolled and received high-frequency rTMS on the ipsilesional dorsolateral prefrontal cortex (DLPFC) for 10 sessions (5 days per week for 2 weeks). Cognitive and affective abilities were assessed at baseline and 2 and 14 weeks after rTMS initiation. To investigate the therapeutic mechanism of rTMS, the mRNA levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, transforming growth factor beta [TGF-β], and tumor necrosis factor alpha [TNF-α]) in peripheral blood samples were quantified using reverse transcription polymerase chain reaction, and cognitive functional magnetic resonance imaging (fMRI) was conducted at baseline and 14 weeks in two randomly selected patients after rTMS treatment.ResultsThe scores of several cognitive evaluations, i.e., the Intelligence Quotient (IQ) of Wechsler Adult Intelligence Scale, auditory verbal learning test (AVLT), and complex figure copy test (CFT), were increased after completion of the rTMS session. After 3 months, these improvements were sustained, and scores on the Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) were also increased (p < 0.05). While the Geriatric Depression Scale (GeDS) did not show change among all patients, those with moderate-to-severe depression showed amelioration of the score, with marginal significance. Expression of pro-inflammatory cytokines was decreased immediately after the ten treatment sessions, among which, IL-1β remained at a lower level after 3 months. Furthermore, strong correlations between the decrease in IL-6 and increments in AVLT (r = 0.928) and CFT (r = 0.886) were found immediately after the rTMS treatment (p < 0.05). Follow-up fMRI revealed significant activation in several brain regions, such as the medial frontal lobe, hippocampus, and angular area.ConclusionsHigh-frequency rTMS on the ipsilesional DLPFC may exert immediate efficacy on cognition with the anti-inflammatory response and changes in brain network in PSCI, lasting at least 3 months.

Comparative efficacy of 5 non-pharmacological therapies for adults with post-stroke cognitive impairment: A Bayesian network analysis based on 55 randomized controlled trials

“…Evidence from the animal study suggests that the neuroprotective and pro-cognitive effects of TMS may exert by enhancing neurogenesis and activating BDNF/TrkB signaling pathway. A prospective pilot study conducted recently demonstrate that the scores of several cognitive evaluations increased after completion of the TMS session (34), which is similar to the results of pooled data in our study. However, it is worth noting that the stimulus parameters for TMS of the studies included in our network meta-analysis were not entirely consistent and subgroup analyses were not performed due to the limited literature, which may affect the reliability of the results to some extent.…”

Mechanical digit sensory stimulation: a randomized control trial on neurological and motor recovery in acute stroke

“…In addition, the rehabilitation and stimulation groups showed significantly lower levels of IL-17A and TNF-α, which tended to be at normal range, and higher levels of VEGF-A, which deviated even more from normal after intervention. These results suggest that both conventional rehabilitation and MDSS therapy were effective in inhibiting the secretion of pro-inflammatory cytokines (i.e., IL-17A and TNF-α) and promoting the production of nerve regeneration factor VEGF-A, thereby reducing neurological impairment and accelerating cognitive and limb motor function recovery (Zhang et al, 2021;Cha et al, 2022). There was no significant difference in the IL-17A, TNF-α, and VEGF-A levels, or the NIHSS, MMSE, FMA, and MBI results between the rehabilitation and stimulation groups after intervention.…”

Urinary dysfunction in patients with vascular cognitive impairment

“…In another study, a 2-week course of low-frequency rTMS (1 Hz) was effective in patients with Parkinson’s disease and UD, suggesting that rTMS could be effective in other neurological disorders with UD ( Brusa et al, 2009 ). A prospective study of 10 patients with post-stroke cognitive impairment receiving 2 consecutive weeks (5 days per week) of high-frequency rTMS (20 Hz) to the ipsilateral dorsolateral prefrontal cortex showed that treatment improved cognitive function and changed brain networks associated with post-stroke cognitive impairment, which lasted at least 3 months ( Cha et al, 2022 ). Although rTMS is now widely used for stroke survivors ( Kim et al, 2020 ; Lefaucheur et al, 2020 ), there are no clinical studies related to rTMS in patients with UD, and VCI and further studies are required.…”