Faculty Bibliography

BACKGROUND:Growing evidence supports the efficacy of restorative cognitive training in people with multiple sclerosis (PwMS), but the effects vary across individuals. Differences in treatment efficacy may be related to baseline individual differences. We investigated clinical characteristics and MRI variables to predict response to a previously validated approach to home-based restorative cognitive training. METHODS:In a single-arm repeated measures study, 51 PwMS completed a 12-week at-home restorative cognitive training program called BrainHQ, shown to be effective in a placebo-controlled clinical trial. Baseline demographic, clinical, neuropsychological, and brain MRI factors were captured and the effects of treatment were quantified with Symbol Digit Modalities Test (SDMT). Also measured were indices of treatment compliance. Regression modeling was employed to identify the factors associated with greatest SDMT improvement. RESULTS:As a group, patients improved significantly after training: mean SDMT improving from 49.6 ± 14.7 to 52.6 ± 15.6 (t = 3.91, p<0.001). Greater SDMT improvement correlated positively with treatment exposure (r = 0.38, p = 0.007). Increased post-rehabilitation improvement on SDMT was predicted by baseline relapsing-remitting course (β=-0.34, p = 0.017), higher trait Conscientiousness-Orderliness (β=0.29, p = 0.040), and higher baseline gray matter volume (GMV; β=0.31, p = 0.030). CONCLUSION/CONCLUSIONS:The study was designed to explore the variables that predict favorable outcome in a home-based application of a validated restorative cognitive training program. We find good outcomes are most likely in patients with higher trait Conscientiousness-Orderliness, and relapsing-remitting course. The same was found for individuals with higher GMV. Future work in larger cohorts is needed to support these findings and to investigate the unique needs of individuals according to baseline factors.

Abstract: Introduction: Fatigue is one of the most prevalent and under-assessed non-motor symptoms in Parkinson's disease (PD). Current therapies have limited effectiveness. Presently, tDCS has shown potential to improve certain symptoms of PD. We designed a tDCS protocol to allow study participation from the patient's home, while maintaining clinical trial standards. We utilized a live video-conferencing platform and specially designed equipment that 'unlocks' one session at a time. Study objective: To assess feasibility and explore the therapeutic potential of remotely supervised tDCS (RS-tDCS) paired with cognitive training (CT) for PD patients suffering from fatigue.
Method(s): Double-blind, randomized, sham controlled study of RS-tDCS paired with CT. Participants completed 10 daily tDCS sessions (20-minute, 2.0-mA, bi-frontal, F3-F4 montage, left anodal), with the option of 10 additional open label sessions. Evaluation of preliminary clinical effects with the fatigue severity scale (FSS) along with tolerability, safety and compliance were completed.
Result(s): Eighteen participants were screened, 17 enrolled (Table 1), one screen failure. Incidence of the systematically recorded side effects were 22.4% tingling, 11.5% burning sensation, 8.2% itching, 3.3% headache, 0.9% nausea, 0.3% dizziness and 0.3% sleepiness. No serious adverse events reported. Compliance and tolerability were 100%. Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of mean FSS only in the real RS-tDCS group of 8.0 (SD 9.82) points (p < 0.05). Further analysis of 20 RS-tDCS sessions (10 DoubleBlind-real+10 Open-label) showed a further significant decrease in mean FSS of 11.47 (SD 10.7) points (p < 0.05).
Conclusion(s): At-home RS-tDCS therapy paired with CT is safe and well tolerated by PD patients, with the advantages of ease of recruitment and optimal subject compliance. At-home RS-tDCS therapy paired with CT shows potential to remediate fatigue symptoms in PD, but the small sample size limits efficacy conclusions. Our paradigm may be influential in designing future studies. [Figure presented] Introduction: Parkinson's Disease (PD) is a progressively disabling disease that affects patients and their caregivers' quality of life. PD is a chronic neurodegenerative disease affecting a large number of dopaminergic neurons in the nigrostriatal pathway, responsible for common motor dysfunction such as slowness, tremor and rigidity. The disease also leads to various non-motor symptoms, in particular, fatigue and cognitive disability. The available pharmacotherapy often allows for a relatively good control of symptoms, but complications could arise from the side effects of medications, or the progressive nature of the disease [1]. Certain alternative therapies have emerged such as non-invasive brain stimulation (NIBS) that may potentially improve declining function. Transcranial direct current stimulation (tDCS) is a low-cost, safe and practical treatment compared to other NIBS. tDCS is a portable device that utilizes a weak electrical current to modulate neuronal membrane potentials and cortical excitability [2-3]. Fatigue is a highly prevalent symptom that is largely unrecognized in PD with no current evidence-based treatment [4]. Since tDCS has shown beneficial effects in motor, mood and cognitive symptoms in PD, it may have potential to ameliorate fatigue in PD.
Method(s): The study design is a double blind randomized, sham controlled trial using at-home tDCS paired with CT. Remote supervision of tDCS sessions was performed through a video-conferencing platform. The tele-rehabilitation design has been recently validated and allows participation of patients from the comfort of their homes [5]. Feasibility and preliminary effects of RS-tDCS in PD were tested using a dorsolateral prefrontal cortex (DLPFC) montage (F3-F4 from the EEG 10x20 system). All participants received a baseline physical, neurological, fatigue and cognitive assessments. Participants were asked to complete 10 daily sessions. Once finalized, they were offered 10 additional open label (OpL) sessions. Using a detailed study "stop" criteria [6, 7] flow chart, participants were cleared at each step for their participation to proceed. The primary objectives of the study were to determine the feasibility of RS tDCS paired with CT and explore the potential to ameliorate fatigue in PD. Clinical effects on fatigue were measured with the fatigue severity scale (FSS), a scale largely validated and recommended for this population [4]. FSS was obtained at baseline and after 10 tDCS sessions of 20 minutes with 2 milliamperes (mA) intensity, while participants engaged in computerized based CT. During the visits, acceptability of therapy, tolerability, side effects and other adverse events (AEs) were collected. An optional OpL period allows for a more comprehensive exploratory evaluation of RS-tDCS effects beyond 10 sessions.
Result(s): Eighteen patients were screened and seventeen were enrolled (one screen failure). Only one participant decided to opt out of the OpL portion of the study. Patient demographic characteristics did not differ between groups (Table 1). Pain tolerability of 2.0 mA stimulation with <=6 on visual analog scale for pain (VAS-Pain) was 100%. Incidence of the systematically recorded side effects were 22.4% tingling, 11.5% burning sensation, 8.2% itching, 3.3% headache, 0.9%, nausea, 0.3% dizziness and 0.3% sleepiness. Other adverse events (AEs) are listed in figure 1. No serious AEs were reported. All required visits were completed with no attrition or interruptions (100% compliance). Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of mean FSS only in the real RS-tDCS group of 8.0 (SD 9.82) points (p < 0.05). Further analysis of 20 RS-tDCS sessions (10 DoubleBlind-real+10 Open-label) showed a further significant decrease in mean FSS of 11.47 (SD 10.7) points (p < 0.05) (Figure 2). [Figure presented] Discussion and
Conclusion(s): This novel design of remotely supervised tDCS has allowed conducting tDCS sessions safely and away from the lab setting, in the comfort of participant's homes. This paradigm of NIBS is particularly suited for medical conditions limiting mobility like PD, participants with busy schedules or living far distances from clinics. The initial results of this study showed that this protocol is feasible, acceptable and safe in PD with no major adverse events. [Figure presented] Our study has shown that RS-tDCS holds therapeutic potential for fatigue in people with PD, and showed 20 sessions seemed more favorable than 10 sessions. Trials with a greater sample size and extended treatment duration might be more suitable to establish the real efficacy for this therapy as a treatment of fatigue. Study Supported by Grant No. PDF-TRG-1722 from the Parkinson's Foundation. References [1] Kalia, L. V., & Lang, A. E. Parkinson's disease. Lancet, 386(9996), 896-912. (2015) [2] Priori, A., Berardelli, A., Rona, S., Accornero, N., & Manfredi, M. Polarization of the human motor cortex through the scalp. Neuroreport, 9(10), 2257-2260. (1998) [3] Nitsche, M. A., & Paulus, W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol, 527 Pt 3, 633-639. (2000) [4] Friedman, J. H., Beck, J. C., Chou, K. L., et al. Fatigue in Parkinson's disease: report from a mutidisciplinary symposium. NPJ Parkinsons Dis, 2. (2016) [5] Biagioni, M. C., Sharma, K., Migdadi, H. A., & Cucca, A. Non-Invasive Neuromodulation Therapies for Parkinson's Disease. IntechOpen, DOI: 10.5772/intechopen.75052. (2018) [6] Kasschau, M., Sherman, K., Haider, L., et al. A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS). J Vis Exp(106), e53542. (2015) [7] Charvet, L. E., Kasschau, M., Datta, A., et al. Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols. Frontiers in Systems Neuroscience, 9(26). (2015)
Copyright