ObjectivesTo assess the feasibility and clinical efficacy of local field potentials (LFPs)–based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study.MethodsWe monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power.ResultsThe beta band power correlated in both experimental sessions with the patient's clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication [3-way analysis of variance, interaction day × medication p = 0.036; 30.5 ± 3.4 vs 22.2 ± 3.3, p = 0.003]), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor “on” states compared to “off” states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias.ConclusionsThe main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations.Classification of evidenceThis study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms.

BACKGROUND: The debilitating fatigue that patients with multiple sclerosis (MS) commonly experience during day-today living activities responds poorly to current therapeutic options. Direct currents (DC) delivered through the scalp (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor cortical excitability that persist for almost an hour after current offset and depend on current polarity. tDCS successfully modulates cortical excitability in various clinical disorders but no information is available for MS related fatigue. OBJECTIVE: In this study we aimed to assess fatigue symptom after five consecutive sessions of anodal tDCS applied over the motor cortex in patients with MS. METHODS: We enrolled 25 patients with MS all of whom experienced fatigue. We delivered anodal and sham tDCS in random order in two separate experimental sessions at least 1 month apart. The stimulating current was delivered for 15 minutes once a day for 5 consecutive days. In each session the Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were administered before the treatment (baseline), immediately after treatment on day five (T1), one week (T2) and three weeks (T3) after the last tDCS session. RESULTS: All patients tolerated tDCS well without adverse events. The fatigue score significantly decreased after anodal tDCS in 65% of the patients (responders). After patients received tDCS for 5 days their FIS scores improved by about 30% and the tDCS-induced benefits persisted at T2 and T3. CONCLUSION: Our preliminary findings suggest that anodal tDCS applied over the motor cortex, could improve fatigue in most patients with MS.

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.