Blinking, a motor act consisting of a closing and an opening eyelid movement, can be performed voluntarily, spontaneously, and reflexly. In this study we investigated the kinematic features of voluntary, spontaneous, and reflex blinking in patients with Parkinson's disease (PD), OFF and ON dopaminergic treatment. Patients were asked to blink voluntarily as fast as possible. Spontaneous blinking was recorded for a minute during which the subjects just relaxed. Reflex blinking was evoked by electrical stimulation on the supraorbital nerve. Eyelid movements were recorded with the SMART analyzer motion system. Patients OFF therapy paused longer than controls during voluntary blinking but not during spontaneous and reflex blinking. The blink rate tended to be lower in patients OFF therapy than in controls and the spontaneous blinking had abnormally low amplitude and peak velocity. Finally, in patients OFF therapy the excitability of the neural circuit mediating the closing phase of the reflex blinking was enhanced. Dopaminergic treatment shortened the pause during voluntary blinking and increased the blink rate. In PD patients the longer pauses between the closing and opening phase in comparison to normal subjects, suggest bradykinesia of voluntary blinking. PD patients also display kinematic abnormalities of spontaneous blinking and changes in the excitability of the closing phase of reflex blinking.

Theta-burst stimulation (TBS) is a technique that elicits long-lasting changes in the excitability of human primary motor cortex (M1). Tonic contraction of the target muscle modifies the aftereffects of TBS, whereas interactions between phasic muscle contraction and the aftereffects of TBS are unknown. In this paper, we investigated whether phasic voluntary movements influence TBS-induced changes in M1 excitability. We examined whether a brief sequence of phasic finger movements performed by healthy humans before both intermittent TBS (iTBS) and continuous TBS (cTBS) influences TBS-induced aftereffects. Ten healthy subjects underwent iTBS and cTBS. To evaluate the TBS-induced aftereffects on M1 excitability, single TMS pulses were given over the FDI motor area before (T0) and 5 (T1), 15 (T2), and 30 min (T3) after TBS. To find out whether finger movements influenced the TBS-induced aftereffects, we tested motor-evoked potentials (MEPs) size by single TMS pulses at T0, immediately after movements, and at T1-T3. We also measured the kinematic variables mean amplitude and mean peak velocity of the movements. When no phasic voluntary movements preceded TBS, iTBS elicited facilitatory and cTBS elicited inhibitory aftereffects on MEP size. Conversely, movements performed before TBS elicited significant changes in the direction of the TBS-induced aftereffects. iTBS produced inhibitory instead of facilitatory aftereffects and cTBS produced facilitatory instead of inhibitory aftereffects. Finger movements alone had no effects on MEPs size tested with single-pulse TMS. Peripheral electrical stimulation had no effect on iTBS-induced aftereffects. Repeated phasic finger movements interfere with TBS-induced aftereffects probably by modulating mechanisms of brain metaplasticity.

The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) ≥ 18 years ≤ 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP(®)) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for these reasons, should encourage future research in this area with large, randomized clinical trials that evaluate the impact of a cognitive rehabilitation in patients with BTRE and cognitive deficits.

We performed a case series analysis to evaluate the effects of levetiracetam (LEV) monotherapy on seizures, adverse events, cognitive functioning and quality of life (QoL) in patients with brain tumor-related epilepsy (BTRE). We also explored the possible effects of systemic therapies on the efficacy of LEV. Twenty-nine patients were followed (13 female, 16 male; age 24-75 years) with 12 months of follow-up. Patients were evaluated by QoL and neuropsychological tests. At final follow-up, mean LEV dosage was 1991.4 mg/day. Among patients who reached the final follow-up of 12 months (n = 15), 1 patient had ≥50% reduction of seizure frequency (SF), and 14/15 were seizure free. The difference in presence/absence of seizures between baseline and final follow-up was significant (p < 0.001). Responder rate was 100%. We observed five side-effects: four mild (reversible) and one severe. Logistic regression revealed that chemotherapy and radiotherapy did not affect the efficacy of LEV in seizure outcome (p = 0.999). The following statistically significant observations emerged by tests' evaluation: less worry about seizures, effects of antiepileptic, and ability to maintain social functions. Our data suggest that seizure occurrence can be an important warning sign that the clinician should heed throughout the duration of the illness. Patients with BTRE represent a unique patient population that presents difficulties regarding management of two very different pathologies: epilepsy on the one hand, and brain tumor on the other. Our data indicate that LEV, in patients with BTRE, is safe and efficacious, with positive impact on QoL.