Is there a correlation between dyslipidemia and cognitive impairment in patients with multiple sclerosis?

Background. Multiple sclerosis (MS) is an autoimmune and demyelination disease of the central nervous system that causes progressive accumulation of disability over time. Recent studies have highlighted the correlation between metabolic disorders and cognitive dysfunctions. The present study aims to evaluate the correlation between components of the lipid profile and cognitive dysfunctions in patients affected by MS.Methods. 90 MS inpatients were included in this study. We divided the sample into three subgroups to evaluate the influence of the presence of dyslipidemia: G1 (patients with dyslipidemia), G2 (patients without dyslipidemia), G3 (patients with a higher than normal lipid value). Patients underwent rehabilitation treatment which included conventional physiotherapy, speech therapy, psychological support, cognitive rehabilitation, nutritional therapy, robotic rehabilitation, cognitive rehabilitation, and virtual reality.Results. The results showed that the three subgroups had a significant improvement in global cognitive functioning (MOCA p < 0.00), working memory (BRB-NV SRT-LTS p < 0.00) and in attention process (BRB-NV SDMT p < 0.00). Only in the G2, we observed a significant improvement in visuospatial abilities (RAO SPART p < 0.00). Moreover, we found that the cholesterol was negatively correlated with the cognitive functioning score of the patients after rehabilitation and the EDSS score. While the triglyceride scores were negatively correlated with the working memory score before and after rehabilitation. BMI scores were negatively correlated with the visuospatial ability score.Conclusion. Investigating these aspects could help in managing patients, preventing alterations that compromise the patient's quality of life.

Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study.

INTRODUCTION: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice. MATERIALS AND METHODS: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms. RESULTS: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group. CONCLUSION: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.

Bridging the Gap Towards Awareness Detection in Disorders of Consciousness: An Experimental Study on the Mirror Neuron System.

Advanced functional neuroimaging approaches dealing with motor imagery have disclosed covert cognitive processes in patients with disorders of consciousness (DoC). However, motor impairment and cognitive-motor dissociation can bias such approaches. Fourteen patients with post-traumatic DoC and ten healthy controls (HC) were provided with three motor tasks related to mirror neuron system (MNS) activation (movement observation, movement execution, and passive motor imagery of a movement) while recording electroencephalographic (EEG) metrics [EEG power and Granger Casualty Index (GCI)] to detect residual signs of conscious awareness. The most relevant finding was that all HCs, all patients with Minimally Conscious State and one with Unresponsive Wakefulness Syndrome demonstrated an event-related synchronization in the gamma range over left frontal regions, with high GCI values, in the passive motor imagery condition. These data significantly correlated with the level of behavioral responsiveness measured by the Coma Recovery Scale-Revised. Thus, our findings may indicate that motor tasks related to MNS can activate frontoparietal networks, although leading to different conscious processes. Hence, MNS assessment can be usefully employed to differentiate among patients with DoC.

Shaping neuroplasticity by using powered exoskeletons in patients with stroke: a randomized clinical trial.

BACKGROUND: The use of neurorobotic devices may improve gait recovery by entraining specific brain plasticity mechanisms, which may be a key issue for successful rehabilitation using such approach. We assessed whether the wearable exoskeleton, Ekso™, could get higher gait performance than conventional overground gait training (OGT) in patients with hemiparesis due to stroke in a chronic phase, and foster the recovery of specific brain plasticity mechanisms. METHODS: We enrolled forty patients in a prospective, pre-post, randomized clinical study. Twenty patients underwent Ekso™ gait training (EGT) (45-min/session, five times/week), in addition to overground gait therapy, whilst 20 patients practiced an OGT of the same duration. All individuals were evaluated about gait performance (10 m walking test), gait cycle, muscle activation pattern (by recording surface electromyography from lower limb muscles), frontoparietal effective connectivity (FPEC) by using EEG, cortico-spinal excitability (CSE), and sensory-motor integration (SMI) from both primary motor areas by using Transcranial Magnetic Stimulation paradigm before and after the gait training. RESULTS: A significant effect size was found in the EGT-induced improvement in the 10 m walking test (d = 0.9, p < 0.001), CSE in the affected side (d = 0.7, p = 0.001), SMI in the affected side (d = 0.5, p = 0.03), overall gait quality (d = 0.8, p = 0.001), hip and knee muscle activation (d = 0.8, p = 0.001), and FPEC (d = 0.8, p = 0.001). The strengthening of FPEC (r = 0.601, p < 0.001), the increase of SMI in the affected side (r = 0.554, p < 0.001), and the decrease of SMI in the unaffected side (r = - 0.540, p < 0.001) were the most important factors correlated with the clinical improvement. CONCLUSIONS: Ekso™ gait training seems promising in gait rehabilitation for post-stroke patients, besides OGT. Our study proposes a putative neurophysiological basis supporting Ekso™ after-effects. This knowledge may be useful to plan highly patient-tailored gait rehabilitation protocols. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03162263 .

Effects of virtual reality-based training with BTs-Nirvana on functional recovery in stroke patients: preliminary considerations.

AIM OF THE STUDY: Cognitive impairment occurs frequently in post-stroke patients. This study aimed to determine the effects of a virtual reality training (VRT) with BTs-Nirvana (BTsN) on the recovery of cognitive functions in stroke patients, using the Interactive-Semi-Immersive Program (I-SIP). MATERIALS AND METHODS: We enrolled 12 subjects (randomly divided into two groups: experimental group (EG); and control group (CG)), who attended the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of Messina from January to June 2016. The EG underwent a VRT with BTsN, whereas CG received a standard cognitive treatment. Both the groups underwent the same conventional physiotherapy program. Each treatment session lasted 45 minutes and was repeated three times a week for 8 weeks. All the patients were evaluated by a specific clinical-psychometric battery before (T0), immediately (T1), and one month (T2) after the end of the training. RESULTS: At T1, the EG presented a greater improvement in the trunk control test (p = 0.03), the Montreal Cognitive Assessment (p = 0.01), the selective attention assessment scores (p = 0.01), the verbal memory (p = 0.03), and the visuospatial and constructive abilities (p = 0.01), as compared to CG. Moreover, such amelioration persisted at T2 only in the EG. CONCLUSIONS: According to these preliminary data, VRT with I-SIP can be considered a useful complementary treatment to potentiate functional recovery, with regard to attention, visual-spatial deficits, and motor function in patients affected by stroke.

Improving Cognitive Function in Patients with Stroke: Can Computerized Training Be the Future?

BACKGROUND: Cognitive impairment after stroke is common and can cause disability with a high impact on quality of life and independence. Cognitive rehabilitation is a therapeutic approach designed to improve cognitive functioning after central nervous system's injuries. Computerized cognitive rehabilitation (CCR) uses multimedia and informatics resources to optimize cognitive compromised performances. The aim of this study is to evaluate the effects of pc cognitive training with Erica software in patients with stroke. METHODS: We studied 35 subjects (randomly divided into 2 groups), affected by either ischemic or hemorrhagic stroke, having attended from January 2013 to May 2015 the Laboratory of Robotic and Cognitive Rehabilitation of Istituto di Ricerca e Cura a Carattere Scientifico Neurolesi in Messina. Cognitive dysfunctions were investigated through a complete neuropsychological battery, administered before (T0) and after (T1) each different training. RESULTS: At T0, all the patients showed language and cognitive deficits, especially in attention process and memory abilities, with mood alterations. After the rehabilitation program (T1), we noted a global cognitive improvement in both groups, but a more significant increase in the scores of the different clinical scales we administered was found after CCR. CONCLUSIONS: Our data suggest that cognitive pc training by using the Erica software may be a useful methodology to increase the post-stroke cognitive recovery.

Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand.

BACKGROUND: Movement disorders associated with complex regional pain syndrome type I have been a subject of controversy over the last 10 years regarding their nature and pathophysiology, with an intense debate about the functional (psychogenic) nature of this disorder. The aim of this study was to test sensorimotor plasticity and cortical excitability in patients with complex regional pain syndrome type I who developed a fixed posture of the hand. METHODS: Ten patients with complex regional pain syndrome type I in the right upper limb and a fixed posture of the hand (disease duration less than 24 months) and 10 age-matched healthy subjects were enrolled. The following parameters of corticospinal excitability were recorded from the abductor pollicis brevis muscle of both hands by transcranial magnetic stimulation: resting and active motor thresholds, short-interval intracortical inhibition and facilitation, cortical silent period, and short- and long-latency afferent inhibition. Sensorimotor plasticity was tested using the paired associative stimulation protocol. RESULTS: Short-interval intracortical inhibition and long-latency afferent inhibition were reduced only in the affected right hand of patients compared with control subjects. Sensorimotor plasticity was comparable to normal subjects, with a preserved topographic specificity. CONCLUSIONS: Our data support the view that motor disorder in complex regional pain syndrome type I is not associated with abnormal sensorimotor plasticity, and it shares pathophysiological abnormalities with functional (psychogenic) dystonia rather than with idiopathic dystonia. © 2016 International Parkinson and Movement Disorder Society.

What Do We Know About the Influence of the Cerebellum on Walking Ability? Promising Findings from Transcranial Alternating Current Stimulation.

Several cerebellar functions related to upper limb motor control have been studied using non-invasive brain stimulation paradigms. We have recently shown that transcranial alternating current stimulation (tACS) may be a promising approach in shaping the plasticity of cerebellum-brain pathways in a safe and effective manner. This study aimed to assess whether cerebellar tACS at different frequencies may tune M1-leg excitability and modify gait control in healthy human subjects. To this end, we tested the effects of different cerebellar tACS frequencies over the right cerebellar hemisphere (at 10, 50, and 300 Hz, besides a sham-tACS) on M1-leg excitability, cerebellum-brain inhibition (CBI), and gait parameters in a sample of 25 healthy volunteers. Fifty and 300 Hz tACS differently modified M1-leg excitability and CBI from both lower limbs, without significant gait perturbations. We hypothesize that tACS aftereffect may depend on a selective entrainment of distinct cerebellar networks related to lower limb motor functions. Therefore, cerebellar tACS might represent a useful tool to modulate walking training in people with cerebellum-related gait impairment, given that tACS may potentially reset abnormal cerebellar circuitries.

Constrained Spherical Deconvolution Tractography Reveals Cerebello-Mammillary Connections in Humans.

According to the classical view, the cerebellum has long been confined to motor control physiology; however, it has now become evident that it exerts several non-somatic features other than the coordination of movement and is engaged also in the regulation of cognition and emotion. In a previous diffusion-weighted imaging-constrained spherical deconvolution (CSD) tractography study, we demonstrated the existence of a direct cerebellum-hippocampal pathway, thus reinforcing the hypothesis of the cerebellar role in non-motor domains. However, our understanding of limbic-cerebellar interconnectivity in humans is rather sparse, primarily due to the intrinsic limitation in the acquisition of in vivo tracing. Here, we provided tractographic evidences of connectivity patterns between the cerebellum and mammillary bodies by using whole-brain CSD tractography in 13 healthy subjects. We found both ipsilateral and contralateral connections between the mammillary bodies, cerebellar cortex, and dentate nucleus, in line with previous studies performed in rodents and primates. These pathways could improve our understanding of cerebellar role in several autonomic functions, visuospatial orientation, and memory and may shed new light on neurodegenerative diseases in which clinically relevant impairments in navigational skills or memory may become manifest at early stages.

Multiple sclerosis and amyotrophic lateral sclerosis: a human leukocyte antigen challenge.

Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are two different central nervous system pathology that, according to the most accredited hypotheses, recognize a different etiopathogenesis. The simultaneous occurrence of MS and ALS is quite unusual. To our knowledge, only three cases have been so far described by clinical, laboratory, and post-mortem studies. We report four new cases of this peculiar combination that have been observed and are herein described, included their human leukocyte antigen (HLA) profile studies. On the basis that three out of four patients in our case series presented HLA-B*18:01A, we may hypothesize that this antigen could play a role in developing both diseases.

Does the radiologically isolated syndrome exist? A dual-task cost pilot study.

Simultaneous performance of motor and cognitive tasks may compete for common brain network resources in aging or patients with some neurological diseases, suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for multiple sclerosis (MS) patients, it never has been tested on asymptomatic subject with magnetic resonance imaging (MRI) findings suggestive of demyelinating disease (i.e., radiologically isolated syndrome: RIS). In this pilot study, 10 RIS subjects and 10 sex/age-matched healthy controls were tested by means of static posturography under eyes opened (single-task trial) and while performing two different cognitive tasks (semantic modified word list generation for first dual-task trial and phonemic semantic modified word list generation for second dual-task trial), to estimate the dual-task cost (DTC) of standing balance. In our sample, under cognitive interference (without any substantial differences between semantic and phonemic modified word list generation), the RIS group showed significance differences in CoP (center of pressure) total sway area, ellipse eccentricity, CoP sway path length, CoP median sway velocity along the AP (anteroposterior) axis and along the ML (mediolateral) axis, reflecting a higher negative DTC respect to healthy subjects (which have simply shown a statistical trend, failing to reach a significance, in some trials). The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography in RIS subjects, too. We hypothesize that this approach could be useful to early reveal the presence of a demyelinating disease and to reach a MS diagnosis in subjects otherwise classified as RIS.

The role of virtual reality in improving motor performance as revealed by EEG: a randomized clinical trial.

BACKGROUND: Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training (RAGT) devices, including Lokomat, for the treatment of lower limb paresis. Virtual reality (VR) has proved to be a valuable tool to improve neurorehabilitation training. The aim of our pilot randomized clinical trial was to understand the neurophysiological basis of motor function recovery induced by the association between RAGT (by using Lokomat device) and VR (an animated avatar in a 2D VR) by studying electroencephalographic (EEG) oscillations. METHODS: Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were randomized into two groups. One group performed 40 sessions of Lokomat with VR (RAGT + VR), whereas the other group underwent Lokomat without VR (RAGT-VR). The outcomes (clinical, kinematic, and EEG) were measured before and after the robotic intervention. RESULTS: As compared to the RAGT-VR group, all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment. Moreover, they showed stronger event-related spectral perturbations in the high-γ and ß bands and larger fronto-central cortical activations in the affected hemisphere. CONCLUSIONS: The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance. EEG data suggest that the use of VR may entrain several brain areas (probably encompassing the mirror neuron system) involved in motor planning and learning, thus leading to an enhanced motor performance. TRIAL REGISTRATION: Retrospectively registered in Clinical Trials on 21-11-2016, n. NCT02971371 .

Transcranial Alternating Current Stimulation in Patients with Chronic Disorder of Consciousness: A Possible Way to Cut the Diagnostic Gordian Knot?

Unresponsive wakefulness syndrome (UWS) is a chronic disorder of consciousness (DOC) characterized by a lack of awareness and purposeful motor behaviors, owing to an extensive brain connectivity impairment. Nevertheless, some UWS patients may retain residual brain connectivity patterns, which may sustain a covert awareness, namely functional locked-in syndrome (fLIS). We evaluated the possibility of bringing to light such residual neural networks using a non-invasive neurostimulation protocol. To this end, we enrolled 15 healthy individuals and 26 DOC patients (minimally conscious state-MCS- and UWS), who underwent a γ-band transcranial alternating current stimulation (tACS) over the right dorsolateral prefrontal cortex. We measured the effects of tACS on power and partial-directed coherence within local and long-range cortical networks, before and after the protocol application. tACS was able to specifically modulate large-scale cortical effective connectivity and excitability in all the MCS participants and some UWS patients, who could be, therefore, considered as suffering from fLIS. Hence, tACS could be a useful approach in supporting a DOC differential diagnosis, depending on the level of preservation of the cortical large-scale effective connectivity.

Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

OBJECTIVE: The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment. SETTING: Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments. SUBJECTS AND METHODS: We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration. RESULTS: One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength. CONCLUSIONS: Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.

A local signature of LTP-like plasticity induced by repetitive paired associative stimulation.

Repetitive paired associative stimulation (rPAS) repeatedly pairs electrical nerve stimulation (ENS) with transcranial magnetic stimulation (TMS) of the contralateral motor hand area (M1) at 5 Hz frequency. So far, there are only few studies concerning the effects of PAS on the modulation of EEG power. Hence, aim of the present study was to investigate rPAS long term after-effects on cortical excitability looking at EEG power spectra. In four experimental sessions, separated by 2 weeks interval, 12 awake subjects received rPAS of the right median nerve and left M1 at a fixed interval (ISI) of 25 ms (real condition), 5 Hz-TMS on left M1, 5 Hz-ENS, of the right median nerve, and rPAS with changing ISI (sham condition). We measured peak-to-peak MEP amplitude, evoked from the target muscle (right abductor pollicis brevis muscle) at rest and the absolute power (POW) in four frequency bands: α (8-12 Hz), ß (13-30), θ (4-7) and δ (1-3), under rest conditions. All these parameters were evaluated in three detection blocks: baseline, immediately after and after 30' from the end of the conditioning protocol. Real rPAS induced a long-lasting homotopic cortical excitability modulation, as indexed by MEP amplitude increase, that was paralleled by a long-lasting reduction of α/ß-POW and by a widespread θ-δ-POW modulation. rPAS applied over the sensory-motor cortex induced an LTP-like plasticity, as indexed by a robust reduction in the α/ß POW positively correlated with the MEP amplitude increase. rPAS25ms may be a useful tool for motor neurorehabilitation promoting a sensory-motor coupling within ß oscillations.

Sativex in the management of multiple sclerosis-related spasticity: role of the corticospinal modulation.

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and Hmax/Mmax ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.

Defective cerebellar control of cortical plasticity in writer's cramp.

A large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer's cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients' maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (-40° to 40°) on the direction of movement of the mouse/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer's cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer's cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer's cramp, but not in healthy subjects, behavioural parameters reflecting their capacity for adapting to the rotation and for washing-out of an earlier adaptation predicted the efficacy of inhibitory cerebellar conditioning to influence sensorimotor plasticity: the better the online adaptation, the smaller the influence of cerebellar inhibitory stimulation on motor cortex plasticity. Altered cerebellar encoding of incoming afferent volleys may result in decoupling the motor component from the afferent information flow, and also in maladjusted sensorimotor calibration. The loss of cerebellar control over sensorimotor plasticity might also lead to building up an incorrect motor program to specific adaptation tasks such as writing.

Brain dynamic neurochemical changes in dystonic patients: a magnetic resonance spectroscopy study.

Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.

Do patients with multiple sclerosis benefit from semi-immersive virtual reality? A randomized clinical trial on cognitive and motor outcomes.

Multiple sclerosis (MS) is a demyelinating disease of autoimmune originate. A large proportion of patient present with cognitive deficits that negatively affect their quality of life, thus, a proper cognitive rehabilitation is mandatory. The aim of this study is to evaluate the effect of semi-immersive virtual reality training (sVRT) on neuropsychological and motor recovery individuals suffering from MS. We enrolled 60 MS patients, randomized into either the control group (CG: 30) undergoing a conventional cognitive training, or the experimental group (EG: 30), which performed sVRT. Cognitive and motor outcomes were investigated through clinical and neuropsychological scales before (T0) and at the end (T1) of each different training. Only in the EG, we observed a significant improvement in cognitive parameters and motor scores. Our data demonstrate that VR cognitive training could potentiate MS patients' rehabilitation outcome, with positive results on both motor and cognitive performance.