Focal muscle vibration and action observation: a combined approach for muscle strengthening.

Muscle strength is essential for autonomy in daily activities and performance in sports activities. Yet, conventional strength training is challenging during recovery from pathological conditions. This study investigates a novel combined intervention employing Focal Muscle Vibration (FMV) and Action Observation (AO) to enhance muscle strength. Twenty-seven healthy volunteers (18 females and 9 males, aged 22 to 42 years) were enrolled for an intervention-control study comparing 2 groups: the intervention group received AO treatment with FMV on the right leg, and the control group underwent only FMV on the right leg.  This design allowed the comparison of four conditions: FMV+AO (intervention group, right leg), AO alone (intervention group, left leg), FMV alone (control group, right leg), and no-treatment NT (control group, left leg). The treatment, conducted five times a week (Mon-Fri) for two weeks, involved a 20-minute session of FMV on the right quadriceps,  coupled, for the intervention group, with the observation of a gym training video. The assessments of Maximum Voluntary Contraction (MVC), and fatigue coefficient (FC) expressed at knee extension bilaterally were measured at the beginning (T0), after the first week (T1), at the end of treatment (T2), and one-week post-intervention for the follow-up (T3). The FMV+AO group demonstrated a significant improvement in MVC over time, reaching statistical significance at T2 and maintaining the gain at T3. In contrast, all the other conditions demonstrated milder MVC increases without statistical significance. FC did not differ significantly in any condition. The combination of FMV and AO optimized muscle strengthening, offering insights for targeted treatments in various settings.

Combining computer-based rehabilitative approach with tDCS for recovering of aphasia: Implications from a single case study.

We present a case of a single left hemisphere temporal-parietal stroke with subacute global aphasia and severe verbal apraxia and moderate dysphagia. The patient underwent a combined transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) and language stimulation with Virtual Reality Rehabilitation System (VRRS). Patient was treated in a 1-h session, for 5 days a week, for 4 consecutive weeks. After treatment, evident improvements in the comprehension of oral and written language, swallowing abilities, and caregiver burden were detected. Power spectrum analysis of EEG data revealed significant enhancements of θ, α, and ß waves from baseline to follow-up. These preliminary results seem to confirm the reliability of the tDCS translational application in conjunction with computer-based cognitive treatment for language disorders in a patient with stroke-induced aphasia.

Electrophysiological Screening to Assess Foot Drop Syndrome in Severe Acquired Brain Injury in Rehabilitative Settings.

BACKGROUND: Foot drop syndrome (FDS), characterized by severe weakness and atrophy of the dorsiflexion muscles of the feet, is commonly found in patients with severe acquired brain injury (ABI). If the syndrome is unilateral, the cause is often a peroneal neuropathy (PN), due to compression of the nervous trunk on the neck of the fibula at the knee level; less frequently, the cause is a previous or concomitant lumbar radiculopathy. Bilateral syndromes are caused by polyneuropathies and myopathies. Central causes, due to brain or spinal injury, mimic this syndrome but are usually accompanied by other symptoms, such as spasticity. Critical illness polyneuropathy (CIP) and myopathy (CIM), isolated or in combination (critical illness polyneuromyopathy, CIPNM), have been shown to constitute an important cause of FDS in patients with ABI. Assessing the causes of FDS in the intensive rehabilitation unit (IRU) has several limitations, which include the complexity of the electrophysiological tests, limited availability of neurophysiology consultants, and the severe disturbance in consciousness and lack of cooperation from patients. OBJECTIVES: We sought to propose a simplified electrophysiological screening that identifies FDS causes, particularly PN and CIPNM, to help clinicians to recognize the significant clinical predictors of poor outcomes in severe ABI at admission to IRU. METHODS: This prospective, single-center study included 20 severe ABI patients with FDS (11 females/9 males, mean age 55.10 + 16.26; CRS-R= 11.90 + 6.32; LCF: 3.30 + 1.30; DRS: 21.45 + 3.33), with prolonged rehabilitation treatment (≥2 months). We applied direct tibialis anterior muscle stimulation (DMS) associated with peroneal nerve motor conduction evaluation, across the fibular head (NCS), to identify CIP and/or CIM and to exclude demyelinating or compressive unilateral PN. RESULTS: At admission to IRU, simplified electrophysiological screening reported four unilateral PN, four CIP and six CIM with a CIPNM overall prevalence estimate of about 50%. After 2 months, the CIPNM group showed significantly poorer outcomes compared to other ABI patients without CIPNM, as demonstrated by the lower probability of achieving endotracheal-tube weaning (20% versus 90%) and lower CRS-R and DRS scores. Due to the subacute rehabilitation setting of our study, it was not possible to evaluate the motor results of recovery of the standing position, functional walking and balance, impaired by the presence of unilateral PN. CONCLUSIONS: The implementation of the proposed simplified electrophysiological screening may enable the early identification of unilateral PN or CIPNM in severe ABI patients, thereby contributing to better functional prognosis in rehabilitative settings.

Risk of injury and kinematic assessment of the shoulder biomechanics during strokes in padel players: a cross-sectional study.

BACKGROUND: Padel players commonly suffer from shoulder pain and the particularly high incidence is probably linked to the high frequency of strokes. In addition, due to the repetitive technical gesture, an adequate technique is essential in terms of performance and injury risk prevention. Aim of this study was to objectively evaluate shoulder kinematic during the athletic gesture to analyze the risk factors linked to padel strokes. METHODS: Professional and amateur padel players underwent a three-dimensional motion analysis of the padel strokes utilizing optoelectronic and surface electromyography systems (BTS Bioengineering, Garbagnate Milanese, Milan, Italy). RESULTS: Twelve padel players were included in this study (10 professional players in Group A and 10 amateurs in Group B). Experience influences the execution of padel strokes with a significant difference between group A and B in terms of gleno-humeral rotation and scapular tilt. Moreover, a subgroup analysis revealed that male players execute voleè with a higher external rotation (P=0.043), and forehand with a higher scapular tilt (P=0.044). CONCLUSIONS: The results confirm that the high ranges of motion of the overhead strokes could rise the risk of slap lesion, impingement, and glenohumeral internal rotation deficit. However, a correct execution of the athletic gesture is linked with a dynamic stabilization of the humeral head. In conclusion, the kinematic analysis could help in the early identification of the kinematic alteration to build a tailored rehabilitation plan based on the athlete's needs.

Efficacy of Visual Feedback Training for Motor Recovery in Post-Operative Subjects with Knee Replacement: A Randomized Controlled Trial.

To evaluate the effects of visual feedback training on motor recovery in postoperative patients with a total knee replacement (TKR). The performance of 40 first-ever TKR patients (27 females; mean age: 70.5 (67.2−74.0) years) was evaluated in a single center, single-blind, randomized controlled study. The patients were randomly and equally distributed into two demographically/clinically matched groups undergoing experimental or traditional treatments. All patients have been treated in a 1 h session, 2/day for 5 days a week, for six consecutive weeks. The first group ("control") underwent conventional physical therapy, whereas the experimental group received advanced knee training with visual feedback using the TecnoBody® device (Walker View 3.0 SCX, Dalmine (BG), Italy). The clinical scales and kinematic parameters coming from the gait analysis were evaluated to demonstrate the dynamic balance function in a standing position before and after each treatment. After the treatment, both experimental and control groups improved significantly and similarly, as measured by the clinical scales (Numeric Rating Scale for Pain and Barthel index). A significant boosting of the motor performance was detected in the experimental group with respect to the control group in the terms of symmetry index 84 (80.8−85.4) vs. 87.15 (84−92.8) p = 0.001 *; single stance support 34.9 (34.1−36.5) vs. 37.8 (36.6−38.9); p < 0.001; and obliquity parameters 58.65 (51.3−70.3) vs. 73 (62.3−82.1); p < 0.001. Applying visual feedback training in addition to traditional rehabilitation strategies improves the knee function and motor control in postoperative TKR patients.

Fractal Dimension Feature as a Signature of Severity in Disorders of Consciousness: An EEG Study.

An accurate diagnosis of the disorder of consciousness (DOC) is essential for generating tailored treatment programs. Accurately diagnosing patients with a vegetative state (VS) and patients in a minimally conscious state (MCS), however, might be very complicated, reaching a misdiagnosis of approximately 40% if clinical scales are not carefully administered and continuously repeated. To improve diagnostic accuracy for those patients, tools such as electroencephalography (EEG) might be used in the clinical setting. Many linear indices have been developed to improve the diagnosis in DOC patients, such as spectral power in different EEG frequency bands, spectral power ratios between these bands, and the difference between eyes-closed and eyes-open conditions (i.e. alpha-blocking). On the other hand, much less has been explored using nonlinear approaches. Therefore, in this work, we aim to discriminate between MCS and VS groups using a nonlinear method called Higuchi's Fractal Dimension (HFD) and show that HFD is more sensitive than linear methods based on spectral power methods. For the sake of completeness, HFD has also been tested against another nonlinear approach widely used in EEG research, the Entropy (E). To our knowledge, this is the first time that HFD has been used in EEG data at rest to discriminate between MCS and VS patients. A comparison of Bayes factors found that differences between MCS and VS were 11 times more likely to be detected using HFD than the best performing linear method tested and almost 32 times with respect to the E. Machine learning has also been tested for HFD, reaching an accuracy of 88.6% in discriminating among VS, MCS and healthy controls. Furthermore, correlation analysis showed that HFD was more robust to outliers than spectral power methods, showing a clear positive correlation between the HFD and Coma Recovery Scale-Revised (CRS-R) values. In conclusion, our work suggests that HFD could be used as a sensitive marker to discriminate between MCS and VS patients and help decrease misdiagnosis in clinical practice when combined with commonly used clinical scales.

The Route of Motor Recovery in Stroke Patients Driven by Exoskeleton-Robot-Assisted Therapy: A Path-Analysis.

Background: Exoskeleton-robot-assisted therapy is known to positively affect the recovery of arm functions in stroke patients. However, there is a lack of evidence regarding which variables might favor a better outcome and how this can be modulated by other factors. Methods: In this within-subject study, we evaluated the efficacy of a robot-assisted rehabilitation system in the recovery of upper limb functions. We performed a path analysis using a structural equation modeling approach in a large sample of 102 stroke patients (age 63.6 ± 13.1 years; 61% men) in the post-acute phase. They underwent 7 weeks of bilateral arm training assisted by an exoskeleton robot combined with a conventional treatment (consisting of simple physical activity together with occupational therapy). The upper extremity section of the Fugl-Meyer (FM-UE) scale at admission was used as a predictor of outcome, whereas age, gender, side of the lesion, days from the event, pain scale, duration of treatment, and number of sessions as mediators. Results: FM-UE at admission was a direct predictor of outcome, as measured by the motricity index of the contralateral upper limb and trunk control test, without any other mediating factors. Age, gender, days from the event, side of lesion, and pain scales were independently associated with outcomes. Conclusions: To the best of our knowledge, this is the first study assessing the relationship between clinical variables and outcomes induced by robot-assisted rehabilitation with a path-analysis model. We define a new route for motor recovery of stroke patients driven by exoskeleton-robot-assisted therapy, highlighting the role of FM-UE at admission as a useful predictor of outcome, although other variables need to be considered in the time-course of disease.

The Timecourse of Electrophysiological Brain-Heart Interaction in DoC Patients.

Disorders of Consciousness (DOC) are a spectrum of pathologies affecting one's ability to interact with the external world. Two possible conditions of patients with DOC are Unresponsive Wakefulness Syndrome/Vegetative State (UWS/VS) and Minimally Conscious State (MCS). Analysis of spontaneous EEG activity and the Heart Rate Variability (HRV) are effective techniques in exploring and evaluating patients with DOC. This study aims to observe fluctuations in EEG and HRV parameters in the morning/afternoon resting-state recording. The study enrolled 13 voluntary Healthy Control (HC) subjects and 12 DOC patients (7 MCS, 5 UWS/VS). EEG and EKG were recorded. PSDalpha, PSDtheta powerband, alpha-blocking, alpha/theta of the EEG, Complexity Index (CI) and SDNN of EKG were analyzed. Higher values of PSDalpha, alpha-blocking, alpha/theta and CI values and lower values of PSD theta characterized HC individuals in the morning with respect to DOC patients. In the afternoon, we detected a significant difference between groups in the CI, PSDalpha, PSDtheta, alpha/theta and SDNN, with lower PSDtheta value for HC. CRS-R scores showed a strong correlation with recorded parameters mainly during evaluations in the morning. Our finding put in evidence the importance of the assessment, as the stimulation of DOC patients in research for behavioural response, in the morning.

Stochastic resonance and 'gamma band' synchronization in the human visual system.

Cortical synchronization in the gamma-frequency range (above ~30.0 Hz) and the signal/noise interplay described by stochastic resonance models have been proposed as basic mechanisms in neuronal synchronization and sensory information processing, particularly in vision. Here we report an observation in humans of linear and inverted-U distributions of the electrophysiological (EEG) responses to visual contrast stimulation in the gamma band and in the low frequency components of the visual evoked responses (VER), respectively. The combination of linear and inverted-U distributions is described by a stochastic resonance model (SR). The observation needs replication in larger subjects' samples. It nevertheless adds to the available evidence of a role of gamma oscillatory signals and SR mechanisms in neuronal synchronization and visual processing. Some functional adaptation in human vision appears conceivable and further investigation is warranted.

A body-weight-supported visual feedback system for gait recovering in stroke patients: A randomized controlled study.

OBJECTIVE: The aim of this study was to determine the effectiveness of a novel body-weight-supported (BWS) gait training system with visual feedback, called Copernicus® (Rehalife, Italy). This computerized device provides comfortable, regular and repeatable locomotion in hemiplegic patients. Through visual real-time monitoring of gait parameters, patients are trained to transfer weight loading alternately on both feet. DESIGN: A single-blind, randomized controlled study. A single center used a computer-generated randomization code to allocate treatments. SETTING: Intensive rehabilitation unit (IRU) at the Institute S. Anna (Italy). PARTICIPANTS: 63 first-ever stroke patients (39 men, age: 66.1 ± 9.6 years; 61.6 % with left-sided lesion) randomly distributed into three demographically/clinically matched groups. TREATMENTS: All groups were treated five times a week for 2 -h sessions for six consecutive weeks. The first group ("control") underwent a conventional physical therapy; the second group performed advanced BWS gait training sessions without visual feedback (Experimental VF- group); whereas the third group used BWS with visual feedback stimulation (Experimental VF+ group). MAIN OUTCOME MEASURES: Absolute changes were recorded using conventional clinical scales and kinematic measurement of static gait balance from baseline to follow-up. RESULTS: Significant interaction Group*Time effects scales (F2,126 = 5.1, p-level = 0.005, η²p = 0.25; F2,126 = 4.7, p-level = 0.007, η²p = 0.19; respectively) were detected in the Functional Independence Measure and Tinetti-Balance scales. Post hoc analysis demonstrated that the recovery of motor functioning was greater for the VF + group with respect to other groups (all p's ≤ 0.001). A similar pattern of findings was also obtained with a stabilometric analysis, demonstrating a better clinical improvement in static balance after VF + treatment. CONCLUSION: The proposed advanced rehabilitation system with visual feedback was more effective in improving gait recovery with respect to conventional and high-tech therapies without a sensor feedback.

The assessment of trunk recovery in stroke patients using 3D kinematic measures.

The kinematic analysis of trunk recovery in patients with stroke has sparsely been investigated. This study is aimed at evaluating the validity of a kinematic system for measuring trunk movements. Forty-five right-handed stroke patients in the post-acute phase were assessed in a within-subject design, before and after intensive conventional neurorehabilitation treatment. An eight-camera system was used to analyze the three-dimensional (3D) kinematics of trunk during typical displacements (anterior/posterior and right/left lateral). Kinematic trunk measurements and clinical evaluations were performed immediately in a blind fashion before and after rehabilitation treatments. Of the 9 kinematic variables, 4 showed a significant relationship with the clinical measure of the trunk: Trunk Control Test (TCT). Among these, only the kinematic evaluation of the lateral pelvic was the best predictor (R2= 0.2; p-level< 0.006; beta= 0.41) of clinical recovery measured with TCT. Here, we present a 3D kinematic system for assessing trunk impairments in stroke patients. We found that different kinematic variables reflect motor recovery as assessed by conventional clinical scale. Further evaluations, including reliability analysis and application on patients with gait impairments, are required.

Data on a new neurorehabilitation approach targeting functional recovery in stroke patients.

Robotic-assisted devices are known to positively affect the recovery of one specific motor effector after stroke. However, it has widely been reported that the functional status of patients is only partially ameliorated after application of this kind of advanced treatment. Here, data about the effect of a new rehabilitation approach has been described in a large population of stroke patients. We sought to validate an integrated rehabilitation system for stroke (IRSS) patients, which is composed of a set of robotic-assisted tools aimed at recovering the entire body. We evaluated the motor recovery in 84 stroke patients equally divided into experimental and control groups to assess the difference between IRSS approach and conventional rehabilitation treatment. We found that IRSS induced a significant improvement as measured by functional neurological scales, such as the barthel index and functional independence measure. The data provided in this article will assist therapists and physicians working for developing new rehabilitation protocols more focused on a holistic functional recovery approach. The data are available at Mendeley Data, https://doi.org/10.17632/wptmgm7zk2.1.

The cooking therapy for cognitive rehabilitation of cerebellar damage: A case report and a review of the literature.

BACKGROUND AND IMPORTANCE: The therapeutic approach for cerebellar damages heavily relies on neurorehabilitation since there are no medications that may improve clinical symptoms mainly those related to cognitive dysfunctions. Nevertheless, neurorehabilitation programs tailored to cerebellar damages have never been validated. Here we describe a new rehabilitation approach based on cooking training (CT). The idea that cooking may stimulate cerebellar activity relies on previous evidence demonstrating the beneficial effect on the executive functions as well as in promoting neural plasticity within the cerebellum. Indeed, CT requires motor/mental coordination, thinking flexibly, planning, implementing strategies, shifting and self-monitoring behaviors, all functions drastically affected in cerebellar disorders. CASE DESCRIPTION: A 68-year-old male stroke patient with isolated right cerebellar ischemia in the posterior cerebellum characterized by mild executive dysfunctions. After intensive six weekly two-hour sessions, we found that CT was effective in improving some cognitive abilities in a context of mild motor impairment. In particular, deficits in the execution of the Symbol digit modality test and Wisconsin card-sorting test were recovered. CONCLUSION: The comparison of our data with those reported in previous studies confirmed the Schmahmann's hypothesis on the effectiveness of neurorehabilitation approaches in cerebellar patients acting as external timekeeping of conscious thoughts.

Interaction of (12)C ions with the mouse retinal response to light.

Astronauts in orbit reported phosphenes varying in shape and orientation across the visual field; incidence was correlated with the radiation flux. Patients with skull tumors treated by (12)C ions and volunteers whose posterior portion of the eye was exposed to highly ionizing particles in early studies reported comparable percepts. An origin in radiation activating the visual system is suggested. Bursts (∼ 4 ms) of (12)C ions evoked electrophysiological mass responses comparable to those to light in the retina of anesthetized wild-type mice at threshold flux intensities consistent with the incidence observed in humans. The retinal response amplitude increased in mice with ion intensity to a maximum at ∼ 2000 ions/burst, to decline at higher intensities; the inverted-U relationship suggests complex effects on retinal structures. Here, we show that bursts of (12)C ions presented simultaneously to white light stimuli reduced the presynaptic mass response to light in the mouse retina, while increasing the postsynaptic retinal and cortical responses amplitude and the phase-locking to stimulus of cortical low frequency and gamma (∼ 25-45 Hz) responses. These findings suggest (12)C ions to interfere with, rather than mimicking the light action on photoreceptors; a parallel action on other retinal structures/mechanisms resulting in cortical activation is conceivable. Electrophysiological visual testing appears applicable to monitor the radiation effects and in designing countermeasures to prevent functional visual impairment during operations in space.

Care and neurorehabilitation in the disorder of consciousness: a model in progress.

The operational model and strategies developed at the Institute S. Anna-RAN to be applied in the care and neurorehabilitation of subjects with disorders of consciousness (DOC) are described. The institute units are sequentially organized to guarantee appropriate care and provide rehabilitation programs adapted to the patients' clinical condition and individual's needs at each phase of evolution during treatment in a fast turnover rate. Patients eligible of home care are monitored remotely. Transferring advanced technology to a stage of regular operation is the main mission. Responsiveness and the time windows characterized by better residual responsiveness are identified and the spontaneous/induced changes in the autonomic system functional state and biological parameters are monitored both in dedicated sessions and by means of an ambient intelligence platform acquiring large databases from traditional and innovative sensors and interfaced with knowledge management and knowledge discovery systems. Diagnosis of vegetative state/unresponsive wakefulness syndrome or minimal conscious state and early prognosis are in accordance with the current criteria. Over one thousand patients with DOC have been admitted and treated in the years 1998-2013. The model application has progressively shortened the time of hospitalization and reduced costs at unchanged quality of services.

Bovine rod rhodopsin: 2. Bleaching in vitro upon 12C ions irradiation as source of effects as light flash for patients and for humans in space.

PURPOSE: In a previous paper, we showed that chemiluminescence from radical recombination (initiated by lipid peroxidation and propagated by polyunsaturated fatty acids [PUFA]) has a bleaching effect comparable to that caused by light on the rhodopsin of retinal rod outer segment (RdOS) prepared from bovine eyes. Photons generated by radical recombination were suggested to be the origin of phosphenes perceived as light flashes by the human eye. Irradiation with (12)C carbon ions was used in this study to stimulate radical production, propagation and recombination leading to photoluminescence. MATERIALS AND METHODS: (12)C radiation bleached RdOS rhodopsin, but structural damage increasing with the radiation dose was also observed. For this reason, only the effects on rhodopsin at doses producing next to negligible biodamage and permitting regeneration have been considered as bleaching effects. RESULTS: (12)C irradiation bleached RdOS rhodopsin, but increasing structural damage with radiation dose was also observed. For the measure of bleaching and to reveal dose response effects on rhodopsin that were able to be regenerated only results from doses producing nearly negligible biodamage have been considered. CONCLUSIONS: Recombination of radicals appears responsible for the release of photons with subsequent bleaching of rhodopsin. This effect could have an important role in the generation of the anomalous visual effects (phosphenes) experienced by patients during hadrotherapy or by astronauts in space.

Cortical source of blink-related delta oscillations and their correlation with levels of consciousness.

Recently, blink-related delta oscillations (delta BROs) have been observed in healthy subjects during spontaneous blinking at rest. Delta BROs have been linked with continuous gathering of information from the surrounding environment, which is classically attributed to the precuneus. Furthermore, fMRI studies have shown that precuneal activity is reduced or missing when consciousness is low or absent. We therefore hypothesized that the source of delta BROs in healthy subjects could be located in the precuneus and that delta BROs could be absent or reduced in patients with disorders of consciousness (DOC). To test these hypotheses, electroencephalographic (EEG) activity at rest was recorded in 12 healthy controls and nine patients with DOC (four vegetative states, and five minimally conscious states). Three-second-lasting EEG epochs centred on each blink instance were analyzed in both time- (BROs) and frequency domains (event-related spectral perturbation or ERSP and intertrial coherence or ITC). Cortical sources of the maximum blink-related delta power, corresponding to the positive peak of the delta BROs, were estimated by standardized Low Resolution Electromagnetic Tomography. In control subjects, as expected, the source of delta BROs was located in the precuneus, whereas in DOC patients, delta BROs were not recognizable and no precuneal localization was possible. Furthermore, we observed a direct relationship between spectral indexes and levels of cognitive functioning in all subjects participating in the study. This reinforces the hypothesis that delta BROs reflect neural processes linked with awareness of the self and of the environment.

Electrophysiological monitoring in patients with tumors of the skull base treated by carbon-12 radiation therapy.

PURPOSE: To report the results of short-term electrophysiologic monitoring of patients undergoing (12)C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery. METHODS AND MATERIALS: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision. RESULTS: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline. CONCLUSIONS: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may help predict, possible late toxicity.