Advances in the rehabilitation of intensive care unit acquired weakness: A case report on the promising use of robotics and virtual reality coupled to physiotherapy.

INTRODUCTION: Traditional physiotherapy is currently the best approach to manage patients with intensive care unit acquired weakness (ICUAW). We report on a patient with ICUAW, who was provided with an intensive, in-patient regimen, that is, conventional plus robot-assisted physiotherapy. Aim of this case study was to assess the efficacy of a combined approach (conventional plus robot-assisted physiotherapy), on muscle strength, overall mobility, and disability burden in a patient with ICUAW in post-ICU intensive rehabilitation setting. PATIENT CONCERNS: A 56-years-old male who was unable to stand and walk independently after hospitalization in an Intensive Care Unit. He initially was provided with daily sessions of conventional physiotherapy for 2 months, with mild results. DIAGNOSIS: The patient was affected by ICUAW. INTERVENTION: Given that the patient showed a relatively limited improvement after conventional physiotherapy, he was provided with daily sessions of robot-aided training for upper and lower limbs and virtual reality-aided rehabilitation for other 4 months, beyond conventional physiotherapy. OUTCOMES: At the discharge (6 months after the admission), the patient reached the standing station and was able to ambulate with double support. CONCLUSIONS: Our case suggests that patients with ICUAW should be intensively treated in in-patient regimen with robot-aided physiotherapy. Even though our approach deserves confirmation, the combined rehabilitation strategy may offer some advantage in maximizing functional recovery and containing disability.

A case report on intensive, robot-assisted rehabilitation program for brainstem radionecrosis.

INTRODUCTION: Radiotherapy is a valid treatment option for nasopharyngeal carcinoma. However, complications can occur following irradiation of the closest anatomical structures, including brainstem radionecrosis (BRN). The rehabilitation is poorly described in patients with BRN, despite its usefulness in improving functional independence in patients with brain tumors. We aimed at testing the usefulness of intensive, robot-assisted neurorehabilitation program to improve functional independence in a 57-year-old male with BRN. PATIENT CONCERNS: A 57-year-old male diagnosed with a nasopharyngeal carcinoma, received a radiation total dose of 72 Gy. Owing to the appearance of a severe symptomatology characterized by dysphagia, hearing loss, and left sided hemiparesis, the patient was hospitalized to be provided with intensive pharmacological and neurorehabilitation treatment. DIAGNOSIS: Follow-up brain magnetic resonance imaging disclosed no residual cancer, but some brainstem lesions compatible with BRN areas were appreciable. INTERVENTION: The patient underwent a 2-month conventional, respiratory, and speech therapy. Given that the patient only mildly improved, he was provided with intensive robot-aided upper limb and gait training and virtual reality-based cognitive rehabilitation for other 2 months. OUTCOMES: The patient reported a significant improvement in functional independence, spasticity, cognitive impairment degree, and balance. CONCLUSION: Our case suggests the usefulness of neurorobotic intensive rehabilitation in BRN to reduce functional disability. Future studies should investigate whether an earlier, even multidisciplinary rehabilitative treatment could lead to better functional outcome in patients with BRN.

Peri-Personal Space Tracing by Hand-Blink Reflex Modulation in Patients with Chronic Disorders of Consciousness.

The assessment of awareness in patients with chronic Disorders of Consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. The level of awareness impairment may depend on the degree of deterioration of the large-scale cortical-thalamo-cortical networks induced by brain injury. Electrophysiological approaches may shed light on awareness presence in patients with DoC by estimating cortical functions related to the cortical-thalamo-cortical networks including, for example, the cortico-subcortical processes generating motor responses to the perturbation of the peri-personal space (PPS). We measured the amplitude, latency, and duration of the hand-blink reflex (HBR) responses by recording electromyography (EMG) signals from both the orbicularis oculi muscles while electrically stimulating the median nerve at the wrist. Such a BR is thought to be mediated by a neural circuit at the brainstem level. Despite its defensive-response nature, HBR can be modulated by the distance between the stimulated hand and the face. This suggests a functional top-down control of HBR as reflected by HBR features changes (latency, amplitude, and magnitude). We therefore estimated HBR responses in a sample of patients with DoC (8 MCS and 12 UWS, compared to 15 healthy controls -HC) while performing a motor task targeting the PPS. This consisted of passive movements in which the hand of the subject was positioned at different distances from the participant's face. We aimed at demonstrating a residual top-down modulation of HBR properties, which could be useful to differentiate patients with DoC and, potentially, demonstrate awareness preservation. We found a decrease in latency, and an increase in duration and magnitude of HBR responses, which were all inversely related to the hand-to-face distance in HC and patients with MCS, but not in individuals with UWS. Our data suggest that only patients with MCS have preserved, residual, top-down modulation of the processes related to the PPS from higher-order cortical areas to sensory-motor integration network. Although the sample size was relatively small, being thus our data preliminary, HBR assessment seems a rapid, easy, and first-level tool to differentiate patients with MCS from those with UWS. We may also hypothesize that such a HBR modulation suggests awareness preservation.

Treatment of pain post-brachial plexus injury using high-frequency spinal cord stimulation.

PURPOSE: Brachial plexopathy can sometimes cause severe chronic pain. There are many possible treatments for such neuropathic pain, including neuromodulation. However, rigorous scientific evidence on the usefulness of spinal cord stimulation (SCS) is still scarce. Here, we report the use of high-frequency (10 kHz) SCS (HFSCS) in a patient with brachial plexus injury (root avulsion). OBJECTIVE: To assess the efficacy of HFSCS in root avulsion and to investigate the putative neurophysiological mechanisms of HFSCS. METHODS: A 32-year-old woman visited our center following an iatrogenic brachial plexus injury. She underwent traditional, paresthesia-inducing, tonic SCS with cervical lead placement. She reported that stimulation-induced paresthesia was uncomfortable, without any pain reduction. After the successful trial of HFSCS, the patient was assessed at 1 month (T1) and 6 months (T6) after HFSCS implantation with pain and quality of life (QoL) scales. Moreover, she underwent a neurophysiological assessment (somatosensory evoked potentials [SEPs], reciprocal inhibition [RI], pain-motor integration [PMI], and the habituation of intraepidermal electrical stimulation-induced evoked potentials [IEPs]) with the stimulator switched on and switched off at T6. RESULTS: The patient reported 100% paresthesia-free pain relief, a consistent improvement of QoL, and a complete discontinuation of her previous pain treatment at T1 and T6. Moreover, we found suppression of SEPs, restored habituation of IEPs, and strengthening of RI and PMI. CONCLUSION: This is the first report to illustrate the usefulness and safety of HFSCS for treating root avulsion in a patient with failed tonic SCS. Our data indicate that HFSCS may either block large-diameter fibers or stimulate medium-/small-diameter fibers, thus inducing analgesia without paresthesia, probably by reducing the activation of the wide-dynamic-range neurons. Moreover, HFSCS seems to modulate spinal inhibitory mechanisms and the descending corticospinal inhibitory output. Thus, HFSCS can be an effective option for treating refractory pain following root avulsion.

Detecting peripersonal space: The promising role of ultrasonics.

INTRODUCTION: The approach of an external stimulus to the peripersonal space (PPS) modifies some physiological measures, including the cerebral blood flow (CBF) in the supplementary motor area and premotor cortex. CBF measurement may be useful to assess brain activations when producing specific motor responses, likely mediated by cortical and subcortical neural circuits. METHODS: This study investigated PPS in 15 healthy humans by characterizing the hemodynamic responses (pulsatility index, PI; and heart rate, HR) related to different directions of movements of individual's hand toward and backward his/her own face, so to perturb PPS). RESULTS: We observed that the CBF and HR were enhanced more when the stimulated hand was inside the PPS of the face in the passive and active condition than when the hand was outside the PPS and during motor imagery task. CONCLUSIONS: These results suggest that the modulation of PPS-related brain responses depends on specific sensory-motor integration processes related to the location and the final position of a target in the PPS. We may thus propose TCD as a rapid and easy approach to get information concerning brain responses related to stimuli approaching the PPS. Understanding the modulations of brain activations during tasks targeting PPS can help to understand the results of psychophysical and behavioral trials and to plan patient-tailored cognitive rehabilitative training.

Evaluating Peripersonal Space through the Functional Transcranial Doppler: Are We Paving the Way for Early Detecting Mild Cognitive Impairment to Dementia Conversion?

BACKGROUND: Identifying the patients with mild cognitive impairment (MCI) who may develop dementia (MDC) is challenging. The study of peripersonal space (PPS) by using functional transcranial Doppler (fTCD) could be used for this purpose. OBJECTIVE: To identify changes in cerebral blood flow (CBF) during motor tasks targeting PPS, which can predict MDC. METHODS: We evaluated the changes in CBF in 22 patients with MCI and 23 with dementia [Alzheimer's disease (AD) and vascular dementia (VaD)] during a motor task (passive mobilization, motor imagery, and movement observation) in which the hand of the subject moved forward and backward the face. RESULTS: CBF increased when the hand approached the face and decreased when the hand moved from the face in the healthy controls (HCs). CBF changed were detectable only in patients with MCI but not in those with the AD and those who were MDC after 8-month follow-up. On the other hand, the patients with VaD presented a paradoxical response to the motor task (i.e., a decrease of CBF rather than an increase, as observed in HCs and MCI). Therefore, we found a modulation of PPS-related CBF only in HCs and patients with stable MCI (at the 8-month follow-up). CONCLUSIONS: fTCD may allow preliminarily differentiating and following-up the patients with MCI and MDC, thus allowing the physician to plan beforehand more individualized cognitive rehabilitative training.

Novel Approaches to the Diagnosis of Chronic Disorders of Consciousness: Detecting Peripersonal Space by Using Ultrasonics.

The assessment of behavioral responsiveness in patients suffering from chronic disorders of consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. Even if a patient is unresponsive, he/she may be covertly aware in reason of a cognitive-motor dissociation, i.e., a preservation of cognitive functions despite a solely reflexive behavioral responsiveness. The approach of an external stimulus to the peripersonal space (PPS) modifies some biological measures (e.g., hand-blink reflex amplitude) to the purpose of defensive responses from threats. Such modulation depends on a top-down control of subcortical neural circuits, which can be explored through changes in cerebral blood flow velocity (CBFV), using functional transcranial Doppler (fTCD) and, thus, gaining useful, indirect information on brain connectivity. These data may be used for the DoC differential diagnosis. We evaluated the changes in CBFV by measuring the pulsatility index (PI) in 21 patients with DoC (10 patients with MCS and 11 with UWS) and 25 healthy controls (HC) during a passive movement and motor imagery (MI) task in which the hand of the subject approached and, then, moved away from the subject's face. In the passive movement task, the PI increased progressively in the HCs when the hand was moved toward the face and, then, it decreased when the hand was removed from the face. The PI increased when the hand was moved toward the face in patients with DoC, but then, it remained high when the hand was removed from the face and up to 30 s after the end of the movement in the patients with MCS (both MCS+ and MCS-) and 1 min in those with UWS, thus differentiating between patients with MCS and UWS. In the MI task, all the HCs, three out of four patients with MCS+, and one out of six patients with MCS- showed an increase-decrease PI change, whereas the remaining patients with MCS and all the patients with UWS showed no PI changes. Even though there is the possibility that our findings will not be replicated in all patients with DoC, we propose fTCD as a rapid and very easy tool to differentiate between patients with MCS and UWS, by identifying residual top-down modulation processes from higher-order cortical areas to sensory-motor integration networks related to the PPS, when using passive movement tasks.

Relationship between Interferon Beta-1A Administration and Intracranial Vascular Tone Regulation in Patients with Relapsing-Remitting Multiple Sclerosis: A Pilot Study.

Interferon beta (IFN-ß) therapy is one of the most commonly prescribed immunomodulatory therapies in relapsing-remitting multiple sclerosis (RRMS). A reversible cerebral vasoconstriction syndrome (RCVS), associated with IFN-ß use, has been recently described. For this reason, we tested the effect of once a week intramuscular administration of IFN-ß-1A on the function of cerebral vessels in a cohort of RRMS patients. Using transcranial Doppler (TCD) ultrasound, we measured the mean blood flow velocity (MFV) in intracranial vessels 10 h after IFN-ß administration. Measurements showed a significant increase in MFV compared to the baseline values in some vessels.

The value of midbrain morphology in predicting prognosis in chronic disorders of consciousness: A preliminary ultrasound study.

Transcranial sonography (TCS) of the brainstem is currently used to support the clinical diagnosis of movement disorders. The aim of the study was to assess the usefulness of midbrain TCS in assessing outcome in patients with Chronic Disorders of Consciousness (DOC). Eleven patients with Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) were included in the study. We measured the area and echogenicity of the midbrain by encoding and digitally analyzing the corresponding images from the orbitomeatal plane, the morphology of brain parenchyma from the thalamic and cella media plane, and the intracranial circulation. All the patients showed an increase of pulsatility index and numerous morphological alterations on all the scan planes. In particular, we found a loss of the characteristic butterfly-shape of the midbrain, which appeared hypoechoic in the UWS but not in the MCS patients. After six months, the patients were clinically assessed by using Glasgow Outcome Scale Extended (GOSE). We found that a higher increase in GOSE scoring at follow-up was correlated with larger area and higher echogenicity of the midbrain at baseline. The present study suggests that TCS data of the midbrain may support clinical assessment of patients with chronic DOC to estimate their outcome.

Transcranial parenchymal sonography in patients with Chronic Disorders of Consciousness: Association with neuroimaging data, and beyond.

Differential diagnosis of patients with Chronic Disorders of Consciousness (DoC) is rather challenging, owing to the lack of objective approaches highlighting residual awareness. Sophisticated functional neuroimaging have provided high diagnostic value, but their application in the clinical setting is limited due to their relative complexity, cost, availability and poor collaboration of persons with DoC. By using a specific ultrasound-based methodology, namely Transcranial B-mode Parenchymal Sonography (TCS), it is possible to obtain images of the main parenchymal brain structures. We assessed the TCS abnormalities in three patients with DoC, demonstrating widespread alterations of brain parenchyma morphology that matched to MRI findings and were associated with the degree of consciousness disorders. Thus, TCS might represent a valuable tool for routine assessment and follow-up of brain structures functioning of patients with DoC, potentially helping in differential diagnosis and prognosis.

Toward a more personalized motor function rehabilitation in Myotonic dystrophy type 1: The role of neuroplasticity.

Myotonic dystrophy type 1 (DM1) is the most prevalent adult muscular dystrophy, often accompanied by impairments in attention, memory, visuospatial and executive functions. Given that DM1 is a multi-system disorder, it requires a multi-disciplinary approach, including effective rehabilitation programs, focusing on the central nervous system neuroplasticity, in order to develop patient-tailored rehabilitative procedures for motor function recovery. Herein, we performed a transcranial magnetic stimulation (TMS) study aimed at investigating central motor conduction time, sensory-motor plasticity, and cortical excitability in 7 genetically defined DM1 patients. As compared to healthy individuals, DM1 patients showed a delayed central motor conduction time and an abnormal sensory-motor plasticity, with no alteration of cortical excitability. These findings may be useful to define patient-tailored motor rehabilitative programs.