Giorgio Maggioni

Limbic hyperconnectivity in the vegetative state

Objective: To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. Methods: We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. Results: In DMN hypoconnectivity conditions, a patients DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Conclusions: Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity.

Results of a prospective study (CATS) on the effects of thalamic stimulation in minimally conscious and vegetative state patients

OBJECTIVE Deep brain stimulation of the thalamus was introduced more than 40 years ago with the objective of improving the performance and attention of patients in a vegetative or minimally conscious state. Here, the authors report the results of the Cortical Activation by Thalamic Stimulation (CATS) study, a prospective multiinstitutional study on the effects of bilateral chronic stimulation of the anterior intralaminar thalamic nuclei and adjacent paralaminar regions in patients affected by a disorder of consciousness. METHODS The authors evaluated the clinical and radiological data of 29 patients in a vegetative state (unresponsive wakefulness syndrome) and 11 in a minimally conscious state that lasted for more than 6 months. Of these patients, 5 were selected for bilateral stereotactic implantation of deep brain stimulating electrodes into their thalamus. A definitive consensus for surgery was obtained for 3 of the selected patients. All 3 patients (2 in a vegetative state and 1 in a minimally conscious state) underwent implantation of bilateral thalamic electrodes and submitted to chronic stimulation for a minimum of 18 months and a maximum of 48 months. RESULTS In each case, there was an increase in desynchronization and the power spectrum of electroencephalograms, and improvement in the Coma Recovery Scale-Revised scores was found. Furthermore, the severity of limb spasticity and the number and severity of pathological movements were reduced. However, none of these patients returned to a fully conscious state. CONCLUSIONS Despite the limited number of patients studied, the authors confirmed that bilateral thalamic stimulation can improve the clinical status of patients affected by a disorder of consciousness, even though this stimulation did not induce persistent, clinically evident conscious behavior in the patients. Clinical trial registration no.: NCT01027572 ( ClinicalTrials.gov ).

Wireless Support to Poststroke Rehabilitation: MyHeart's Neurological Rehabilitation Concept

Recent studies suggest that the quality of recovery after a stroke can be increased by early and more intensive rehabilitation. Portable unobtrusive devices are promising candidates for the realization of stroke-rehabilitation systems that complement care in the post-acute rehabilitation phase, both in the clinic and at home. The proposed system allows patients to increase the amount of motor exercise they can perform in autonomy, providing them with a real-time feedback based on wearable sensors embedded in the garments tissue across the upper limb and trunk. A dynamic time warping algorithm allows for the recognition of correct and incorrect motor exercises. After the feedback phase, data are stored in a central location for review and statistics. Workstations can be installed either at home or at the hospital to support patients, independent of their location. The performance of the system on healthy subjects was quantified for seven types of motor exercises for upper limbs rehabilitation. Finally, we present the preliminary results of a pilot clinical study to test the systems acceptability and usability by post-stroke patients, and physicians in a clinical setting.

The prognostic value of sleep patterns in disorders of consciousness in the sub-acute phase

OBJECTIVE This study aimed to evaluate, through polysomnographic analysis, the prognostic value of sleep patterns, compared to other prognostic factors, in patients with disorders of consciousness (DOCs) in the sub-acute phase. METHODS Twenty-seven patients underwent 24-h polysomnography and clinical evaluation 3.5 ± 2 months after brain injury. Their clinical outcome was assessed 18.5 ± 9.9 months later. Polysomnographic recordings were evaluated using visual and quantitative indexes. A general linear model was applied to identify features able to predict clinical outcome. Clinical status at follow-up was analysed as a function of the baseline clinical status, the interval between brain injury and follow-up evaluation, patient age and gender, the aetiology of the injury, the lesion site, and visual and quantitative sleep indexes. RESULTS A better clinical outcome was predicted by a visual index indicating the presence of sleep integrity (p=0.0006), a better baseline clinical status (p=0.014), and younger age (p=0.031). Addition of the quantitative sleep index strengthened the prediction. CONCLUSIONS More structured sleep emerged as a valuable predictor of a positive clinical outcome in sub-acute DOC patients, even stronger than established predictors (e.g. age and baseline clinical condition). SIGNIFICANCE Both visual and quantitative sleep evaluation could be helpful in predicting clinical outcome in sub-acute DOCs.

Active music therapy approach in disorders of consciousness: a controlled observational case series

Disorders of Consciousness (DoC) represent a serious difficulty for caring interventions and they are a diagnostic, clinical and rehabilitative problem [1]. In the last few years, great attention has been developed towards rehabilitative treatments and protocols of different interventions to better define improvements and variations of the consciousness state level [2]. The literature concerning music therapy (active and receptive techniques) is scant and based mainly on single cases or small samples [3–6]. The present study aimed at evaluating the effects of active music therapy (AMT) on some physiological parameters and on behavioural responses in DoC. This controlled observational case series study involved 10 patients with severe brain injuries (5 with a Cerebral Anoxia, 4 with a Brain Haemorrhage and 1 with Head Injury). Informed consent was obtained from proxies of all patients. The patients were divided into two sub-groups. Four of those were in a minimally conscious state (Glasgow Outcome Scale score = 4) and six in a vegetative state (Glasgow Outcome Scale score = 2). All patients had undergone two cycles of 15 AMT sessions (T1 and T3) spaced out by 2 weeks of a pause period (T2). Pharmacological treatments and other conditions did not change during treatment time. The administered individual AMT sessions (three times a week, 30 min each) were based on a direct contact between patient and music therapist. The therapist stimulated patients mostly using rhythmic and melodic patterns, modulating and adapting the sonorousmusical proposals: these matched the arousal level and emotional, motor, behavioural and sonorous-musical responses of patients to stimuli [6, 7]. To measure the effect of AMT some physiological parameters (blood pressure, heart and respiration rate, blood oxygenation) and behavioural responses were evaluated. Physiological parameters were monitored immediately before and after each session and everyday (at the same time) during T2 by nursing staff. Behavioural responses were observed by trained music therapists (not involved in the therapeutic process) using an observational scheme while watching of video-recorded sessions. Effects of both cycles of AMT on physiological parameters were assessed by means of repeated measures analysis of variance. Bonferroni correction was applied as multiplicity test. Behaviours of patients following AMT intervention were summarised as medians and interquartile ranges. The main results concerning the assessed physiological parameters are summarised in Table 1. A significant difference was found comparing T3 with T2 data in the vegetative state group, both in the systolic (p = 0.023) and diastolic pressure (p = 0.050). Systematic observations showed improvements, mainly in the minimally conscious state group, in some observed behaviours: eye contacts, smiles, communicative use of instruments/ voice, reduction of annoyance and suffering expressions. In the vegetative state group only eye contacts strongly increased during the treatment (Table 2). A. Raglio (&) E. Granieri Department of Biomedical and Specialistic Surgical Sciences, Section of Neurology, University of Ferrara, Via A. Moro 8, Cona 44124, Ferrara, Italy e-mail: raglioa@tin.it; alfredo.raglio@unife.it

Early rehabilitation of Disorders of Consciousness (DOC): management, neuropsychological evaluation and treatment

ABSTRACT In order to ensure the best possible rehabilitation plan and best outcome for patients with Disorders of Consciousness (DOC), optimal management of the early phase of rehabilitation is fundamental. This includes a correct diagnosis, accurate assessment of the patient’s state of alertness and the main comorbidities, appropriate neurophysiological and neuroradiology examinations, and education of the caregiver and family so that they can provide the best assistance. Thirty years ago, specialists first began applying a systematic approach to the rehabilitation of patients with DOC, but still today many problems remain unsolved: the rate of misdiagnosis is still high, and recommendations about the most appropriate mode of rehabilitation are lacking, both as regards the timing of interventions and what the best techniques to use are. In a medical sector where nosography has changed over the last decade and where the documented evidence, though increasing, still remains insufficient, we discuss in this brief review the main assessment tools and disability scales to use and the key issues that need to be considered when a patient with DOC is admitted to the rehabilitation unit and decisions about the early rehabilitation plan are made.

Measurement of Lower Limb Spasticity Using an Inertial Sensor

Spasticity is a common motor impairment in patients with neurological disorders. The aim of this study was to investigate the test-retest reliability of the Wartenberg pendulum test using an inertial sensor. The analysis was conducted in six healthy subjects and six patients in vegetative state with severe brain damage secondary to traumatic brain injury (n=3) or cerebrovascular disease (n=3). The reliability analysis showed high intraclass correlation coefficients (ICC = 0.77 to 0.89) and low SEM for all measured parameters. The instrumentation here described can provide a reliable measurement of spasticity and be easily applied in the clinical environment.

Instrumental Kinesiology Approach in Neurorehabilitation Follow-up

Stroke is a serious neurological accident which accounts for a wide fraction of the healthcare costs. Recovery from stroke includes motor rehabilitation. The MyHeart consortium is addressing several aspects of Neurological Rehabilitation (NR) management by combining clothes with embedded biomedical sensors. This Poster describes how MyHeart¿s Concept NR is structured to support motor rehabilitation.