A simple intervention for disorders of consciousness- is there a light at the end of the tunnel?

Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30-71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low (M: 31%, Range: 13-66.4%, SD: 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant (p = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant (p = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level (p = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC.

Repeated Clinical Assessment Using Sensory Modality Assessment and Rehabilitation Technique for Diagnosis in Prolonged Disorders of Consciousness.

Purpose: The recommended way to assess consciousness in prolonged disorders of consciousness is to observe the patient's responses to sensory stimulation. Multiple assessment sessions have to be completed in order to reach a correct diagnosis. There is, however, a lack of data on how many sessions are sufficient for validity and reliability. The aim of this study was to identify the number of Sensory Modality Assessment and Rehabilitation Technique (SMART) assessment sessions needed to reach a reliable diagnosis. A secondary objective was to identify which sensory stimulation modalities are more useful to reach a diagnosis. Materials and Methods: A retrospective analysis of all the adult patients (who received a SMART assessment) admitted to a specialist brain injury unit over the course of 4 years was conducted (n = 35). An independent rater analyzed the SMART levels for each modality and session and provided a suggestive diagnosis based on the highest SMART level per session. Results: For the vast majority of patients between 5 and 6 sessions was sufficient to reach the final clinical diagnosis. The visual, auditory, tactile, and motor function modalities were found to be more associated with the final diagnosis than the olfactory and gustatory modalities. Conclusion: These findings provide for the first time a rationale for optimizing the time spent on assessing patients using SMART.

Education Program for Carers in Facilities with Neuro Disabled Subjects EPoCFiNDS.

The prevalence of chronic illness and the disabilities they cause are strongly associated with age. According to the United Nations, in most countries around the world, 8-10% of the population has some form of disability. Carers are helping subjects who have severe or profound core activity limitations in the community and hospice facilities. The skills acquired by carers in their caring role are relevant to the competencies required for occupations and qualifications in community, aged care, health, youth, housing and disability support services. With the aging population the number of subjects with neurological lesions living in hospices and long-term care facilities is increased. It makes a strong case to educate carers to help these subjects. There is a lack of evidence on how to design and implement mechanisms such as foundation skills courses and programs to best meet the needs of carers. The goal of Education Program for Carers in Facilities with Neuro Disabled Subjects (EPoCFiNDS), is to create training programs for carers in neurodisabled subjects living in various facilities. In Europe we need to develop educational programs, aimed at volunteers, relatives or any other group of people so that they better organize benefits care for neurodisabled subjects.

Patients with a severe prolonged Disorder of Consciousness can show classical EEG responses to their own name compared with others' names.

Patients in Vegetative State (VS), also known as Unresponsive Wakefulness State (UWS) are deemed to be unaware of themselves or their environment. This is different from patients diagnosed with Minimally Conscious state (MCS), who can have intermittent awareness. In both states, there is a severe impairment of consciousness; these disorders are referred to as disorders of consciousness (DOC) and if the state is prolonged, pDOC. There is growing evidence that some patients who are behaviourally in VS/UWS can show neural activation to environmental stimuli and that this response can be detected using functional brain imaging (fMRI/PET) and electroencephalography (EEG). Recently, it has also been suggested that a more reliable detection of brain responsiveness and hence a more reliable differentiation between VS/UWS and MCS requires person-centred and person-specific stimuli, such as the subject's own name stimulus. In this study we obtained event related potential data (ERP) from 12 healthy subjects and 16 patients in pDOC, five of whom were in the VS/UWS and 11 in the Minimally Conscious State (MCS). We used as the ERP stimuli the subjects' own name, others' names and reversed other names. We performed a sensor level analysis using Statistical Parametric Mapping (SPM) software. Using this paradigm in 4 DOC patients (3 in MCS, and 1 in VS/UWS) we detected a statistically significant difference in EEG response to their own name versus other peoples' names with ERP latencies (~300 ms and ~700 ms post stimuli). Some of these differences were similar to those found in a control group of healthy subjects. This study shows the feasibility of using self-relevant stimuli such as a subject's own name for assessment of brain function in pDOC patients. This neurophysiological test is suitable for bed-side/hospital based assessment of pDOC patients. As it does not require sophisticated scanning equipment it can feasibly be used within a hospital or care setting to help professionals tailor medical and psycho-social management for patients.

Late recovery of awareness in prolonged disorders of consciousness -a cross-sectional cohort study.

PURPOSE: To detect any improvement of awareness in prolonged disorders of consciousness in the long term. METHODS: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21-73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2-16 years later using Coma Recovery Scale-Revised. RESULTS: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76). CONCLUSIONS: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered. Implications for rehabilitation Long-term regular follow-up of people with prolonged disorders of consciousness is important. Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases. Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

Can behavioural observations made during the SMART assessment detect the potential for later emergence from vegetative state?

The management of prolonged disorders of consciousness (PDOC) such as vegetative state (VS) is a major clinical challenge. Presently there are no validated prognostic markers for emergence from VS apart from age, aetiology and time spent in VS. This study explores whether or not the behavioural observation component of the SMART assessment can detect the potential for later emergence from VS. For this retrospective study 14 patients were selected who were originally assessed by the SMART as being in VS. Clinical records showed that seven of these patients have since emerged from VS (Group 1) and the other half have remained in VS (Group 2). The number, type and frequency of behaviours observed during the first five and the last five sessions of the SMART assessment were compared between the groups. The results suggest that the patients who emerged exhibited a significantly higher number of different behaviour types than those who remained in VS (p = .045). Finding an accurate predictor of prognosis for emergence from VS would assist in optimising the treatment and cost-effective management of this population in the future. Since this is a small sample the results should be reviewed with some caution but they suggest that the patients who later emerge from VS can be differentiated behaviourally from those who remain in VS.

The psychological impact of prolonged disorders of consciousness on caregivers: a systematic review of quantitative studies.

OBJECTIVE: Systematic review of the nature, frequency and severity of psychological experiences of people who have a close relationship with a person with a prolonged disorder of consciousness. DATA SOURCES: Cochrane Library, Web of Science, PsycINFO, PubMed, Embase®, MEDLINE®, Allied and Complementary Medicine™, were searched from inceptions until December 2016 with additional hand searching of reference lists of included articles. REVIEW METHODS: Studies were included that used quantitative methodologies and psychological measures to investigate experiences. The PRISMA statement was followed with inclusion criteria set a priori. A data synthesis summarized psychological constructs studied. RESULTS: A total of 18 studies (ranging between n = 16-487 participants) met the inclusion criteria with 15 of 18 studies focused on the primary caregiver. A total of 23 standardized psychological measures were identified to assess four primary psychological constructs: Loss and grief, psychological wellbeing changes, burden and use of coping strategies. CONCLUSIONS: Small sample sizes, limited variables and reliance on observational methods affected quality. Caregivers do find ways to manage independently, but some exhibit clinically significant psychological distress that does not change over time alone and may get worse.

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness.

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task.

A rehabilitation unit at night: environmental characteristics of patient rooms.

PURPOSE: The aim of this study was first of all to investigate the sound, light, temperature and humidity levels in a rehabilitation ward and to establish whether the measured levels were within the recommended levels or not; secondly to explore influence of the type of the patient rooms on obtained measurements. METHODS: Measurements of environmental characteristics were recorded on three non-consecutive nights by data loggers in a 12-bedded residential neurological rehabilitation unit for patients with disorders of consciousness. The obtained measurements were compared with the recommendations of the World Health Organization and the Society of Light and Lighting. RESULTS: Recordings were within recommended levels for light and humidity overnight. Average noise levels were above the recommended levels. There were abrupt increases of light and noise levels which were high enough to cause sleep fragmentation. Mean temperature levels were higher than recommended. CONCLUSIONS: Our results indicated that the patients are at risk of disturbed sleep for the duration of their stay in rehabilitation unit. Exposure to generally high noise levels, as well as the sudden increases of noise and light intensities can prevent reaching restful night-time sleep and may negatively impact on rehabilitation process due to impaired memory, learning and well-being. Implications for Rehabilitation Standards for ward based hospital environments to minimize sleep disturbance exist and can be used to examine the environmental characteristics of patients' rooms in different healthcare settings including rehabilitation units. This study shows that measurements of environmental factors were not always within the recommended levels in the rehabilitation unit and presence of abrupt increase of noise and light levels are likely to cause sleep disturbance of patients. Assessment of current practice, education and training of night staff to raise awareness on importance of sleep and environmental factors and development of strategies are required in order to improve quality of sleep in rehabilitation settings.

Randomized control of extracorporeal shock wave therapy versus placebo for chronic decubitus ulceration.

OBJECTIVE: To assess whether extracorporeal shock wave therapy increases the rate of healing in chronic decubitus ulceration. DESIGN: Double-blind randomized cross-over study. SETTING: A large, long-stay hospital specializing in the management of people with complex neurological disabilities. SUBJECTS: The total population of available patients with chronic neurological conditions and chronic decubitus ulceration who met the inclusion criteria. INTERVENTIONS: Ulcers were randomized into receiving either the extracorporeal shock wave therapy or the placebo for a four-week period, followed by a two-week 'washout' period followed by a four-week period of the cross-over treatment/ placebo. MAIN MEASURES: Measurement of the area of the ulceration. For each observation the average of three measurements were taken. RESULTS: Nine ulcers (in eight patients) were included in the study: five on the buttocks/sacrum/trochanter and four on the feet/ankles. All those with static chronic ulcers showed improved healing starting 6-8 weeks after the start of extracorporeal shock wave therapy, whether treated first with the placebo or the therapy. CONCLUSIONS: Extracorporeal shock wave therapy has a potential part to play in the treatment of chronic skin ulceration.

Hippocampal neurons in organotypic slice culture are highly resistant to damage by endogenous and exogenous nitric oxide.

Nitric oxide (NO) has been proposed to mediate neurodegeneration arising from NMDA receptor activity, but the issue remains controversial. The hypothesis was re-examined using organotypic slice cultures of rat hippocampus, with steps being taken to avoid known artefacts. The NO-cGMP signalling pathway was well preserved in such cultures. Brief exposure to NMDA resulted in a concentration-dependent delayed neuronal death that could be nullified by administration of the NMDA antagonist MK801 (10 microm) given postexposure. Two inhibitors of NO synthesis failed to protect the slices, despite fully blocking NMDA-induced cGMP accumulation. By comparing NMDA-induced cGMP accumulation with that produced by an NO donor, toxic NMDA concentrations were estimated to produce only physiological NO concentrations (2 nm). In studies of the vulnerability of the slices to exogenous NO, it was found that continuous exposure to up to 4.5 microm NO failed to affect ATP levels (measured after 6 h) or cause damage during 24 h, whereas treatment with the respiratory inhibitors myxothiazol or cyanide caused ATP depletion and complete cell death within 24 h. An NO concentration of 10 microm was required for ATP depletion and cell death, presumably through respiratory inhibition. It is concluded that sustained activity of neuronal NO synthase in intact hippocampal tissue can generate only low nanomolar NO concentrations, which are unlikely to be toxic. At the same time, the tissue is remarkably resistant to exogenous NO at up to 1000-fold higher concentrations. Together, the results seriously question the proposed role of NO in NMDA receptor-mediated excitotoxicity.