Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Motor priming to enhance the effect of physical therapy in people with spinal cord injury.

CONTEXT: Brain-Computer Interface (BCI) is an emerging neurorehabilitation therapy for people with spinal cord injury (SCI). OBJECTIVE: The study aimed to test whether priming the sensorimotor system using BCI-controlled functional electrical stimulation (FES) before physical practice is more beneficial than physical practice alone. METHODS: Ten people with subacute SCI participated in a randomized control trial where the experimental (N = 5) group underwent BCI-FES priming (∼15 min) before physical practice (30 min), while the control (N = 5) group performed physical practice (40 min) of the dominant hand. The primary outcome measures were BCI accuracy, adherence, and perceived workload. The secondary outcome measures were manual muscle test, grip strength, the range of motion, and Electroencephalography (EEG) measured brain activity. RESULTS: The average BCI accuracy was 85%. The experimental group found BCI-FES priming mentally demanding but not frustrating. Two participants in the experimental group did not complete all sessions due to early discharge. There were no significant differences in physical outcomes between the groups. The ratio between eyes closed to eyes opened EEG activity increased more in the experimental group (theta Pθ = 0.008, low beta Plß = 0.009, and high beta Phß = 1.48e-04) indicating better neurological outcomes. There were no measurable immediate effects of BCI-FES priming. CONCLUSION: Priming the brain before physical therapy is feasible but may require more than 15 min. This warrants further investigation with an increased sample size.

The impact of COVID-19 and associated lockdowns on traumatic spinal cord injury incidence: a population based study.

STUDY DESIGN: Natural experiment OBJECTIVES: To determine whether COVID-19 restrictions were associated with changes in the incidence of traumatic spinal cord injury (TSCI) in Scotland. SETTING: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole provider of treatment for TSCI in Scotland. METHODS: Time series analysis of all admissions for TSCI between 1st January 2015 and 31st August 2022. RESULTS: Over the 8-year study period, 745 patients were admitted to the QENSIU with a TSCI. Interrupted time series analysis showed that level 3 and 4 COVID-19 lockdown restrictions (the most severe levels) were associated with lower incidence of TSCI (RR 0.63, CI% CI 0.47, 0.82, p < 0.001). The associations were stronger in people aged over 45 (additive interaction p = 0.001), males (additive interaction p = 0.01) and non-tetraplegia (additive interaction p = 0.002). The incidence of TSCI due to deliberate self-harm was higher (0.41 versus 0.23 per month) during restrictions. CONCLUSIONS: Overall, TSCI incidence reduced in Scotland when lockdowns were implemented, presumably due to lower engagement in risky activities. The increase in TSCI due to deliberate self-harm may reflect increased mental health problems and social isolation and should be anticipated and targeted in future pandemics. The change in incidence during the COVID-19 pandemic may have an economic impact and see a temporary reduction in the burden on health and social care. The results of this study will be useful for resource planning in future pandemics.

A pressure monitoring approach for pressure ulcer prevention.

BACKGROUND: A pressure ulcer (PU) is a debilitating condition that disproportionately affects people with impaired mobility. PUs facilitate tissue damage due to prolonged unrelieved pressure, degrading quality of life with a considerable socio-economic impact. While rapid treatment is crucial, an effective prevention strategy may help avoid the development of PUs altogether. While pressure monitoring is currently used in PU prevention, available monitoring approaches are not formalised and do not appropriately account for accumulation and relief of the effect of an applied pressure over a prolonged duration. The aim of this study was to define an approach that incorporates the accumulation and relief of an applied load to enable continuous pressure monitoring. RESULTS: A tunable continuous pressure magnitude and duration monitoring approach that can account for accumulated damaging effect of an applied pressure and pressure relief over a prolonged period is proposed. Unlike classic pressure monitoring approaches, the presented method provides ongoing indication of the net impact of a load during and after loading. CONCLUSIONS: The tunable continuous pressure magnitude and duration monitoring approach proposed here may further development towards formalised pressure monitoring approaches that aim to provide information on the risk of PU formation in real-time.

Regional and temporal variation in bone loss during the first year following spinal cord injury.

Osteoporosis is a consequence of spinal cord injury (SCI) that leads to fragility fractures. Visual assessment of bone scans suggests regional variation in bone loss, but this has not been objectively characterised. In addition, substantial inter-individual variation in bone loss following SCI has been reported but it is unclear how to identify fast bone losers. Therefore, to examine regional bone loss, tibial bone parameters were assessed in 13 individuals with SCI (aged 16-76 years). Peripheral quantitative computed tomography scans at 4 % and 66 % tibia length were acquired within 5 weeks, 4 months and 12 months postinjury. Changes in total bone mineral content (BMC), and bone mineral density (BMD) were assessed in ten concentric sectors at the 4 % site. Regional changes in BMC and cortical BMD were analysed in thirty-six polar sectors at the 66 % site using linear mixed effects models. Relationships between regional and total loss at 4 months and 12 months timepoints were assessed using Pearson correlation. At the 4 % site, total BMC (P = 0.001) decreased with time. Relative losses were equal across the sectors (all P > 0.1). At the 66 % site, BMC and cortical BMD absolute losses were similar (all P > 0.3 and P > 0.05, respectively) across polar sectors, but relative loss was greatest in the posterior region (all P < 0.01). At both sites, total BMC loss at 4 months was strongly positively associated with the total loss at 12 months (r = 0.84 and r = 0.82 respectively, both P < 0.001). This correlation was stronger than those observed with 4-month BMD loss in several radial and polar sectors (r = 0.56-0.77, P < 0.05). These results confirm that SCI-induced bone loss varies regionally in the tibial diaphysis. Moreover, bone loss at 4 months is a strong predictor of total loss 12 months postinjury. More studies on larger populations are required to confirm these findings.

The predictive value of cortical activity during motor imagery for subacute spinal cord injury-induced neuropathic pain.

OBJECTIVE: The aim of this study is to explore whether cortical activation and its lateralization during motor imagery (MI) in subacute spinal cord injury (SCI) are indicative of existing or upcoming central neuropathic pain (CNP). METHODS: Multichannel electroencephalogram was recorded during MI of both hands in four groups of participants: able-bodied (N = 10), SCI and CNP (N = 11), SCI who developed CNP within 6 months of EEG recording (N = 10), and SCI who remained CNP-free (N = 10). Source activations and its lateralization were derived in four frequency bands in 20 regions spanning sensorimotor cortex and pain matrix. RESULTS: Statistically significant differences in lateralization were found in the theta band in premotor cortex (upcoming vs existing CNP, p = 0.036), in the alpha band at the insula (healthy vs upcoming CNP, p = 0.012), and in the higher beta band at the somatosensory association cortex (no CNP vs upcoming CNP, p = 0.042). People with upcoming CNP had stronger activation compared to those with no CNP in the higher beta band for MI of both hands. CONCLUSIONS: Activation intensity and lateralization during MI in pain-related areas might hold a predictive value for CNP. SIGNIFICANCE: The study increases understanding of the mechanisms underlying transition from asymptomatic to symptomatic early CNP in SCI.

Impressive neurological recovery following C-spine dislocation in a patient on long term immunosuppression.

We report excellent neurological improvement in a patient with C6/C7 dislocation following a high speed road traffic accident. This case in particular is unusual because the patient was the recipient of an organ transplant during childhood and was therefore on long term immunosuppressant medication at the time of injury. In this report we reflect on the role of steroid use in traumatic spinal cord injury and put our case within the context of current evidence and this unusual clinical scenario.

Effective Connectivity in Spinal Cord Injury-Induced Neuropathic Pain.

AIM: The aim of this study was to differentiate the effects of spinal cord injury (SCI) and central neuropathic pain (CNP) on effective connectivity during motor imagery of legs, where CNP is typically experienced. METHODS: Multichannel EEG was recorded during motor imagery of the legs in 3 groups of people: able-bodied (N = 10), SCI with existing CNP (N = 10), and SCI with no CNP (N = 20). The last group was followed up for 6 months to check for the onset of CNP. Source reconstruction was performed to obtain cortical activity in 17 areas spanning sensorimotor regions and pain matrix. Effective connectivity was calculated using the directed transfer function in 4 frequency bands and compared between groups. RESULTS: A total of 50% of the SCI group with no CNP developed CNP later. Statistically significant differences in effective connectivity were found between all groups. The differences between groups were not dependent on the frequency band. Outflows from the supplementary motor area were greater for the able-bodied group while the outflows from the secondary somatosensory cortex were greater for the SCI groups. The group with existing CNP showed the least differences from the able-bodied group, appearing to reverse the effects of SCI. The connectivities involving the pain matrix were different between able-bodied and SCI groups irrespective of CNP status, indicating their involvement in motor networks generally. SIGNIFICANCE: The study findings might help guide therapeutic interventions targeted at the brain for CNP alleviation as well as motor recovery post SCI.

Spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury in skeletally mature rats.

Objective: Characterise the spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury (SCI) in the skeletally mature rat in the acute (4-week) period following injury. Methods: The spinal cord of 5-month old male rats was transected at the T9 level. Outcome measures were assessed using micro-computed tomography, three-point bending and serum markers at 1-, 2-, and 4-weeks post-transection. Comparison was made with time-0 and sham animals. Results: Lower levels of circulating serum bone formation markers and higher bone resorption markers suggested uncoupled bone turnover as early at 1-week post-transection. Micro-computed tomography showed metaphyseal and epiphyseal trabecular bone loss was observed only at 4-weeks post-transection. The bone loss was site-specific with a more severe reduction in trabecular BV/TV observed in the metaphyseal (50%) relative to epiphyseal (19%) region. Metaphyseal trabecular bone exhibited a 54% reduction in connectivity density while the epiphyseal trabecular bone was unaffected. Cortical bone deficits were not seen over the time periods examined. Conclusions: The study demonstrates that the skeletally mature spinal cord transected rat model replicates the biphasic pattern of osteoporotic changes observed in the human SCI population, providing a relevant model for testing the efficacy of interventions against SCI-induced osteoporosis.

Fibula response to disuse: a longitudinal analysis in people with spinal cord injury.

Fibular response to disuse has been described in cross-sectional but not longitudinal studies. This study assessed fibular bone changes in people with spinal cord injury. Fibular bone loss was less than in the tibia and was not correlated together. This might explain low fibular fracture incidents in these patients. PURPOSE: Cross-sectional studies suggest that the fibula responds differently to loading and disuse compared to the tibia. Whilst tibial bone changes following spinal cord injury (SCI) have been established in longitudinal studies, fibular changes remain unexplored. METHODS: Fibular and tibial bone parameters were assessed in 13 individuals with SCI (aged 16-76 years). Peripheral quantitative computed tomography scans were acquired at 4%, 38% and 66% distal-proximal tibia length at 5 weeks and 12 months post-injury. Changes in 4% site total bone mineral content (BMC), total cross-sectional area (CSA) and bone mineral density (BMD), and 38% and 66% sites total BMC, total CSA, cortical BMD and cortical CSA were assessed using paired T-tests. Relationships between bone loss in the two bones at equivalent sites were assessed using paired T-tests and correlation. RESULTS: At the 4% site, fibular total BMC and BMD losses were less than tibial losses (- 6.9 ± 5.1% and - 6.6 ± 6.0% vs - 14.8 ± 12.4% and - 14.4 ± 12.4%, p = 0.02 and p = 0.03, respectively). Similarly, at the 66% site, fibular BMC losses were less than those in the tibia (- 2.0 ± 2.6% vs - 4.3 ± 3.6%, p = 0.03), but there was no difference at 38% (- 1.8 ± 3.5% vs - 3.8 ± 2.1%, p = 0.1). No correlation was observed for BMC changes between the two bones (all p > 0.25). CONCLUSION: These results support cross-sectional evidence of smaller disuse-related bone loss in the fibula compared to the tibia. These results may in part explain lower incidence of fibula fractures in individuals with chronic SCI. The lack of association between losses in the two bones might point to different underlying mechanisms.

Transcutaneous spinal cord stimulation combined with locomotor training to improve walking ability in people with chronic spinal cord injury: study protocol for an international multi-centred double-blinded randomised sham-controlled trial (eWALK).

STUDY DESIGN: An international multi-centred, double-blinded, randomised sham-controlled trial (eWALK). OBJECTIVE: To determine the effect of 12 weeks of transcutaneous spinal stimulation (TSS) combined with locomotor training on walking ability in people with spinal cord injury (SCI). SETTING: Dedicated SCI research centres in Australia, Spain, USA and Scotland. METHODS: Fifty community-dwelling individuals with chronic SCI will be recruited. Participants will be eligible if they have bilateral motor levels between T1 and T11, a reproducible lower limb muscle contraction in at least one muscle group, and a Walking Index for SCI II (WISCI II) between 1 and 6. Eligible participants will be randomised to one of two groups, either the active stimulation group or the sham stimulation group. Participants allocated to the stimulation group will receive TSS combined with locomotor training for three 30-min sessions a week for 12 weeks. The locomotor sessions will include walking on a treadmill and overground. Participants allocated to the sham stimulation group will receive the same locomotor training combined with sham stimulation. The primary outcome will be walking ability with stimulation using the WISCI II. Secondary outcomes will record sensation, strength, spasticity, bowel function and quality of life. TRIAL REGISTRATION: ANZCTR.org.au identifier ACTRN12620001241921.

Markers of Central Neuropathic Pain in Higuchi Fractal Analysis of EEG Signals From People With Spinal Cord Injury.

Central neuropathic pain (CNP) negatively impacts the quality of life in a large proportion of people with spinal cord injury (SCI). With no cure at present, it is crucial to improve our understanding of how CNP manifests, to develop diagnostic biomarkers for drug development, and to explore prognostic biomarkers for personalised therapy. Previous work has found early evidence of diagnostic and prognostic markers analysing Electroencephalogram (EEG) oscillatory features. In this paper, we explore whether non-linear non-oscillatory EEG features, specifically Higuchi Fractal Dimension (HFD), can be used as prognostic biomarkers to increase the repertoire of available analyses on the EEG of people with subacute SCI, where having both linear and non-linear features for classifying pain may ultimately lead to higher classification accuracy and an intrinsically transferable classifier. We focus on EEG recorded during imagined movement because of the known relation between the motor cortex over-activity and CNP. Analyses were performed on two existing datasets. The first dataset consists of EEG recordings from able-bodied participants (N = 10), participants with chronic SCI and chronic CNP (N = 10), and participants with chronic SCI and no CNP (N = 10). We tested for statistically significant differences in HFD across all pairs of groups using bootstrapping, and found significant differences between all pairs of groups at multiple electrode locations. The second dataset consists of EEG recordings from participants with subacute SCI and no CNP (N = 20). They were followed-up 6 months post recording to test for CNP, at which point (N = 10) participants had developed CNP and (N = 10) participants had not developed CNP. We tested for statistically significant differences in HFD between these two groups using bootstrapping and, encouragingly, also found significant differences at multiple electrode locations. Transferable machine learning classifiers achieved over 80% accuracy discriminating between groups of participants with chronic SCI based on only a single EEG channel as input. The most significant finding is that future and chronic CNP share common features and as a result, the same classifier can be used for both. This sheds new light on pain chronification by showing that frontal areas, involved in the affective aspects of pain and believed to be influenced by long-standing pain, are affected in a much earlier phase of pain development.

Osteoporosis after spinal cord injury: aetiology, effects and therapeutic approaches.

Osteoporosis is a long-term consequence of spinal cord injury (SCI) that leads to a high risk of fragility fractures. The fracture rate in people with SCI is twice that of the general population. At least 50% of these fractures are associated with clinical complications such as infections. This review article presents key features of osteoporosis after SCI, starting with its aetiology, a description of temporal and spatial changes in the long bones and the subsequent fragility fractures. It then describes the physical and pharmacological approaches that have been used to attenuate the bone loss. Bone loss after SCI has been found to be highly site-specific and characterised by large inter-variability and site-specific changes. The assessment of the available interventions is limited by the quality of the studies and the lack of information on their effect on fractures, but this evaluation suggests that current approaches do not appear to be effective. More studies are required to identify factors influencing rate and magnitude of bone loss following SCI. In addition, it is important to test these interventions at the sites that are most prone to fracture, using detailed imaging techniques, and to associate bone changes with fracture risk. In summary, bone loss following SCI presents a substantial clinical problem. Identification of at-risk individuals and development of more effective interventions are urgently required to reduce this burden.

On the way home: a BCI-FES hand therapy self-managed by sub-acute SCI participants and their caregivers: a usability study.

BACKGROUND: Regaining hand function is the top priority for people with tetraplegia, however access to specialised therapy outwith clinics is limited. Here we present a system for hand therapy based on brain-computer interface (BCI) which uses a consumer grade electroencephalography (EEG) device combined with functional electrical stimulation (FES), and evaluate its usability among occupational therapists (OTs) and people with spinal cord injury (SCI) and their family members. METHODS: Users: Eight people with sub-acute SCI (6 M, 2F, age 55.4 ± 15.6) and their caregivers (3 M, 5F, age 45.3 ± 14.3); four OTs (4F, age 42.3 ± 9.8). User Activity: Researchers trained OTs; OTs subsequently taught caregivers to set up the system for the people with SCI to perform hand therapy. Hand therapy consisted of attempted movement (AM) of one hand to lower the power of EEG sensory-motor rhythm in the 8-12 Hz band and thereby activate FES which induced wrist flexion and extension. Technology: Consumer grade wearable EEG, multichannel FES, custom made BCI application. LOCATION: Research space within hospital. Evaluation: donning times, BCI accuracy, BCI and FES parameter repeatability, questionnaires, focus groups and interviews. RESULTS: Effectiveness: The BCI accuracy was 70-90%. Efficiency: Median donning times decreased from 40.5 min for initial session to 27 min during last training session (N = 7), dropping to 14 min on the last self-managed session (N = 3). BCI and FES parameters were stable from session to session. Satisfaction: Mean satisfaction with the system among SCI users and caregivers was 3.68 ± 0.81 (max 5) as measured by QUEST questionnaire. Main facilitators for implementing BCI-FES technology were "seeing hand moving", "doing something useful for the loved ones", good level of computer literacy (people with SCI and caregivers), "active engagement in therapy" (OT), while main barriers were technical complexity of setup (all groups) and "lack of clinical evidence" (OT). CONCLUSION: BCI-FES has potential to be used as at home hand therapy by people with SCI or stroke, provided it is easy to use and support is provided. Transfer of knowledge of operating BCI is possible from researchers to therapists to users and caregivers. Trial registration Registered with NHS GG&C on December 6th 2017; clinicaltrials.gov reference number NCT03257982, url: https://clinicaltrials.gov/ct2/show/NCT03257982 .

Ultrasound Imaging as a Diagnostic Tool to Assess the Functional Status of Muscles after a Spinal Cord Injury.

The aim of this study was to evaluate the use of ultrasound imaging (USI) as a diagnostic tool to assess muscle function after a spinal cord injury (SCI). Ultrasound videos of the gastrocnemius medialis muscle were recorded both at rest and during attempted maximum voluntary contraction (MVC) for fifteen participants with a SCI and fifteen able-bodied controls. Measurements were repeated at monthly intervals for participants in the SCI group during their inpatient stay. Differences in muscle echogenicity and thickness were detected between both able-bodied and SCI groups and subgroups of SCI participants, suggesting USI can detect and monitor changes in muscle structure which are characteristic of atrophy. Decreased muscle movement in the SCI groups was also detected during attempted MVC. The ability of USI to distinguish between different levels of function demonstrates the potential of USI as a quantitative tool to assess muscles.

EEG Correlates of Self-Managed Neurofeedback Treatment of Central Neuropathic Pain in Chronic Spinal Cord Injury.

BACKGROUND: Neurofeedback (NFB) is a neuromodulatory technique that enables voluntary modulation of brain activity in order to treat neurological condition, such as central neuropathic pain (CNP). A distinctive feature of this technique is that it actively involves participants in the therapy. In this feasibility study, we present results of participant self-managed NFB treatment of CNP. METHODS: Fifteen chronic spinal cord injured (SCI) participants (13M, 2F), with chronic CNP equal or greater than 4 on the Visual Numeric Scale, took part in the study. After initial training in hospital (up to 4 sessions), they practiced NF at home, on average 2-3 times a week, over a period of several weeks (min 4, max 20). The NFB protocol consisted of upregulating the alpha (9-12 Hz) and downregulating the theta (4-8 Hz) and the higher beta band (20-30 Hz) power from electrode location C4, for 30 min. The output measures were pain before and after NFB, EEG before and during NFB and pain questionnaires. We analyzed EEG results and show NFB strategies based on the Power Spectrum Density of each single participant. RESULTS: Twelve participants achieved statistically significant reduction in pain and in eight participants this reduction was clinically significant (larger than 30%). The most successfully regulated frequency band during NFB was alpha. However, most participants upregulated their individual alpha band, that had an average dominant frequency at αp = 7.6 ± 0.8 Hz (median 8 Hz) that is lower than the average of the general population, which is around 10 Hz. Ten out of fifteen participants significantly upregulated their individual alpha power (αp ± 2 Hz) as compared to 4 participants who upregulated the power in the fixed alpha band (8-12 Hz). Eight out of the twelve participants who achieved a significant reduction of pain, significantly upregulated their individual alpha band power. There was a significantly larger increase in alpha power (p < 0.0001) and decrease of theta power (p < 0.04) in participant specific rather than in fixed frequency bands. CONCLUSION: Neurofeedback is a neuromodulatory technique that gives participants control over their pain and can be self-administered at home. Regulation of individual frequency band was related to a significant reduction in pain.

Understanding and modelling the economic impact of spinal cord injuries in the United Kingdom.

STUDY DESIGN: Economic modelling analysis. OBJECTIVES: To determine lifetime direct and indirect costs from initial hospitalisation of all expected new traumatic and non-traumatic spinal cord injuries (SCI) over 12 months. SETTING: United Kingdom (UK). METHODS: Incidence-based approach to assessing costs from a societal perspective, including immediate and ongoing health, rehabilitation and long-term care directly attributable to SCI, as well as aids and adaptations, unpaid informal care and participation in employment. The model accounts for differences in injury severity, gender, age at onset and life expectancy. RESULTS: Lifetime costs for an expected 1270 new cases of SCI per annum conservatively estimated as £1.43 billion (2016 prices). This equates to a mean £1.12 million (median £0.72 million) per SCI case, ranging from £0.47 million (median £0.40 million) for an AIS grade D injury to £1.87 million (median £1.95 million) for tetraplegia AIS A-C grade injuries. Seventy-one percent of lifetime costs potentially are paid by the public purse with remaining costs due to reduced employment and carer time. CONCLUSIONS: Despite the magnitude of costs, and being comparable with international estimates, this first analysis of SCI costs in the UK is likely to be conservative. Findings are particularly sensitive to the level and costs of long-term home and residential care. The analysis demonstrates how modelling can be used to highlight economic impacts of SCI rapidly to policymakers, illustrate how changes in future patterns of injury influence costs and help inform future economic evaluations of actions to prevent and/or reduce the impact of SCIs.

Prediction of central neuropathic pain in spinal cord injury based on EEG classifier.

OBJECTIVES: To create a classifier based on electroencephalography (EEG) to identify spinal cord injured (SCI) participants at risk of developing central neuropathic pain (CNP) by comparing them with patients who had already developed pain and with able bodied controls. METHODS: Multichannel EEG was recorded in the relaxed eyes opened and eyes closed states in 10 able bodied participants and 31 subacute SCI participants (11 with CNP, 10 without NP and 10 who later developed pain within 6 months of the EEG recording). Up to nine EEG band power features were classified using linear and non-linear classifiers. RESULTS: Three classifiers (artificial neural networks ANN, support vector machine SVM and linear discriminant analysis LDA) achieved similar average performances, higher than 85% on a full set of features identifying patients at risk of developing pain and achieved comparably high performance classifying between other groups. With only 10 channels, LDA and ANN achieved 86% and 83% accuracy respectively, identifying patients at risk of developing CNP. CONCLUSION: Transferable learning classifier can detect patients at risk of developing CNP. EEG markers of pain appear before its physical symptoms. Simple and complex classifiers have comparable performance. SIGNIFICANCE: Identify patients to receive prophylaxic treatment of CNP.

Electroencephalographic Predictors of Neuropathic Pain in Subacute Spinal Cord Injury.

It is widely believed that cortical changes are a consequence of longstanding neuropathic pain (NP). In this article, we demonstrate that NP in individuals with subacute spinal cord injury (SCI) has characteristic electroencephalography markers (EEG) that precede the onset of pain. EEG was recorded in a relaxed state and during motor imagination tasks in 10 able-bodied participants and 31 patients with subacute SCI (11 with NP, 10 without NP, and 10 who had pain develop within 6 months of EEG recording). All 20 patients with SCI initially without NP were tested for mechanically induced allodynia, but only 1 patient, who later had pain develop, reported an unpleasant sensation. The EEG reactivity to eye opening was reduced in the alpha band and absent in the theta and beta bands in the patients who later developed pain and was reduced in those who already had pain. Alpha band power was reduced at BA7 in both the relaxed state and during motor imagination in patients who either had or later developed pain compared with those without pain. All SCI groups had reduced dominant alpha frequency and beta band power at BA7. EEG reactivity to eye opening and reduced spontaneous and induced alpha activity over the parietal cortex were predictors of future NP, as well as markers of existing NP. Clinical Trial Registration Number: NCT02178917 PERSPECTIVE: We demonstrate that brain activity in patients with subacute SCI reveals both early markers and predictors of NP, which may manifest before sensory discomfort. These markers and predictors may complement known sensory phenotypes of NP. They may exist in other patient groups suffering from NP of central origin.

Patient-specific bone mineral density distribution in the tibia of individuals with chronic spinal cord injury, derived from multi-slice peripheral Quantitative Computed Tomography (pQCT) - A cross-sectional study.

BACKGROUND: The high risk of fracture associated with chronic spinal cord injury (SCI) is attributed to extensive disuse-related bone loss in previously weight-bearing long bones. Changes in bone mineral density (BMD) after SCI have been documented extensively for the epiphyses of the tibia and femur, fracture-prone sites in this patient group. Less attention has been given to patterns of cortical bone loss in the diaphyses, but variability in BMD distributions throughout the long bones may contribute to some patients' increased susceptibility to shaft fractures in chronic SCI. AIM: A cross-sectional study was carried out to determine whether BMD distributions along the tibia differ between individuals with chronic SCI and healthy able-bodied (AB) controls, in both the trabecular and cortical bone compartments. The effects of time post-injury and gender on BMD distribution were also explored. METHODS: Individuals with chronic (≥6months post-injury) motor-complete SCI were recruited from the Queen Elizabeth National Spinal Injuries Unit (Glasgow, UK). AB control subjects were recruited to achieve similar age and gender profiles for the SCI and control groups. Multi-slice pQCT (XCT3000, Stratec) was performed along the length of the tibia (2mm thickness, 0.5mm voxel size), at 1% intervals in the epiphyses and 5% intervals in the diaphysis (34 slices in total). These were used to reconstruct full 3-D subject-specific models (Mimics, Materialise) of BMD distribution, by interpolating between slices. Subjects with chronic SCI were subdivided into 'early' (<4years post-injury) and 'established' SCI (≥4years post-injury). Subject-specific BMD distribution was described according to new parameters determined from the 3-D patient-specific models, quantifying descriptors of the trabecular and cortical BMD regions separately (volume, peak BMD, half-peak width, area under the curve). These were compared between sub-groups (using independent-samples t-tests or Mann-Whitney tests, significance level of 5%). RESULTS: 11 men (age range 17-59years old; mean 35.7±10.6) and 3 post-menopausal women (age range 56-58years old; mean 56.7±1.2years) with motor-complete SCI (ranging from 6months to 27years post-injury) were recruited; 6 men (age range 20-56years old; 33.0±12.7years) and 1 post-menopausal woman (56years) formed the AB control group. Overall, SCI resulted in lower BMD at both trabecular and cortical regions of the tibia. In men, longer time since injury resulted in greater BMD differences when compared to AB, throughout the tibia. For the post-menopausal women, differences in BMD between SCI and AB were greater in cortical bone than in trabecular bone. From the models, individual BMD distribution curves showed healthy double-peaks in AB subjects: one trabecular peak (around 200-300mg/cm3) and the other cortical (around 1000-1100mg/cm3). In most subjects with established SCI, trabecular peaks were exaggerated whilst the cortical peaks were barely discernible, with crucially some individuals already exhibiting a diminishing cortical BMD peak even <4years post-injury. CONCLUSIONS: These findings may have implications for determining the fracture susceptibility of the long bones in individual patients with SCI. Epiphyseal fractures associated with low trabecular BMD are well characterised, but our data show that some individuals with SCI may also be at higher risk of shaft fractures. The proposed BMD distribution description parameters, determined from patient-specific models, could be used to identify patients with a weakened diaphysis who may be susceptible to fractures of the tibial shaft, but this requires validation.