What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (ß = 0.836, p < 0.001), older publication year (ß = 0.404, p = 0.038) and higher proportion of non-White FEP patients (ß = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.

Crossed-reflex in antiphospholipid chorea.

Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases.

Socio-ecological Barriers to Leisure Time Physical Activity in Spanish Wheelchair Users With Spinal Cord Injury: Associations With Sociodemographic Characteristics and Functional Independence.

OBJECTIVE: (1) To assess prevalence and severity of socio-ecological barriers to leisure time physical activity (LTPA) in a sample of adults with spinal cord injury (SCI); (2) to examine the association of these barriers with sociodemographic characteristics and functional independence (FI); and (3) to explore which socio-ecological levels of barriers might be associated with LTPA. DESIGN: Cross-sectional study. SETTING: Neurorehabilitation Hospital specialized in SCI. PARTICIPANTS: 207 wheelchair users with SCI living in the community who attended a comprehensive check-up (22.7% women, 47.5±10.7 mean age; N=207). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The short version of the Barriers to Physical Activity Questionnaire for People with Mobility Impairments was used to measure socio-ecological barriers to LTPA. The Spinal Cord Independence Measure III was used to measure FI. The Physical Activity Recall Assessment for People with SCI was used to quantify LTPA. Several multiple linear regression models were computed to examine the associations between socio-ecological barriers and sociodemographic factors, LTPA and FI. RESULTS: A high prevalence of barriers to LTPA was found. Seven of these barriers (2 intrapersonal, 3 organizational, and 2 community) were present for >60% of the participants. Intrapersonal and organizational barriers had a higher effect on participants with lower FI and women. Interpersonal barriers were higher for older participants and with lower FI, while community barriers were higher for unemployed participants. Finally, intrapersonal and interpersonal barriers were negatively associated with LTPA, and FI revealed as a moderator of the intrapersonal barriers-LTPA relation. CONCLUSIONS: Given their high prevalence and their association with LTPA, the development of interventions targeting socio-ecological barriers to LTPA in people with SCI becomes crucial. The associations of these barriers with FI and sociodemographic characteristics should also be considered for these interventions to be as specific and effective as possible.

Epidemiology of pediatric spinal trauma with neurological deficits in Catalonia: a 36-year experience.

PURPOSE: Existing literature on pediatric traumatic spinal cord injury (PTSCI) demonstrates large variations in characteristics, incidence, time-periods and etiology, worldwide. Epidemiological studies addressing injuries to the total spine, conducted in Southern European regions are remarkably scarce; therefore we aimed to investigate long-term trends analyzing etiology, fracture location and type, single or multiple fractures, associated lesions and neurological status in Catalonia, Spain. METHODS: We conducted a retrospective observational study. We analyzed post-acute patients after PTSCI, aged 0-17, admitted with neurological deficits between 1986 and 2022 to a specialized hospital in Catalonia. Neurological deficits were assessed using the American Spinal Injury Association Impairment Scale (AIS). RESULTS: Two hundred and forty nine children were included, 174 (69.9%) boys and 75 (30.1%) girls; mean age was 13.9 years (range, 2 months to 17 years). Two hundred and four children (82%) had ≥ 1 spinal fractures, 66 (26.5%) dislocations and 8 (3.2%) SCIWORA. Fractures were multilevel contiguous in 108 (43.4%) cases. Fracture types comprised 81 vertebral compactions (32.5%), 22 burst fractures (8.8%), 7 odontoid (2.8%) and 4 tear-drops (1.6%). There were ≥ 1 associated lesions in 112 cases (45%): in limbs in 23 cases (9.2%), thorax or abdomen in 59 (23.7%) and skull or face in 81 (32.5%). In 44 cases (39% of the 112) there were multiple lesions. Locations comprised cervical spine in 105 cases (42%), thoracic spine in 124 (49%), lumbar spine in 18 (7%), and sacrum in 2 (0.8%). Road traffic accidents (RTAs) were the main etiology (62.2%) over the whole period. However, from 2016 onwards, RTAs dropped below the rate of falls and sports injuries. The most common sites for injury in those aged 9 years or older were in the cervical (41.1%) and thoracic (50.7%) regions. Those aged 8 or under were far more likely to sustain a complete SCI (80.0%) or an accompanying traumatic brain injury (45.0%) likely due to higher numbers of pedestrian versus car RTAs. A significant peak in the occurrence of cases during 2006-2010 (20.1%) was identified with an absolute drop immediately after, during 2011-2015 (8.8%). A marked shift in trend is observed between 2016-2022 regarding age of injuries (an increase in 9 years or older), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical versus lumbar and thoracic injuries). CONCLUSIONS: A shift in trend is observed in the past 7 years regarding age of injuries (increase in those older than 9), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical). LEVEL OF EVIDENCE: IV.

Improvement in Motor and Walking Capacity during Multisegmental Transcutaneous Spinal Stimulation in Individuals with Incomplete Spinal Cord Injury.

Transcutaneous multisegmental spinal cord stimulation (tSCS) has shown superior efficacy in modulating spinal locomotor circuits compared to single-site stimulation in individuals with spinal cord injury (SCI). Building on these findings, we hypothesized that administering a single session of tSCS at multiple spinal segments may yield greater enhancements in muscle strength and gait function during stimulation compared to tSCS at only one or two segments. In our study, tSCS was applied at single segments (C5, L1, and Coc1), two segments (C5-L1, C5-Coc1, and L1-Coc1), or multisegments (C5-L1-Coc1) in a randomized order. We evaluated the 6-m walking test (6MWT) and maximum voluntary contraction (MVC) and assessed the Hmax/Mmax ratio during stimulation in ten individuals with incomplete motor SCI. Our findings indicate that multisegmental tSCS improved walking time and reduced spinal cord excitability, as measured by the Hmax/Mmax ratio, similar to some single or two-site tSCS interventions. However, only multisegmental tSCS resulted in increased tibialis anterior (TA) muscle strength. These results suggest that multisegmental tSCS holds promise for enhancing walking capacity, increasing muscle strength, and altering spinal cord excitability in individuals with incomplete SCI.

Neural correlates of referential/persecutory delusions in schizophrenia: examination using fMRI and a virtual reality underground travel paradigm.

BACKGROUND: The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable. METHOD: Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages. RESULTS: Compared to the empty condition, viewing the full carriage was associated with activations in the visual cortex, the cuneus and precuneus/posterior cingulate cortex, the inferior parietal cortex, the angular gyrus and parts of the middle and superior temporal cortex including the temporoparietal junction bilaterally. There were no significant differences in activation between groups. Nor were there activations associated with referentiality or presence of delusions generally in the patient group. However, patients with persecutory delusions showed a cluster of reduced activation compared to those without delusions in a region in the right temporal/occipital cortex. CONCLUSIONS: Performance of the metro task is associated with a widespread pattern of activations, which does not distinguish schizophrenic patients and controls, or show an association with referentiality or delusions in general. However, the finding of a cluster of reduced activation close to the right temporoparietal junction in patients with persecutory delusions specifically is of potential interest, as this region is believed to play a role in social cognition.

Do the negative symptoms of schizophrenia reflect reduced responsiveness to reward? Examination using a reward prediction error (RPE) task.

BACKGROUND: A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations. METHODS: Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS, N = 27) or absent negative symptoms (ANS, N = 27) and healthy controls (HC, N = 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE. RESULTS: In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI. CONCLUSIONS: The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.

Multicentric investigation on the safety, feasibility and usability of the ABLE lower-limb robotic exoskeleton for individuals with spinal cord injury: a framework towards the standardisation of clinical evaluations.

BACKGROUND: Robotic lower-limb exoskeletons have the potential to provide additional clinical benefits for persons with spinal cord injury (SCI). However, high variability between protocols does not allow the comparison of study results on safety and feasibility between different exoskeletons. We therefore incorporated key aspects from previous studies into our study protocol and accordingly conducted a multicentre study investigating the safety, feasibility and usability of the ABLE Exoskeleton in clinical settings. METHODS: In this prospective pretest-posttest quasi-experimental study across two SCI centres in Germany and Spain, in- and outpatients with SCI were recruited into a 12-session training and assessment protocol, utilising the ABLE Exoskeleton. A follow-up visit after 4 weeks was included to assess after-training outcomes. Safety outcomes (device-related adverse events (AEs), number of drop-outs), feasibility and usability measures (level of assistance, donning/doffing-time) were recorded at every session together with changes in gait parameters and function. Patient-reported outcome measures including the rate of perceived exertion (RPE) and the psychosocial impact of the device were performed. Satisfaction with the device was evaluated in both participants and therapists. RESULTS: All 24 participants (45 ± 12 years), with mainly subacute SCI (< 1 year after injury) from C5 to L3, (ASIA Impairment Scale A to D) completed the follow-up. In 242 training sessions, 8 device-related AEs (pain and skin lesions) were reported. Total time for don and doff was 6:50 ± 2:50 min. Improvements in level of assistance and gait parameters (time, steps, distance and speed, p < 0.05) were observed in all participants. Walking function and RPE improved in participants able to complete walking tests with (n = 9) and without (n = 6) the device at study start (p < 0.05). A positive psychosocial impact of the exoskeleton was reported and the satisfaction with the device was good, with best ratings in safety (participants), weight (therapists), durability and dimensions (both). CONCLUSIONS: Our study results prove the feasibility of safe gait training with the ABLE Exoskeleton in hospital settings for persons with SCI, with improved clinical outcomes after training. Our study protocol allowed for consistent comparison of the results with other exoskeleton trials and can serve as a future framework towards the standardisation of early clinical evaluations. Trial Registration https://trialsearch.who.int/ , DRKS00023503, retrospectively registered on November 18, 2020.

Diaphragm Pacing in Patients with Spinal Cord Injury: A European Experience.

BACKGROUND: Patients with high spinal cord injury (SCI) are unable to breathe on their own and require mechanical ventilation (MV). The long-term use of MV is associated with increased morbidity and mortality. In patients with intact phrenic nerve function, patients can be partially or completely removed from MV by directly stimulating the diaphragm motor points with a diaphragm pacing system (DPS). OBJECTIVES: We describe our multicenter European experience using DPS in SCI patients who required MV. METHODS: We conducted a retrospective study of patients who were evaluated for the implantation of DPS. Patients evaluated for DPS who met the prospectively defined criteria of being at least 1 year of age, and having cervical injury resulting in a complete or partial dependency on MV were included. Patients who received DPS implants were followed for up to 1 year for device usage and safety. RESULTS: Across 3 centers, 47 patients with high SCI were evaluated for DPS, and 34 were implanted. Twenty-one patients had 12 months of follow-up data with a median DPS use of 15 h/day (interquartile range 4, 24). Eight patients (38.1%) achieved complete MV weaning using DPS 24 h/day. Two DPS-related complications were surgical device revision and a wire eruption. No other major complications were associated with DPS use. CONCLUSIONS: Diaphragm pacing represents an attractive alternative stand-alone treatment or adjunctive therapy compared to MV in patients with high SCI. After a period of acclimation, the patients were able to reduce the daily use of MV, and many could be completely removed from MV.

Clinical Prediction Rule Validation for Ambulation Outcome After Traumatic Spinal Cord Injury in a Spanish Population.

BACKGROUND: Predicting the ability to walk after traumatic spinal cord injury is of utmost importance in the clinical setting. Nevertheless, only a small fraction of predictive models are evaluated on their performance by other authors using external data. The Dutch Clinical Prediction Rule for long-term walking ability was developed and validated using neurological assessments performed within 15 days postinjury. However, in reality, this assessment is most often performed between 11 and 55 days. When considering a longer time from injury to neurological assessments, the Dutch Clinical Prediction Rule has only been externally validated for patients after non-traumatic spinal cord injury. OBJECTIVE: We aimed to validate the Dutch Clinical Prediction Rule with neurological assessment performed within 3-90 days after traumatic spinal cord injury, using (a) the Dutch Clinical Prediction Rule logistic regression coefficients (Equation 1); (b) the Dutch Clinical Prediction Rule weighted coefficients (Equation 2); and (c) the reestimated (using a Spanish population) weighted coefficients (Equation 3). METHODS: We conducted a retrospective (STROBE-compliant) study involving 298 adults with traumatic spinal cord injury admitted to a hospital between 2010 and 2019 in Spain. The Spinal Cord Independence Measure item-12 was used for walking assessment. RESULTS: Using Equation 1, the model yielded 86.2% overall classification accuracy, 94.5% sensitivity, and 83.4% specificity (area under the curve [AUC] = 0.939, 95% confidence interval [CI]: 0.915-0.965; p < .001).Using Equation 2 yielded 86.2% overall classification accuracy, 93.2% sensitivity, and 83.9% specificity (AUC = 0.9392, 95% CI: 0.914-0.964; p < .001).Using Equation 3 yielded 86.9% overall classification accuracy, 68.9% sensitivity, and 92.8% specificity (AUC = 0.939, 95% CI: 0.914-0.964; p < .001). CONCLUSIONS: This study validates the Dutch Clinical Prediction Rule in a Spanish traumatic spinal cord injury population with assessments performed up to 90 days postinjury with similar performance, using the original coefficients and including a reestimation of the coefficients.

Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

PURPOSE: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. RESULTS: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. CONCLUSION: Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study.

BACKGROUND AIMS: Spinal cord injury (SCI) represents a devastating condition leading to severe disability related to motor, sensory and autonomic dysfunction. Stem cell transplantation is considered a potential emerging therapy to stimulate neuroplastic and neuroregenerative processes after SCI. In this clinical trial, the authors investigated the safety and clinical recovery effects of intrathecal infusion of expanded Wharton jelly mesenchymal stromal cells (WJ-MSCs) in chronic complete SCI patients. METHODS: The authors designed a randomized, double-blind, crossover, placebo-controlled, phase 1/2a clinical trial (NCT03003364). Participants were 10 patients (7 males, 3 females, age range, 25-47 years) with chronic complete SCI (American Spinal Injury Association A) at dorsal level (T3-11). Patients were randomly assigned to receive a single dose of intrathecal ex vivo-expanded WJ-MSCs (10 × 106 cells) from human umbilical cord or placebo and were then switched to the other arm at 6 months. Clinical evaluation (American Spinal Injury Association impairment scale motor and sensory score, spasticity, neuropathic pain, electrical perception and pain thresholds), lower limb motor evoked potentials (MEPs) and sensory evoked potentials (SEPs), Spinal Cord Independence Measure and World Health Organization Quality of Life Brief Version were assessed at baseline, 1 month, 3 months and 6 months after each intervention. Urodynamic studies and urinary-specific quality of life (Qualiveen questionnaire) as well as anorectal manometry, functional assessment of bowel dysfunction (Rome III diagnostic questionnaire) and severity of fecal incontinence (Wexner score) were conducted at baseline and at 6 months after each intervention. RESULTS: Intrathecal transplantation of WJ-MSCs was considered safe, with no significant side effects. Following MSC infusion, the authors found significant improvement in pinprick sensation in the dermatomes below the level of injury compared with placebo. Other clinically relevant effects, such as an increase in bladder maximum capacity and compliance and a decrease in bladder neurogenic hyperactivity and external sphincter dyssynergy, were observed only at the individual level. No changes in motor function, spasticity, MEPs, SEPs, bowel function, quality of life or independence measures were observed. CONCLUSIONS: Intrathecal transplantation of human umbilical cord-derived WJ-MSCs is a safe intervention. A single intrathecal infusion of WJ-MSCs in patients with chronic complete SCI induced sensory improvement in the segments adjacent to the injury site.

Detection of Sleep-Disordered Breathing in Patients with Spinal Cord Injury Using a Smartphone.

Patients with spinal cord injury (SCI) have an increased risk of sleep-disordered breathing (SDB), which can lead to serious comorbidities and impact patients' recovery and quality of life. However, sleep tests are rarely performed on SCI patients, given their multiple health needs and the cost and complexity of diagnostic equipment. The objective of this study was to use a novel smartphone system as a simple non-invasive tool to monitor SDB in SCI patients. We recorded pulse oximetry, acoustic, and accelerometer data using a smartphone during overnight tests in 19 SCI patients and 19 able-bodied controls. Then, we analyzed these signals with automatic algorithms to detect desaturation, apnea, and hypopnea events and monitor sleep position. The apnea-hypopnea index (AHI) was significantly higher in SCI patients than controls (25 ± 15 vs. 9 ± 7, p < 0.001). We found that 63% of SCI patients had moderate-to-severe SDB (AHI ≥ 15) in contrast to 21% of control subjects. Most SCI patients slept predominantly in supine position, but an increased occurrence of events in supine position was only observed for eight patients. This study highlights the problem of SDB in SCI and provides simple cost-effective sleep monitoring tools to facilitate the detection, understanding, and management of SDB in SCI patients.

COVID-19 related mental health issues: a narrative review of psychometric properties of scales and methodological concerns in scale development.

OBJECTIVES: The global crisis of COVID-19 and its consequential strict public health measures placed around the world have impacted mental health. New scales and tools have been developed to measure these mental health effects. This narrative review assesses the psychometric properties of these scales and tools and methodological aspects of their development. METHODS: PubMed, PubMed Central, and Google Scholar were searched for articles published from 15 May 2020 to 15 August 2020. This search used three groups of terms ("tool" OR "scale" AND "mental" OR "psychological"; AND "COVID-19" OR "coronavirus"). The identified scales were further evaluated for their psychometric properties and methodological aspects of their development. RESULTS: Though the studies developing these scales (n = 12) have demonstrated their robust psychometric properties, some methodological concerns are noteworthy. Most of the scales were validated using internet-based surveys, and detailed descriptions of the mode of administration, sampling process, response rates, and augmentation strategies were missing. CONCLUSIONS: The heterogeneous and inadequate reporting of methods adopted to evaluate the psychometric properties of the identified scales can limit their utility in clinical and research settings. We suggest developing guidelines and checklists to improve the design and testing, and result in reporting of online-administered scales to assess the mental health effects of the COVID-19 pandemic.

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report.

BACKGROUND: We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. METHODS: The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. RESULTS: Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5-2.5, 2.5-3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5-3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5-2.5, 2.5-3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). CONCLUSIONS: In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.

Placebo-controlled study of rTMS combined with Lokomat® gait training for treatment in subjects with motor incomplete spinal cord injury.

High-frequency rTMS combined with gait training improves lower extremity motor score (LEMS) and gait velocity in SCI subjects who are able to walk over ground. The aim of this study was to optimize the functional outcome in early phases of gait rehabilitation in SCI using rTMS as an additional treatment to physical therapy. The present study included 31 motor incomplete SCI subjects randomized to receive real or sham rTMS, just before Lokomat gait training (15 subjects for real, 16 for sham rTMS). rTMS consisted of one daily session for 20 days over vertex (at 20 Hz). The subjects were evaluated using modified Ashworth scale (MAS) for spasticity, upper and lower extremity motor score (UEMS and LEMS, respectively), ten meters walking test (10MWT) and Walking Index for SCI (WISCI-II) for gait at baseline, after last rTMS session, and during follow-up. UEMS and LEMS improved significantly after last session in both groups and during follow-up period. The improvement was greater in real than in sham rTMS group. At follow-up, 71.4 % of the subjects after real rTMS and 40 % of the subjects after sham rTMS could perform 10MWT without significant differences in gait velocity, cadence, step length and WISCI-II between both groups. We conclude that 20 sessions of daily high-frequency rTMS combined with Lokomat gait training can lead to clinical improvement of gait in motor incomplete SCI. Such combined treatment improved motor strength in lower extremity in incomplete SCI subjects and in upper extremity in those with cervical SCI.

Influence of spinal cord lesion level and severity on H-reflex excitability and recovery curve.

INTRODUCTION: Changes in spinal reflexes can result from alterations in the spinal cord and descending pathways. We studied whether H-reflex excitability and its recovery depend on the level and/or severity of spinal cord injury (SCI). METHODS: The soleus Hmax and Mmax responses and the H-reflex recovery curve (HRC) at interstimulus intervals (ISIs) ranging from 50 to 1,000 ms were recorded in 38 SCI individuals and 18 healthy subjects. RESULTS: Amplitude of Mmax correlated with level and severity of lesion (smaller amplitude correlated with more severe SCI or with more caudal lesion). Hmax/Mmax correlated only with age in the SCI group. HRC was increased significantly in complete SCI at ISIs < 500 ms and in incomplete SCI at ISIs > 200 ms with respect to healthy subjects. CONCLUSIONS: The changes in spinal reflexes as measured by the H-reflex and its recovery curve after SCI depend on the severity, but not on the level of the lesion.

Incidence of skeletal fractures after traumatic spinal cord injury: a 10-year follow-up study.

OBJECTIVE: To analyse the incidence and factors related to the development and clinical evolution of fractures in patients with traumatic spinal cord injury. DESIGN: A retrospective 10-year follow-up study. SETTING: Neurorehabilitation centre. SUBJECTS: Sixty-three patients (50M/13F) with a mean age of 36 ± 20 years with recent traumatic spinal cord injury attended over a one-year period (January to December 2000). MAIN MEASURES: Medical reports were reviewed, evaluating risk factors for osteoporosis, fracture incidence during the 10 years following spinal cord injury, severity (ASIA score) and level of spinal cord injury (paraplegia/tetraplegia), type of lesion (spastic/flaccid), weight-bearing standing activity, and the cause, location and evolution of the fracture. RESULTS: Of the 129 patients attending during the study period, 75 had traumatic spinal cord injury (7 died and 5 had no follow-up). Finally, 63 patients were included. Fifty-four per cent had complete motor injury (ASIA A). Twenty-five per cent of these patients developed fractures, with 2.9 fractures per 100 patient-years. The femur was the most frequent location of the fractures. Fractures were observed 6.4 ± 2.4 years after spinal cord injury (range 2-10 years), all in males. Most fractures (70%) were related to low-impact injuries. Fifty per cent presented with associated clinical complications and only 20% of the patients had received anti-osteoporotic treatment. Spinal cord injury severity was the only risk factor for the development of fractures (complete spinal cord injury (ASIA A)) (RR 4.043; 95% confidence interval (CI) 1.081-23.846, P = 0.037). CONCLUSION: The incidence of fractures after spinal cord injury is high, with severity and time since spinal cord injury being the main determinants for their development. Fractures were frequently associated with clinical complications. However, the use of anti-osteoporotic treatment was uncommon.