Screening for treatment-required sleep apnoea in patients with spinal cord injury within one year after injury in a rehabilitation setting.

PURPOSE: The current study aims to assess the efficacy of the Stop-Bang Questionnaire (SBQ) in screening treatment-required sleep apnoea following Spinal Cord Injury (SCI). Additionally, we explore the performance of combined questionnaires and pulse oximetry to determine the most cost-effective method. METHODS: The study employs a cross-sectional observational design. All patients admitted to in-hospital rehabilitation at the Spinal Cord Injury Centre of Western Denmark from September 2022 to February 2023 were continuously enrolled. Participating patients underwent SBQ screening, a standard sleep questionnaire, and cardiorespiratory monitoring, followed by an individual consultation with a physician. RESULTS: During the study period, 35 SCI patients were admitted, with 24 providing informed consent. Among the 24 included patients, there was a 75% prevalence of mild to severe sleep apnoea, and 46% had treatment-required sleep apnoea. The SBQ missed only one patient with treatment-required sleep apnoea but misclassified eight patients. Combining SBQ with the pulse oximetry demonstrated the best performance in identifying patients with sleep apnoea. CONCLUSION: The study indicates that SBQ alone is insufficient for screening treatment-required sleep apnoea. Exploratory analysis suggests that combining SBQ with a simple pulse oximetry measurement might enhance accuracy.

"Stroke - 65 plus. Continued active life." A randomized controlled trial of a self-management neurorehabilitation intervention for elderly people after stroke.

PURPOSE: Post-stroke sequelae among elderly often lead to a more inactive life while carrying a risk of overburdening close relatives. The objective of the present study was to determine if a novel self-management neuro-rehabilitation intervention added to usual treatment for people with stroke over the age of 65 years improved their self-efficacy. METHODS: This randomised controlled trial included participants two weeks before discharge from subacute rehabilitation. All participants received usual treatment. The intervention entailed an add-on of six to eight self-management sessions lasting 45-60 min within a period of nine months after discharge. This novel neuro-rehabilitation intervention focused on promoting growth, development and self-efficacy by facilitating the participants' self-management strategies regarding their activities and social network. All participants were assessed at baseline, three months and nine months after discharge. The primary outcome was self-efficacy measured by the Stroke Self-Efficacy Questionnaire. RESULTS: Sixty-nine individuals with stroke aged > 65 years were randomised. Their mean(SD) age was 76(6) years; 32 (46%) were female. No significant difference was found between the groups at baseline. Improvement recorded in the intervention group did not significantly differ from that of the control group with regard to primary outcome or secondary outcomes. CONCLUSIONS: This novel self-management intervention had no significant effect measured by the primary outcome self-efficacy or quality of life. Furthermore, no impact was observed on participation and autonomy compared with usual treatment.Clinical trial registration-URL: ClinicalTrials.gov, NCT03183960. Registered on 12 June 2017.

The present study testing a novel self-management neuro-rehabilitation intervention for people with stroke aged more than 65 years failed to improve self-efficacy, quality of life, and impact on participation and autonomy.Post hoc analyzes showed a lower caregiver burden at three and nine months in the intervention group as compared to the control group.The approach of perceiving the stroke individual and the informal caregiver as one unit (dyad), involving both in decisions regarding everyday activities and roles in everyday life especially within their shared part of life, appears important and warrants further development.

Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study.

BACKGROUND: Concussion leads to persistent post-concussion symptoms (PPCS) in up to one-third of those affected. While previous research has linked the initial trauma to elevated serum levels of neurofilament light chain (NFL), inflammatory markers, and neurotoxic metabolites within the kynurenine pathway, few studies have explored their relevance in PPCS. This study aims to investigate these biomarkers in PPCS patients, elucidating their relevance in the prolonged phase of concussion. METHODS: Serum samples from 86 PPCS individuals aged 18-30 years, 2-6 months post-trauma were analyzed, with 54 providing follow-up samples after seven months. NFL was measured using single-molecule array (Simoa) technology, 13 inflammatory markers via a Luminex immunoassay, and five kynurenine metabolites using liquid chromatography-mass spectrometry. A control group of 120 healthy anonymous blood donors was recruited for comparison. RESULTS: No significant NFL differences were found in PPCS participants compared with healthy individuals (p = 0.22). Intriguingly, a subset (9.3%) of PPCS participants initially exhibited abnormally high NFL levels (>9.7 pg/mL), which normalized upon follow-up (p = 0.032). Additionally, serum levels of the inflammatory markers, monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1/CCL11 were 25-40% lower than in healthy individuals (p ≤ 0.001). As hypothesized, PPCS participants exhibited a 22% reduction in the ratio of kynurenic acid to quinolinic acid (neuroprotective index) (p < 0.0001), indicating a shift towards the formation of neurotoxic metabolites. CONCLUSION: NFL may serve as a biomarker to monitor recovery, and future studies should investigate the potential therapeutic benefits of modulating the kynurenine pathway to improve PPCS.

Convergence insufficiency in patients with post-concussion syndrome is accompanied by a higher symptom load: a cross-sectional study.

OBJECTIVE: To estimate the prevalence of convergence insufficiency (CI) in adult patients with post-concussion syndrome and determine the impact of CI on symptom load. METHODS: Cross-sectional study of 103 patients with neurological symptoms 2-6 months after a concussion. Symptoms were assessed with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and CI was diagnosed using near point of convergence, vergence facility, and the Convergence Insufficiency Symptom Survey. The RPQ score for patients with and without CI was compared, and sensitivity, specificity, and area under the receiver operating characteristic curve for the two visually related RPQ questions as indicators of CI were calculated. RESULTS: The proportion of patients diagnosed with symptomatic CI was 20.4% (95% confidence interval: 13.1-29.5%). The RPQ score was significantly higher for patients with symptomatic CI both before (p = .01) and after removal of the two visually related questions in the RPQ-questionnaire (p = .03). The two visually related RPQ questions were unable to detect CI. CONCLUSION: In patients with post-concussion syndrome, the load of nonvisual symptoms is higher in the presence of CI. A prospective interventional study on CI is required to study the relationship between CI and other post-concussion symptoms.

Serum calcitonin gene-related peptide in patients with persistent post-concussion symptoms, including headache: a cohort study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology, and post-traumatic headache (PTH) frequently presents with migraine-like features. Despite several clinical similarities, few studies have explored CGRP in PTH and concussion. This study investigates serum CGRP levels in patients with persistent post-concussion symptoms (PPCS), including PTH. METHODS: This cohort study was based on serum samples from individuals aged 18-30 years with PPCS who participated in a previously published randomized controlled trial of a non-pharmacological intervention. The primary outcome was serum CGRP concentrations, determined at baseline before randomization and at follow-up 7 months later, using an enzyme-linked immunosorbent assay (ELISA). CGRP levels at baseline were compared with healthy anonymous blood donors in the same age group. RESULTS: Baseline serum samples were collected from 86 participants with PPCS. The participants were most often female (78%) and migraine-like headache was the most frequent headache phenotype (74%). Serum CGRP levels were higher in participants with PPCS than in 120 healthy individuals (median: 158.5 pg/mL vs. 76.3 pg/mL, p = 0.050). A stratified analysis revealed that females with PPCS had a fivefold higher median than healthy females (166.3 pg/mL vs. 32.1 pg/mL, p = 0.0006), while no differences were observed in males (p = 0.83). At follow-up, CGRP levels decreased with a median change of - 1.3 pg/mL (95% confidence interval: - 17.6-0, p = 0.024). DISCUSSION: Elevated serum levels of CGRP in patients with PPCS and a decrease over time suggest an involvement of CGRP in PTH/PPCS. If confirmed in other studies, it could pave the way for CGRP-targeted therapies, which could have clinical significance.

Safety and efficacy of blood flow restriction exercise in individuals with neurological disorders: A systematic review.

OBJECTIVES: This systematic review evaluated the safety and efficacy of blood flow restriction exercise (BFRE) on skeletal muscle size, strength, and functional performance in individuals with neurological disorders (ND). METHODS: A literature search was performed in PubMed, CINAHL, and Embase. Two researchers independently assessed eligibility and performed data extraction and quality assessments. ELIGIBILITY CRITERIA: Study populations with ND, BFRE as intervention modality, outcome measures related to safety or efficacy. RESULTS: Out of 443 studies identified, 16 were deemed eligible for review. Three studies examined the efficacy and safety of BFRE, one study focused on efficacy results, and 12 studies investigated safety. Disease populations included spinal cord injury (SCI), inclusion body myositis (sIBM), multiple sclerosis (MS), Parkinson's disease (PD), and stroke. A moderate-to-high risk of bias was presented in the quality assessment. Five studies reported safety concerns, including acutely elevated pain and rating of perceived exertion levels, severe fatigue, muscle soreness, and cases of autonomic dysreflexia. Two RCTs reported a significant between-group difference in physical function outcomes, and two RCTs reported neuromuscular adaptations. CONCLUSION: BFRE seems to be a potentially safe and effective training modality in individuals with ND. However, the results should be interpreted cautiously due to limited quality and number of studies, small sample sizes, and a general lack of heterogeneity within and between the examined patient cohorts.

Expanding the Spectrum of Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures (CONDSIAS).

Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an extremely rare, autosomal recessive neurodegenerative disorder. It is caused by biallelic pathogenic variants in the ADPRS gene, which encodes an enzyme involved in DNA repair, and is characterized by exacerbations in relation to physical or emotional stress, and febrile illness. We report a 24-year-old female, who was compound heterozygous for two novel pathogenic variants revealed by whole exome sequencing. Additionally, we summarize the published cases of CONDSIAS. In our patient, onset of symptoms occurred at 5 years of age and consisted of episodes of truncal dystonic posturing, followed half a year later by sudden diplopia, dizziness, ataxia, and gait instability. Progressive hearing loss, urinary urgency, and thoracic kyphoscoliosis ensued. Present neurological examination revealed dysarthria, facial mini-myoclonus, muscle weakness and atrophy of hands and feet, leg spasticity with clonus, truncal and appendicular ataxia, and spastic-ataxic gait. Hybrid [18F]-fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) of the brain revealed cerebellar atrophy, particularly of the vermis, with corresponding hypometabolism. MRI of the spinal cord showed mild atrophy. After informed consent from the patient, we initiated experimental, off-label treatment with minocycline, a poly-ADP-polymerase (PARP) inhibitor, which has shown beneficial effects in a Drosophila fly model. The present case report expands the list of known pathogenic variants in CONDIAS and presents details of the clinical phenotype. Future studies will reveal whether PARP inhibition is an effective treatment strategy for CONDIAS.

Occurrence, presence and severity of bruxism and its association with altered state of consciousness in individuals with severe acquired brain injury.

BACKGROUND: Excessive jaw muscle activity is a frequent complication after acquired brain injury (ABI). OBJECTIVE: The study aimed to identify the occurrence and severity of jaw muscle activity and its association with altered state of consciousness in patients with ABI. METHODS: A total of 14 severe ABI patients with varied altered state of consciousness were recruited. A single-channel electromyographic (EMG) device was used to assess the jaw muscle activity for three consecutive nights during Week 1 and Week 4 following admission. Differences in number of EMG episodes/h between Week 1 and 4 were analysed using non-parametric tests and association between the EMG activity and altered state of consciousness were analysed using Spearman's correlation test. RESULTS: Nine of fourteen (64%) patients showed indications of bruxism (cutoff: >15 EMG episodes/h). The average EMG episodes/h at admission were 44.5 ± 13.6 with no significant changes after Week 4 of admission (43 ± 12.9; p = .917). The EMG episodes/h ranged from 2 to 184 during Week 1 and 4-154 during Week 4. There were no significant correlations between the number of EMG episodes/h during the three nights and the individuals altered state of consciousness during Week 1 and Week 4. CONCLUSION: Patients with ABI had a conspicuously high but variable level of jaw muscle activity at admission and it tend to remain high after 4 week of hospitalisation which could potentially lead to adverse effects such as excessive tooth wear, headaches and pain in jaw muscles. The lack of associations between individuals altered level of consciousness and EMG activity could be due to low sample size and further studies are clearly warranted in this patient group with special needs. Single-channel EMG devices can record jaw muscle activity early in the hospitalisation period and might be a helpful tools for early detection of bruxism in ABI patients.

A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by the intra- and extracellular accumulation of amyloid-ß (Aß) peptides. How Aß aggregates perturb the proteome in brains of patients and AD transgenic mouse models, remains largely unclear. State-of-the-art mass spectrometry (MS) methods can comprehensively detect proteomic alterations, providing relevant insights unobtainable with transcriptomics investigations. Analyses of the relationship between progressive Aß aggregation and protein abundance changes in brains of 5xFAD transgenic mice have not been reported previously. METHODS: We quantified progressive Aß aggregation in hippocampus and cortex of 5xFAD mice and controls with immunohistochemistry and membrane filter assays. Protein changes in different mouse tissues were analyzed by MS-based proteomics using label-free quantification; resulting MS data were processed using an established pipeline. Results were contrasted with existing proteomic data sets from postmortem AD patient brains. Finally, abundance changes in the candidate marker Arl8b were validated in cerebrospinal fluid (CSF) from AD patients and controls using ELISAs. RESULTS: Experiments revealed faster accumulation of Aß42 peptides in hippocampus than in cortex of 5xFAD mice, with more protein abundance changes in hippocampus, indicating that Aß42 aggregate deposition is associated with brain region-specific proteome perturbations. Generating time-resolved data sets, we defined Aß aggregate-correlated and anticorrelated proteome changes, a fraction of which was conserved in postmortem AD patient brain tissue, suggesting that proteome changes in 5xFAD mice mimic disease-relevant changes in human AD. We detected a positive correlation between Aß42 aggregate deposition in the hippocampus of 5xFAD mice and the abundance of the lysosome-associated small GTPase Arl8b, which accumulated together with axonal lysosomal membranes in close proximity of extracellular Aß plaques in 5xFAD brains. Abnormal aggregation of Arl8b was observed in human AD brain tissue. Arl8b protein levels were significantly increased in CSF of AD patients. CONCLUSIONS: We report a comprehensive biochemical and proteomic investigation of hippocampal and cortical brain tissue derived from 5xFAD transgenic mice, providing a valuable resource to the neuroscientific community. We identified Arl8b, with significant abundance changes in 5xFAD and AD patient brains. Arl8b might enable the measurement of progressive lysosome accumulation in AD patients and have clinical utility as a candidate biomarker.

Cerebellar ataxia-neuropathy-vestibular areflexia-syndrome.

CANVAS including its clinical components of cerebellar ataxia, sensory neuropathy and vestibular areflexia is presented in this review. An intronic biallelic pentanucleotide expansion in RFC1 is the genetic cause of CANVAS. Several patients diagnosed with isolated "idiopathic" neurological or otological conditions might have a CANVAS spectrum disorder. The number of CANVAS patients may well increase considerably in the near future, making it important to consider the diagnostic set-up and infrastructure for counselling, treatment and follow-up in the Danish healthcare system.

Chenodeoxycholic acid rescues axonal degeneration in induced pluripotent stem cell-derived neurons from spastic paraplegia type 5 and cerebrotendinous xanthomatosis patients.

BACKGROUND: Biallelic mutations in CYP27A1 and CYP7B1, two critical genes regulating cholesterol and bile acid metabolism, cause cerebrotendinous xanthomatosis (CTX) and hereditary spastic paraplegia type 5 (SPG5), respectively. These rare diseases are characterized by progressive degeneration of corticospinal motor neuron axons, yet the underlying pathogenic mechanisms and strategies to mitigate axonal degeneration remain elusive. METHODS: To generate induced pluripotent stem cell (iPSC)-based models for CTX and SPG5, we reprogrammed patient skin fibroblasts into iPSCs by transducing fibroblast cells with episomal vectors containing pluripotency factors. These patient-specific iPSCs, as well as control iPSCs, were differentiated into cortical projection neurons (PNs) and examined for biochemical alterations and disease-related phenotypes. RESULTS: CTX and SPG5 patient iPSC-derived cortical PNs recapitulated several disease-specific biochemical changes and axonal defects of both diseases. Notably, the bile acid chenodeoxycholic acid (CDCA) effectively mitigated the biochemical alterations and rescued axonal degeneration in patient iPSC-derived neurons. To further examine underlying disease mechanisms, we developed CYP7B1 knockout human embryonic stem cell (hESC) lines using CRISPR-cas9-mediated gene editing and, following differentiation, examined hESC-derived cortical PNs. Knockout of CYP7B1 resulted in similar axonal vesiculation and degeneration in human cortical PN axons, confirming a cause-effect relationship between gene deficiency and axonal degeneration. Interestingly, CYP7B1 deficiency led to impaired neurofilament expression and organization as well as axonal degeneration, which could be rescued with CDCA, establishing a new disease mechanism and therapeutic target to mitigate axonal degeneration. CONCLUSIONS: Our data demonstrate disease-specific lipid disturbances and axonopathy mechanisms in human pluripotent stem cell-based neuronal models of CTX and SPG5 and identify CDCA, an established treatment of CTX, as a potential pharmacotherapy for SPG5. We propose this novel treatment strategy to rescue axonal degeneration in SPG5, a currently incurable condition.

Golgi fragmentation - One of the earliest organelle phenotypes in Alzheimer's disease neurons.

Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aß) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model. We recapitulated characteristic late AD phenotypes, such as increased Aß secretion and Tau hyperphosphorylation, as well as previously well documented mitochondrial and synaptic deficits. Intriguingly, we identified Golgi fragmentation as one of the earliest AD phenotypes, indicating potential impairments in protein processing and post-translational modifications. Computational analysis of RNA sequencing data revealed differentially expressed genes involved in glycosylation and glycan patterns, whilst total glycan profiling revealed minor glycosylation differences. This indicates general robustness of glycosylation besides the observed fragmented morphology. Importantly, we identified that genetic variants in Sortilin-related receptor 1 (SORL1) associated with AD could aggravate the Golgi fragmentation and subsequent glycosylation changes. In summary, we identified Golgi fragmentation as one of the earliest disease phenotypes in AD neurons in various in vivo and in vitro complementary disease models, which can be exacerbated via additional risk variants in SORL1.

Exploring Physical Activity During the Discharge Transition Phase in People With Acquired Brain Injury-An Observational Study.

Objective: To explore physical activity trajectories during the discharge transition phase after in-hospital rehabilitation after acquired brain injury (ABI). Design: A cross-sectional observational study. Setting: Transition from an in-hospital rehabilitation center to community-based living. Participants: Independently walking patients with ABI (n=10) who were ready for discharge. Interventions: Not applicable. Main Outcome Measures: Two weeks of physically active time continuously monitored with an accelerometer and classified by a machine learning algorithm summed as daily average and total active time for each participant and classified into standing, walking, running, bike riding, stair climbing, ambulation, and sedentary time. Physical activity trajectories showing the total daily active time for all participants were inspected before and after discharge, and the average active time per participant was plotted against self-reported scores of potentially explanatory factors. Results: Average total physically active time was 5:49 hours (range 4:26-7:13 hours). Average daily physically active time for participants appeared to be related to functional independence measure sub scores, fatigue, and pre-morbid physical activity level. Individual physical activity trajectories showed a decreased walking activity after discharge, which increased again after 1-2 days. Conclusions: Daily total physically active time among participants was higher than expected. Factors expectedly related to physical activity trajectories in the discharge transition phase were explored and showed some relation to functional scores.

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia.

Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

Simultaneous measurement of kynurenine metabolites and explorative metabolomics using liquid chromatography-mass spectrometry: A novel accurate method applied to serum and plasma samples from a large healthy cohort.

Kynurenine metabolites are emerging as promising clinical biomarkers in several diseases, especially within psychiatry. Unfortunately, they are difficult to detect, particularly the challenging neurotoxic metabolite quinolinic acid (QUIN). The aim of this study was twofold: First, to develop a liquid chromatography-mass spectrometry method (LC-MS) for simultaneous targeted quantification of key kynurenine metabolites together with untargeted metabolomics, and second, to demonstrate the feasibility of the method by exploring serum/plasma and gender differences in 120 healthy young adults between 18 and 30 years of age. A range of analytical columns (C18 and biphenyl columns) and mobile phases (acidic and alkaline) were systematically evaluated. The optimized LC-MS method was based on a biphenyl column, a water-methanol gradient with 0.2% formic acid, and authentic isotope-labeled standards for each kynurenine metabolite. Precision and accuracy of targeted quantification of the key kynurenine metabolites tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and QUIN were excellent, far exceeding the acceptance criteria specified by international guidelines. Median inter- and intra-day precision were < 6% in serum and plasma; the median accuracy was 2.4% in serum and 8% in plasma. Serum concentrations were ≤ 10% different from the corresponding concentrations in plasma for all kynurenine metabolites in healthy young adults. Men had higher levels (8-18%) of TRP, KYN, and KYNA than women (p ≤ 0.009), while no differences were observed for 3-HK and QUIN (p > 0.70). Incurred sample reanalysis of 10% of the samples yielded a median difference < 5% from the initial measurement, demonstrating the robustness of the method. Besides the targeted quantification of key kynurenine metabolites, our method was found to be suitable for simultaneous untargeted metabolomics analyses of hundreds of metabolites. A range of compound classes could be detected including amino acids, nucleic acids, dipeptides, antioxidants, and acylcarnitines, making explorative studies highly feasible. For example, we identified an additional kynurenine metabolite, 2-Quinolinecarboxylic acid, which was 47% higher in males than females (adjusted p-value = 0.001). In conclusion, in this study, we present a reliable and robust LC-MS method for simultaneous targeted and untargeted metabolomics ready for both research and clinical use. We show that both serum and plasma can be used for kynurenine studies, and the reported gender differences are in accordance with the literature. Future studies should consider using biphenyl-based LC-MS columns to successfully detect QUIN.

Malnutrition in Patients With Moderate to Severe Acquired Brain Injury: Prevalence During 4 Weeks of Subacute Rehabilitation.

ABSTRACT: BACKGROUND: Malnutrition is associated with high rates of complication, longer hospital stays, and increased morbidity and mortality. Malnutrition defined as undernutrition is common in patients with acquired brain injury (ABI); however, estimates vary remarkably. This study aimed to describe malnutrition at admission and after 4 weeks of subacute inpatient neurorehabilitation in patients with ABI using the new global consensus definition of malnutrition. METHODS: One hundred thirty-three patients with moderate to severe ABI consecutively admitted to a specialized neurorehabilitation hospital within a period of 4 months were screened for inclusion, of which 92 were included. Malnutrition was defined as at least 1 phenotypic criterion (weight loss, low body mass index, low muscle mass) and at least 1 etiologic criterion (reduced food intake, inflammation). Malnutrition on admission and after 4 weeks was compared using the McNemar test. RESULTS: The proportion of patients with malnutrition at admission was 42%, with more men (46%) than women (36%) fulfilling the criteria for malnutrition. The most frequent phenotypic and etiologic criteria were weight loss (56%) and inflammation (74%), respectively. During the 4 weeks of rehabilitation, the proportion of male patients fulfilling the individual criteria "weight loss" (difference, -21.4%) and "inflammation" (difference, -18.9%) decreased significantly; "low muscle mass" decreased borderline significant (difference, -8.9%), whereas "low body mass index" did not change. The proportion of female patients fulfilling individual criteria for malnutrition was stable or increased nonsignificantly. CONCLUSION: Malnutrition was common at admission to neurorehabilitation in patients with moderate to severe ABI, with more men than women fulfilling the criteria for malnutrition. The nutritional status improved after 4 weeks of rehabilitation in male patients, whereas it was largely unchanged in female patients. The results provide the basis for monitoring high-quality nutritional nursing care.

Regression-based prognostic models for functional independence after postacute brain injury rehabilitation are not transportable: a systematic review.

BACKGROUND AND OBJECTIVES: To identify and summarize validated multivariable prognostic models for the Functional Independence Measure® (FIM®) at discharge from post-acute inpatient rehabilitation in adults with acquired brain injury (ABI). METHODS: This review was conducted based on the recommendations of the Cochrane Prognosis Methods Group and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases were systematically searched in May 2021 and updated in April 2022. Main inclusion criteria were: a) adult patients with ABI, b) validated multivariable prognostic model, c) time of prognostication within 1-week of admission to post-acute rehabilitation, and d) outcome was the FIM® at discharge from post-acute rehabilitation. RESULTS: The search yielded 3,169 unique articles. Three articles fulfilled the inclusion criteria, accounting for n = 6 internally and n = 2 externally validated prognostic models. Discrimination was estimated as an area under the curve between 0.76 and 0.89. Calibration was deemed to be assessed insufficiently. The included models were judged to be of high risk of bias. CONCLUSION: Current prognostic models for the FIM® in post-acute rehabilitation for patients with ABI lack the methodological rigor to support clinical use outside the development setting. Future studies addressing functional independence should ensure appropriate model validation and conform to uniform reporting standards for prognosis research.

Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation.

Introduction: Increasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. Methods: Combining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. Results: Compared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. Discussion: Lower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. Highlights: CSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.

A national needs assessment to identify technical procedures in plastic surgery for simulation-based training.

Medical simulation is not developed and integrated into plastic surgery unlike other surgical specialties despite the procedures being complex and require practice. First step in enhancing simulation in plastic surgery is to clarify the need among peers. The objective of the study was to identify and prioritize the technical procedures that should be included in a simulation-based curriculum for residency training in plastic surgery. A panel of participants with key roles in the Danish plastic surgery specialist training program was appointed. Participation was voluntary. A national need assessment study was performed using a three-round Delphi process to collect information from the participants. In round 1, participants reported all the procedures that a newly qualified specialist in plastic surgery should be able to perform. In round 2, participants replied to a survey exploring the frequency of the procedures, the number of surgeons performing the procedure, the risk or discomfort for patients treated by an inexperienced surgeon and the feasibility of training the procedure in simulation, resulting in a preliminary ranking of procedures. In round 3, participants eliminated and reprioritized the identified procedures according to importance. Thirty-five of 37 agreed to enter the expert panel. The response rate was 97%, 86% and 86% for rounds 1, 2 and 3, respectively. Twenty-nine of 136 procedures identified in round 1 reached the final prioritized list of procedures relevant for simulation training in plastic surgery.

Does time heal fatigue, psychological, cognitive and disability problems in people who experience an out-of-hospital cardiac arrest? Results from the DANCAS survey study.

AIMS: Out-of-hospital cardiac arrest (OHCA) survivors may suffer short-term fatigue, psychological, cognitive and disability problems, but we lack information on the proportion of survivors with these problems in the long-term. Hence, we investigated these problems in survivors 1-5 years post-OHCA and whether the results are different at different time points post-OHCA. METHODS: All adults who survived an OHCA in Denmark from 2016 to 2019 were identified using the Danish Cardiac Arrest Registry and invited to participate in a survey between October 2020 and March 2021. The survey included the Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, "Two simple questions" (everyday activities and mental recovery), and the 12-item World Health Organisation Disability Assessment Schedule 2.0. To investigate results at different time points, survivors were divided into four time-groups (12-24, 25-36, 37-48 and 49-56 months post-OHCA). Differences between time-groups were determined using the Kruskall-Wallis test for the mean scores and Chi-square test for the proportion of survivors with symptoms. RESULTS: Total eligible survey population was 2116, of which 1258 survivors (60 %) responded. Overall, 29 % of survivors reported fatigue, 20 % anxiety, 15 % depression, and 27 % disability. When survivors were sub-divided by time since OHCA, no significant difference was found on either means scores or proportion between time groups (p = 0.28 to 0.88). CONCLUSION: Up to a third of survivors report fatigue, anxiety, depression, reduced mental function and disability 1-5 years after OHCA. This proportion is the same regardless of how much time has passed supporting early screening and tailored post-OHCA interventions to help survivors adapt to their new situation.