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Professor Peter Rothwell FMedSci has been appointed the new Action Research Professor of Clinical Neurology in the Nuffield Department of Clinical Neurosciences, succeeding Professor George Ebers.
SNR‐efficient whole‐brain pseudo‐continuous arterial spin labeling perfusion imaging at 7 T
AbstractPurposeTo optimize pseudo‐continuous arterial spin labeling (PCASL) parameters to maximize SNR efficiency for RF power constrained whole brain perfusion imaging at 7 T.MethodsWe used Bloch simulations of pulsatile laminar flow to optimize the PCASL parameters for maximum SNR efficiency, balancing labeling efficiency and total RF power. The optimization included adjusting the inter‐RF pulse spacing (TRPCASL), mean B1+ (B1+ave), slice‐selective gradient amplitude (Gmax), and mean gradient amplitude (Gave). In vivo data were acquired from six volunteers at 7 T to validate the optimized parameters. Dynamic B0‐shimming and flip angle adjustments were used to avoid needing to make the PCASL parameters robust to B0/B1+ variations.ResultsThe optimized PCASL parameters achieved a significant (3.3×) reduction in RF power while maintaining high labeling efficiency. This allowed for longer label durations and minimized deadtime, resulting in a 118% improvement in SNR efficiency in vivo compared to a previously proposed protocol. Additionally, the static tissue response was improved, reducing the required distance between labeling plane and imaging volume.ConclusionThese optimized PCASL parameters provide a robust and efficient approach for whole brain perfusion imaging at 7 T, with significant improvements in SNR efficiency and reduced specific absorption rate burden.
A survey of perioperative medicine services with a focus on provision for older surgical patients in the UK and Republic of Ireland: SNAP-3.
BACKGROUND: Perioperative medicine aims to improve care for high-risk patients, and is endorsed by national guidelines in the UK and Republic of Ireland (ROI). However, comprehensive perioperative medicine services are not yet uniformly available. This survey addressed the current state of perioperative medicine services for older surgical patients in the UK and ROI and how these services align with current national guidance. METHODS: A survey was distributed electronically to all publicly administered UK and ROI hospitals performing surgical procedures. The survey examined perioperative care against national recommendations regarding service organisation and conduct. RESULTS: Of 339 eligible hospitals, 54.9% (186/339) responded. A hospital frailty lead was appointed in 54% (101/186) of hospitals, and 9% (16/186) had a designated anaesthetist for cognitive impairment. Hospital anaesthetic services outside the theatre were focused on preoperative assessment clinics (146/172), with few reporting routine postoperative involvement (17/166). Nurse-led preoperative assessments of frailty, cognition, and delirium risk were conducted in 49.5% (90/182), 44.3% (78/176), and 13.7% (24/175) of hospitals, respectively. The Clinical Frailty Scale was used in 87.0% (147/169) of hospitals for frailty screening. The 4 'A's Test (45.7% [85/186]) and Abbreviated Mental Test (43.0% [80/186]) were the preferred cognitive assessment tools. CONCLUSIONS: The survey highlights the variation in perioperative medicine services that exist for older surgical patients despite national guidelines advocating their widespread implementation. Opportunity exists to develop interspecialty perioperative services further and promote identification of frailty, cognitive impairment, and delirium, all of which negatively impact postoperative outcomes for older surgical patients.
Specific overexpression of contactin-associated protein-like 2 and its effects on pain-related behaviour in mice
Abstract Introduction: Hyperexcitability, particularly of DRG neurons, is a key driver of persistent pain states including neuropathic pain. Contactin-associated protein-like 2 (CASPR2) is transmembrane protein known to interact and regulate the function of Kv1 channels, important determinants of neuronal excitability. Patients with autoantibodies (-Abs) against CASPR2 commonly have neuropathic pain, and these patient-Abs enhance the excitability of DRG neurons secondary to Kv1 channel disruption, leading to pain-related hypersensitivity. This is also observed after genetic ablation of CASPR2. Conversely, increasing CASPR2 levels in DRG neurons reduces excitability. Objectives: The aim of this study was to assess whether overexpressing CASPR2 could be a potential approach to treat pain. Methods: We generated a Cre-dependent mouse line to express human CASPR2 (R26LSL:hCNTNAP2(+/+) (CASPR2OE)) and crossed this with either Hoxb8Cre or Nav1.8Cre mice for CASPR2 overexpression in either all DRG neurons or to target nociceptors more selectively. Results: In both lines, CASPR2 was significantly overexpressed in DRG neurons, including at the cell membrane. In comparison to control littermates, overexpression of CASPR2 did not affect acute pain–related behaviour to mechanical or thermal stimulation or nerve injury–induced pain-related hypersensitivity. However, in both overexpression mouse lines, there were significantly reduced nocifensive responses to capsaicin. Although CASPR2 overexpression increased the contribution of α-dendrotoxin–sensitive Kv1 channels to the slowly inactivating outward current IKD, it did not affect total IKD. Conclusion: CASPR2 overexpression in DRG neurons can affect nociception, reducing pain-related behaviours to the noxious stimulant capsaicin, yet is insufficient to reduce mechanical pain–related hypersensitivity caused by nerve injury.
Comorbidities Are Associated With Unfavorable Outcome in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Exploratory Study From the CROCTINO Cohort.
BACKGROUND: Comorbidities occur in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD), potentially contributing to a less favorable disease course. OBJECTIVES: To characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4-NMOSD. METHODS: Four hundred and forty-two participants from the CROCTINO cohort were evaluated for comorbidities. RESULTS: In AQP4-NMOSD patients (n = 360), 43.5% (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) single and 25% (n = 5) multiple. In DN-NMOSD (n = 33), 36.4% (n = 12) had comorbidities equally split. AQP4-NMOSD patients had more multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4%, n = 65) than MOGAD (20%, n = 4, p = 0.09) and DN-NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4-NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN-NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN-NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4-NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs. 0.49 ± 0.98, p
Learning How to Improve the Treatment of Persecutory Delusions: Using a Principal Trajectories Analysis to Examine Differential Effects of Two Psychological Interventions (Feeling Safe, Befriending) in Distinct Groups of Patients.
BACKGROUND: A theory-driven cognitive therapy (Feeling Safe) has produced much better outcomes for patients with persecutory delusions. There are four distinct response classes: very high delusion conviction with large improvement, very high delusion conviction with no response, high delusion conviction with large improvement, and high delusion conviction with modest improvement. Our objective was to apply principal trajectories analysis, a novel statistical method, to original trial data to estimate whether these groups may have responded differently to a different intervention: befriending. DESIGN: One hundred and thirty patients with persistent persecutory delusions were randomised to six months of Feeling Safe or befriending. Baseline assessments were used to assign patients allocated to befriending (who did not receive Feeling Safe) into the four Feeling Safe response classes. The treatment effect, including on potential mediators, was then estimated for these classes. RESULTS: Patients in two treatment response classes (Very high conviction/large improvement, High conviction/large improvement) benefited more from Feeling Safe, patients in one group (Very high conviction/no improvement) benefited more from befriending, and patients in the remaining group (High conviction/moderate improvement) benefited equally from the interventions. Mechanism differences were detected when Feeling Safe was superior to befriending, but not when befriending was superior. CONCLUSIONS: There may be patients with psychosis who benefit more from one type of therapy than another, likely due to different change mechanisms. The application of principal trajectories has generated testable hypotheses and a potential step toward personalised treatment. We recommend an investigation of whether sequential provision of the treatment types could enhance patient outcomes. Keywords: persecutory, delusions, outcome trajectories, psychosis, cognitive therapy.
Anatomic Relationship Between the Greater Occipital Nerve and the Axis: Is It Possible to Safely Insert a Percutaneous C2 Screw Without Causing Occipital Neuralgia?
BACKGROUND AND OBJECTIVES: Harms' technique is a widely used method for atlantoaxial stabilization. In recent years, minimally invasive surgery (MIS) using various robotic systems for percutaneous C1 to C2 screw insertion has started to be used. However, MIS raises concerns about the precision required to avoid injury to vascular and neural structures. The greater occipital nerve (GON) primarily arises from the C2 spinal root, located between the posterior arch of the C1 vertebra and the lamina of the C2 vertebra. The first bend of the GON could potentially overlay the lateral aspect of the C2 vertebra, specifically between the superior and inferior facets, ie, the interarticular part (IAP), making it susceptible to injury during C2 pedicle screw insertion causing the occipital neuralgia. That is why the aim of our study is to investigate the relationship of the GON to the axis and to assess the risk of its violation during C2 pedicle screw insertion. METHODS: Eight cadaveric specimens, embalmed in classical formaldehyde solution, were dissected to describe the position of the GON in relation to the axis. RESULTS: The apex of the first GON bend was localized 3.9 ± 2.2 mm from the lateral margin of the C2 IAP, 10.5 ± 2.7 mm caudal from the superior facet joint of the axis. The apex of the first bend was 3.5 ± 2.0 mm above the surface of the C2 IAP. The width of the C2 IAP was 14.2 ± 3.8 mm while the height was 15.9 ± 1.3 mm. CONCLUSION: The GON overlaid the cranial two-thirds of the IAP surface and can cross the entry point of the C2 screw. Therefore, we recommend using the most caudal entry point as possible, with steeper cranial angle controlled with navigation, to avoid the GON injury during MIS.
A cross-sectional investigation of the ophthalmological impact of loiasis in Cameroon, Central Africa
Background Current knowledge of ocular manifestations of loiasis is limited to the transient subconjunctival passage of the adult filaria and anecdotal reports of posterior segment lesions. Therefore, the ocular burden of loiasis is likely underestimated since it has never been systematically assessed at the population level. We aimed to evaluate the relationship of Loa loa microfilaremia and recent eye worm passage with chronic ocular lesions identified through comprehensive ophthalmological assessment in an endemic area. Methodology/principal findings Subjects aged ≥ 15 years, residing in Akonolinga for ≥ 5 years, without filaricidal treatment for ≥3 years, were screened for filariases. After excluding participants with onchocerciasis lesions, a subset of randomly selected participants was assessed by ophthalmologists blinded to blood test results then allocated to four groups defined by microfilarial load (MFL) on calibrated thick blood film: G1 (Loa MFL = 0), G2 (MFL < 8000/mL), G3 (MFL ≥ 8000/mL), G4 (co-infestation with Mansonella MFL > 100/mL). The ophthalmological assessment comprised distance visual acuity, examination of the anterior segment with a slit lamp, and fundoscopy. The primary analysis consisted of univariable comparisons of the frequency of abnormal findings across four groups (G1 – 4) or two groups defined by history of eye worm passage. The secondary analysis consisted of a multivariable logistic regression analysis of the relationship of high Loa MFL (≥8000/mL) with chorioretinitis and eye worm passage with unilateral ametropia, adjusting for confounders. Of 1511 subjects screened, 200 underwent ophthalmological assessment, including 65, 69, 35, and 16 in G1 to 4. History of eye worm passage in the previous year was reported by 121 participants (65.4%). Unilateral ametropia was more prevalent in people with history of eye worm passage in the previous year (26.5% versus 10.9%, p = 0.014). Chorioretinitis was the most frequent posterior segment lesion (n = 11, 6.1%) and was most prevalent in G3 (14.3%). The frequency of chorioretinitis was higher in participants with moderate-to-severe visual impairment (27.3% versus 4.4%, p = 0.002). High Loa MFL was an independent predictor of chorioretinitis (adjusted OR=5.28; p = 0.01). History of eye worm passage in the previous year was independently associated with unilateral ametropia (adjusted OR=3.27, p = 0.0088). Conclusions/significance This study has, for the first time, provided evidence of independent association between history of eye worm passage and unilateral ametropia, and between high Loa MFL and severe chorioretinal lesions. This suggests that loiasis should be classified as a neglected tropical disease.
Academia in the throes of faceless bureaucracy
Pansieri et al. argue that bureaucracy is suffocating research, as an ever increasing administrative burden consumes researchers’ time and diverts focus from discovery to compliance. They highlight ways in which red tape delays progress, wastes funding, and drives researchers out of academia, and call for systemic change.
Submaximal 2-day cardiopulmonary exercise testing to assess exercise capacity and post-exertional symptom exacerbation in people with long COVID.
Long COVID has a complex pathology and a heterogeneous symptom profile that impacts quality of life and functional status. Post-exertional symptom exacerbation (PESE) affects one-third of people living with long COVID, but the physiological basis of impaired physical function remains poorly understood. Sixty-eight people (age (mean ± SD): 50 ± 11 years, 46 females (68%)) were screened for severity of PESE and completed two submaximal cardiopulmonary exercise tests separated by 24 h. Work rate was stratified relative to functional status and was set at 10, 20 or 30 W, increasing by 5 W/min for a maximum of 12 min. At the first ventilatory threshold (VT1), V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ was 0.73 ± 0.16 L/min on Day 1 and decreased on Day 2 (0.68 ± 0.16 L/min; P = 0.003). Work rate at VT1 was lower on Day 2 (Day 1 vs. Day 2; 28 ± 13 vs. 24 ± 12 W; P = 0.004). Oxygen pulse on Day 1 at VT1 was 8.2 ± 2.2 mL/beat and was reduced on Day 2 (7.5 ± 1.8 mL/beat; P = 0.002). The partial pressure of end tidal carbon dioxide was reduced on Day 2 (Day 1 vs. Day 2; 38 ± 3.8 vs. 37 ± 3.2 mmHg; P = 0.010). Impaired V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ is indicative of reduced transport and/or utilisation of oxygen. V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ at VT1 was impaired on Day 2, highlighting worsened function in the 24 h after submaximal exercise. The data suggest multiple contributing physiological mechanisms across different systems and further research is needed to investigate these areas.
Prior Expectations of Volatility Following Psychotherapy for Delusions: A Randomized Clinical Trial.
IMPORTANCE: Persecutory delusions are common, distressing, and difficult to treat. Testing computational neuroscience models of delusions can identify new therapeutic targets. OBJECTIVE: To determine whether change in delusion severity is associated with a corresponding change in volatility priors and brain activation estimated during a belief updating task. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from April 9, 2021, to December 5, 2023, within the Vanderbilt University Medical Center Psychiatric Hospital and at a community mental health center in Nashville, Tennessee. Participants were adults (aged between 18 and 65 years) with schizophrenia spectrum or delusional disorder and an active, persistent (≥3 months) persecutory delusion with strong conviction (>50%). Participants were randomly assigned 1:1 to either cognitive behavioral therapy for psychosis (CBTp)-based intervention or befriending therapy. Intention-to-treat analysis was performed from June 1 to October 31, 2024. INTERVENTION: The CBTp was a manualized intervention targeting persecutory delusions. The befriending therapy involved engaging in conversations and activities focused on neutral topics. Both interventions were provided in person, lasted for 8 weeks, and included standard care. Standard care consisted of medication management and ancillary services. MAIN OUTCOMES AND MEASURES: Primary outcomes were volatility priors (ie, prior expectations of volatility) derived from a 3-option probabilistic reversal learning task; persecutory delusion severity measured by the Psychotic Symptom Rating Scales (PSYRATS delusion subscale; score range: 0-16, with the highest score indicating severe preoccupation, distress, conviction, and functioning impact); and brain activation in the striatum and prefrontal cortex measured by blood oxygenation level-dependent signal change. Associations between volatility priors, clinical improvement, and change in neural activation were examined. RESULTS: Sixty-two participants (median [range] age, 31 [19-63] years; 38 males [61%]) were randomly assigned to the CBTp (n = 32) or befriending therapy (n = 30) arms. A subgroup of 35 participants (57%) completed functional magnetic resonance imaging. Volatility priors decreased following treatment (F1,112 = 7.7 [P = .006]; Cohen d = 0.52 [95% CI, 0.15-0.90]), as did delusion severity (F1,112 = 59.7 [P
Validation of the “Patient‐Acceptable Symptom State” Question as Outcome Measure in AChR Myasthenia Gravis: A Multicentre, Prospective Study
ABSTRACTIntroductionPatient Acceptable Symptom State (PASS) is emerging as a valuable subjective measure of the overall myasthenia gravis (MG)‐related burden. This study aimed at identifying PASS‐positive thresholds for the most used clinical scales, investigating whether PASS and MGFA post‐intervention status capture different aspects of the disease outcome, and identifying clinical variables associated with PASS=YES response.MethodsAdult AChR‐MG patients were prospectively enrolled at two Italian Centres (Rome: index cohort; Florence: validation cohort). PASS thresholds for MG‐ADL, QMG, and MG‐QOL15r were defined in the index cohort by ROC analysis and validated in the validation cohort; predictors of favorable PASS were identified by multivariable analysis.ResultsThis study included 173 patients (44% females, median age at onset: 53 years). PASS=YES patients had significantly lower median MG‐ADL, QMG, and MG‐QOL15r scores, with the following thresholds for PASS=YES: MG ADL ≤ 2, QMG ≤ 8 and MG‐QOL15r ≤ 6. The MG‐ADL (OR = 0.46, 95% CI = 0.36–0.60, p < 0.001), QMG (OR = 0.72, 95% CI = 0.64–0.81, p < 0.001) and MG‐QOL15r (OR = 0.76, 95% CI = 0.70–0.84, p < 0.001), were independently associated with a favorable PASS. The degree of ocular involvement in each scale was the strongest negative determinant of PASS=YES.ConclusionsThis study validates the PASS question and highlights the relevance of ocular complaints in patients' perception of MG burden.
Postural sway variability in young adults presents higher complexity during morning compared to evening hours while in older adults remains the same
Human movement variability reflects the adaptive capacity of the nervous system, yet how it is influenced by aging and circadian rhythms remain unclear. Therefore, the purpose of this study was to investigate postural sway variability as a function of aging and time of day. Nineteen young and nineteen older adults completed one 60-s quite stance trial with eyes open while standing on a force platform, at 12 p.m. and 12 a.m. Postural sway variability was evaluated regarding both its magnitude (total travel distance and interquartile range) and the complexity (a exponent using Detrended Fluctuation Analysis) of its temporal structure using the center of pressure time series. A two-way ANOVA (2 age groups × 2 times of day) was used. Correlation analysis was also performed to further investigate the relationship between circadian regulation and postural sway complexity. Complexity was higher for the young compared to the older group independently of the time of day. Furthermore, young adults presented higher values during the morning as compared to evening, while older adults did not reveal significant differences within the day. Finally, a strong correlation was found but only for young adults. In general, our results suggested that complexity of postural sway variability is affected both by age and time of day. Aging impacts postural control by reducing the complexity of sway variability and diminishing its sensitivity to circadian influences. Future work will address the effect of chronotype, sleep, and arousal levels on these novel findings and assess their impact on overall health.