Basal parasympathetic deficits in C9orf72 hexanucleotide repeat expansion carriers relate to smaller frontoinsula and thalamus volume and lower empathy.

Diminished basal parasympathetic nervous system activity is a feature of frontotemporal dementia that relates to left frontoinsula dysfunction and empathy impairment. Individuals with a pathogenic expansion of the hexanucleotide repeat in chromosome 9 open reading frame 72 (C9orf72), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, provide a unique opportunity to examine whether parasympathetic activity is disrupted in genetic forms of frontotemporal dementia and to investigate when parasympathetic deficits manifest in the pathophysiological cascade. We measured baseline respiratory sinus arrhythmia, a parasympathetic measure of heart rate variability, over two minutes in a sample of 102 participants that included 19 asymptomatic expansion carriers (C9+ asymp), 14 expansion carriers with mild cognitive impairment (C9+ MCI), 16 symptomatic expansion carriers with frontotemporal dementia (C9+ FTD), and 53 expansion-negative healthy controls (C9- HC) who also underwent structural magnetic resonance imaging. In follow-up analyses, we compared baseline respiratory sinus arrhythmia in the C9+ FTD group with an independent age-, sex-, and clinical severity-matched group of 26 people with sporadic behavioral variant frontotemporal dementia. The Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating-Sum of Boxes score was used to quantify behavioral symptom severity, and informant ratings on the Interpersonal Reactivity Index provided measures of participants' current emotional (empathic concern) and cognitive (perspective-taking) empathy. Results indicated that the C9+ FTD group had lower baseline respiratory sinus arrhythmia than the C9+ MCI, C9+ asymp, and C9- HC groups, a deficit that was comparable to that of sporadic behavioral variant frontotemporal dementia. Linear regression analyses indicated that lower baseline respiratory sinus arrhythmia was associated with worse behavioral symptom severity and lower empathic concern and perspective-taking across the C9orf72 expansion carrier clinical spectrum. Whole-brain voxel-based morphometry analyses in participants with C9orf72 pathogenic expansions found that lower baseline respiratory sinus arrhythmia correlated with smaller gray matter volume in the left frontoinsula and bilateral thalamus, key structures that support parasympathetic function, and in the bilateral parietal lobes, occipital lobes, and cerebellum, regions that are also vulnerable in individuals with C9orf72 expansions. This study provides novel evidence that basal parasympathetic functioning is diminished in FTD due to C9orf72 expansions and suggests that baseline respiratory sinus arrhythmia may be a potential non-invasive biomarker that is sensitive to behavioral symptoms in the early stages of disease.

Optic Atrophy From Retrograde Transsynaptic Axonal Degeneration Following Pediatric Brain Injury.

BACKGROUND: The patterns of optic atrophy due to retrograde transsynaptic degeneration (RTSD) have not been well characterized in children. This study aimed to characterize optic atrophy in pediatric patients with focal intracerebral lesions. METHODS: A retrospective review of children with optic atrophy and focal intracerebral lesions was conducted. Ophthalmic data were recorded, including visual acuity, color vision, formal automated visual fields and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell layer. RESULTS: Six patients (83.33% male) were included. The mean visual acuity (VA) of all eyes was 0.30 logMAR (20/40 Snellen), with no significant difference in the mean logMAR VA in the ipsilateral eye to the location of the lesion compared with the contralateral eye (0.30 vs 0.30, P = 1.000). Color vision (available in 5 patients) was normal in 2, mildly reduced in one and markedly reduced in 2. Bitemporal optic disc pallor was observed in 5 out of 6 patients. OCT data revealed that pRNFL thickness was most significantly diminished in the temporal (95% CI: -44.71 to -14.18 µm, P = 0.0021), inferotemporal (95% CI: -75.06 to -5.17 µm, P = 0.0294), and superotemporal (95% CI: -76.82 to -18.51 µm, P = 0.0055) sectors. Average pRNFL thickness was significantly reduced compared with normative data in both the ipsilateral (95% CI: -40.76 to -11.69 µm, P = 0.0003) and the contralateral eye (95% CI: -38.46 to -5.83 µm, P = 0.0063). When only nasal and temporal data were analyzed, mean pRNFL thickness was still diminished compared with normative data (95% CI: -33.01 to -9.77 µm, P = 0.0012). CONCLUSIONS: Children presenting with optic atrophy, particularly with bitemporal optic atrophy, should have neuroimaging to exclude any underlying serious intracranial pathology.

Prevalence of HIV-related stigma among people with HIV in Switzerland: addressing the elephant in the room.

OBJECTIVES: We aimed to determine the prevalence of HIV-related stigma among people with HIV (PWH) in Switzerland. DESIGN: A cross-sectional multicentre study nested within the Swiss HIV Cohort Study (SHCS). METHODS: We included adult PWH enrolled in the SHCS, attending follow-up between March 1st, 2020, and January 31st, 2021. Inability to speak English, French, German, or Italian was the only exclusion criterion. Participants were invited to complete a validated 12-item HIV-stigma questionnaire comprising four stigma subscales (negative self-image, personalised stigma, disclosure concerns, and concerns regarding public attitudes), plus two healthcare-related stigma items. Questionnaire responses were graded using a four-point Likert-type scale, higher scores indicating higher stigma. "Non-applicable", inferring HIV-status non-disclosure, was possible for personalised stigma; stigma scores from participants answering "non-applicable" to ≥1 items were analysed separately. Factors associated with HIV-stigma were identified through multivariable linear models. RESULTS: Of 9643 PWH with a SHCS visit, 5563 participated in the study: 26% were female, 13% Black and 37% heterosexual; median age was 53 years (interquartile range 44-59); 2067 participants (37%) gave ≥1 "non-applicable" responses. Disclosure concerns had the highest stigma scores and were reported by 4656/5563 (84%). HIV-stigma was reported across all demographic groups. However, being female, Black, and heterosexual were independently associated with higher scores. Higher education and longer follow-up duration were associated with lower scores. Healthcare-related stigma was reported in 37% of participants. CONCLUSIONS: HIV-stigma was prevalent across all demographic groups. The association with being female and Black suggests that HIV-stigma accentuates pre-existing gender and race inequalities.

Perceptions of digital technology use for monitoring health in people living with neurological disorders.

BACKGROUND: Digital technology offers individuals the opportunity to monitor their symptoms. Information gathered from apps, devices, and web platforms may be used to direct clinical care and to support research. AIM: Using this survey, we aim to explore the views of people attending the Anne Rowling Regenerative Neurology Clinic (ARRNC) and their relatives/caregivers regarding the use of digital health technologies to monitor health. METHOD: People attending the ARRNC were invited to complete a structured 18-item questionnaire evaluating their experience and attitudes to using technology for monitoring health. People with neurodegenerative disease (pwND) and their caregivers completed a mix of closed and open-ended questions. RESULTS: 249 people responded, 51 relatives/caregivers and 198 pwND. 67.1% (n= 167) of respondents do not use technology for monitoring their health, but 98.2% (n = 164) of these are interested in their future use. 29.7% (n = 74) respondents currently use a smartphone for health monitoring, 20.9% (n = 52) use a wearable device, and 13.3% (n = 33) use a tablet. 79.3% (n = 65) of users use their technology for monitoring physical activity, 37.8% (n = 31) use it for assisting with self-management, and 41.5% (n = 34) use it for tracking sleep. Factors which would encourage use of technology are ease of access to devices and ability to monitor health. Respondents reported data security concerns and difficulty using technology as potential barriers. CONCLUSION: People attending a neurology clinic, and their relatives/caregivers, support the use of digital technologies as an adjunct to routine care. There is a need for coordinated digital strategies for development and delivery of validated measures.

Navigating HIV-Related Stigma in Switzerland: A Qualitative Study.

Objectives: This study sought to understand how people living with HIV experience, perceive, and navigate stigma in their everyday life and in care settings in an urban French-speaking area in Switzerland. Methods: Semi-structured interviews were carried out with 19 people living with HIV in Lausanne concerning their experience of HIV-related stigma in both everyday life and in healthcare settings. Content analysis was performed to identify main and sub-themes. Results: "Living with HIV" posed little or no difficulty for participants. However, the burden of anticipated and internalized HIV-related stigma played a disproportionately large role in their lives. Participants considered the general population's low level of knowledge about HIV as problematic in this regard. While participants reported few examples of enacted stigma generally, healthcare environments were sometimes experienced as sites of prejudice and discrimination. However, some healthcare professionals were also sources of information and knowledge, contributing to participants' "journeys of self-acceptance." Conclusion: Even in an urban environment in a country with ready access to healthcare and education, HIV-related stigma remains a concern for people living with HIV.

Curds in the way: A milk curd obstruction review and normal sonographic bowel appearances using a novel scoring system in neonates on fortified breast milk feeds.

INTRODUCTION: Fortified expressed breast milk (FEBM) is a standard of care for premature and low birth weight neonates, but comes with an elevated risk of a rare but re-emergent pathology called milk curd obstruction (MCO). Little is known about normal sonographic appearances of bowel contents in this feeding setting, making the recognition of abnormalities difficult. Thus, we aimed to describe appearances that may be considered typical pre- and post-fortifier inclusion. METHODS: Ten neonates of <32 weeks' gestation or a birth weight of <1,800 g recruited from Auckland City Hospital Neonatal Intensive Care between 1/5/2019 and 10/9/2019 received bowel ultrasounds within 24 h before and 10-14 days after starting FEBM. Bowel contents in six abdominal regions were assigned scores of 1-6 based on increasing solidification. RESULTS: Lower gestational age was correlated with more solid contents on the pre-fortifier ultrasound (P = 0.02). Fortifier was significantly associated with increasing solidity, particularly in the left abdomen (P < 0.001). The left lower quadrant and rectum accounted for much of this change (P = 0.012 and P = 0.002). One subject who subsequently developed a clinical picture consistent with early MCO had uniquely demonstrated non-rectal solid contents (score 6). The interobserver kappa score for two assessors was 0.91 (95% CI 0.94-0.99) on still images. CONCLUSION: This small cohort demonstrated increasing bowel content solidification after breast milk fortification using a novel ultrasound scoring system with good interobserver agreement. Non-rectal solid contents (score 6) appeared atypical. Ultrasound shows promise for its non-irradiating diagnostic utility in the setting of early milk curd disease evaluation of the premature neonate.

A systematic review and narrative analysis of digital speech biomarkers in Motor Neuron Disease.

Motor Neuron Disease (MND) is a progressive and largely fatal neurodegeneritve disorder with a lifetime risk of approximately 1 in 300. At diagnosis, up to 25% of people with MND (pwMND) exhibit bulbar dysfunction. Currently, pwMND are assessed using clinical examination and diagnostic tools including the ALS Functional Rating Scale Revised (ALS-FRS(R)), a clinician-administered questionnaire with a single item on speech intelligibility. Here we report on the use of digital technologies to assess speech features as a marker of disease diagnosis and progression in pwMND. Google Scholar, PubMed, Medline and EMBASE were systematically searched. 40 studies were evaluated including 3670 participants; 1878 with a diagnosis of MND. 24 studies used microphones, 5 used smartphones, 6 used apps, 2 used tape recorders and 1 used the Multi-Dimensional Voice Programme (MDVP) to record speech samples. Data extraction and analysis methods varied but included traditional statistical analysis, CSpeech, MATLAB and machine learning (ML) algorithms. Speech features assessed also varied and included jitter, shimmer, fundamental frequency, intelligible speaking rate, pause duration and syllable repetition. Findings from this systematic review indicate that digital speech biomarkers can distinguish pwMND from healthy controls and can help identify bulbar involvement in pwMND. Preliminary evidence suggests digitally assessed acoustic features can identify more nuanced changes in those affected by voice dysfunction. No one digital speech biomarker alone is consistently able to diagnose or prognosticate MND. Further longitudinal studies involving larger samples are required to validate the use of these technologies as diagnostic tools or prognostic biomarkers.

Diminished baseline autonomic outflow in semantic dementia relates to left-lateralized insula atrophy.

In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD.

Typing myalgic encephalomyelitis by infection at onset: A DecodeME study.

Background: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Detailed questionnaire responses from UK-based participants who all reported being diagnosed with ME/CFS by a health professional provided an unparalleled opportunity to investigate, using logistic regression, whether ME/CFS severity or onset type is significantly associated with sex, age, illness duration, comorbid conditions or symptoms. Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females tend to have more comorbidities than males. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia. Conclusions: DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is a chronic disease that affects an estimated 250,000 people in the UK. Its defining symptom is post-exertional malaise, an excessive delayed worsening of symptoms following even minor physical or mental exertion. For those with it, ME/CFS means disability and poor quality of life. DecodeME is a research study which is looking for DNA differences between people with ME/CFS and people without any health problems. People with ME/CFS who take part in DecodeME complete a questionnaire that assesses their symptoms and whether they will then be invited to donate a DNA sample. This paper analyses the answers to this questionnaire; we will publish results of the DNA analysis separately. So far, more than 17 thousand people with ME/CFS have completed the DecodeME questionnaire. Their answers help us to address the question: "Are there different types of ME/CFS linked to different causes and how severe it becomes?" Results show that people with ME/CFS do not form a single group reporting similar symptoms and additional medical conditions. Instead, participants who had an infection at the start of their ME/CFS reported a different pattern of symptoms and conditions compared to those without an infection. It is well known that most people with ME/CFS are females. What was not clear previously was that females tend to have more additional health conditions. Also, being female, being older and being over 10 years from ME/CFS onset all make it more likely that someone is more severely affected by their ME/CFS. These findings could indicate that by studying people with different ME/CFS onset-types separately ­ rather than analysing all people with ME/CFS together ­ it will be easier to understand what is going wrong.

Alzheimer's pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome.

BACKGROUND: Traumatic encephalopathy syndrome (TES) is a clinical phenotype sensitive but non-specific to underlying chronic traumatic encephalopathy (CTE) neuropathology. However, cognitive symptoms of TES overlap with Alzheimer's disease (AD), and features of AD pathology like beta-amyloid (Aß) plaques often co-occur with CTE, making clinical-to-pathological conclusions of TES diagnoses challenging. We investigated how Alzheimer's neuropathological changes associated with cognition, brain volume, and plasma biomarkers in patients with repetitive head impacts (RHI)/TES, clinical AD, or typically aging controls. METHODS: We studied 154 participants including 33 with RHI/TES (age 61.5 ± 11.5, 100% male, 11/33 Aß[ +]), 62 with AD and no known prior RHI (age 67.1 ± 10.2, 48% male, 62/62 Aß[ +]), and 59 healthy controls without RHI (HC; age 73.0 ± 6.2, 40% male, 0/59 Aß[ +]). Patients completed neuropsychological testing (memory, executive functioning, language, visuospatial) and structural MRI (voxel-based morphometry analysis), and provided plasma samples analyzed for GFAP, NfL, IL-6, IFN-γ, and YKL-40. For cognition and plasma biomarkers, patients with RHI/TES were stratified as Aß[ +] or Aß[ -] and compared to each other plus the AD and HC groups (ANCOVA adjusting for age and sex). Differences with at least a medium effect size (Cohen's d > 0.50) were interpreted as potentially meaningful. RESULTS: Cognitively, within the TES group, Aß[ +] RHI/TES performed worse than Aß[-] RHI/TES on visuospatial (p = .04, d = 0.86) and memory testing (p = .07, d = 0.74). Comparing voxel-wise brain volume, both Aß[ +] and Aß[ -] RHI/TES had lower medial and anterior temporal lobe volume than HC and did not significantly differ from AD. Comparing plasma biomarkers, Aß[ +] RHI/TES had higher plasma GFAP than HC (p = .01, d = 0.88) and did not significantly differ from AD. Conversely, Aß[ -] RHI/TES had higher NfL than HC (p = .004, d = 0.93) and higher IL-6 than all other groups (p's ≤ .004, d's > 1.0). CONCLUSIONS: Presence of Alzheimer's pathology in patients with RHI/TES is associated with altered cognitive and biomarker profiles. Patients with RHI/TES and positive Aß-PET have cognitive and plasma biomarker changes that are more like patients with AD than patients with Aß[ -] RHI/TES. Measuring well-validated Alzheimer's biomarkers in patients with RHI/TES could improve interpretation of research findings and heighten precision in clinical management.

Neuropsychiatric symptoms and imbalance of atrophy in behavioral variant frontotemporal dementia.

Behavioral variant frontotemporal dementia is characterized by heterogeneous frontal, insular, and anterior temporal atrophy patterns that vary along left-right and dorso-ventral axes. Little is known about how these structural imbalances impact clinical symptomatology. The goal of this study was to assess the frequency of frontotemporal asymmetry (right- or left-lateralization) and dorsality (ventral or dorsal predominance of atrophy) and to investigate their clinical correlates. Neuropsychiatric symptoms and structural images were analyzed for 250 patients with behavioral variant frontotemporal dementia. Frontotemporal atrophy was most often symmetric while left-lateralized (9%) and right-lateralized (17%) atrophy were present in a minority of patients. Atrophy was more often ventral (32%) than dorsal (3%) predominant. Patients with right-lateralized atrophy were characterized by higher severity of abnormal eating behavior and hallucinations compared to those with left-lateralized atrophy. Subsequent analyses clarified that eating behavior was associated with right atrophy to a greater extent than a lack of left atrophy, and hallucinations were driven mainly by right atrophy. Dorsality analyses showed that anxiety, euphoria, and disinhibition correlated with ventral-predominant atrophy. Agitation, irritability, and depression showed greater severity with a lack of regional atrophy, including in dorsal regions. Aberrant motor behavior and apathy were not explained by asymmetry or dorsality. This study provides additional insight into how anatomical heterogeneity influences the clinical presentation of patients with behavioral variant frontotemporal dementia. Behavioral symptoms can be associated not only with the presence or absence of focal atrophy, but also with right/left or dorsal/ventral imbalance of gray matter volume.

[Mindfulness meditation in somatic medicine. A management tool for physical and psychological pain]. / Applications de la méditation de pleine conscience dans différents secteurs de médecine somatique. Un outil de gestion de la douleur physique et morale.

Mindfulness meditation is a mind-body approach that helps to cope with psychological or physical symptoms such as pain. To date, this approach is still not widely available to patients in our French-speaking somatic clinical settings, despite its scientific validation. This article describes three mindfulness meditation programs delivered at Lausanne University Hospital (CHUV) to people living with HIV, cancer or chronic pain. It highlights the issues related to the involvement of participants in these programs as well as those related to their implementation in a Swiss somatic, teaching French-speaking hospital.

La méditation de pleine conscience est une approche corps-esprit qui permet de faire face à des symptômes psychiques ou physiques tels que la douleur. À ce jour, malgré sa validation scientifique, cette approche reste peu accessible pour les patient-e-s dans nos contextes cliniques somatiques romands. Cet article décrit trois programmes de méditation de pleine conscience délivrés au sein du CHUV (Lausanne), à des personnes qui vivent avec un VIH, un cancer ou une douleur chronique. Il met en lumière les enjeux liés à l'engagement des participant-e-s dans ces programmes mais aussi ceux en lien avec leur implémentation dans un contexte hospitalier somatique romand.

[Innovative responses to HIV-related issues in a university hospital in Switzerland]. / Réponses innovantes pour faire face aux enjeux liés au VIH dans un hôpital universitaire en Suisse.

HIV remains a highly stigmatized condition, negatively impacting social and psychological outcomes for those living with the virus. Services for people living with HIV need to reflect this reality and be relevant to their needs. In this article, we describe initiatives at the Infectious Diseases Outpatients' Service at Lausanne University Hospital. Peer-based social support, the acquisition and consolidation of knowledge and competence through therapeutic education programs, employing people living with HIV within the service, and involving them in research processes: these all contribute to the empowerment of those concerned, and to fighting the stigma they might anticipate or encounter. In conjunction with - and complementary to - medical care, these services play an important role in improving the quality of life of people living with HIV today.

Le VIH demeure une maladie chronique hautement stigmatisée, avec un impact psychologique et social important chez les personnes concernées. Il est alors nécessaire de proposer des prestations adaptées et pertinentes aux besoins réels de ces dernières. Dans cet article, nous présentons les initiatives mises en place par la consultation des maladies infectieuses ambulatoire du CHUV. Le soutien social entre pairs, le renforcement et/ou l'acquisition de compétences et connaissances via l'éducation thérapeutique, l'embauche des personnes vivant avec le VIH et leurs implications dans la recherche : autant de facteurs qui contribuent à l'empowerment, et qui tendent à lutter contre la stigmatisation et l'isolement. Complémentaires à la prise en charge médicale, ces éléments jouent un rôle important en améliorant la qualité de vie des personnes concernées.

Behavioural subphenotypes and their anatomic correlates in neurodegenerative disease.

Patients with neurodegenerative disorders experience a range of neuropsychiatric symptoms. The neural correlates have been explored for many individual symptoms, such as apathy and disinhibition. Atrophy patterns have also been associated with broadly recognized syndromes that bring together multiple symptoms, such as the behavioural variant of frontotemporal dementia. There is substantial heterogeneity of symptoms, with partial overlap of behaviour and affected neuroanatomy across and within dementia subtypes. It is not well established if there are anatomically distinct behavioural subphenotypes in neurodegenerative disease. The objective of this study was to identify shared behavioural profiles in frontotemporal dementia-spectrum and Alzheimer's disease-related syndromes. Additionally, we sought to determine the underlying neural correlates of these symptom clusters. Two hundred and eighty-one patients diagnosed with one of seven different dementia syndromes, in addition to healthy controls and individuals with mild cognitive impairment, completed a 109-item assessment capturing the severity of a range of clinical behaviours. A principal component analysis captured distinct clusters of related behaviours. Voxel-based morphometry analyses were used to identify regions of volume loss associated with each component. Seven components were identified and interpreted as capturing the following behaviours: Component 1-emotional bluntness, 2-emotional lability and disinhibition, 3-neuroticism, 4-rigidity and impatience, 5-indiscriminate consumption, 6-psychosis and 7-Geschwind syndrome-related behaviours. Correlations with structural brain volume revealed distinct neuroanatomical patterns associated with each component, including after controlling for diagnosis, suggesting that localized neurodegeneration can lead to the development of behavioural symptom clusters across various dementia syndromes.

Patterns of Trauma Among Youth Seeking Mental Health Services at a Community-Based Clinic: A Latent Class Analysis Approach.

We examine the association between trauma patterns, gender identity, ethnicity, foster care involvement, and mental health needs in a sample of low-income youth. Our community sample included 2,175 clients aged 6 or older (Mage = 11.9), has a closely-even gender ratio (55% female and 45% male and others) and is ethnically diverse (37% Black, 31% Multiracial, 14% Latinx, 9% White, 10% Others). 61% of youth in this sample have involvement with the foster care system. Latent class analysis was used to identify trauma patterns, explore predictors of latent class membership, and estimate the cumulative mental health needs for each trauma class. Results revealed four trauma patterns (Low Trauma, Caregiving Disruption, Community Violence, and Multiple Trauma). Girls were more likely than boys to be in the high-trauma groups. Compared to Black youth, Latinx youth were more likely to be in the Multiple Trauma class, whereas White youth were less likely to be in the high trauma classes. Youth with past or current involvement with the foster care system were more likely than those without to be in the high-trauma classes. Mental health needs for youth in Low Trauma and Caregiving Disruption were comparable, but were highest for those in Community Violence. Contrary to expectation, the Multiple Trauma group did not have the highest-level mental health needs. Interventions for low-income youth can benefit from knowing which trauma patterns are associated with various levels of mental health needs. Newer models of care focusing on building healthy communities may be the way forward.

Current and future funding streams for paediatric postmortem imaging: European Society of Paediatric Radiology survey results.

BACKGROUND: Perinatal and childhood postmortem imaging has been accepted as a noninvasive alternative or adjunct to autopsy. However, the variation in funding models from institution to institution is a major factor prohibiting uniform provision of this service. OBJECTIVE: To describe current funding models employed in European and non-European institutions offering paediatric postmortem imaging services and to discuss the perceived barriers to future postmortem imaging service provision. MATERIALS AND METHODS: A web-based 16-question survey was distributed to members of the European Society of Paediatric Radiology (ESPR) and ESPR postmortem imaging task force over a 6-month period (March-August 2021). Survey questions related to the radiologic and autopsy services being offered and how each was funded within the respondent's institute. RESULTS: Eighteen individual responses were received (13/18, 72.2% from Europe). Only one-third of the institutions (6/18, 33.3%) have fully funded postmortem imaging services, with the remainder receiving partial (6/18, 33.3%) or no funding (5/18, 27.8%). Funding (full or partial) was more commonly available for forensic work (13/18, 72%), particularly where this was nationally provided. Where funding was not provided, the imaging and reporting costs were absorbed by the institute. CONCLUSION: Increased access is required for the expansion of postmortem imaging into routine clinical use. This can only be achieved with formal funding on a national level, potentially through health care commissioning and acknowledgement by health care policy makers and pathology services of the value the service provides following the death of a fetus or child. Funding should include the costs involved in training, equipment, reporting and image acquisition.

A systematic review of digital technology to evaluate motor function and disease progression in motor neuron disease.

Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional Rating Scale-Revised (ALS-FRS(R)), a clinician-administered questionnaire providing a composite score on physical functioning. Technology offers a potential alternative for assessing motor progression in both a clinical and research capacity that is more sensitive to detecting smaller changes in function. We reviewed studies evaluating the utility and suitability of these devices to evaluate motor function and disease progression in people with MND (pwMND). We systematically searched Google Scholar, PubMed and EMBASE applying no language or date restrictions. We extracted information on devices used and additional assessments undertaken. Twenty studies, involving 1275 (median 28 and ranging 6-584) pwMND, were included. Sensor type included accelerometers (n = 9), activity monitors (n = 4), smartphone apps (n = 4), gait (n = 3), kinetic sensors (n = 3), electrical impedance myography (n = 1) and dynamometers (n = 2). Seventeen (85%) of studies used the ALS-FRS(R) to evaluate concurrent validity. Participant feedback on device utility was generally positive, where evaluated in 25% of studies. All studies showed initial feasibility, warranting larger longitudinal studies to compare device sensitivity and validity beyond ALS-FRS(R). Risk of bias in the included studies was high, with a large amount of information to determine study quality unclear. Measurement of motor pathology and progression using technology is an emerging, and promising, area of MND research. Further well-powered longitudinal validation studies are needed.

Enhanced positive emotional reactivity in frontotemporal dementia reflects left-lateralized atrophy in the temporal and frontal lobes.

In frontotemporal dementia (FTD), left-lateralized atrophy patterns have been associated with elevations in certain positive emotions. Here, we investigated whether positive emotional reactivity was enhanced in semantic variant primary progressive aphasia (svPPA), an FTD syndrome that targets the left anterior temporal lobe. Sixty-one participants (16 people with svPPA, 24 people with behavioral variant FTD, and 21 healthy controls) viewed six 90-sec trials that were comprised of a series of photographs; each trial was designed to elicit a specific positive emotion, negative emotion, or no emotion. Participants rated their positive emotional experience after each trial, and their smiling behavior was coded with the Facial Action Coding System. Results indicated that positive emotional experience and smiling were elevated in svPPA in response to numerous affective and non-affective stimuli. Voxel-based morphometry analyses revealed that greater positive emotional experience and greater smiling in the patients were both associated with smaller gray matter volume in the left superior temporal gyrus (pFWE < .05), among other left-lateralized frontotemporal regions. Whereas enhanced positive emotional experience related to atrophy in middle superior temporal gyrus and structures that promote cognitive control and emotion regulation, heightened smiling related to atrophy in posterior superior temporal gyrus and structures that support motor control. Our results suggest positive emotional reactivity is elevated in svPPA and offer new evidence that atrophy in left-lateralized emotion-relevant systems relates to enhanced positive emotions in FTD.

DecodeME: community recruitment for a large genetics study of myalgic encephalomyelitis / chronic fatigue syndrome.

BACKGROUND: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy. METHODS: Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants' saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants' genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology. DISCUSSION: The DecodeME study has been reviewed and given a favourable opinion by the North West - Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online ( www.decodeme.org.uk ). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.

Cochlear nerve deficiency in SOX11-related Coffin-Siris syndrome.

The phenotypic spectrum of SOX11-related Coffin-Siris syndrome (CSS) is expanding with reports of new associations. SOX11 is implicated in neurogenesis and inner ear development. Cochlear nerve deficiency, absence or hypoplasia, is commonly associated with cochlear canal stenosis or with CHARGE syndrome, a monogenic condition that affects inner ear development. SOX11 is a transcription factor essential for neuronal identity, highly correlated with the expression of CHD7, which regulates SOX11. We present two unrelated probands, each with novel de novo SOX11 likely pathogenic variants and phenotypic manifestations of CSS including global developmental delay, growth deficiency, and hypoplastic nails. They have unilateral sensorineural hearing loss due to cochlear nerve deficiency confirmed on MRI. SOX11 is implicated in sensory neuron survival and maturation. It is highly expressed in the developing inner ear. Homozygous ablation of SOX11 in a mouse model resulted in a reduction in sensory neuron survival and decreased axonal growth. A heterozygous knockout mice model had hearing impairment with grossly normal inner ear structures like the two probands reported. We propose cochlear nerve deficiency as a new phenotypic feature of SOX11-related CSS. Magnetic resonance imaging is useful in delineating the cochlear nerve deficiency and other CSS-related brain malformations.