DNMT1-associated sensory neuropathy and cerebellar ataxia: A novel variant and review of genotype-phenotype correlation.

AIM: Hereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy. METHODS: A 42-year-old man presented with imbalance, lancinating pain, numerous paucisymptomatic injuries, progressive deafness since his mid-20s, mild cognitive decline and apathy. Examination revealed abnormalities of eye movements, distal sensory loss to all modalities, areflexia without weakness and lower limb ataxia. MRI brain and FDG-PET scan demonstrated biparietal and cerebellar atrophy/hypometabolism. Whole exome sequencing detected a heterozygous likely pathogenic missense variant in DNMT1, c.1289G > A, p.Cys430Tyr. Cochlear implant was performed at 44 years for the bilateral high frequency sensorineural hearing loss with improvement in hearing and day-to-day function. RESULTS AND CONCLUSION: We describe a novel variant in DNMT1 and confirm that an overlapping HSN1E-cerebellar phenotype can occur. Only one prior case of cochlear implant in HSN1E has been reported to date but this case adds to that literature, suggesting that cochlear implant can be successful in such patients. We further explore the clinical and radiological signature of the cognitive syndrome associated with this disorder.

The Experiences of Post-ICU COVID-19 Survivors: An Existential Perspective using Interpretative Phenomenological Analysis.

COVID-19 has highlighted the vulnerability of intensive care unit (ICU) patients and the negative sequelae associated with ICU treatment. While the potentially traumatic impact of ICU is well documented, less is known about the ICU survivor's subjective experience and how it influences life post-discharge. Existential psychology addresses the universal concerns of existence, including death, isolation, and meaninglessness, and offers a holistic view of human experience beyond diagnostic categories. An existential psychological understanding of ICU COVID-19 survivorship may therefore provide a rich account of what it means to be among the worst affected by a global existential crisis. This study employed interpretive phenomenological analysis of qualitative interviews with 10 post-ICU COVID-19 survivors (aged 18-78). Interviews were structured on existential psychology's 'Four Worlds' model that explores the physical, social, personal, and spiritual dimensions of human experience. The essential meaning of ICU COVID-19 survival was conceptualised as 'Trying to Reconnect with a Changed Reality' and consisted of four themes. The first, Between Shifting Realities in ICU, described the liminal nature of ICU and the need to ground oneself. The second, What it Means to Care and Be Cared For, captured the emotive nature of personal interdependence and reciprocity. The third, The Self is Different, described survivors' struggle to reconcile old and new selves. The fourth, A New Relationship with Life, outlined how survivors' experiences shaped their new worldviews. Findings evidence the value of holistic, existentially informed psychological support for ICU survivors.

Acquired brain injury services in the Republic of Ireland: experiences and perceptions of families and professionals.

PRIMARY OBJECTIVE: This study aimed to highlight the experiences and perceptions of rehabilitation services among families of people with Acquired Brain Injury (ABI) and among professionals working in ABI rehabilitation services in Ireland. RESEARCH DESIGN: A qualitative, exploratory study used focus groups to gather data. Data were analysed through a system of qualitative content analysis. METHOD: Three focus groups were carried out involving families of people with ABI from different parts of Ireland and one focus group was carried out with professionals working in rehabilitation services. Participants in all groups responded to five broad semi-structured questions. MAIN RESULTS: Analysis revealed five categories across the family focus groups and, separately, five categories within the professional group. Both groups highlighted that: there is a need to develop rehabilitation services in Ireland, building and expanding on current services; there is a need to make information and education related to brain injury more widely available and to ensure it is accessible for families; and there is a need to improve co-ordination and communication between services. A range of relationship issues were also highlighted. CONCLUSIONS: Much remains to be done to improve the experiences and perceptions of brain injury rehabilitation services among families and professionals.

A 20-Year Systematic Review of the 'Reading the Mind in the Eyes' Test across Neurodegenerative Conditions.

Social cognition has a broad theoretical definition, which includes the ability to mentalise, i.e., recognise and infer mental states to explain and predict another's behaviour. There is growing recognition of the clinical, diagnostic, and prognostic value of assessing a person's ability to perform social cognitive tasks, particularly aspects of theory of mind, such as mentalising. One such measure of mentalising is the 'Reading the Mind in the Eyes' test (RMET). This systematic review and meta-analysis consider performance on the RMET, applied to people with neurodegenerative conditions in matched control studies, since its publication in 2001. Overall, this review includes 22 papers with data from N = 800 participants with neurodegenerative conditions: Alzheimer's disease, n = 31; Parkinson's disease, n = 221; Lewy body dementia, n = 33; motor neuron disease, n = 218; Huntington's disease n = 80; multiple sclerosis, n = 217; and N = 601 matched typical controls. Our meta-analyses show that deficits in mentalising, as measured by the RMET, are consistently reported across neurodegenerative conditions, with participants in both early and late disease stages being affected. Social cognition is an emerging field of cognitive neuroscience requiring specific and sensitive measurement across each subdomain. Adult-based meta-normative data feature, for which future groups or individuals could be compared against, and hypotheses relating to the source of these mentalising deficits are further discussed. This review was registered with PROSPERO (CRD42020182874).

Living with others with behaviours that challenge: experiences and perceptions of adults with intellectual disabilities.

BACKGROUND: This study explored the experiences of people with intellectual disabilities who live with others who display behaviours that challenge. Previous research has focused on the impact of behaviours that challenge on staff and families but less is known about the effect it has on service-users. METHOD: Semi-structured interviews were conducted with six participants who were recruited from a service specialising in the management of behaviours that challenge. Data were transcribed verbatim and analysed using Interpretative Phenomenological Analysis. RESULTS: Four superordinate themes were identified: the emotional impact of others' behaviours that challenge; participants' perceptions of behaviours that challenge; participants' own experiences engaging in behaviours that challenge; and things that help. Sub-themes were also identified under each superordinate theme. CONCLUSIONS: People with an intellectual disability are knowledgeable about behaviours that challenge, have insight into potential causes, and can offer suggestions as to what might help. Results were discussed in relation to clinical implications and methodological strengths.IMPLICATIONS FOR REHABILITATIONLiving with others who engage in behaviours that challenge has a significant impact on the well-being of people with an intellectual disability.People with an intellectual disability need to be empowered through inclusion in the decisions that concern them, especially in relation to their living circumstances.This is vital in order to improve the quality of life and mental well-being, enhance opportunities for skill development and promote independence.

Post-Intensive Care COVID Survivorship Clinic: A Single-Center Experience.

Patients discharged from the ICU post-COVID-19 pneumonitis may experience long-term morbidity related to their critical illness, the treatment for this and the ICU environment. The aim of this study was to characterize the cognitive, psychologic, and physical consequences of COVID-19 in patients admitted to the ICU and discharged alive. DESIGN: Prospective cohort study. SETTING: Post-intensive care syndrome (PICS) follow-up clinic at Tallaght University Hospital, a tertiary referral center with a 16-bed mixed medical-surgical ICU, including critical care physicians, a psychologist, a physiotherapist, and a research nurse. PATIENTS: Patients who had been admitted to the ICU in our tertiary referral center with COVID-19 pneumonitis 6 months earlier. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 22 patients attended the 6-month PICS follow-up clinic following admission to ICU with COVID-19 pneumonitis. Mean grip strength was low at the 6-month follow-up at 24.1 pounds (sd 9.8) with a minimally active median metabolic equivalent (MET) of 970 METs/wk (interquartile range, 0-7,794 METs/wk). Only 59% of patients were independent with regard to their activities of daily living. Eight of 14 patients (57%) had returned to work by 6 months post-ICU discharge. Their mean Intensive Care Psychological Assessment Tool (IPAT) score was 6.6 (sd 4.6) with a Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5th Edition (PCL-5) score of 21.1 (sd 17.5) and a mean Montreal Cognitive Assessment (MoCA) score of 24 (sd 8.4); suggestive of mild cognitive impairment. In a multivariable regression model, only Acute Physiology and Chronic Health Evaluation II score was significantly independently associated with MoCA score as a cognitive PICS outcome (beta-coefficient, -1.6; se, 0.6; p = 0.04). None of the predictor variables were significantly independently associated with IPAT and PCL-5 as psychologic outcomes, nor with International Physical Activity Questionnaire-Short Form as a physical PICS outcome. CONCLUSIONS: In this single-center prospective cohort study, we found that patients have a high burden of physical and psychologic impairment at 6 months following ICU discharge post-COVID-19 pneumonitis; in many cases requiring specialist referrals for long-term input. We advocate for increased resources for this much needed follow-up multidisciplinary intervention for an ever-growing population of patients.