Search

The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I 2 . Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies ( n  = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high ( I 2  = 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Guarantors of Brain.)

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers., Competing Interests: Competing interests: JPR has received payment from the Alberta Psychiatric Association for a lecture and has held one unpaid advisory meeting with representatives from Promentis Pharmaceuticals regarding drug development. LT is in receipt of a bursary as part of the Royal College of Psychiatrists PsychStar scheme. By winning a prize from the Royal College of Psychiatrists, she has received prize money and free attendance at a meeting. She is President of the University of Birmingham Psychiatry Society. IK has been supported by the Medical Research Council through Dementias Platform UK and by the National Institute for Health Research (NIHR) through the Oxford Health Biomedical Research Centre. He has been a medical advisor to Mantrah and Sharp Therapeutics, digital technology start-ups. He holds stock options in Sharp Therapeutics. TS is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (grant nos. IS-HPU-1112-10117 and NIHR200907), NIHR Programme Grant for Applied Research (no. RP-PG-0108-10,048), NIHR Global Health Research Group on Brain Infections (no. 17/63/110), and the European Union’s Horizon 2020 research and innovation programme ZikaPLAN (Preparedness Latin America Network), grant agreement no. 734584. He receives royalties from Oxford University Press, Elsevier, Liverpool University Press and Cambridge University Press. He is a consultant for the MHRA Vaccine Benefit Risk Expert Working Group. He filed for a patent on a test for bacterial meningitis based on a blood test (no. GB1606537.7 14 April 2016). He was on the Data Safety Monitoring Committee of the GSK Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Children GSK3390107A (ChAd3 EBO-Z) vaccine. He chaired the Siemens Healthineers Clinical Advisory Board (1) Data Safety Monitoring Board: Study of Ebola vaccine ChAd3-EBO-Z-Commercial entity. He holds shares in Medefer Solutions. BDM has received payment for a lecture for Valneva., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Alexander Disease (AxD) is a rare leukodystrophy caused by missense mutations of glial fibrillary acidic protein (GFAP). Primarily seen in infants and juveniles, it can present in adulthood. We report a family with inherited AxD in which the mother presented with symptoms many years after her daughter. We reviewed the age of onset in all published cases of familial AxD and found that 32 of 34 instances of parent-offspring pairs demonstrated an earlier age of onset in offspring compared to the parent. We suggest that genetic anticipation occurs in familial AxD and speculate that genetic mosaicism could explain this phenomenon.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition that primarily affects the motor system and shares many features with frontotemporal dementia (FTD). Evidence suggests that ALS is a 'dying-back' disease, with peripheral denervation and axonal degeneration occurring before loss of motor neuron cell bodies. Distal to a nerve injury, a similar pattern of axonal degeneration can be seen, which is mediated by an active axon destruction mechanism called Wallerian degeneration. Sterile alpha and TIR motif-containing 1 (Sarm1) is a key gene in the Wallerian pathway and its deletion provides long-term protection against both Wallerian degeneration and Wallerian-like, non-injury induced axonopathy, a retrograde degenerative process that occurs in many neurodegenerative diseases where axonal transport is impaired. Here, we explored whether Sarm1 signalling could be a therapeutic target for ALS by deleting Sarm1 from a mouse model of ALS-FTD, a TDP-43 Q331K , YFP-H double transgenic mouse. Sarm1 deletion attenuated motor axon degeneration and neuromuscular junction denervation. Motor neuron cell bodies were also significantly protected. Deletion of Sarm1 also attenuated loss of layer V pyramidal neuronal dendritic spines in the primary motor cortex. Structural MRI identified the entorhinal cortex as the most significantly atrophic region, and histological studies confirmed a greater loss of neurons in the entorhinal cortex than in the motor cortex, suggesting a prominent FTD-like pattern of neurodegeneration in this transgenic mouse model. Despite the reduction in neuronal degeneration, Sarm1 deletion did not attenuate age-related behavioural deficits caused by TDP-43 Q331K . However, Sarm1 deletion was associated with a significant increase in the viability of male TDP-43 Q331K mice, suggesting a detrimental role of Wallerian-like pathways in the earliest stages of TDP-43 Q331K -mediated neurodegeneration. Collectively, these results indicate that anti-SARM1 strategies have therapeutic potential in ALS-FTD.

Purpose: To report the outcomes of combined cataract surgery with toric intraocular lens (IOL) implantation when performed in conjunction with transconjunctival sutureless pars plana vitrectomy., Design: Retrospective interventional case series., Participants: Consecutive series of 55 eyes of 51 patients from April 2007 to December of 2010., Methods: All eyes underwent combined simultaneous small incision cataract surgery, toric IOL implantation, and transconjunctival sutureless vitrectomy surgery., Main Outcome Measures: Postoperative visual acuity, postoperative astigmatism, and rotational stability of the IOL., Results: Preoperative best-corrected visual acuity was 0.32 ± 0.15 logMar (Snellen 20/43) and improved to 0.16 ± 0.10 (Snellen 20/29) postoperatively uncorrected (P < 0.01) and to 0.08 ± 0.11 best-corrected (Snellen 20/24) (P < 0.01). Preoperative astigmatism was 1.75 ± 1.0 diopters (D) (range, 0-4.75 D) and improved to 0.5 ± 0.50 D (range, 0-2.5 D) postoperatively (P < 0.01). Final measured postoperative IOL axis deviation from target axis was 4 ± 6° (range, 0-32). Final IOL axis was within 5° of target in 47 (85%) eyes, within 10 degrees of target in 51 (93%) eyes, and was within 15° of target in 52 (95%) eyes., Conclusion: Toric lens position and axis remained stable after implantation during combined cataract surgery and transconjunctival sutureless vitrectomy.

Purpose: To clarify and delineate conceptualizations of the effects of caregiving for nursing research and practice with family caregivers., Organizing Construct: The biopsychosocial (psychosocial and physiological) sequelae, both negative and positive, associated with providing care for a relative or friend with a chronic illness., Methods: Literature reviewed was obtained via searches of CINAHL, MEDLINE, and PsycInfo computerized databases through mid-2002. Key words for the searches were caregiver, caregiving, family caregiving, caregiver burden, and caregiver appraisal. Reports of both earlier reviews of literature and original research were included., Findings: Negative concepts included caregiver burden, hassles, strain, and stress. Positive concepts included caregiver esteem, uplifts of caregiving, caregiver satisfaction, finding or making meaning through caregiving, and gain in the caregiving experience. A neutral concept for describing the caregiving process is caregiver appraisal. Although earlier studies were focused on negative aspects of caregiving, more recent research has also included positive aspects., Conclusions: More attention should be given to (a) gender and cultural differences in caregiving, (b) development of flexible interventions, and (c) the biophysical sequelae of caregiving.