Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives.

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.

'A Labour of Love': A King's College London Psychiatry Society Event to challenge the stigma attached to mental health problems in post-natal women.

BACKGROUND: On the 9th October 2000, Dr Daksha Emson, a London based psychiatrist with bipolar affective disorder, tragically killed herself and her three-month-old baby daughter during a psychotic episode. An independent inquiry into Dr Emson's death concluded that mental health stigma in the National Health Service was a factor that contributed to her death. Despite the morbidity and mortality attributed to the stigma attached to post-natal mental health problems there are very few programmes that have been developed to challenge it. King's College London Undergraduate Psychiatry Society organized an event entitled, 'A Labour of Love': Perinatal Mental Health to address this issue. The event included a talk from an expert by experience, a mother who developed post-partum mental health problems. DESIGN: We conducted a single-arm, pre-post comparison study on participants who attended the KCL Psych Soc event. Validated stigma scales on knowledge (Mental Health Knowledge Schedule (MAKS)), attitudes (Community Attitudes towards the Mentally Ill (CAMI)) and behaviour (Reported and Intended Behaviour Scale (RIBS)) were administered before and immediately after exposure to the event. RESULTS: 27/27 (100%) of participants recruited responded. There was a statistically significant difference in the pre-MAKS score compared to the post-MAKS score (p=0.0003), the pre-RIBS score compared to the post-RIBS score (p=0.0068) and in the pre-CAMI score compared to the post-CAMI score (p=0.0042). DISCUSSION: There were statistically significant reductions in stigma in the domains of knowledge, attitude and behavior following exposure to the KCL Psych Soc event and no adverse effects were reported. Our study revealed that a brief intervention made a highly significant impact and maybe useful in challenging the stigma around post-natal mental illness. However, more research in this area is required to determine if the changes are sustained before we can consider rolling out and scaling up such an initiative nationally and internationally.

A King's College London Undergraduate Psychiatry Society event to challenge the stigma attached to psychological problems in healthcare professionals and students.

BACKGROUND: There are higher levels of psychological distress in healthcare professionals and students compared to the general population. Yet, despite the availability of effective treatment, many in this group continue to suffer in silence. Fear of exposure to stigmatization has been identified to be a major barrier to accessing and using mental health services. King's College London Undergraduate Psychiatry Society (KCL PsychSoc) organized an event entitled, 'What does bipolar disorder even mean? Psychological distress: How can we challenge the stigma?'. Healthcare professionals who themselves recovered from psychological problems and a mental health advocate with first-hand experience of psychological distress were invited to deliver talks followed by an interactive question and answer session. DESIGN: We conducted a single-arm pre-post comparison study. People who attended the KCL Psych Soc event were recruited to participate. Validated stigma scales on knowledge (Mental Health Knowledge Schedule (MAKS), attitudes (Community Attitudes towards the Mentally Ill) and behavior (Reported and Intended Behavior Scale (RIBS)) were administered on participants before and immediately after exposure to the event. RESULTS: 44/44 of the participants recruited completed the study (100% response rate). There were statistically significant changes in the respondents' scores for all 3 stigma scales (p value MAKS<0.0001, p value CAMI<0.0001, p value RIBS=0.0011). DISCUSSION: As far as the authors are aware, this is the first study to date of an anti-stigma intervention comprised of healthcare professionals with first-hand experience of psychological distress. The KCL PsychSoc event was associated with statistically significant changes in the respondents' scores in all three of the stigma scales. More robust research in this area is needed before scaling up similar anti-stigma initiatives.

The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data.

BACKGROUND: A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies. METHODS: The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann-Whitney Test (U). The protocol was prospectively registered (CRD42018082210). RESULTS: Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04). CONCLUSIONS: Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings.

Emerging Knowledge of the Neurobiology of COVID-19.

Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge; however, the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into 2 broad categories: neuropsychiatric deficits occurring after severe (hospitalized) COVID-19 and "long COVID," which occurs in many patients with a milder acute COVID-19 illness.

Neuroanatomy of Patients with Deficit Schizophrenia: An Exploratory Quantitative Meta-Analysis of Structural Neuroimaging Studies.

Little is known regarding the neuroanatomical correlates of patients with deficit schizophrenia or persistent negative symptoms. In this meta-analysis, we aimed to determine whether patients with deficit schizophrenia have characteristic brain abnormalities. We searched PubMed, CINAHL and Ovid to identify studies that examined the various regions of interest amongst patients with deficit schizophrenia, patients with non-deficit schizophrenia and healthy controls. A total of 24 studies met our inclusion criteria. A random-effects model was used to calculate a combination of outcome measures, and heterogeneity was assessed by the I2 statistic and Cochran's Q statistic. Our findings suggested that there was statistically significant reduction in grey matter volume (-0.433, 95% confidence interval (CI): -0.853 to -0.014, p = 0.043) and white matter volume (-0.319, 95% CI: -0.619 to -0.018, p = 0.038) in patients with deficit schizophrenia compared to healthy controls. There is also statistically significant reduction in total brain volume (-0.212, 95% CI: -0.384 to -0.041, p = 0.015) and white matter volume (-0.283, 95% CI: -0.546 to -0.021, p = 0.034) in patients with non-deficit schizophrenia compared to healthy controls. Between patients with deficit and non-deficit schizophrenia, there were no statistically significant differences in volumetric findings across the various regions of interest.

Transient Musical Hallucinations in a Young Adult Male Associated with Alcohol Withdrawal.

We present the case of a 25-year-old male who presented to A&E with isolated musical hallucinations, in the absence of audiological or neurological disease. The patient had a history of recreational drug use and a family history of psychosis. Hallucinations, which were preceded by discontinuation of alcohol and reinitiation of citalopram for depression, resolved spontaneously after three days. Aetiological factors are discussed alongside the existing literature. Whilst the underlying mechanisms underpinning musical hallucinations remain elusive, the case illustrates the potential role of alcohol withdrawal, serotonin toxicity, recreational drug use, and genetic vulnerability.