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BackgroundParkinson disease (PD) is a major cause of disability affecting >6 million people worldwide. The incidence/prevalence of PD is generally higher in males than females. It is unclear whether male predominance is observed in low- and middle-income countries, where the fastest apparent rate of increase of PD has been observed.MethodsWe searched MEDLINE, SCOPUS and OVID for articles published between 2014-2021 for incidence of PD, 2011-2021 for prevalence, and updated previously published systematic reviews for which the last date of inclusion had been 2014 and 2011. We included 32 articles for prevalence and 30 for incidence. We calculated male/female (M/F) prevalence and incidence ratios, and investigated heterogeneity in estimates.ResultsThe combined M/F prevalence ratio was 1.18 (95% CI 1.03-1.36) and incidence ratio was1.37 (95% CI 1.22-1.53), lowest in Asian populations. These were not influenced by study type, national economy or mean participant age. The female-to-male gap in life expectancy did partly account for data heterogeneity.ConclusionThe sex gap for prevalence of PD was smaller than has previously been reported. More studies are needed to understand the determinants of sex imbalance in PD.

BackgroundParkinson disease (PD) is the second most common neurodegenerative disease and the burden appears to be growing fastest in middle-low and low income countries. In the majority of obser- vational studies of PD, White, well-educated and affluent participants are over-represented.AimsOur aim was to engage a diverse group of people with Parkinson disease (PwP) from East London and build a research platform for previously under-represented groups.MethodsWe created a register of PwP from the Royal London Hospital which includes approximately 400 patients. In parallel, we have recruited participants to the East London Parkinson’s disease (ELPD) project; a case-control study of phenotype, genotype and biomarker characteristics. Clinical manifes- tations, UPDRS scores, data on non-motor symptoms, as well as biospecimens (buccal and skin swabs, serum samples) have been obtained.Results145 patients and 80 controls have been recruited so far. The mean age of PwP was 67.81 (SD 10.4); 62% were male and 59% identified as being from South Asian or Black ethnicity. The most common presenting symptom was tremor (55.9%), followed by gait impairment (16.6%).ConclusionThe ELPD project is a platform study for under-represented patients with PD which provides important opportunities for collaboration and research to improve health inequalities.

BackgroundWe report the case of a 62-year-old female with demyelinating sensorimotor polyneuropathy in the context of lymphoplasmacytic lymphoma.Case Presentation62-year-old woman presenting with distal lower limb numbness bilaterally, with a 9-year progressive course. Over the next 3 years, foot drop developed with gradual lower and upper limb involvement.Investigations showed raised IgM paraprotein, 20 g/dL. Bone marrow biopsy identified 2-B cell clonal populations with positive MYD88 mutation in keeping with lymphoplasmacytic lymphoma (LPL). Neuro- physiological studies showed very severe length-dependent, sensorimotor neuropathy. She was VEGF/anti-MAG negative, but anti-GM2 positive. Widely-spaced myelin and moderate axonal loss were seen on sural nerve biopsy.She was diagnosed with a progressive demyelinating neuropathy in the context of LPL.Initial IVIG treatment failed.Second line treatment – cyclophosphamide/rituximab/dexamethasone, improved her lower limb weakness. Ibrutinib later stabilised her weakness in the lower but not upper limbs.Plexus nerve biopsy showed general inflammation, excluding direct clonal infiltration and amyloid deposi- tion. This reconfirmed the diagnosis: inflammatory neuropathy driven by a haematological malignancy. She received further treatment with rituximab-bendamustine.ConclusionUnderstanding the pathological mechanism of polyneuropathies in haematological malignan- cies is of paramount importance for choosing the most effective therapy, as illustrated by the above cas8e7.a.zirra@nhs.net

The aim of this study was to assess the impact on health status of a multiple sclerosis (MS) nurse specialist telephone assessment/triage (the NeuroDirect integrated pathway), coupled with standard treatment for significant MS relapses. This evaluation study considered a prospective case series of 108 patients experiencing relapse symptoms who contacted NeuroDirect, a National Hospital for Neurology and Neurosurgery telephone assessment service, in the period from February 2012 to October 2013. The MS specialist nurse-led teletriage centre applied the EQ5D-5L measure of health-related quality of life (HRQoL) at the initial assessment and the planned 6-8 weeks follow-up. The scores were converted into health state utility values (HSUVs). These showed a statistically significant improvement in health status, of 0.15, at 52 days follow-up on average in patients on the NeuroDirect pathway who also received standard clinical care. The study demonstrates that an efficient teletriage relapse pathway combined with usual care has a clear effect on improving HRQoL, as measured for the first time by the EQ5D-5L instrument in this population.

The recent outbreak of the novel coronavirus, SARS-CoV-2 – which causes COVID-19 – has rapidly reached pandemic proportions, causing widespread morbidity and mortality It has had a major impact on society in general, and in medicine and health in particular Although primarily a potentially fatal respiratory pathogen, SARS-CoV-2, like other coronaviruses, can be neurotropic Its receptor, angiotensin-converting enzyme 2 (ACE2), is expressed in endothelial cells in the brain and can be induced in neural cells COVID-19 is therefore of high relevance to neurological disease Indeed, various neurological manifestations are increasingly being reported On the other hand, COVID-19 has a major impact on people with certain neurological diseases Patients with neuroimmune disorders such as multiple sclerosis or myasthenia gravis who are on immunomodulatory or immunosuppressive treatments may be more susceptible to infection or have a more severe disease due to a blunted immune response Patients with many neurological disorders may be at risk of severe COVID-19 infection, due to immobility, frailty, disability, diminished respiratory capacity or cognitive dysfunction Disease-specific patient organisations and neurological societies have been prompt in providing advice and generating guidelines for various neurological conditions Local, national and international registers are being created and will be essential in monitoring the disease and its outcomes New knowledge about COVID-19, including issues of relevance to neurology, is generated daily This review presents some succinct background information on coronaviruses and its neuro-invasive potential, the current knowledge of neurological manifestations, and the impact of COVID-19 on individuals with neurological disease Some disease-specific recommendations are briefly listed or referenced

Introduction Identification of patients with acute-on-chronic liver failure(ACLF) who will benefit from ongoing support on intensive care unit(ICU) remains a challenge. There is no agreed marker of futility or time-point. There has been recent consensus regarding the definition of ACLF grades, and chronic liver failure-sequential organ failure assessment(CLIF-SOFA) score has been adopted. We aimed to determine if evolution in CLIF-SOFA or other markers of disease severity can predict mortality and survival in ACLF patients admitted to ICU. Methods Prospectively recorded data was collected on 48 ACLF patients admitted to ICU at Guy’s and St Thomas’ hospital, a tertiary non-transplant centre, from May 2013 – May 2016. Scores were calculated at D0, D2, D5, D7. Results The majority were male (n=34,700.8%), mean age was 57.4±10.3 years and major aetiologies were ALD (n=34,700.8%) and viral hepatitis (n=11,290.2%). The major indication for ICU admission was infection (n=29,600.4%). Mean Child-Pugh(CP) score on admission to ICU was 12±2 and the mean MELD 24±9. Mortality at 7, 28 and 90 days was 16/48 (33.3%), 30/48 (62.5%), 36/48 (75%). The best predictive model proved to be difference in CLIF-SOFA (‘delta C-SOFA’) scores between D2 and D5 or D7. Mean delta C-SOFA D2-D5 was −2.25±1.9 and mean delta C-SOFA D2-D7 was −3.36±2 for survivors compared to 0.19±1.73(p The mean survival time (days) for patients with improvement in delta C-SOFA between D2 and D5/D7 was 837±144 and 814±149 vs patients with worsening or static scores 33.8±14.5 (p Other prognostic scores at a single time point on D7 predicted survival at D28 and D90 with AUC of: CP (0.75/0.67), MELD (0.73/0.79), UKELD (0.79/0.84), ACLF (0.75/0.78) and CLIF-SOFA (0.75/0.83). Conclusions The evolution in CLIF-SOFA score between D2 and D5/7 is superior to evolution in other scores and scores assessed at single time points when predicting 90 day survival. The delta C-SOFA at D5 and D7 are comparable, thus delta C-SOFA D2-D5 may be used to guide therapeutic decisions.

The structure of messenger RNA is important for post-transcriptional regulation, mainly because it affects binding of trans-acting factors. However, little is known about the in vivo structure of full-length mRNAs. Here we present hiCLIP, a biochemical technique for transcriptome-wide identification of RNA secondary structures interacting with RNA-binding proteins (RBPs). Using this technique to investigate RNA structures bound by Staufen 1 (STAU1) in human cells, we uncover a dominance of intra-molecular RNA duplexes, a depletion of duplexes from coding regions of highly translated mRNAs, an unexpected prevalence of long-range duplexes in 3' untranslated regions (UTRs), and a decreased incidence of single nucleotide polymorphisms in duplex-forming regions. We also discover a duplex spanning 858 nucleotides in the 3' UTR of the X-box binding protein 1 (XBP1) mRNA that regulates its cytoplasmic splicing and stability. Our study reveals the fundamental role of mRNA secondary structures in gene expression and introduces hiCLIP as a widely applicable method for discovering new, especially long-range, RNA duplexes.

BackgroundWe report a rare case of reflex epilepsy in a 36-year-old female who was initially diagnosed with juvenile myoclonic epilepsy (JME).Case PresentationAged 15, spontaneous left sided myoclonic jerks and rare generalised tonic clonic seizures (GTCS) began. JME was diagnosed then, based on generalised spike wave discharges.As GTCS occurred once a year, she opted against treatment. Aged 26, due to seizure exacerbation, levetiracetam was commenced with complete seizure cessation.Aged 34, ascending electric-shock-like sensations from her feet with myoclonic jerks occurred exclusively whilst performing or even thinking about specific tasks such as hair brushing and complex arithmetic. No spontaneous seizures occurred. She was diagnosed with anxiety and referred to the epilepsy clinic at NHNN.Borderline hypothyroidism was diagnosed 6 months prior to symptom onset and treated with levothyroxine. There was otherwise no change in behaviour or cognitive function.On video-telemetry habitual reflex events were preceded by brief bursts of predominantly left fronto-central spike-and-slow wave complexes. Inter-ictally there were independent left central spike-wave-complexes suggesting a left fronto-central focal reflex epilepsy syndrome.Levetiracetam was optimised and lamotrigine commenced with complete cessation of seizures.ConclusionIt is important to recognise reflex epilepsy syndromes, rare entities, as they are frequently misdiagnosed.