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Diseases of the oral cavity present with varying degrees of mucosal changes, ranging from erythema, atrophy or ulceration to white or hyperkeratotic areas or pigmentation. These are frequently chronic and can occur because of underlying systemic disease. Diagnosis can be challenging because of similarities in clinical presentation between different conditions. The most common presentations include mucosal ulceration and abnormalities of the lips and tongue. Ulceration represents a full-thickness breach in the epithelium. This can result in pain and difficulty with eating, drinking, speech and maintaining oral hygiene. The wide range of causes of oral ulceration includes trauma, recurrent aphthous stomatitis, lichen planus, immunobullous disease, drugs and erythema multiforme. Lesions on the tongue can be caused by primary oral disease or secondary to systemic disease. Abnormalities include nutrient-deficient glossitis, geographic tongue, burning mouth syndrome and, more rarely, amyloidosis. The lips can be affected by skin diseases such as eczema (exfoliative cheilitis) and actinic damage or conditions with potential systemic involvement such as orofacial granulomatosis. The priority with mucosal lesions is to exclude carcinoma, as early detection and treatment significantly decreases morbidity and mortality. This article reviews these disorders and their distinguishing features and highlights the importance of history-taking, clinical examination and further investigation in making a definitive diagnosis.

Objective\ud Dissociative traits represent a disturbance in selfhood that may predispose to, and trigger, functional seizures (FSs). The predictive representation and control of the internal physiological state of the body (interoception) are proposed to underpin the integrity of the sense of self (“minimal selfhood”). Therefore, discrepancies between objective and subjective aspects of interoception may relate to symptom expression in patients with FSs. Here, we tested whether individual differences in trait measures of interoception relate to dissociative symptoms, and whether state interoceptive deficits predict FS occurrence.\ud \ud Methods\ud Forty‐one participants with FSs and 30 controls completed questionnaire ratings of dissociation, and measures of (1) interoceptive accuracy (IA)—objective performance on heartbeat detection tasks; (2) trait interoceptive sensibility—subjective sensitivity to internal sensations (using the Porges Body Perception Questionnaire); and (3) state interoceptive sensibility—subjective trial‐by‐trial measures of confidence in heartbeat detection. Interoceptive trait prediction error (ITPE) was calculated from the discrepancy between IA and trait sensibility, and interoceptive state prediction error (ISPE) from the discrepancy between IA and state sensibility.\ud \ud Results\ud Patients with FSs had significantly lower IA and greater trait interoceptive sensibility than healthy controls. ITPE was the strongest predictor of dissociation after controlling for trait anxiety and depression in a regression model. ISPE correlated significantly with FS frequency after controlling for state anxiety.\ud \ud Significance\ud Patients with FSs have disturbances in interoceptive processing that predict both dissociative traits reflecting the disrupted integrity of self‐representation, and the expression of FSs. These findings provide insight into the pathophysiology of functional neurological disorder, and could lead to novel diagnostic and therapeutic approaches.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. These symptoms are varied and include abnormal control of movement, episodes of altered awareness resembling epileptic seizures and abnormal sensation and are often comorbid with chronic pain, fatigue and cognitive symptoms. There is increasing evidence for the role of neurologists in both the assessment and management of FND. The aim of this review is to discuss strategies for the management of FND by focusing on the diagnostic discussion and general principles, as well as specific treatment strategies for various FND symptoms, highlighting the role of the neurologist and proposing a structure for an interdisciplinary FND service.

Autism spectrum disorder is an umbrella term for a group of neurodevelopmental disorders that is associated with impairments to social interaction, communication, and behaviour. Typically, autism spectrum disorder is first detected with a screening tool (e.g. modified checklist for autism in toddlers). However, the interpretation of autism spectrum disorder behavioural symptoms varies across cultures: the sensitivity of modified checklist for autism in toddlers is as low as 25 per cent in Sri Lanka. A culturally sensitive screening tool called pictorial autism assessment schedule has overcome this problem. Low- and middle-income countries have a shortage of mental health specialists, which is a key barrier for obtaining an early autism spectrum disorder diagnosis. Early identification of autism spectrum disorder enables intervention before atypical patterns of behaviour and brain function become established. This article proposes a culturally sensitive autism spectrum disorder screening mobile application. The proposed application embeds an intelligent machine learning model and uses a clinically validated symptom checklist to monitor and detect autism spectrum disorder in low- and middle-income countries for the first time. Machine learning models were trained on clinical pictorial autism assessment schedule data and their predictive performance was evaluated, which demonstrated that the random forest was the optimal classifier (area under the receiver operating characteristic (0.98)) for embedding into the mobile screening tool. In addition, feature selection demonstrated that many pictorial autism assessment schedule questions are redundant and can be removed to optimise the screening process.

Chronic hyperplastic candidiasis (CHC) clinically presents with white plaques involving the post-commissural buccal mucosa and less frequently, the tongue. Common risk factors include xerostomia, smoking, post-chemotherapy or radiotherapy, antibiotic use, vitamin deficiency and immunosuppression. Here, we present a case of CHC secondary to secukinumab. A 38-year-old man presented with a 6-month history of asymptomatic white plaques involving the lateral tongue and buccal mucosa. The medical history included chronic plaque psoriasis controlled with secukinumab 300 mg monthly, initiated 6 months prior to presentation. Intraoral examination revealed dense homogenous keratosis involving the right and left posterior lateral tongue and posterior buccal mucosa. Histopathological examination was consistent with chronic hyperplastic candidiasis. Special stains for fungal hyphae were positive. In situ hybridization for EBV were negative. Serology was negative for HIV. He was managed with fluconazole 100 mg daily for 1 week and placed on a prophylactic antifungal regime of chlorhexidine 0.2% mouthwash to reduce overall Candida load; however, the white plaques remained unchanged. He subsequently discontinued secukinumab and switched to certolizumab, resulting in complete resolution of oral candidiasis. In psoriasis, dysfunction in the cytokine pathway results in excessive production of IL-17A. Secukinumab, a next-generation anti-IL-17A biologic, is being used more commonly to manage moderate–severe plaque psoriasis. Clinicians should be aware of the risk of development of candidiasis as a potential complication of secukinumab due to the concurrent role of IL-17 in innate and adaptive immunity against Candida. Early recognition of oral Candida lesions with diagnostic biopsy is paramount to exclude dysplasia.

Functional seizures are a common neurological presentation but access to evidence-based treatments is sporadic and often delayed. Patient engagement is an essential prerequisite to any treatment benefits, but previous research has not investigated engagement with psychological group treatments. In this service evaluation, we compared patients who initially engaged and disengaged from an online CBT-based group treatment on demographic and clinical variables, and illness-related beliefs. A self-report survey was used to explore reasons for disengagement. Of 64 patients invited to the group treatment, 39 (60.1%) disengaged before the first session. Older age was associated with engagement with the functional seizures group. There were no other group differences between demographic, clinical, or belief-based variables. Patients who disengaged reported the timing and format as barriers to joining and had preferences for individual and in-person interventions. These findings have implications for the role of clinicians in providing regular tangible information about referral pathways, and motivating patients to engage with available treatments.

Summary Background Patients with severe autosomal recessive congenital ichthyosis (ARCI) show a T helper 17/interleukin 17 (Th17/IL17) skewing in their skin and serum, resembling the inflammatory profile of psoriatic patients. Secukinumab, an IL‐17A inhibitor, has shown clinical efficacy in patients with moderate‐to‐severe plaque psoriasis. Aims To test the clinical efficacy and safety of secukinumab in a paediatric patient with ATP‐binding cassette subfamily A member 12 deficiency‐related severe erythrodermic ARCI. Materials & Methods 6‐months therapeutic trial. During the first 4‐weeks induction period, the patient received weekly subcutaneous injections of 150 mg secukinumab (five injections in total). During the following 20‐weeks maintenance period, the patient was given a subcutaneous injection of 150 mg secukinumab every 4 weeks. Result & Discussion After the 6‐months therapy period, there was a 48% reduction from the baseline Ichthyosis‐Area‐Severity‐Index (‐Erythema/‐Scaling) score. The treatment was well tolerated. Moreover, cytokine analysis revealed a reduction of keratinocyte‐derived proinflammatory cytokines and an abrogation of Th17‐skewing during therapy. Conclusion Further studies are needed to evaluate the effects of the use of IL‐17A inhibition in ARCI patients.

Previous research into Functional Neurological Disorder (FND) has shown that there are significant barriers in providing patient-centred care. However, there has been no specific research into whether patient experiences of care for FND meet the current standards of care. This study aimed to investigate the types of problems experienced by FND patients, and whether these differed to patients with multiple sclerosis (MS). FND (n = 40) and MS patients (n = 37) were recruited from NHS tertiary neurology clinics and completed questionnaires on their experiences of health care services. Significant differences in experiences of care between the two patient groups were found, with FND patients reporting significantly more problems in their diagnosis and treatment (p = 0.003), patient-centred care (p < 0.001), relationships with healthcare professionals (p < 0.001), and in accessing community care (p = 0.001). Limitations include a small sample size, specificity to a single centre, and cross-sectional design. The results suggest that current care for FND patients is not meeting expected standards for long-term neurological conditions, highlighting the need for structured care pathways and patient-centred care.

Introduction\ud A three-level model of interoception has recently been defined. We aim to study the interoceptive processing in individuals with functional motor disorder (FMD).\ud \ud Methods\ud Twenty-two patients with FMD were compared to 23 healthy controls. They underwent a protocol measuring different levels of interoception including: accuracy (a heart-beat tracking task), awareness (participant's confidence level) and sensibility (the Body Awareness Questionnaire-BAQ). Depression, anxiety and alexithymia were assessed by means of validated clinical scales.\ud \ud Results\ud The FMD group showed a lower cardiac interoceptive accuracy and sensibility than healthy controls but they did not differ in terms of awareness (p = 0.03 and 0.005 respectively). They were aware of their poor performance in the accuracy task. Cardiac interoceptive accuracy positively correlated with the BAQ sub-scales “Predict Body Reaction” (r = 0.49, p = 0.001) and “Sleep-Wake Cycle” (r = 0.52, p < 0.001). A mediation analysis showed a significant indirect effect of group on cardiac interoceptive accuracy through BAQ “Predict Body Reaction” (b = −2.95, 95% BCa CI[-7.2;-0.2]). The direct effect of group on “Predict Body Reaction” was still significant (b = − 6.95, p = 0.02, 95% CI[-13.18;-0.73]).\ud \ud Conclusions\ud People with FMD have impaired cardiac interoceptive accuracy and sensibility but no difference in metacognitive interoception compared to healthy controls.

Introduction The pressure of the global COVID-19 pandemic led to unprecedented changes in the delivery of healthcare services in a short period of time. Due to the nature of cardiothoracic surgery, there was an urgent need to adapt and continue delivery of services whilst maintaining patient and staff safety (1) St. Bartholomew's Hospital is a Cardiothoracic tertiary centre. The trust underwent mass redistribution of intensive care services and creation of a new hospital (The Nightingale) to manage the influx of COVID-19 patients. Therefore, the delivery of cardiothoracic perioperative services changed significantly, requiring online or telephone appointments for pre-op assessment clinic; strict no visitors policy and the need for patient self-isolation prior to hospital admission. Delivering perioperative care in this new environment was challenging and we wanted to investigate how these changes impacted the perioperative experiences of cardiothoracic patients during this time with the aim of improving any shortcomings identified. Methods Between 7-8th September 2020, all patients who were at least 48h post-procedure were given a self-administered paper questionnaire after verbal consent was obtained. This consisted of a total of eight structured and unstructured questions. These were analysed using simple frequency analysis and manual analysis respectively. Common themes were identified. Results 51 patients completed the questionnaire - 39 cardiac and 12 thoracic patients. The main themes were pain and surviving the operation with concerns regarding family. 88% of patients positively recalled speaking to an anaesthetist face to face, with over half of these interaction being a day before their surgery. 92% felt meeting the anaesthetist was useful in addressing their worries and helped with anxiety. Information delivery regarding post-operative pain was an overwhelming theme and potential area for improvement. 88% of patients would recommend St. Bartholomew's hospital to friends and family. 64.8% who completed the question “Is there anything else you want to tell your anaesthetists or critical care doctors?” wanted to express their gratitude to all healthcare professionals involved in their care. Interestingly, a number of patients reported that they would like information about lifestyle changes and identified a potential window for signposting for more support. Discussion Unfortunately, there is little national or international data for direct comparison of our findings. Post-operative pain expectations can be further explored to establish whether more preoperative information surrounding analgesia is required. Anaesthetists should be aware that the perioperative period for major surgery is a teachable moment for potential lifestyle changes and could play an important part in utilising this opportunity. We hope that this simple questionnaire can provide healthcare staff a better insight into perioperative patient experience and the importance of preoperative provision of information. Despite significant changes during the pandemic, it is reassuring to know that the overall patient experience was positive.

Introduction Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN. Methods English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models. Results Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1). Conclusion In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.

Introduction: Previous studies had provided evidence that vitamin D deficiency is a strong negative predictor for survival and recovery after severe vascular events but national estimate on disability related burden is not clear. Hypothesis: We evaluate the prevalence of vitamin D deficiency (VDD) amongst patients with cardiovascular disease (CVD) and cerebrovascular disorders (CeVD) and to find out whether or not CVD and CeVD in the presence of VDD increases the disability. Methods: We performed a retrospective analysis of the Nationwide Inpatient Sample data (years 2016-2017) in adults (≥18 years) hospitalizations. We identified patients with secondary diagnosis of VDD and primary diagnosis of CVD (AFib, CHF, IHD, acute MI, and angina) and CeVD (AIS, TIA, ICeH and SAH) using ICD-10-CM codes. We performed a chi-square test and multivariable survey logistic regression to analyze disability of patients with CVD and CeVD in presence of VDD. Disability/loss of function was investigated by APRDRGs severity using 3M Health Information Systems software. (Score 1-4 indicates minor to extreme loss of function) Results: Among 58,259,589 US hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23% and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH and SAH, respectively and 1.82% had VDD. Prevalence of hospitalizations due to CHF (14.66% vs 11.43%), AIS (1.87% vs 1.71%) and TIA (0.4% vs 0.38%) was higher; and IHD (2.62% vs 3.45%), acute MI (1.58% vs 2.16), angina (0.05% vs 0.06%), AFib (1.14% vs 1.28%), ICeH (0.17% vs 0.23%) and SAH (0.05% vs 0.08%) was lower among VDD patients in compare to non-VDD. (p Conclusions: CVD and CeVD in presence of VDD increase the disability amongst US hospitalizations. Future studies should be planned to evaluate the discharge outcomes as well as the effect of identification and in-hospital management of VDD on improvement of the outcomes.

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016&ndash, 2017) of adult (&ge, 18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p &lt, 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07&ndash, 1.09), IHD (aOR 1.24, 95% CI 1.21&ndash, 1.28), acute MI (aOR 1.23, 95% CI 1.19&ndash, 1.28), AFib (aOR 1.21, 95% CI 1.16&ndash, 1.27), and TIA (aOR 1.19, 95% CI 1.11&ndash, 1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06&ndash, 1.14), ICeH (aOR 1.22, 95% CI 1.08&ndash, 1.38), TIA (aOR 1.36, 95% CI 1.25&ndash, 1.47), IHD (aOR 1.37, 95% CI 1.33&ndash, 1.41), acute MI (aOR 1.44, 95% CI 1.38&ndash, 1.49), AFib (aOR 1.10, 95% CI 1.06&ndash, 1.15), and CHF (aOR 1.03, 95% CI 1.02&ndash, 1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes.

Epilepsy is one of the commonest neurological disorders, affecting approximately 50 million people worldwide, and it is now recognized as a disorder of the brain characterized not only by recurrent seizures, but also by its neurobiological, cognitive, psychological, and social consequences. In general, psychiatric disorders show a uniformly increased prevalence in epilepsy, as compared to the general population. This chapter focuses on major axis I disorders encountered in adults with epilepsy, namely mood and anxiety disorders and psychoses, with special emphasis on differential diagnosis and treatment. The contribution of epilepsy treatment, such as epilepsy surgery and antiepileptic drugs, is also discussed. Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but they are not caused by ictal epileptiform activity. PNES represent another frequently encountered condition in neuropsychiatric clinics. Epidemiology, differential diagnosis and management of PNES are discussed.

A 57-year-old man presented with a progressive flaccid symmetrical motor and sensory neuropathy following a 1-week history of cough and malaise. He was diagnosed with Guillain-Barré syndrome secondary to COVID-19 and started on intravenous immunoglobulin. He proceeded to have worsening respiratory function and needed intubation and mechanical ventilation. This is the first reported case of this rare neurological complication of COVID-19 in the UK, but it adds to a small but growing body of international evidence to suggest a significant association between these two conditions. Increasing appreciation of this by clinicians will ensure earlier diagnosis, monitoring and treatment of patients presenting with this.

Mood disorders such as depression and anxiety have a high prevalence in adult patients with epilepsy, and their evaluation is crucial in choosing the most appropriate antiepileptic drug (AED) with regard to side effects, which can account for long-term discontinuation, poor compliance, and ultimately, failure of seizure control. While more evidence is provided for older AEDs on their effect on mood changes, newer AEDs such as lacosamide have not yet been extensively studied. We performed a systematic review of the literature available on the impact of lacosamide on mood in adult patients with epilepsy. A literature search on MEDLINE, COCHRANE, Scielo, and Clinicaltrials.gov databases was performed, and articles where mood scales where specifically reported as primary or secondary outcome measures were included. Articles differed greatly in terms of inclusion criteria, concomitant AEDs, seizure reduction control, and outcome measures. If lacosamide is used as add-on, two studies point towards a beneficial effect on depressive and anxiety symptoms, two studies claim no effects on mood, and one reports a positive effect only in patients with major depressive symptoms at baseline. Additional evidence from either retrospective or comparative drug studies indicates no effects of lacosamide on mood. Even though presently, a negative effect on mood seems unlikely, whether lacosamide could exert a beneficial impact on mood remains controversial. Multicenter, randomized, controlled, double-blind studies are needed to assess the impact on lacosamide on mood disorders, given the low evidence level (Class III and IV) of currently available studies.

There is an increasing interest in using venoarterial extracorporeal membrane oxygenation (VA-ECMO) to manage out-of-hospital cardiac arrest, termed extracorporeal cardiopulmonary resuscitation (E-CPR).1 VA-ECMO, used in intensive care medicine for cardiorespiratory support, involves draining blood through a cannula sited in a large vein passage through a pump and a membrane oxygenator and returning it under pressure through another cannula sited in a large artery. The time between cardiac arrest and implementation of E-CPR is a major prognostic factor2 with data suggesting improved survival if instituted within 30 min.3 UK practice for out-of-hospital cardiac arrest involves advanced life support on scene for 20 min seeking return of spontaneous circulation and transport of appropriate patients to secondary care if initial efforts fail. Thus, if VA-ECMO is only commenced in hospital, eligible patients might not be stabilised until after 30 min, reducing the chance of neurologically intact survival. We performed a high-fidelity simulation to assess the possibility of implementing prehospital E-CPR for a simulated patient within 30 min of a call to emergency services and the logistics of transfer and handover to a heart attack centre. Our aim was to facilitate learning between prehospital, paramedic and ECMO teams to help coordinate future attempts at the intervention and plan a formal feasibility trial. We also hoped that this novel simulation would form a basis for future training in prehospital E-CPR. …

Background: Inter-hospital communication frequently requires mediation via a switchboard. Identifying and eliminating switchboard inefficiencies may improve patient care. Methods: All 175 acute hospital switchboards in England were contacted six times. Call contents and duration were recorded. No clinician calls or bleeps were connected. Results: The mean delay before contacting a switchboard operative was 55±46 seconds. 115 hospitals (66%) used automated switchboards; 34 of these (30%) had infection control messages. Robot operators introduced an additional 40 second delay versus humans (mean 70.3±28 versus 29.8±23 seconds, p

A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from the Mayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariable analysis performed on the Mayo cohort identified high risk karyotype, platelet count 65 years and transfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in complete remission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-year survival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patients achieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p

Objectives/AimsPrevious research into Functional Neurological Disorder (FND) has shown that there are significant barriers in providing multidisciplinary, patient-centred care for these patients, including stigmatising attitudes, poor knowledge about FND, and a lack of structured care pathways. However, there has been no specific research into patient experiences of care for FND within NHS services to date, and whether these experiences meet the standards of care expected for long-term neurological conditions (LTNCs). The current study thus aimed to investigate the types of problems experienced by FND patients, and whether they differed in frequency and type to patients with another LTNC, multiple sclerosis (MS).MethodsBoth FND (n = 40) and MS patients (n = 37) were recruited from tertiary neurology clinics at an NHS hospital and completed two questionnaires on their experiences of health and social care services and on their level of disability.ResultsThe results indicated significant differences in experiences of care between the two patient groups, with FND patients reporting significantly more problems (p<0.001)overall. These problems were reported in relation to their diagnosis and treatment, relationships with healthcare professionals, and difficulties in accessing services. This was despite FND patients reporting significantly higher levels of disability (p=0.001), highlighting the burden of care experienced by FND patients as a result of these difficulties in accessing and receiving care. A small sample size, specificity to a single neurology centre, and a cross-sectional design are acknowledged as limitations.ConclusionsTogether, these results suggest that current care for FND patients is not meeting the standards expected for LTNCs, and highlight the need for further research and the development of structured, multidisciplinary pathways with a patient-centred approach.

Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells. Downstream AIM2-induced genes, CARD16, caspase-1 and IL-1β were also up-regulated and caspase-1 was activated to form cleaved caspase-1 p20 subunits. As evidenced by 7-AAD positivity, pyroptosis was confirmed in infected cells. Overall, these findings have a strong correlation with decreases in viral titers, copy numbers and proteins, and reduced proportions of infected cells. AIM2 and viral antigens were detected by immunohistochemistry in infected neurons in inflamed areas of the CNS in EV-A71 encephalomyelitis. In infected AIM2-knockdown cells, AIM2 and related downstream gene expressions, and pyroptosis were suppressed, resulting in significantly increased virus infection. These results support the notion that AIM2 inflammasome-mediated pyroptosis is an important mechanism of neuronal cell death and it could play an important role in limiting EV-A71 replication.

Myeloproliferative neoplasms (MPNs) operationally include essential thrombocythemia, polycythemia vera, primary myelofibrosis (PMF), and prefibrotic PMF. All 4 MPN variants might progress into blast-phase disease (MPN-BP). For essential thrombocythemia, reported risk factors for leukemic transformation include advanced age, extreme thrombocytosis, anemia, leukocytosis, and sequence variants/mutations involving TP53 and EZH2 (for expansion of gene symbols, see www.genenames.org); for polycythemia vera, advanced age, leukocytosis, abnormal karyotype, mutations involving SRSF2 and IDH2, and treatment with pipobroman, chlorambucil, or P32; and for PMF, increased blast percentage, thrombocytopenia, abnormal karyotype, triple-negative driver mutational status, and sequence variants/mutations involving SRSF2, RUNX1, CEBPA, and SH2B3. The reported median survival figures for MPN-BP range from 1.5 to 2.5 months in patients treated with supportive care only, from 2.5 to 10 months in those receiving hypomethylating agents or low-dose chemotherapy, and from 3.9 to 9.4 months in those receiving induction chemotherapy. Three-year survival after allogeneic stem cell transplant was reported in 16% to 33% of patients. These observations validate the extremely poor prognosis associated with MPN-BP and the lack of effective drug therapy and highlight the need for urgent assessment of therapeutic values of investigational agents. In the meantime, affected patients might be best served with aggressive chemotherapy followed by allogeneic stem cell transplant after adequate blast clearance.

Despite advances in the acute myeloid leukemia (AML) treatment armamentarium over the last 4 years, patients with relapsed/refractory (R/R) AML have dismal outcomes [1]. Clonal evolution drives rel...

Background\ud Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency.\ud \ud Methods\ud In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.\ud \ud Findings\ud Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0–20] in the CBT plus standardised medical care group vs 7 seizures [1–35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56–1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference −0·53 [95% CI −0·97 to −0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference −4·12 [95% CI −6·35 to −1·89]; p

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease epidemics with neurological complications and fatalities. However, the neuropathogenesis of EV-A71 remains poorly understood. In mice, adaptation and virulence determinants have been mapped to mutations at VP2-149, VP1-145 and VP1-244. We investigate how these amino acids alter heparin-binding phenotype and shapes EV-A71 virulence in one-day old mice. We constructed six viruses with varying residues at VP1-98, VP1-145 (which are both heparin-binding determinants) and VP2-149 (based on the wild type 149K/98E/145Q, termed KEQ) to generate KKQ, KKE, KEE, IEE and IEQ variants. We demonstrated that the weak heparin-binder IEE was highly lethal in mice. The initially strong heparin-binding IEQ variant acquired an additional mutation VP1-K244E, which confers weak heparin-binding phenotype resulting in elevated viremia and increased virus antigens in mice brain, with subsequent high virulence. IEE and IEQ-244E variants inoculated into mice disseminated efficiently and displayed high viremia. Increasing polymerase fidelity and impairing recombination of IEQ attenuated the virulence, suggesting the importance of population diversity in EV-A71 pathogenesis in vivo. Combining in silico docking and deep sequencing approaches, we inferred that virus population diversity is shaped by electrostatic interactions at the five-fold axis of the virus surface. Electrostatic surface charges facilitate virus adaptation by generating poor heparin-binding variants for better in vivo dissemination in mice, likely due to reduced adsorption to heparin-rich peripheral tissues, which ultimately results in increased neurovirulence. The dynamic switching between heparin-binding and weak heparin-binding phenotype in vivo explained the neurovirulence of EV-A71., Author summary Enterovirus A71 (EV-A71) is the primary cause of hand, foot and mouth disease, and it can also infect the central nervous system and cause fatal outbreaks in young children. EV-A71 pathogenesis remains elusive. In this study, we demonstrated that EV-A71 variants with strong affinity to heparan sulfate (heparin) have a growth advantage in cell culture, but are disadvantaged in vivo. When inoculated into one-day old mice, strong heparin-binding virus variants are more likely to be adsorbed to peripheral tissues, resulting in impaired ability to disseminate, and are cleared from the bloodstream rapidly. The lower viremia level resulted in no neuroinvasion. In contrast, weak heparin-binding variants show greater levels of viremia, dissemination and subsequent neurovirulence in mice. We also provide evidence that the EV-A71 heparin-binding pattern is mediated by electrostatic surface charges on the virus capsid surface. In mice, EV-A71 undergoes adaptive mutation to acquire greater negative surface charges, thus generating new virulent variants with weak heparin-binding ability which allows greater viral spread. Our study underlines the importance of electrostatic surface charges in shaping EV-A71 virulence.

Children with autism spectrum disorder (ASD) have altered behaviors in communication, social interaction, and activity, out of which communication has been the most prominent disorder among many. Despite the recent technological advances, limited attention has been given to screening and diagnosing ASD by identifying the speech deficiencies (SD) of autistic children at early stages. This research focuses on bridging the gap in ASD screening by developing an automated system to distinguish autistic traits through speech analysis. Data was collected from 40 participants for the initial analysis and recordings were obtained from 17 participants. We considered a three-stage processing system; first stage utilizes thresholding for silence detection and Vocal Activity Detection for vocal isolation, second stage adopts machine learning technique neural network with frequency domain representations in developing a reliant utterance classifier for the isolated vocals and stage three also adopts machine learning technique neural network in recognizing autistic traits in speech patterns of the classified utterances. The results are promising in identifying SD of autistic children with the utterance classifier having 78% accuracy and pattern recognition 72% accuracy.

Background Erythropoietin (EPO) is an independent predictor for survival in chronic heart failure, myocardial infarction and other cardiac disorders. In a prospective observational study, independent prognostic value of EPO levels in patients with symptomatic aortic stenosis undergoing TAVR was investigated. Methods All consecutive patients undergoing TAVR in a high-volume centre in a 19-month period were included. A 1-year follow-up was completed. Patients with eGRF 90), 2 (60–90), 3a (45–59), 3b (30–44). Pre-procedural anaemia status, EPO levels and iron deficiency were compared in 1-year survivors vs. non-survivors. Log-EPO levels were used for a univariate Cox regression analysis of 1-year mortality. Baseline variables considered to be clinically relevant or found significant in univariate analysis were included in multivariate analysis. Kaplan-Meier curves were constructed for patients in each EPO quartile. Results 185 patients with complete data were included in analyses. Mean age was 81.8 years, 58.4% were male, and 72.4% had NYHA III/IV. Baseline anaemia was present in 51.4% and iron deficiency in 49.2%. Median ferritin was 149.5 (16–1995) μg/L, mean transferrin saturation index was 150±46.7% and median EPO was 13.8 (2.7–231.6) mU/mL. Thirty-day and 1-year mortality were 3.8%, and 18.9%. Baseline anaemia was significantly associated to 1-year mortality: 29.5% vs 7.8%, p=0.001. Iron deficiency had no impact on mortality (18.1% vs 19.8%, p=ns). At 1 year, pre-procedural EPO levels in non-survivors were significantly higher than in survivors: median 20.30 (6.1–231.6) vs 12.9 (2.7–136) mU/mL; p=0.001. Higher log-EPO levels predicted 1-year mortality in univariate analysis (HR 6.1, 95% CI 2.5–14.9, p=0.0001). Other significant univariate predictors were pre-procedural anaemia (HR 4.2, 95% CI 1.8–9.7, p=0.001), eGFR, EuroSCORE II, body mass index, and previous atrial fibrillation. A multivariate analysis of EPO after adjusting for such factors was also significant (HR 3.1, 95% CI 1.06–8.9, p=0.039). Kaplan-Meier analyses showed early diverging curves for anaemia vs non-anaemia, whereas the curves for patients in various EPO level quartiles started to diverge at about 100 days after the intervention, with differences consistently increasing during the whole follow-up period. Curve slopes were increasingly higher in successively higher quartiles (figure). 1-year Kaplan-Meier for EPO and anemia Conclusion Differently from anaemia, a strong predictor for both early and late mortality after TAVR, high pre-procedural EPO levels were an independent predictor for mid-term mortality, with its predictive value only emerging after post-procedural recovery was completed. EPO predictive value was independent from anaemia or renal dysfunction.

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease epidemics with neurological complications and fatalities. However, the neuropathogenesis of EV-A71 remains poorly understood. In mice, adaptation and virulence determinants have been mapped to mutations at VP1-145, VP1-244 and VP2-149. We hypothesized that heparin-binding phenotype shapes EV-A71 virulence in mice. We constructed six viruses with varying residues at VP1-98, VP1-145 (which are both heparin-binding determinants) and VP2-149 (based on the wild type 98E/145Q/149K, termed EQK) to generate KQK, KEK, EEK, EEI and EQI variants. We demonstrated that the weak heparin-binder EEI was highly lethal in mice. The initially strong heparin-binding EQI variant acquired an additional mutation VP1-K244E, which confers weak heparin-binding phenotype resulting in elevated viremia and increased brain inflammation and virus antigens in mice, with subsequent high virulence. EEI and EQI-K244E variants inoculated into mice disseminated efficiently and displayed high viremia. Increasing polymerase fidelity and impairing recombination of EQI attenuated virulence, suggesting the importance of population diversity in EV-A71 pathogenesisin vivo. Combiningin silicodocking and deep sequencing approaches, we inferred that virus population diversity is shaped by electrostatic interactions at the five-fold axis of the virus surface. Electrostatic surface charges facilitate virus adaptation by generating poor heparin-binding variants for betterin vivodissemination in mice, likely due to reduced adsorption to heparin-rich peripheral tissues, which ultimately results in increased neurovirulence. The dynamic switching from heparin-binding to weak heparin-binding phenotypein vivoexplained the neurovirulence of EV-A71.Author summaryEnterovirus A71 (EV-A71) is the primary cause of hand, foot and mouth disease, and it can also infect the central nervous system and cause fatal outbreaks in young children. EV-A71 pathogenesis remains elusive. In this study, we demonstrated that EV-A71 variants with strong affinity to heparan sulfate (heparin) have a growth advantage in tissue culture, but are disadvantageousin vivo. When inoculated into mice, strong heparin-binding virus variants are more likely to be adsorbed to peripheral tissues, resulting in impaired ability to disseminate and being cleared from the bloodstream rapidly. The lower viremia level resulted in no neuroinvasion. In contrast, weak heparin-binding variants show greater levels of viremia, dissemination and subsequent neurovirulence in mice. We also provide evidence that the ability of EV-A71 to bind heparin is mediated by electrostatic surface charges due to amino acids on the virus capsid surface. In mice, EV-A71 undergoes adaptive mutation to acquire greater negative surface charges, thus generating new virulent variants with weak heparin-binding which allows greater viral spread. Our study underlines the importance of electrostatic surface charges in shaping EV-A71 virulence.

Objectives/Aims Functional neurological disorders (FND) account for 20% of patients in neurology clinics and can lead to functional impairment, multiple re-attendances and significant cost. However, diagnosing FND remains challenging; identifying associated factors could aid earlier diagnosis. We aimed to determine the value of self-reported multi-allergies as predictor for FND. Methods We retrospectively reviewed records of consecutive patients from two clinics (General Neurology and FND), St George’s Hospital, January 2015–June 2018. A logistic regression model was used in conditional fashion; statistically significant variables in univariate analysis were included. Results Of 720 patients with definitive diagnosis, 243 (33.8%) had FND and 477 (66.3%) another neurological disorder. Mean age was 43 years (range 16–93), 63.9% (453) were female. 81 patients with FND (33%) had Non-epileptic attack disorder (NEAD). In multivariate analysis, factors associated with FND were female sex (Odds Ratio [95% Confidence Intervals], OR=0.49 [0.33, 0.73], p Increased number of allergies increased the probability of FND: one allergy OR=4.53 [3.08, 6.65, p Conclusions Previous studies highlighted the increased prevalence of allergies in NEAD compared to epilepsy. Our study expand this to all FND, as only 1 in 3 FND patients had NEAD. Presence of allergies, particularly to multiple agents, should raise the suspicion of FND.

Deficits in social cognition are an increasingly recognized complication of epilepsy and contribute to the deficits in social functioning and well-being experienced by patients with epilepsy. Although there has been an increase in studies exploring the measurement and biology of social cognition in patients with epilepsy, there are relatively few examining its clinical implications. Those studies that have been published highlight that social cognitive deficits contribute to impaired quality of life (QoL) in patients with epilepsy, independent of other comorbidities such as depression, anxiety, seizure frequency, and impairment in other cognitive domains. This raises the possibility of novel therapeutic approaches to improving the social well-being of patients with epilepsy.

St George's Hospital hyperacute neurology service (HANS) is a comprehensive, consultant-delivered service set in a teaching hospital regional neuroscience centre. The service addresses deficiencies in acute neurological care previously highlighted by the Royal College of Physicians and the Association of British Neurologists. HANS adopts a disease-agnostic approach to acute neurology, prioritising the emergency department (ED) management of both stroke and stroke mimics alike alongside proactive daily support to the acute medical unit and acute medical take. Rapid access clinics provide a means to assess ambulatory patients, providing an outlet to reduce the burden of referral from primary care to acute medicine. This paper reports the results from the first year of the service. Admission was avoided in 25% of the cases reviewed in the ED. Compared to historic data, there was a significant improvement in the length of stay for non-stroke disorders while the occupancy of stroke beds by non-stroke cases reduced by 50%. The configuration of this service is replicable in other neuroscience centres and provides a framework to reduce the barriers facing patients who present with acute neurological symptoms.

Sexual dysfunction is common in patients with epilepsy, and its manifestations include hyposexuality and erectile dysfunction. The cause of this dysfunction is multifactorial and includes changes in the levels of sex hormones, the effects of antiepileptic drugs on neurotransmission, the epilepsy itself, and psychosocial factors associated with it. Traditional antiepileptic drugs, which induce the cytochrome P450 enzyme system, have the highest rates of sexual dysfunction, which is mediated by changes in sex hormone levels. In contrast newer antiepileptic drugs may cause sexual dysfunction by direct effects on neurotransmitter systems. Some antiepileptic drugs, such as oxcarbazepine and lamotrigine, may improve sexual function but can also rarely be associated with sexual dysfunction. The management of sexual dysfunction depends on its putative cause. If it is caused by antiepileptic drugs, the offending drug should be switched to alternative antiepileptic drugs that do not have a deleterious effect on sexual function. Conversely, if psychosocial factors are thought to play a role, these should be addressed in turn.

The diagnosis of functional neurological disorder (FND) relies on the demonstration of positive symptoms and signs, as supported by recent changes in DSM5. We recorded the findings of routine clinical eye movement assessment in 101 consecutive new patients with FND. Clinical examination triggered facial and eye movement disorders in 46% of patients, all with positive characteristics of functional movement disorder. These are useful as supporting features in making a positive diagnosis of FND.

Bullous systemic lupus erythematosus is one of the rare autoantibody mediated skin manifestation of systemic lupus erythematosus (SLE) demonstrating subepidermal blistering with neutrophilic infiltrate histologically. We present a case of a 40-year-old Hispanic female who presented with a several months’ history of multiple blistering pruritic skin lesions involving the face and trunk, a photosensitive rash over the face and neck, swelling of the right neck lymph node, and joint pain involving her elbows and wrist. Her malady was diagnosed as bullous systemic lupus erythematosus based on the immunological workup and biopsy of her skin lesions. The patient also complained of odynophagia and endoscopy revealed esophagitis dissecans superficialis which is a rare endoscopic finding characterized by sloughing of the esophageal mucosa. The bullous disorders typically associated with esophagitis dissecans superficialis are pemphigus and rarely bullous pemphigoid. However, this is the first reported case of bullous systemic lupus erythematosus associated with esophagitis dissecans superficialis.

Patient: Female, 51 Final Diagnosis: Cocaine induced vasculitis Symptoms: — Medication: — Clinical Procedure: None Specialty: Rheumatology Objective: Rare disease Background: Cocaine is a highly abused substance in United States with almost 70 % of cocaine adulterated with levamisole. It is known to cause vasculitis involving multiple organs due to its direct toxic effect and by the contribution of levamisole or a combined effect of both. Case Report: A 51-year-old woman complained of painful erythematous rash in her hands and lower extremities that started few hours after smoking cocaine and progressed to blistering dark lesions in her lower extremities. She denied any other systemic complaints. Although she has been smoking cocaine for more than 35 years, these skin eruptions started only 4 years ago. Examination revealed tender retiform purpura in the hand and tender retiform purpura with hemorrhagic bulla in the legs. Initially, she had only a significantly positive atypical p-ANCA and later developed combined positivity of both Myeloperoxidase (MPO) and Anti-proteinase-3(PR3) antibodies with a p-ANCA pattern on immunofluorescence. We report a unique case of cocaine (likely contaminated with levamisole)-induced delayed recurrent vasculitis with varying vasculitic antibodies over the years. Conclusions: This case highlights the fact that patients can develop cocaine-related vasculitis after many years of uneventful abuse. Cocaine, with its adulterant levamisole, has the propensity to trigger diverse immunological reactions, which is evident by the varying antibody profile seen in the same patient over time.

Background Sexual dysfunction is very common in patients with epilepsy. Objective We sought to review the published literature around sexual dysfunction in epilepsy, and particularly the role played by anticonvulsant drugs. Method We searched all related articles on PubMed using the search terms sexual dysfunction, various AEDs and epilepsy, and restricted the search to English language articles. Results The most common manifestations of sexual dysfunction in patients with epilepsy are hyposexuality and erectile dysfunction. The cause of this dysfunction is multifactorial and overlapping, and includes changes in the levels of sex hormones, anti-convulsants, the epilepsy itself and psychosocial factors. Traditional anti-convulsants which induce the cytochrome P450 enzyme system have the highest rates of sexual dysfunction, which is primarily mediated by changes in sex hormone levels. Sexual dysfunction associated with newer anti-convulsants is likely to occur through different mechanisms. Some anti-convulsants such as oxcarbazepine and lamotrigine may improve sexual function, but can also rarely be associated with sexual dysfunction. Conclusion Management of sexual dysfunction thought to be caused by anti-convulsants should include the cessation of the offending drug, and consideration of switching to alternative anti-convulsants that have been reported to improve sexual function such as oxcarbazepine, and lamotrigine.

Purpose To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Methods Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Results Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square = 16.762; df = 3; p = 0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square = 11.462; df = 3; p = 0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square = 11.547; df = 3; p = 0.009). Conclusions One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Objective : Central nervous system (CNS) involvement is a known phenomenon of acute lymphoblastic leukemia. However little is known about the incidence of CNS involvement in acute myeloid leukemia (AML) as routine lumbar punctures are not done if patients are asymptomatic at diagnosis. Our practice has been to obtain lumbar puncture (LP) at or after complete remission (CR) for patients that present with any one of the following high risk features;hyperleukocytosis with WBC >10,000 or blastic crisis, extramedullary disease,monocytic differentiation. Methods: We reviewed our leukemia database at Mayo Clinic to determine the incidence of CNS involvement in patients with high risk features after due IRB approval. We also compared baseline demographic characteristics, blood counts, cytogenetic risk groups, presence of extramedullary disease, relapse rate ,transplant rate and overall survival (OS) among patients with and without CNS involvement. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Results: 298 patients with AML were identified with presence of at least 1 risk factor for CNS involvement. The results of LP were only available for 126 (42%) patients. The overall incidence of CNS involvement was 12% (15/126, figure 1). Among the patients with positive disease 3 had CSF examination at diagnosis prior to CR due to the presence of CNS myeloid sarcoma (n=2) and ambiguous lineage myeloid leukemia and were excluded from further evaluation. The incidence of CSF involvement at CR1 was 9.7% (12/123). All patient with CNS positive disease received intrathecal chemotherapy with alternating cytarabine and methotrexate until they cleared their blast and additional 2-4 treatments as per treating physician's discretion .The CNS positive and negative patients were compared and did not show any statistical difference in age, gender, presence of extramedullary disease ,cytogenetic risk group, relapse rate and transplant rate as shown in table1. Molecular data was not available in most of the patients and hence was not included for analysis. The median OS was significantly lower among patients with CNS involvement compared to absence of CNS involvement but was not statistically significant likely due to small sample size (3.9 vs12.8 years (p=0.2), figure 2). The overall CNS relapse rate in patients who did not have a LP done at CR was 5.8%(10/172). Conclusions : CNS evaluation should be done in AML patients with high risk features before declaring CR. CNS disease portends overall a poor prognosis with impaired overall survival and high relapse rate. However the sample size was small and true incidence of CNS disease will need routine diagnostic LP in all high risk patients. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

7053 Background: The revised International Prognostic Scoring System (IPSS-R) aids in prognosticating MDS. The percentage (%) of blasts in the bone marrow is one of the major determinants of the scoring system. The aspirate blast % is utilized as the standard of care, but there could be discrepancies in the blast % reported by the aspirate and the biopsy. We aim to study the possible use of bone marrow biopsy blasts in MDS-EB in calculating IPSS-R. Methods: The MDS database was reviewed for cases of MDS-EB after due IRB approval. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and biopsy blast % (IPSS-RBx). The biopsy blast % was reported morphologically or by the CD34 stain. Whenever a range was reported the highest value was utilized as the blast %. Suboptimal aspirates were excluded from the study. The overall survival (OS) was determined by IPSS-RAsp, IPSS-RBx and IPSS-R highest blast (IPSS-RHi). OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno’s concordance statistic was used to compare all 3 risk scoring systems. Results: Of 1322 patients, 431 (33%) cases were identified with MDS-EB; out of which 173 cases had both blasts reported in the biopsy and the aspirate. Out of 173 cases, 35 (20%) had MDS-EB1, and 61 (35%) had MDS EB-2 based on both biopsy and aspirate (concordant cases). Seventy seven (45%) patients changed from EB-1 to EB2 or vice versa based on the biopsy blast (44/77 (57%) cases were upstaged). The OS outcomes based on the IPSS-RBx biopsy showed a clear and meaningful separation with median OS decreasing with increased risk but IPSS-RAsp and IPSS-RHi did not (Table). We compared the 3 models for observed OS differences using the Uno model and there was no statistically significant difference. Conclusions: IPSS-RBx (but not IPSS-RAsp and IPSS-RHi) identified prognostic groups for OS with median OS decreasing with increased risk. The small sample size may have led to an insignificant effect on model power by Uno model. This finding needs to be validated by other centers. [Table: see text]

Anterior temporal lobe resection controls seizures in 50-60% of patients with intractable temporal lobe epilepsy but may impair memory function, typically verbal memory following left, and visual memory following right anterior temporal lobe resection. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated the reorganization of memory function in patients with temporal lobe epilepsy before and after left or right anterior temporal lobe resection and the efficiency of postoperative memory networks. We studied 46 patients with unilateral medial temporal lobe epilepsy (25/26 left hippocampal sclerosis, 16/20 right hippocampal sclerosis) before and after anterior temporal lobe resection on a 3 T General Electric magnetic resonance imaging scanner. All subjects had neuropsychological testing and performed a functional magnetic resonance imaging memory encoding paradigm for words, pictures and faces, testing verbal and visual memory in a single scanning session, preoperatively and again 4 months after surgery. Event-related analysis revealed that patients with left temporal lobe epilepsy had greater activation in the left posterior medial temporal lobe when successfully encoding words postoperatively than preoperatively. Greater pre- than postoperative activation in the ipsilateral posterior medial temporal lobe for encoding words correlated with better verbal memory outcome after left anterior temporal lobe resection. In contrast, greater postoperative than preoperative activation in the ipsilateral posterior medial temporal lobe correlated with worse postoperative verbal memory performance. These postoperative effects were not observed for visual memory function after right anterior temporal lobe resection. Our findings provide evidence for effective preoperative reorganization of verbal memory function to the ipsilateral posterior medial temporal lobe due to the underlying disease, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after anterior temporal lobe resection. Early postoperative reorganization to ipsilateral posterior or contralateral medial temporal lobe structures does not underpin better performance. Additionally our results suggest that visual memory function in right temporal lobe epilepsy is affected differently by right anterior temporal lobe resection than verbal memory in left temporal lobe epilepsy.

Psychogenic non-epileptic seizures (PNES) are the most common manifestation of functional (psychogenic) neurological symptoms. Clinically, they consist of intermittent episodes that resemble epileptic seizures and can involve changes in behaviour, movement, sensation, autonomic function or consciousness. To date, there are no positive EEG features that have been identified that are diagnostic of PNES and therefore, the diagnosis is primarily based on clinical assessment and the absence of epileptic activity during the seizure. Our goal was to identify a positive marker of PNES, by assessing EEG spectral power changes prior to non-epileptic attacks. We hypothesised that decreases in β power (desynchronisation in the 13–30 Hz band) might occur prior to a non-epileptic seizure. β-Desynchronisation is known to occur prior to cued movement (event-related desynchronisation, ERD) or self-paced movement and was recently shown to occur prior to functional myoclonic jerks.1 ### Participants We recruited three patients previously diagnosed with PNES from the Movement Disorder outpatient clinics at the National Hospital for Neurology and Neurosurgery. Three EEG recordings of patients with convulsive epileptic attacks were used as control. The study was approved by the local Ethics Committee and informed consent was obtained. ### Procedure Patients were seated in a comfortable chair while a 32-channel EEG was recorded and a video was made. We asked each participant to sit in a relaxed position with their eyes open and to let attacks happen in their usual way …

OBJECTIVE: PAX6 is a pleiotropic transcription factor essential for the development of several tissues including the eyes, central nervous system, and some endocrine glands. Recently it has also been shown to be important for the maintenance and functioning of corneal and pancreatic tissues in adults. We hypothesized that PAX6 is important for the maintenance of brain integrity in humans, and that adult heterozygotes may have abnormalities of cortical patterning analogous to those found in mouse models. METHODS: We used advanced magnetic resonance imaging techniques, including surface-based morphometry and region-of-interest analysis in adult humans heterozygously mutated for PAX6 mutations (n = 19 subjects and n = 21 controls). Using immunohistochemistry, we also studied PAX6 expression in the adult brain tissue of healthy subjects (n = 4) and patients with epilepsy (n = 42), some of whom had focal injuries due to intracranial electrode track placement (n = 17). RESULTS: There were significant reductions in frontoparietal cortical area after correcting for age and intracranial volume. A greater decline in thickness of the frontoparietal cortex with age, in subjects with PAX6 mutations compared to controls, correlated with age-corrected, accelerated decline in working memory. These results also demonstrate genotypic effects: those subjects with the most severe genotypes have the most widespread differences compared with controls. We also demonstrated significant increases in PAX6-expressing cells in response to acute injury in the adult human brain. INTERPRETATION: These findings suggest a role for PAX6 in the maintenance and consequent functioning of the adult brain, homologous to that found in other tissues. This has significant implications for the understanding and treatment of neurodegenerative diseases.

Parathyroid hormone mediated hypercalcemia is not always exclusively primary hyperparathyroidism and rarely could be due to ectopic parathyroid hormone secretion from tumor cells. We present a case of 86-year-old female with metastatic gall bladder adenocarcinoma diagnosed eight months back who presented with generalized fatigue and poor oral intake and was found to be hypercalcemic with elevated parathyroid hormone levels. Imaging with technetium 99 m sestamibi scintigraphy with dual phase, subtraction thyroid scan (dual isotope scintigraphy), magnetic resonance imaging and ultrasonography did not demonstrate any parathyroid lesion in normal or ectopic sites. We believe that the tumor cells were the source of ectopic parathyroid hormone secretion as we had excluded all the other possibilities with extensive combined imaging thereby increasing the sensitivity of our testing. We report the first case of metastatic gall bladder adenocarcinoma with paraneoplastic ectopic parathyroid hormone secretion.

X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.

Kikuchi-Fujimoto disease is a rare benign condition of necrotising histiocytic lymphadenitis with unknown aetiology. We describe here a 30-year-old African American female who presented with fever, generalized rash, cervical lymphadenopathy, and oral candidiasis and was found to have Kikuchi-Fujimoto disease on lymph node biopsy with low CD4 count. The initial presentation was concerning for acute retroviral infection. Her HIV serology and HIV RNA PCR were negative however she had low CD4 count with reversal of CD4/CD8 ratio. Although low CD4 count has been associated with autoimmune disease, it has not been described with Kikuchi-Fujimoto disease. We report the first case of Kikuchi-Fujimoto disease associated with symptomatic CD4 lymphocytopenia.