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Corticosteroids are established as the first-line treatment of progressive HTLV-1-associated myelopathy (HAM), but evidence to guide management of refractory cases is lacking. We present a case of subacute onset HAM, in which a marked improvement was seen following administration of second line pulsed IV cyclophosphamide. We are aware of only one previous case report of cyclophosphamide being used to treat HAM.A 57-year-old man of Jamaican descent presented with a 4-month history of progressive spastic para- paresis. At presentation, he was paraplegic with Medical Research Council (MRC) scores of 0-1 in all lower limb muscle groups. MR imaging revealed longitudinally extensive intramedullary T2-hyperintensity. Following positive serology, the diagnosis of HAM was confirmed by demonstration of a high CSF/blood ratio for HTLV-1 viral load in mononuclear cells. Intravenous methylprednisolone 1000mg daily was given for three days, followed by prednisolone 60mg daily for four weeks. MRC scores did not improve, so on week five pulsed intravenous cyclophosphamide was commenced (six 1.2g pulses given over 13 weeks), and prednisolone was tapered to 15mg daily. By week 18 MRC scores had improved to 4-5 and he could walk 20m with a Zimmer frame.

IntroductionMonitoring respiratory function is a critical part of the management of patients with acute neuromuscular disease. Single breath count (SBC) testing is often performed as a surrogate for the Forced Vital Capacity (FVC), especially in resource poor environments. However, equivalence of these two tests has not been formally evaluated.MethodsWe will compare the SBC and FVC in 50 healthy adults. Correlation will be evaluated using linear regression and factors influencing the SBC and FVC will be investigated.ResultsTo date 10 participants have been recruited (4 male, 6 female, mean age 30 years). Provisional analysis has shown a mean best SBC and FVC was 71 (SD 19) and 4.8 Litres (SD 1.3) respectively. In this small sample a significant correlation between SBC and FVC was demonstrated (p=0.03, R-squared=0.47). Recruitment is on schedule to complete by March 2020 and full results will be available for presentation at the conference.DiscussionTo our knowledge no study has directly compared SBC and FVC in healthy adult population. Our study will provide useful data to help understand the appropriateness of interchanging these tests in clinical practice.aram.aslanyan@srft.nhs.uk

Bedside forced vital capacity (FVC) monitoring is the gold standard in detecting impending respiratory failure in patients with neuromuscular disease. However, bedside spirometry is often unavailable, especially in resource-limited settings, and facial muscle weakness can lead to unreliable measurements. In these settings the single breath count (SBC) is a potential alternative as it does not require specialised equipment nor is it affected by facial muscle weakness.However, uncertainties remain about its reliability in assessing patients with neuromuscular diseases such as myasthenia gravis in clinical practice.We compared SBC and FVC in 43 healthy adult volunteers and in 15 patients with seropositive myasthenia gravis in the outpatient setting. The myasthenic cohort, who were all anti-acetylcholine receptor antibody positive, had varying degrees of neuromuscular (bulbar and limb) weakness. Using linear regression, we showed a positive correlation between FVC and SBC in both healthy volunteers (R = 0.73, p<0.001) and myasthenia gravis patients (R= 0.59. P< 0.002). These results provide further evidence that SBC is a reliable and reproducible alternative FVC in settings where spirometry is unavailable.Khaizer.rizvi@nhs.net

Our patient presented initially at the age of 59 in 2012 to the Neurology service with abnormal movements with a background history of fibromyalgia and chronic fatigue syndrome. The movements were felt to be choreiform in nature, and allowing for her diagnosis of CFS the rest of the neurological examination was normal. Her initial MRI revealed abnormalities in the basal ganglia and differentials of extrapontine myelinolysis, Wernicke’s and small vessel disease were raised. In 2016 she presented with deterioration in cognition followed a by a seizure and reduced GCS. Repeat Imaging showed significant deterioration in the basal ganglia changes and a CT chest showed mediastinal and hilar lymphadenopathy consistent with sarcoidosis. Lymph node biopsy showed granulomatous inflammation again consistent with sarcoidosis. She was treated with steroids and there was a dramatic improvement. Neurosarcoidosis is a rare association of an already fairly rare condition, affecting around 5% of people with sarcoidosis. Of these 5% the neurological symptoms are the first presentation of the sarcoidosis in around 50%. Whilst there are many presentations of neurosarcoidosis, most commonly cranial neuropathies or pituitary axis involvement, there is little in the literature describing neurosarcoidosis presenting with chorea.

BackgroundHexanucleotide repeat expansions of C9ORF72 account for a significant proportion of autosomal dominant neurodegenerative diseases in the amyotrophic lateral sclerosis (ALS)–frontotemporal dementia spectrum. In the absence of a family history, clinical identification of such patients remains difficult. We aimed to identify differences in demographics and clinical presentation between patients with C9ORF72 gene-positive ALS (C9pALS) versus C9ORF72 gene-negative ALS (C9nALS), to aid identification of these patients in the clinic and examine differences in outcomes including survival.MethodsWe retrospectively reviewed the clinical presentations of 32 patients with C9pALS and compared their characteristics with a cohort of 46 patients with C9nALS from the same tertiary neurosciences centre.ResultsPatients with C9pALS more commonly presented with mixed upper and lower motor signs (C9pALS 87.5%, C9nALS 65.2%; p=0.0352), but less frequently presented with purely upper motor neuron signs (C9pALS 3.1%, C9nALS 21.7%; p=0.0226). The C9pALS cohort had a higher frequency of cognitive impairment (C9pALS 31.3%, C9nALS 10.9%; p=0.0394) and bulbar disease (C9pALS 56.3%, C9nALS 28.3%; p=0.0186). There were no differences between cohorts in age at diagnosis, gender, limb weakness, respiratory symptoms, presentation with predominantly lower motor neuron signs or overall survival.DiscussionAnalysis of this ALS clinic cohort at a UK tertiary neurosciences centre adds to the small but growing understanding of the unique clinical features of patients with C9pALS. In the age of precision medicine with expanding opportunities to manage genetic diseases with disease-modifying therapies, clinical identification of such patients is increasingly important as focused therapeutic strategies become available.

A 62-year-old lady presented to hospital with thunderclap headache and was found to have a grade 1 subarachnoid haemorrhage due to ruptured anterior communicating artery (ACoA) aneurysm, treated by endovascular coiling. Two small coincidental left middle cerebral artery (MCA) aneurysms were managed conservatively.Follow-up imaging at 6 months showed only minor ischaemic changes. Routine 2 year follow up magnetic resonance angiography (MRA) showed the coiled aneurysm to be secure with unchanged coincidental MCA aneurysms but multiple new right cerebral hemisphere lesions with extensive perilesional oedema. These lesions showed punctate enhancement on contrast MRI. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging showed normal brain FDG update.The patient developed focal left-sided motor seizures, prompting readmission, and empirical treatment with corticosteroids, antibiotics and aspirin in addition to levetiracetam. Cerebral spinal fluid constituents were normal. Routine bloods, inflammatory markers and blood cultures were normal or negative, as was an echocardiogram. There were no further seizures, and subsequent improvement was noted in the right cerebral hemisphere imaging appearances.Foreign material emboli following endovascular coiling is described in the literature but, to our knowledge, its presentation in this manner with this latency has not been reported.

Background Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. Methods A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. Results Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline’s PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. Conclusions The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV.

In this article, we make the case that social epidemiology provides a useful framework to define the environment within gene–environment (G×E) research. We describe the environment in a multilevel, multidomain, longitudinal framework that accounts for upstream processes influencing health outcomes. We then illustrate the utility of this approach by describing how intermediate levels of social organization, such as neighborhoods or schools, are key environmental components of G×E research. We discuss different models of G×E research and encourage public health researchers to consider the value of including genetic information from their study participants. We also encourage researchers interested in G×E interplay to consider the merits of the social epidemiology model when defining the environment.

A summary genetic measure, called a “polygenic score,” derived from a genome-wide association study (GWAS) of education can modestly predict a person’s educational and economic success. This prediction could signal a biological mechanism: Education-linked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents’ position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother’s polygenic score predicted her child’s attainment over and above the child’s own polygenic score, suggesting parents’ genetics can also affect their children’s attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals’ family-oforigin environments and their social mobility.