BackgroundPodcasts are increasingly used as a learning resource in medicine. However, evidence illustrating their impact is limited.ObjectiveTo assess use and utility of podcasts in IMT ...induction/introduction to specialist neurology services in NHNN.Method: A survey of the 2019/20 IMT cohort revealed 85.7% to be ‘not confident’ in the management of patients with neurological disorders at induction. The same proportion had no previous neurology clinical experience. Podcast format, topics and content were derived from this feedback.We developed 5 open-ended questions on 10 topics (neuropathy, PLEX, DBS, seizure management, IVIg, CSF analysis, MG, GBS, myelopathy and demyelination) and recorded live Q&A sessions with specialist consultants and nurses after approval by UCLH comms team. The podcasts were launched 1 week pre- induction August 2020 on the NHNN education website via a link sent to all new starters. The website is accessible by IMT and specialist trainees after registration with a nhs.net email.A repeat survey was performed 1month post-induction and download data accessed from the website in January 2021.Results/Conclusion 85.71% felt ‘confident’ in the management of neurological conditions. The podcasts have been played 560 times in 6 months, 453 times outside London suggesting transferable utility beyond NHNN.siqbal2482@gmail.com|ABN Bursary65
A 17yo Filipino man presented with a rapid onset meningoencephalitic illness, dysautonomia (cardiovas- cular and genitourinary), neuropsychiatric, myoclonus and cerebellar symptoms. Examination ...revealed lower limb proprioceptive loss and areflexia.CSF showed lymphocytosis, hypoglycorrachia and glial fibrillary acidic protein (GFAP) antibodies. MRI head was normal on D4 and D11, but repeat imaging (D25) showed a reversible splenial T2 hyperintensity, which improved by D40. Neurophysiology showed a sensory neuronopathy. Autonomic function testing confirmed sympathetic cardiovascular failure. Pupillometry showed bilateral Horner’s indicating further sympathetic deficit. Dynamic sweat testing showed evidence of post-ganglionic sudomotor dysfunction.He received treatment with IV methylprednisolone followed by a prednisolone taper with good response.GFAP is an intracytoplasmic protein, found in astrocytes, unmyelinated nerve fibres as well as dorsal root ganglia, in keeping with our patient’s clinical presentation. However, literature review shows signifi- cant heterogenicity in presentation and pathogenicity of the GFAP antibody is unclear, as it could be a bystander protein.Dysautonomia is reported in 24–57% of GFAP astrocytopathy, but has not been well-characterised. We describe the first in-depth autonomic testing in GFAP astrocytopathy which shows sympathetic cardio- vascular failure and evidence of sudomotor post-ganglionic dysfunction.yeeyen.goh@nhs.net|ABN Bursary
This is a practical guide to diagnosing and managing multiple system atrophy (MSA). We explain the newly published Movement Disorders Society Consensus Diagnostic Criteria, which include new ...'Clinically Established MSA' and 'Possible Prodromal MSA' categories, hopefully reducing time to diagnosis. We then highlight the key clinical features of MSA to aid diagnosis. We include a list of MSA mimics with suggested methods of differentiation from MSA. Lastly, we discuss practical symptom management in people living with MSA, including balancing side effects, with the ultimate aim of improving quality of life.
Objective
There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist ...that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI).
Methods
We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy.
Results
Quantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI‐derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection.
Interpretation
Patients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group‐based findings to individualize prediction of patient outcomes. Ann Neurol 2015;77:760–774
Background:
Azathioprine (AZA) is a common immunosuppressive drug used for relapse prevention in neuromyelitis optica (NMO).
Objectives:
The objective of this paper is to assess efficacy, ...tolerability and retention of AZA in a large NMO cohort.
Methods:
We conducted a retrospective review of medical records of 103 aquaporin-4 antibody-positive NMO and NMO spectrum disorder (NMOSD) patients treated with AZA.
Results:
This is the largest reported cohort of AQP4-Ab positive patients treated with AZA. Eighty-nine per cent (n = 92) had reduction in median annualised relapse rates from 1.5 (IQR 0.6–4.0) to 0 (IQR 0–0.27, p < 0.00005) with treatment. Sixty-one per cent (n = 63) remained relapse free at a median follow-up of 18 months. Neurological function improved or stabilised in 78%. At last follow-up, treatment was discontinued in 46% (n = 47). Of these, 62% (n = 29) were because of side effects, 19% (n = 9) because of death, 15% (n = 7) because of ongoing disease activity, and 2% (n = 1) because of pregnancy. Using Kaplan-Meyer curves, we estimate that 73%, 58%, 47% and 33% of patients will remain on AZA for longer than one, three, five and 10 years, respectively, after initiation of treatment.
Conclusions:
AZA is a modestly effective treatment for NMO. However, many patients discontinue AZA over time and this seems to reflect poor tolerability more than lack of efficacy.
Background
Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) show a high prevalence and rapid progression of dysphagia, which is associated with ...reduced survival. Despite this, the evidence base for gastrostomy is poor, and the optimal frequency and outcomes of this intervention are not known. We aimed to characterise the prevalence and outcomes of gastrostomy in patients with these three atypical parkinsonian disorders.
Method
We analysed data from the natural history and longitudinal cohorts of the PROSPECT‐M‐UK study with up to 60 months of follow‐up from baseline. Survival post‐gastrostomy was analysed using Kaplan–Meier survival curves.
Results
In a total of 339 patients (mean age at symptom onset 63.3 years, mean symptom duration at baseline 4.6 years), dysphagia was present in >50% across all disease groups at baseline and showed rapid progression during follow‐up. Gastrostomy was recorded as recommended in 44 (13%) and performed in 21 (6.2%; MSA 7, PSP 11, CBS 3) of the total study population. Median survival post‐gastrostomy was 24 months compared with 12 months where gastrostomy was recommended but not done (p = 0.008). However, this was not significant when correcting for age and duration of symptoms at the time of procedure or recommendation.
Conclusions
Gastrostomy was performed relatively infrequently in this cohort despite the high prevalence of dysphagia. Survival post‐gastrostomy was longer than previously reported, but further data on other outcomes and clinician and patient perspectives would help to guide use of this intervention in MSA, PSP and CBS.
Long-range chromatin contacts between specific DNA regulatory elements play a pivotal role in gene expression regulation, and a global characterization of these interactions in the 3-dimensional (3D) ...chromatin structure is imperative in understanding signaling networks and cell states. Chromatin Interaction Analysis using Paired-End Tag sequencing (ChIA-PET) is a method which converts functional chromatin structure into millions of short tag sequences. Combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors. Here, we describe the detailed procedures of the ChIA-PET methodology, unraveling transcription-associated chromatin contacts in a model human cell line.
Aims:
Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by ...speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis.
Methods and results:
LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I–II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 0.66–0.83;
P
< 0.001) and calibration (Hosmer-Lemeshow χ
2
= 6.37;
P
= 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 3.3, 42.2 months. Patients with LV-GLS > −15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < −21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between −21.0 and −15.0% (log-rank
P
< 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e′.
Conclusion:
LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.
The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in ...relation to clinical and echocardiographic variables and N-terminal pro-B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction > 50%.
LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk.
Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range IQR, 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value.
In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.
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