bluuebunny/crossref_metadata_2025_split huggingface dataset:
212  Preventing blindness for patients with optic disc swelling: improving care using transformative new technology
Authors: Braithwaite Tasanee , Wu Kit , Saunders Katherine , Teo James , Yorke Richard , Moosai Shivir , Brex Peter , O’Sullivan Eoin 
Published: May 2022

IntroductionOptic disc swelling (ODS) is a non-specific sign with clinical consequences ranging from benign to irreversible blindness. It is often a challenge to manage: patients present to different specialities and there is no unifying clinical pathway.Objectives/Aims1. to identify all patients presenting to King’s College Hospital with ODS using a translational informatics digital platform (Cogstack); 2. to develop an electronic care pathway with an integrated decision support tool.MethodWe used a digital translational informatics platform called Cogstack, developed in-house by King’s College London, to search 1.4billion EPR data files during a 12-week period. We engaged an MDT team to developed a clinical decision support tool, containing ‘red flag’ symptoms and signs for patients presenting with ODS.ResultsCogstack identified 407 patients with ODS in a 12-week period. Of these, 15% were new cases, 24% were not seen or referred to (neuro)/ophthalmology.The care pathway ensured that patients received timely investigation and initial management facilitated by transformative new technology. This translated into saving time, standardising care and enhanced patient safety.ConclusionThis technology-facilitated care pathway provides a proof of concept for other institutions. Its development supports the topical agenda of NHS improvement, to ‘Get it Right First Time’, and the aim to deliver a value-based healthcare.kitwu@doctors.org.uk
214  DCE-MRI in neurological disease: how to do it
Authors: Varatharaj Aravinthan , Darekar Angela , Cramer Stig P , Larsson Henrik BW , Galea Ian 
Published: May 2022

MRI with gadolinium-based contrast agent is widely used in clinical practice and is a key tool for the diagnosis and monitoring of diseases such as multiple sclerosis. Dynamic contrast-enhanced MRI (DCE-MRI) is an advanced technique which maps the time course of T1 signal enhancement. Quantitative informa- tion regarding tissue properties can be extracted, providing additional utility compared to conventional contrast MRI. No further contrast injection is required, and the impact on total scan time can be minimal. Maps of blood-brain barrier permeability can be produced, with an ability to detect leakage well below the threshold of conventional MRI. This practical poster outlines a step-by-step protocol for setting up brain DCE-MRI, analysing the data with minimal user input, and incorporating it into research and future clinical practice. Common pitfalls and their solutions are addressed. The information is not vendor-specific so can easily be applied to any MR hardware.a.varatharaj@soton.ac.uk
215  Interstitial fluid drainage along cranial nerves in humans
Authors: Varatharaj Aravinthan , Gawne-Cain Mary , Galea Ian 
Published: May 2022

Brain interstitial fluid (ISF) drainage plays an important role in neurological disease. A complete picture of ISF drainage pathways is still being pieced together. Most current data are from animals not humans. ISF may enter the cerebrospinal fluid (CSF), which then leaves via arachnoid granulations, dural lymphatics, the cribriform plate, and cranial and spinal nerve root sleeves. CSF-independent routes of ISF drainage are less clear, and include the peri-arterial pathway, a controversial peri-venous route, and possibly brain- to-blood efflux across capillary endothelium. We present an exploratory study of the cranial nerve ISF outflow in humans, using high-resolution magnetic resonance imaging pre- and post- administration of gadolinium-based contrast agent, in a healthy volunteer and in a person with a large enhancing multiple sclerosis (MS) brainstem lesion. We reasoned that the high contrast concentration in the restricted interstitial space of the lesioned brainstem would highlight drainage pathways. While cranial nerve enhancement was present in both cases, it was most marked in the MS case. Through analysis of the spatial and temporal kinetics of enhancement we explore ISF drainage along cranial nerves and its dependence on transfer to CSF. These findings have implications for our understanding of brain ISF movement in health and disease.a.varatharaj@soton.ac.uk
221  Adhesive spinal arachnoiditis following subarachnoid haemorrhage mimicking a multiple sclerosis relapse
Authors: Farag Mena , Younus Osman , Hampton Timothy , Walsh Daniel , Silber Eli 
Published: May 2022

We present a case of adhesive spinal arachnoiditis, as a complication of a fall with traumatic subarach- noid haemorrhage, in a patient with progressive multiple sclerosis (MS).A 68 year-old woman with MS and spasticity, on Baclofen, Pregabalin and Nabiximols, was admitted following a fall. CT scanning demonstrated traumatic subarachnoid haemorrhage. She was admitted to the ITU initially and managed conservatively. Four months later, while undergoing inpatient rehabilitation, her condition deteriorated over six weeks with worsening paraparesis, neurogenic bladder and bowel dys- function with a C5–6 sensory level. She received steroids and underwent MRI of her neuroaxis. Imaging of her brain showed unchanged demyelinating lesions. Spinal imaging identified distortion with considerable T2 signal change in the cervical and thoracic regions, extending from the C5/6 to the T8/9 level, radiologi- cally consistent with a syrinx and myelopathy. It was felt her deterioration was not due to demyelination but secondary to cervicothoracic adhesions ventral to the cord as sequelae of cerebral haemorrhage. Following neurosurgical review, the patient underwent C4-T1 laminoplasty, adhesionolysis and expansion duraplasty with histopathology showing calcified connective tissue but the clinical outcome has thus far been poor. It is important to consider all the causes of deterioration in patients with progressive MS.menafarag@doctors.org.uk
Epilepsy-related causes of mortality in people with epilepsy: a systematic review of systematic reviews
Authors: Mbizvo Gashirai K , Bennett Kyle , Simpson Colin R , Duncan Susan E , Chin Richard FM 
Published: May 2022

PurposeThis systematic review of epilepsy mortality systematic reviews evaluates comparative risks, causes, and risk factors for all-cause mortality in people with epilepsy (PWE) to specifically establish the burden of epilepsy-related deaths.MethodMEDLINE and Embase were searched from conception to 26/12/2018 for systematic reviews evaluating all-cause mortality in PWE of any age. Two authors performed independent study selection, data extraction and quality assessment. Deaths were separated into epilepsy-related and unrelated using a recently published classification system. Outcomes included standardised mortality ratio (SMR) and mortality rate (MR) in a primary analysis of comparative risks, causes, and risk factors for all-cause and epilepsy-related mortality. A narrative synthesis of review findings was used to present results.ResultsSix moderate- or high-quality systematic reviews were included, evaluating 103 observational studies. All-cause mortality remained similarly high between 1950 and present (median SMR range 2.2–3.4). Africa had the highest SMR (median 5.4, range 2.6–7.2). SMRs were also higher for children < 18 years (median 7.5, range 3.1–22.4) than adults (median 2.6, range 1.3–8.7), and for epilepsy-related (median 3.8, range 0.0–82.4) than unrelated causes (median 1.7, range 0.7–17.6). Structural brain disease conferred the greatest risk for all-cause mortality (SMR range 24.0–41.5). Common epilepsy-related death causes included SUDEP, alcohol, drowning, pneumonia, and suicide.ConclusionPremature all-cause mortality remains a major problem in PWE globally, particularly in children and young adults, with most being epilepsy-related and potentially preventable.mbizvogkm@gmail.com
231  A Phase2 study evaluating safety and efficacy of prasinezumab in early Parkinson’s disease (PASADENA)
Authors: Pagno A , Anzures-Cabrera J , I Taylor K , Nikolcheva T , Zago W , Svoboda H , Doody R , Fontoura P , Umbricht D , Bonni A 
Published: May 2022

AimsTo describe the design and baseline data of the PASADENA studyMethodsPrasinezumab is a humanized IgG1 monoclonal antibody, which selectively binds aggregated α-synuclein, potentially reducing neuronal toxicity and slowing disease progression. This Phase 2 multicentre, randomised, double-blind, placebo-controlled study evaluated safety and efficacy of 4 weekly intravenous prasinezumab, at high dose (4500 mg/3500 mg body weight ≥65 kg/<65 kg) or low dose (1500 mg), versus placebo in patients with early Parkinson’s disease (NCT03100149). The study has two parts: a 52-week, double-blind, placebo-controlled treatment period (Part 1) followed by all-participants-on-active-treat- ment blinded extension for 52 weeks (Part 2). Primary endpoint is change in MDS-UPDRS total score from baseline at 52-weeks. Secondary endpoints include time to disease progression/disability and ipsilateral putamen DaT-SPECT uptakes. Skin biopsies determine the presence of pathological alpha-synuclein.Results316 patients enrolled in Austria, France, Germany, Spain and US (June 2017 - November 2018). Participant baseline data, including demographic characteristics, motor and non-motor symptoms, imaging and non-imaging biomarkers will be presented.ConclusionsPASADENA will provide an initial evaluation of prasinezumab’s effects on clinical progres- sion and loss of dopaminergic terminals in patients with early Parkinson’s disease, to inform future patient selection and Phase 3 study design. This study was funded by F. Hoffmann-La Roche Ltd. These data will be presented at Advances in Alzheimer’s and Parkinson’s Therapies gennaro.pagano@roche.com
241  Intrathecal antisense oligonucleotide delivery in HD: experience from RG6042 programme and best practice considerations
Authors: Leavitt Blair , Wild Edward , Bang Jee , Smith Anne , Schlegel Valerie , Schobel Scott , Nicotra Alessia , Landwehrmeyer Bernhard , Tabrizi Sarah ,   Mark Guttman on behalf of the OLE Investigator Network
Published: May 2022

Intrathecal administration involves the introduction of a drug substance into the subarachnoid space of the spinal column through a needle inserted into the lower back via lumbar puncture (LP) or via a special device. This procedure is used when drugs cannot cross the blood-brain barrier. Once injected, drugs are distributed within the cerebrospinal fluid from which they can access target tissues in spinal cord and brain.We use the intrathecal route to deliver RG6042 (previously HTTRx), an investigational, huntingtin mRNA- targeting antisense oligonucleotide to patients with Huntington’s disease (HD). Experience on intrathe- cal administration via LP has been gained in the RG6042 clinical development programme, including the double-blind, placebo-controlled, multiple ascending dose, Phase I/IIa study (NCT02519036) in 46 patients with early manifest HD and an open-label extension (NCT03342053) where patients received 120 mg RG6042 monthly or every other month in a 62-week treatment period (total procedures ≥400 in the programme to date).We will report on the experience with intrathecal drug delivery across these two studies and present information on suggested best practices in HD. Procedure-related videos will be shared, including use of spinal ultrasound. Finally, we will describe real-world considerations of implementing intrathecally delivered therapies in the clinical interface.alessia.nicotra@roche.com
242  A systematic review on the benefit of multidisciplinary care for patients with atypical parkinsonian syndromes
Authors: Niaz Usman , Ghosh Boyd , Donnelly Jade 
Published: May 2022

BackgroundAtypical Parkinsonian Syndromes (APS) are a rare group of neurodegenerative diseases comprising of Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Corticobasal Syndrome (CBS). There are current guidelines recommending Multidisciplinary team care in APS, but there have been no systematic reviews investigating this.MethodsSystematic searches of Medline, EMBASE, CINAHL and Open Grey were conducted and litera- ture which met the inclusion criteria were further screened.Results887 results were found across the 4 databases of which 192 remained after title screening and 70 after abstract screening. Of these 70 papers, 9 were included in the final review; data was synthesised from them along with the case studies and conference abstracts. The MDT papers demonstrated benefits of a multifaceted approach in the patients’ physical symptoms, along with an improved quality of life and reduced caregiver burden. However, the papers generally lacked methodological rigour, with a common deficiency being the absence of a control group and small sample sizes.ConclusionMDT care and its various facets seem to have benefits for patients suffering from APS, however the lack of statistical power in the current literature makes this conclusion difficult to draw. Further research of higher quality is recommended.un1g16@soton.ac.uk
247  Unusual presentation to an emergency department
Authors: Yoganathan Katie , Shah Apeksha , Marta Monica 
Published: May 2022

24-year-old man presented with drowsiness, worsening cognitive impairment and a mixed movement disorder. He was adopted as a child and was reported to be independent and working one year before admission, but progressively slow and unable to self-care since. On examination, he was cognitively impaired on all domains. He had increased tone, brisk reflexes and extensor plantars. There were dysto- nia-parkinsonian features of dystonic tremor and bradykinesia, slow saccades and oculomotor apraxia, along with motor impersistence. After exclusion of chronic infections, the working diagnosis was of a neurodegenerative movement disorder. Whilst there was no overt chorea, the differentials for juvenile Huntingdon’s disease (HD) were explored, and HD ultimately confirmed on genetic testing.Learning PointsJuvenile HD patients may not have chorea but may be rigid or parkinsonian.Slow saccades are most prominent in juvenile HD patients, even early.Involuntary movements are often partially suppressible, and mild chorea is easily overlooked. Look for involuntary head turns, fidgety movements of the fingers and toes, frequent blinking and odd facial expressions.Test for motor impersistence in these individuals.Gait may appear normal but tandem walk may bring out chorea, imbalance, or other problems.katieyoganathan@gmail.com
248  Tremor frequency can be measured using smartphone video
Authors: Williams Stefan , Fang Hui , Wong David C , Relton Samuel D , Alam Taimour , Alty Jane E 
Published: May 2022

Textbook descriptions of tremulous disorders typically mention the tremor frequencies characteristic of particular conditions, and determination of frequency can aid diagnosis. However, current clinical practice does not involve routine accelerometry or EMG for most tremulous patients, or use of smartphone accel- erometer, and the human eye cannot accurately measure tremor frequency.37 hand videos were recorded with smartphone camera from 5 essential tremor participants, 10 Parkin- son’s participants and 1 functional tremor participant, either showing a hand resting or held in posture. Tremor was simiultaneously measured using a commercially available accelerometer for clinical use (‘Natus Neurology’). The computing technique of ‘optical flow’ was applied to the smartphone video to measure pixel movement over time in two directions perpendicular to the long axis of the hand. Dominant frequencies were extracted from smartphone video optical flow and from clinic accelerometer data using fast Fourier transform.Bland-Altman analysis showed a mean of the difference in measurements between smartphone video (pixel optical flow) and accelerometer of 0.05 Hz (SD 0.16 Hz) with 95% confidence intervals for this mean difference of -0.26 Hz to +0.36 Hz.We demonstrate excellent agreement between our computing method for smartphone video tremor measurement and the gold standard of accelerometry. Our computing technique suggests that neu- rologists already have ‘point and press’ contactless equipment in their pocket that has the potential to augment routine clinical assessment by measuring tremor frequency.stefanwilliams@doctors.org.uk
249  Slow motion analysis of repetitive tapping (SMART) test: a new measurement of bradykinesia
Authors: Simonet Cristina , Lambert Christian , Rees Richard , Galmes Miquel Angel , Schrag Anette , Noyce Alastair 
Published: May 2022

ObjectivesTo develop a quantitative and objective tool to track repetitive tapping movements (RTM) using a slow motion capture and and compare patients with Parkinson’s disease (PD), REM-sleep behaviour disorder (RBD) and healthy controls (HC).MethodsWe assessed 48 participants (PD=20, RBD=5, HC=23). For each participant, RTM was recorded during 20s by a smartphone at 240 frames/s and then analysed using novel Python scripts. Two kinetic parameters were extracted: amplitude between fingers and frequency (number of taps/s). Linear regres- sion was used to determine the trend of movement over time.ResultsAlthough HC and RBD group (64.8±8.7yo and 68.4±8.2yo respectively) were older than PD group (58.1±12.8yo), the PD group performed the task significantly slower (p=0.0003) and with greater, but not significant, amplitude decrement than HC (p=0.5). RBD group was similar to PD group with significant slower RTM (p<0.0001) and non-significant amplitude decrement (p=0.3). SMART test was able to differentiate between all three groups, with a positive goodness of fit between PD and HC. The frequency parameter displayed 92.8% and 100% of sensibility (for 60.8% and 13% specificity with respective AUC=0.84 and 0.92) when comparing PD vs HC and RBD vs HC respectively.ConclusionsWe present an accurate way to quantify motor dysfunction in PD. Despite the small number of subjects, the fact that RBD group presented objective motor impairment could help with the early diagnosis at the prodromal phase of PD.15c6.simonet@qmul.ac.uk
256  FIREFISH part 2: risdiplam efficacy and safety in type 1 SMA
Authors: Baranello Giovanni , Servais Laurent , Masson Riccardo , Mazurkiewicz-Bełdzińska Maria , Khairi Muna El- , Fuerst-Recktenwald Sabine , Gerber Marianne , Gorni Ksenija , Darras Basil T ,   on behalf of the FIREFISH Study Group
Published: May 2022

FIREFISH (NCT02913482) is an ongoing, multicentre, open-label study of risdiplam in infants aged 1–7 months with Type 1 spinal muscular atrophy (SMA) and two SMN2 gene copies. FIREFISH aims to determine the efficacy and safety of risdiplam, an orally administered, centrally and peripherally distributed SMN2 pre-mRNA splicing modifier.FIREFISH Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. In FIREFISH Part 1 there have been no drug-related safety findings leading to withdrawal from the study following ≤30 (median 19) months of treatment (data-cut: 2nd July 2019). The confirmatory Part 2 (n=41) investigates the efficacy of risdiplam at the dose selected in Part 1. The primary efficacy endpoint is the proportion of infants sitting without support after 12 months on treatment, as assessed by Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition.Here we report efficacy and safety data from the confirmatory Part 2 of the FIREFISH study in participants who have received treatment with risdiplam for a minimum of 12 months. FIREFISH Part 2 will provide important data on the efficacy and safety of risdiplam in infants with Type 1 SMA.g.baranello@ucl.ac.uk
262  Limb-shaking linked to haemodynamic cerebrovascular disease
Authors: Cleaver Jonathan , Pope Laura , Mayo Thomas , Gbadamoshi Lukuman 
Published: May 2022

Limb-shaking transient ischaemic attacks (TIAs) are under-recognised in neurology and typically consists of involuntary movements resembling focal seizure-like activity. This form of TIA suggests severe carotid occlusive disease and is a warning for future strokes. Awareness can help avoid unnecessary medication, lifestyle measures and driving implications.We present a case of a 61-year-old patient who developed transient but persistent right upper limb shaking and syncope on turning to the left. He suffered a recent NSTEMI causing severe left ventricular dysfunction and associated anaemia. His ictal EEG was unremarkable. CT angiography and doppler ultrasound revealed severe left internal carotid artery stenosis. This suggested an underlying low-flow TIA and symptoms resolved with blood pressure optimisation and blood transfusions.Cerebrovascular events typically present with acute negative symptoms including loss of power, sensation, vision or speech. Alternatively, focal movement abnormalities would generally make the physician think of a non-cerebrovascular disorder. This stresses the need to raise awareness of limb-shaking TIAs to expedite diagnosis and instigate management strategies to lower future stroke risk.Along with secondary stroke prevention, attacks can be abolished by improving blood supply through optimisation of blood pressure, cardiac function and treating anaemia. Failing this, surgical revasculari- sation procedures should be considered.jkcleaver88@gmail.com
UK Multiple Sclerosis service audit of 70 centres: access to neuroradiology
Authors: Rog David , Hobart Jeremy , Matthews Joela ,   Raising the Bar 4 MS UK MS Study Group
Published: May 2022

IntroductionThe UK MS service audit builds upon GIRFT’s recommendation for disease-specific data. Here, we address access to Neuroradiology and Neuroradiologists.AimTo document the variability in access to Neuroradiology support, for UK MS Teams.MethodsWe asked all MS services to complete service questionnaires, supplemented with individual clinician interviews. Specifically, we asked about access to specialist Neuroradiologists, timeliness, out- sourcing and quality of MRI reporting and impact upon care.Results70 MS centres contributed MS service data, encompassing over 105522 people with MS, ≈85% of the UK MS population.76% of respondents felt at least half of MRI scans were reported in a timely manner, however 46% felt lack of access to MRI impacted upon the care they could offer. 68% of centres had scans reported by a neuroradiologist, however 63% of centres outsourced reporting and 69% of centres were concerned about reporting quality and the necessity for re-reporting.ConclusionsSignificant variability exists in the reporting of MS scans in the UK. This could impact upon access to, and use of, DMTs in centres and is increasingly important, given the availability of high efficacy DMTs, their sequencing and their potential adverse events.We recommend partnership working between MS Teams and Neuroradiologists to maximise dissemina- tion of expertise and minimise inefficiency in access to, reporting and discussion of, MS scans, at local, regional network and national levels.david.rog@srft.nhs.uk