bluuebunny/crossref_metadata_2025_split huggingface dataset:
230 A dog with a bone (marrow biopsy)
Authors: Li Vivien , Kapoor Mahima , Lunn Michael , Cwynarski Kate , Carr Aisling 
Published: March 2023

A 71-year-old woman presented with severe painful meningoradiculoneuritis progressing over 6 weeks. She had localised breast cancer treated 13 years prior. Differentials included a vasculitic or infiltrative process.Neurophysiology showed a patchy, predominantly proximal axonal process with widespread active denervation. MRI revealed asymmetrical enhancement of the brachial plexus, left S1 and multiple cranial nerves. CSFs were lymphocytic (normal T-cells predominant), with elevated protein and negative cytology. FDG-PET was negative for malignancy. BMAT showed no evidence of a lymphoproliferative condition.Left sural nerve biopsy was non-diagnostic. Right brachial plexus biopsy showed mixed T-/B-cell endoneurial inflammation not fulfilling criteria for vasculitis. She was stabilised with high-dose steroids and cyclophosphamide, followed by mycophenolate for inflammatory myeloradiculoneuritis. However, symptoms recurred when prednisolone was weaned.Although T-cell receptor gene analysis from the initial BMAT demonstrated clonal rearrangements, it was only when the same clones were identified on two repeat BMATs and CSF that T-cell neurolymphomatosis was diagnosed. Poor performance status precluded chemotherapy. She continued on prednisolone and cyclosporine for 3.5 years, before dying of sepsis.T-cell neurolymphomatosis is exceedingly rare. Clonality assessment can increase yield when other investigations including histology are non-diagnostic. This case highlights the value of repeated investigations when clinical suspicion is high.
238 Usefulness of concomitant peripheral nerve and muscle biopsy
Authors: Cooper Rebecca , Bunting Eva , Jaunmuktane Zane , Merve Ashirwad , Rosser Alex , Laura Matilde , Manji Hadi , Reilly Mary M , Lunn Mike P , Carr Aisling S 
Published: March 2023

A previous evaluation of concomitant nerve and muscle biopsy in the Centre for Neuromuscular Diseases, NHNN suggested that the addition of muscle (vastus lateralis) to nerve (sural) tissue examination did not improve diagnostic yield in suspected vasculitis. Here we assess it may be beneficial in other circumstances.We reviewed diagnostic yield from combined nerve and muscle biopsies performed between 2013 and 2018. Basic demographic, clinical and histological information was collected retrospectively from the complete list of locally performed biopsies during the study period.230 nerve and 49 muscle biopsies were performed on 223 patients. 26 superficial peroneal/peroneus brevis, 20 sural/vastus lateralis, and 3 other combinations. Overall nerve biopsy was diagnostic in 38% of individuals; confirming clinical suspicion in 64.5%. The addition of muscle tissue did not provide histological evidence of vasculitic pathology in any case. However, 8 cases provided evidence of co-existent muscle pathology (myopathic changes), with mitochondrial changes in 4/8 and lipid abnormalities in 2/8 informing further genetic tests and leading to diagnosis in 3/8. 5/5 TTR amyloidosis and 2/3 neurolymphomatosis cases showed histopathology in both tissues.This analysis suggests that in certain clinical situations the addition of muscle biopsy may be helpful in the investigation of neuropathy.
11.27 Late onset multiple sclerosis in north wales
Authors: Karthikeayan Venkatraman , Copeland Yvonne , Fearn Catriona , Whittam Daniel , Elsone Liene , Huda Saif , Jacob Anu 
Published: March 2023

IntroductionMS patients who have their first symptom onset after 50 years of age are defined as Late onset Multiple Sclerosis (LOMS). Our study analyses the clinical profile of patients with LOMS in North Wales region of United KingdomMethods and materialsA retrospective medical record review of all patients attending regional MS clinic in North Wales, based at Glan Clwyd Hospital (2007–2018) was done.ResultsOf 648 patients with MS, 60 (9.2%) had LOMS. Mean age at onset was 55.3 years and the M: F ratio was 1:1.85. 63% and 28% of LOMS were progressive and relapsing types respectively.At a mean of 7.8 years follow up, 31% of relapsing patients converted to SPMS. Majority of LOMS presented with gait difficulties-67% (97% in Progressive MS and 23% in relapsing).Only 15% of the relapsing MS patients were eligible or chose DMT.ConclusionsLOMS forms at least 9% of this MS cohort with majority presenting with a progressive course at diagnosis. The high proportion of LOMS in this cohort may reflect, delayed reporting of symptoms or slower access to care.
15.33 AVXS-101 in presymptomatic spinal muscular atrophy (SMA)
Authors: Strauss Kevin A , Swoboda Kathryn J , Farrar Michelle A , McMillan Hugh J , Parsons Julie , Krueger Jena M , Iannaccone Susan T , Chiriboga Claudia A , Kwon Jennifer M , Saito Kayoko , Scoto Mariacristina , Kausar Imran , Schultz Meredith , Kernbauer Elaine , Farrow Marcia , Ogrinc Francis G , Kavanagh Sarah , Feltner Douglas E , McGill Bryan E , Spector Sidney A , L’Italien James , Sproule Douglas M , Muntoni Francesco 
Published: March 2023

BackgroundOnasemnogene abeparvovec (AVXS-101) is a gene-replacement therapy that treats the genetic root cause of SMA, biallelic survival motor neuron 1 gene (SMN1) deletion/mutation. In a phase 1 study, AVXS-101 improved survival and motor function of symptomatic SMA type 1 patients. In SPR1NT (NCT03505099), AVXS-101 is being evaluated in presymptomatic newborns with SMA.MethodsSPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2xSMN2or 3xSMN2. Asymptomatic infants aged ≤6 weeks receive a one-time, intravenous AVXS-101 infusion. Safety and efficacy are assessed through 18 or 24 months for patients with 2x or 3xSMN2, respectively. Primary outcomes are independent sitting ≥30 seconds (2xSMN2) or assisted standing (3xSMN2).ResultsAs of 8 March 2019, 18 infants aged 8–40 days received AVXS-101 (11 female; 8 with 2xSMN2; 9 with 3xSMN2; 1 with 4xSMN2). Among patients with 2xSMN2, mean CHOP-INTEND at baseline was 44.0 points, which increased by 14.4 points at 3 months (n=7); 6/8 patients scored ≥60 points; 3/8 reached maximum score. 4/8 patients sat unassisted; all ages of sitting milestone achievements were within the WHO range (1st–99th percentile: 3.8–9.2 months).ConclusionsPreliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.
250 AVXS-101 phase 3 study in spinal muscular atrophy type 1
Authors: Day John W , Chiriboga Claudia A , Crawford Thomas O , Darras Basil T , Finkel Richard S , Connolly Anne M , Iannaccone Susan T , Kuntz Nancy L , Peña Loren DM , Schultz Meredith , Shieh Perry B , Smith Edward C , Kausar Imran , Feltner Douglas E , Ogrinc Francis G , Ouyang Haojun , Macek Thomas A , Kernbauer Elaine , Muehring Lynlee M , L’Italien James , Sproule Douglas M , Kaspar Brian K , Mendell Jerry R 
Published: March 2023

BackgroundOnasemnogene abeparvovec (AVXS-101), a one-time intravenous gene-replacement therapy, treats the genetic root cause of spinal muscular atrophy (SMA). In the phase 1 study, AVXS-101 dramatically improved survival, motor function, and motor milestone achievement in SMA type 1 (SMA1) patients.MethodsSTR1VE is a phase 3, multicenter, open-label study (NCT03306277) in SMA1 patients <6 months (bi-allelic survival motor neuron 1 gene [SMN1] mutations/deletions, 2SMN2copies). Primary outcomes are independent sitting ≥30 seconds at 18 months of age, and survival (no death/permanent ventilation) at 14 months. Secondary outcomes include ability to thrive and ventilatory support at 18 months. Exploratory outcomes include CHOP-INTEND and Bayley-III.ResultsEnrollment is complete (22 patients dosed). Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support. Mean baseline CHOP-INTEND: 32.6 (17.0–52.0) points; increased by 6.9 (-4.0–16.0), 9.2 (0–18.0), and 11.7 (-3.0–23.0) points at 1, 2, and 3 months; independent sitting: 11/22 patients; survival at 13.6 months: 13/15 (87%) (8 March 2019 datacut).ConclusionsPreliminary data from the AVXS-101 phase 3 study show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
256 Thrombectomy in clinical practice, patient selection factors
Authors: Stahl Rose , Littleton Edward , Nader Kurdow 
Published: March 2023

BackgroundSuccessful stroke treatment with mechanical thrombectomy (MT) involves appropriate patient selection and rapid re-canalisation. Queen Elizabeth Hospital Birmingham provides MT to patients presenting to our own Emergency Department (group A) or transferred from other regional hospitals (group B).AimsTo assess timelines in MT delivery and patient selection factors which may affect outcomes.MethodsData from all stroke patients receiving MT in 2015–2018 were collected retrospectively. Change in NIHSS score (at presentation and at 24 hours) and procedure success (TICI score 2b or 3) were recorded.Results102 patients underwent MT (group A=43, group B=59).Mild initial deficit (NIHSS <6) and any pre-existing disability (Modified Rankin >0) were associated with worsening NIHSS scores (+2 and +13.5 respectively). >80% of these patients were in group A, indicating a tendency to select local patients with radiological evidence of proximal MCA thrombus or with dysphasia but mild NIHSS, whereas NIHSS-based patient selection was more strictly applied for group B. We found no differences in outcome dependent on delivery of MT inside/outside the 6-hour window.ConclusionsIn the absence of clinical trial evidence for MT in patients with low NIHSS, caution in selecting these patients for MT is advised.
258 Can clinical experts agree on a diagnosis of TIA?
Authors: Lee Seong Hoon , Aw Kah Long , McVerry Ferghal , McCarron Mark 
Published: March 2023

BackgroundTransient ischaemic attacks (TIAs) are sudden onset focal neurological deficits of vascular pathogenesis that resolve within 24 hours. TIAs remain a diagnostic challenge due to its clinical heterogeneity and lack of biomarkers. Previous studies on the diagnostic accuracy of TIAs by non-specialists have used TIA experts (neurologists or stroke physicians) as the gold standard. However, the inter-rater variability in TIA diagnoses among these experts is not firmly established. Here we conduct a meta-analysis of the inter-rater variability of TIA diagnosis between experts.MethodsWe performed a systematic review of studies from 1988 to present day using MEDLINE, EMBASE, and PubMed. Two reviewers independently screened for eligible studies and extracted inter-rater variability measurements using Cohen’s Kappa scores between expert clinicians.Results14 original studies reporting on variability in TIA diagnosis for 15,907 patients were found. Meta-analysis revealed an overall agreement between experts of κ=0.73 (95%CI 0.63–0.84)ConclusionsOverall agreement between experts is good for TIA diagnosis, but variation still exists for a sizable proportion of cases. Further research into reliability of the accepted gold standard as well as alternative clinical, imaging or blood biomarkers are required given the important clinical implications for making a TIA diagnosis.
259 Use of internet connected cloud devices in stroke rehab-experience with a patient
Authors: Dey K , Das S 
Published: March 2023

We provided Alexa devices-Amazon Echo Show and Echo Spot to a 56- year old patient recovering from an ischaemic stroke at home. Amazon Echo device is a WiFi connected device driven by Alexa, a voice assistant. We trained our patient on the use and control of the devices using her voice and provided technical know how. Once set up, she was able to use the voice control to perform several tasks-listening to newslistening to music and radioplaying sounds for meditationturning on and off lightssetting up alarms for medicationssetting up times for doing scheduled exercisemaking hands free phone callsThis was especially useful when her carer was not present by her side. Later on we added Amazon cloud cam to the set up so that family members could remotely monitor her activity.She was able to make the physiotherapy sessions fun and interesting with the help of apps running on the devices upon voice prompts.In the emerging economies the joint family structure is breaking down. The relatives working as informal carers are disappearing fast. The main care is often provided by the privately hired nurses or health care assistants provided by local agencies. The cost of such private care is high. In this background, the voice activated cloud devices could play a significant role in the rehabilitation following a stroke.
09.00 Saved by the skin of his teeth: a job well done!
Authors: Jaffer Fatima , Sibtain Naomi , Holmes Paul 
Published: March 2023

A 31-year-old former Game Ranger from South Africa presented with subacute onset parieto-occipital headache, photophobia, and vomiting, followed by diplopia, bradykinesia and progressive unsteadiness. There was a history of neonatal eczema, recurrent skin abscesses, osteomyelitis, tuberculosis, hepatitis A, and Rickettsia.On examination he had meningism, papilloedema, bilateral sixth nerve palsies, left lower motor neurone facial weakness and left upper limb pyramidal weakness. He was areflexic with normal sensation. Mild bilateral extrapyramidal signs, postural instability and gait initiation failure were observed. During admission, he developed acute left lumbar polyradiculopathy. Deep set eyes, coarse facial features, bony deformities, and retention of primary teeth were noted on examination.MRI showed bilateral globus pallidus necrosis, basal leptomeningeal enhancement, and multilevel lumbar root thickening and enhancement.CSF culture confirmed Cryptococcus gattii infection and an apical lung opacity seen on chest x-ray was consistent with a cryptococcoma. Twelve months of antifungal therapy was commenced with full symptom resolution.HIV was negative. Immunological tests revealed elevated IgE levels and IL-17 deficiency. A de novo mutation in the STAT3 gene (c.1241G>C; p.Arg414Thr) confirmed the diagnosis of autosomal dominant Hyperimmunoglobulin E (Job’s) syndrome.We discuss Job’s syndrome, the challenges in managing cryptococcal infection and immunological testing in non-HIV patients.
267 Motor system biomarkers in amyotrophic lateral sclerosis
Authors: Edmond Evan C , Menke Ricarda , Proudfoot Malcolm , Talbot Kevin , Stagg Charlotte J , Turner Martin R 
Published: March 2023

Therapeutic options for the fatal neurodegenerative disorder ALS are urgently needed. Trials rely on blunt outcome measures such as survival because of a lack of objective markers of disease activity and progression. The C9orf72 hexanucleotide repeat expansion (HRE) is associated with 10% of all cases of ALS, bringing the near-future prospect of oligonucleotide therapeutic trials.The development of biomarkers will reduce trial duration and cost by providing more sensitive measures of disease-slowing and/or evidence of target engagement. ALS is consistently associated with cortical hyperexcitability (CE), based on transcranial magnetic paired stimulation (TMS) to induce short-interval cortical inhibition (SICI). This project builds on the potential shown by non-invasive neuroimaging to provide biomarkers in ALS. We develop functional neuroimaging biomarkers that reflect the phenomenon of CE, including markers of pre-symptomatic pathology.Affected ALS patients carrying the C9orf72 HRE and a group of asymptomatic carriers are studied using a combined functional MRI (FMRI and MRS) and neurophysiological (MEG) readout. This study offers novel non-invasive biomarkers based on a consistent neurophysiological mechanism in ALS to advance therapeutic development
269 Prevention of hypertensive injury to the brain by intensive treatment in intracerebral haemorrhage (PROHIBIT-ICH): protocol for a randomised controlled trial of telemetric home BP monitoring
Authors: McGurgan Iain , Butt Shahena , Silver Louise , Werring David , Rothwell Peter 
Published: March 2023

BackgroundIntracerebral haemorrhage (ICH) accounts for about 10% of strokes in the UK and is a major cause of severe disability and death. Sustained post-acute blood pressure (BP) management arguably holds the most potential to improve long-term prognosis, but there have been no trials to guide the optimal strategy for BP lowering after ICH. Telemetric home BP monitoring is a promising intervention to improve control.Methods112 adult survivors of hypertension-related ICH across multiple UK sites will be randomised to intensive telemetric home BP monitoring-guided treatment (intervention) to achieve a target of <120/80 mmHg or standard care (control).OutcomesEfficacy: the magnitude of difference in BP at 3 months in the intervention arm versus the control arm compared with baseline measuresFeasibility: consent rate; dropout rate from the intervention prior to 1 month; patient approval of the monitoring processSafety: serious adverse events related to reducing BP in the intervention armConclusionThe BP monitoring component of PROHIBIT-ICH will determine whether a strategy of intensive BP treatment guided by telemetric monitoring for an extended period of time after spontaneous ICH is feasible, safe and effective in reducing BP.
270 Queen square test of auditory cognition (QSTAC): diagnosing dementia with sound
Authors: Johnson Jeremy CS , Hardy Chris JD , Utoomprukporn Nttawan , Rohrer Jonathan D , Bamiou Doris-Eva , Warren Jason D 
Published: March 2023

Hearing impairment has emerged as a potent association of cognitive decline in dementia and a promising treatment target. To realise this promise, we need to resolve fundamental questions concerning the roles of peripheral versus central auditory deficits in different dementias, which hearing measures best capture cognitive symptoms and disability and whether hearing measures predict clinical course and brain atrophy.Using pre-existing and novel stimuli, created at the Dementia Research Centre, University College London, we have designed a unique test battery to assess central auditory function. This will be used to ‘phenotype’ central auditory dysfunction in Alzheimer’s disease (AD) and the primary progressive aphasias (PPA) and compare them with controls as well as across disease groups.This will provide new tools to determine how auditory measures relate to clinical symptoms and daily-life disability and care burden. Using voxel-based morphometry (VBM) we also aim to correlate test measures with regional brain degeneration and measure how hearing deficits predict longitudinal clinical course.Here we present the make-up of the battery, explaining the motivation behind component tests and how they probe different stations of the auditory hierarchy. We also make predictions of likely group-specific outcomes, based on neuroanatomical disease predilection.
272 Inherited peripheral neuropathies: analysis of PDXK gene identifies a new treatable disorder
Authors: Chelban Viorica , Wilson Matthew , Zanetti Natalia , Zamba-Papanicolaou Eleni , Conte Maria , Cordivari Carla , Mills Philippa , Wood Nicholas , Clayton Peter , Houlden Henry 
Published: March 2023

Polyneuropathies are amongst the most common neurological conditions worldwide affecting over 20 million people. However, 40% of patients with primary polyneuropathies have no disease-causing mutation identified.We investigated patients with gene-negative primary polyneuropathies using a combination of whole genome sequencing, homozigosity mapping and segregation analysis. Pathogenicity was confirmed via enzymatic assays and mass spectroscopy on recombinant protein and patient-derived fibroblasts, plasma and erythrocytes. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the ATP binding.We report that biallelic mutations in human PDXK are associated with primary axonal polyneuropathy and optic atrophy. Pyridoxal kinase (PDXK) is involved in converting vitamin B6 to its active form, pyridoxal 5’-phosphate (PLP). We show that PDXK mutations lead to disease via decreased plasma PLP concentrations. Our functional studies revealed conformational rearrangement in the mutant enzyme around the kinase ATP-binding pocket with impaired PDXK ability to bind ATP and leading to reduced erythrocyte PDXK activity. We show that both the human clinical picture and biochemical profile in PDXK mutations are rescued by PLP supplementation. Patients regained their ability to walk independently. Furthermore, treatment-led normalisation of plasma PLP levels, correlated with reduction of neurofilament light chain concentrations, a biomarker of axonal breakdown.In conclusion, biallelic mutations in human PDXK are associated with a novel disorder leading to treatable primary axonal polyneuropathy and optic atrophy and identifies PLP as therapeutic target.
273 Risk of recurrent stroke in patients with intracranial stenosis: a population based study
Authors: Hurford Robert , Wolters Frank J , Li Linxin , Kuker Wilhelm , Rothwell Peter M 
Published: March 2023

IntroductionIntracranial stenosis (ICS) is believed to convey a high risk of recurrent ischaemic stroke, but the SAMMPRIS trial failed to show superiority of ICS stenting over intensive medical management. However, the risk of recurrent stroke in the medical arm was low, leading to questions about generalisability. We studied the long-term risk of recurrent stroke in patients with ICS in a population-based setting.MethodsPatients with TIA or minor stroke [NIHSS £3] underwent MRA in the Oxford Vascular Study. Stroke risk was determined by face-to-face follow-up out to 7-years with a policy of intensive medical treatment and no stenting.ResultsOf 1026 patients (686-TIA; 340-stroke) who underwent MRA, 210 (20.5%) had >50% ICS (TIA=18.5%; stroke=24.4%). Compared to patients with no ICS, risk of recurrent ischaemic stroke was not increased in those with recently symptomatic ICS (HR=1.36, 95%CI=0.54–3.44) or in those with any ICS (1.28, 0.70–2.35) Moreover, the absolute risk of stroke in those with recently symptomatic ICS was lower than reported in the medical arm of SAMMPRIS (2-year risks: 1.6%, 0–4.7 vs 14.1%, 10.1–19.4)ConclusionThe ‘real-world’ prognosis of patients with ICS on intensive medical treatment is more benign than supposed, indicating that the findings of SAMMPRIS are generalisable.
09.24 Phone a friend?
Authors: Minton Thomas , Fuller Geraint , Rinaldi Simon , Fehmi Janev , Bosnell Rose , Barton Eleanor 
Published: March 2023

A 72-year-old man with type 2 diabetes mellitus was admitted under nephrology with malaise. He was diagnosed with acute kidney injury secondary to urinary retention and hydronephrosis. Over 10 days during this admission he developed progressive symmetrical limb paraesthesia and weakness with areflexia.Neurophysiological studies demonstrated a severe demyelinating polyneuropathy with widespread motor slowing and prolonged distal motor latencies. CSF was acellular with a protein of 5.9 g/L. He was treated with IV immunoglobulins and stabilised for 2 weeks. He then deteriorated over the next four weeks despite IV methylprednisolone, oral corticosteroids and 5 cycles of plasma exchange. He had profound limb weakness (0/5) and required ventilation. He had hypoalbuminaemia, with 1.5 g proteinuria consistent with a nephrotic syndrome.We phoned a friend.IgG4 anti–contactin-1 (CNTN1) antibodies were identified in serum with a CNTN1 at 1:1600.He received 4 cycles of Rituximab. After 6 weeks he was off ventilation with grade 4 power in both arms.Recently autoantibodies against node of Ranvier proteins have emerged in a subset of patients with CIDP. These patients have a homogenous clinical phenotype with an aggressive polyneuropathy, proteinuria and poor response to conventional therapy, but seem to respond to other agents, including Rituximab and Cyclophosphamide.