bluuebunny/crossref_metadata_2025_split huggingface dataset:
085  Durvalumab-induced fatal myasthenia gravis
Authors: Dodd Katherine , Sussman Jonathan 
Published: May 2022

In recent years a number of immune checkpoint inhibitors (ICIs) have been developed for use in oncology, as treatment strategies increasingly focus on targeted therapies and immunotherapies. These include monoclonal antibodies against programmed cell death receptor-1 (PD-1), it’s ligand programmed death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). ICIs aim to prevent tumour cells from evading immune attack by downregulating T cell responses, and are proving to be clinically beneficial compared with standard chemotherapy in various advanced solid tumours. The main side effect is of immune dysregulation, causing or exacerbating pre-existing autoimmune conditions, such as myasthe- nia gravis (MG).We report a case of a 77 year old gentleman, treated with durvalumab (a PD-L1 inhibitor), for clear cell renal carcinoma, who developed severede novoMG, refractory to treatment, and died. We summarise the literature onde novoand exacerbations of pre-existing or subclinical MG with ICI use, and the high mortality rates seen with these. We believe that this is the first reported case of MG presenting in a patient with sole durvalumab use; without an additional ICI. It adds to the growing literature on the risks of severe ICI-related MG.katherine.dodd@srft.nhs.uk
086  Thymectomy in myasthenia gravis – a review of 36 patients
Authors: Sumangala Salini , Sehmbi Gurpreet , Payyappilly Sherin Jos , Kalkat Maninder , Jacob Saiju 
Published: May 2022

Guidelines set by the Association of British Neurologists recommend thymectomy for patients under the age of 45 with positive AChR antibodies or thymoma. Previous literature supports this, as thymectomy had been shown to improve clinical outcomes and reduce the need for immunosuppressive therapy. However, given the advancement of more successful immunosuppressive medicine the need for thymec- tomy can be questioned.Aim- to identify whether thymectomy aids Myasthenia Gravis (MG) management by reducing the need for immunosuppressive medication.Method- A retrospective evaluation identified 173 patients who had thymectomy in the UHB trust in the past 10 years, from which patients who had a primary indication of MG were extracted. Patient records were reviewed to collate data. Relevant trusts departments were contacted to fill the missing data.Results- 36 patients filled the criteria for inclusion. The average dose of prednisolone had an insignificant reduction by 22mg (STD- 10mg). 16 patients (44%) had a lower dose of prednisolone than prior to surgery. The average dose of Azathioprine had an insignificant increase since surgery by 18mg. There was also a reduction in the use of IVIG and plasma exchange.Conclusion- Thymectomy is unlikely to cause a significant reduction in the need for immunosuppressive therapy. Further research may be required to secure a larger sample size over a longer time period.saiju.jacob@uhb.nhs.uk
090  Clinical trials in amyotrophic lateral sclerosis: a systematic review
Authors: Wong Charis , Dakin Rachel , Chataway Jeremy , Swingler Robert , Weir Christopher , Stallard Nigel , Parmar Mahesh , Macleod Malcolm , Pal Suvankar , Chandran Siddharthan 
Published: May 2022

BackgroundAmyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disease. Despite decades of clinical trials, there remains a pressing unmet need for effective treatments. We reviewed past and present ALS clinical trials to understand the methodological challenges in trial design and delivery.MethodsTrial registry databases including clinicaltrials. gov, International Clinical Trials Registry Platform, European Union Clinical Trials Register, and PubMed were systematically searched to identify Phase II, Phase II/III and Phase III Clinical Trials of Investigational Medicinal Products (CTIMPs) assessing potential disease modifying treatments in ALS. Trials registered, completed or published during 2008–2019 were included.Results125 CTIMPs, evaluating 76 drugs, involving 15647 people with ALS (pwALS) were reviewed. Ten drugs were tested in three or more trials. Trials employed predominantly traditional two-arm designs; only 12 used novel designs. Median number of participants was 86. 40% of trials had an attrition rate ≥ 20%. There was a wide variation of primary outcome measures and primary endpoints used.ConclusionHistorically, limited participation of pwALS in trials, resources and outcome measures hindered definitive and timely evaluation of drugs in two-arm trials. We propose that future trials will need to be more flexible, scalable and acceptable to all stakeholders.charis.wong@ed.ac.uk
093  Tracheostomy in plw motor neuron disease – prolonged survival with continuous ventilation via a cuffed tube
Authors: Ramsay Michelle , Kaltsakas George , Howard Leo , Sheridan Shauna , Marino Phillip , Murphy Patrick , Hart Nick , Howard Robin 
Published: May 2022

The role of tracheostomy in the management of ventilatory failure due to motor neuron disease (MND) remains controversial. Although it is an effective alternative to non-invasive ventilation (NIV) in supporting ventilation, the risk of prolonged survival in the face of reduced quality of life is a concern.We present 25 patients living with (plw) MND who underwent tracheostomy. There were 16 males, the mean age was 64.0 yrs (36–83), 13 patients underwent tracheostomy prior to the diagnosis and could not be weaned, the mean duration of tracheostomy to death or December 2019 was 3.4 yrs (0.2–8.7). 19 patients required continuous ventilation using a permanently cuffed tube. All the patients became entirely dependant, and 8 had limited or no communication despite eye gaze or environmental control systems. 14 patients were in care homes and 11 required 24 hr support at home.Several patients expressed their desire to maintain invasive ventilatory support despite inevitable and progressively increasing dependence.Many plw MND become dependent on invasive ventilatory support before the diagnosis is established and may live for prolonged periods following tracheostomy despite total dependence. The use of tra- cheostomy in MND raises issues about the balance of patient autonomy, resource allocation and the role of medical professionals.robinhoward@nhs.net
097  An undisputed case of left hand weakness
Authors: Morrison Hamish , Walton Edward , Fox Mike , Stevens James 
Published: May 2022

IntroductionNeurogenic thoracic outlet syndrome (NTOS) is a rare and sometimes overlooked cause of upper limb pain, weakness and disability and presents to a range of different healthcare professionals. Here we present a case of severe NTOS with characteristic clinical, radiological and electroclinical findings.HistoryA 16 year old right-handed female presented with a two year history of progressive symptoms affecting her left hand. Initially she noticed weakness affecting initially the 4thand 5thleft digits which progressed to involve the whole hand. She described a burning sensation affecting the medial aspect of her left forearm at night.ExaminationExamination of the left arm revealed decreased bulk of the thenar, hypothenar and inter- ossei intrinsic muscles of the hand, power diminished to grade 4 in the left ADM, APB, FDIO and to grade 4+ in left EDC, and altered sensation in the T1 dermatome.InvestigationsA lordotic chest radiograph revealed bilaterally elongated C7 transverse processes, a finding confirmed on retrospective review of the brachial plexus MRI, which also revealed bilateral grade 1 cervical ribs and increased signal on STIR sequence of the left C8 and T1 nerve roots. Nerve conduction studies revealed electroclinical evidence of a left lower trunk brachial plexopathy.OutcomeThe patients neuropathic pain responded to low dose gabapentin. She was assessed at the Peripheral Nerve Injuries Unit at RNOH Stanmore and recently underwent successful left thoracic outlet decompression.hamish.morrison@nhs.net
099  High relapse rate with steroid monotherapy in non-systemic vasculitic neuropathy
Authors: Bunting Eva , Cooper Rebecca , Seral M , Manji H , Rossor A , Reilly MM , Lunn MP , Bennett D , Hadden R , Carr AS 
Published: May 2022

IntroductionHistorically, single tissue vasculitis has been managed with steroid monotherapy. Recent data from large longitudinal databases on systemic vasculitis suggest Non-Systemic Vasculitic Neuropathy (NSVN) has higher rates of relapse, recommending that more aggressive immunotherapy is employed.AimTo investigate the relapse rate in NSVN in response to steroid monotherapy.MethodsA retrospective case note review of clinically and/or pathologically defined cases of (Systemic Vasculitic Neuropathy) SVN and NSVN in two London specialist peripheral nerve centres, between 2005- 2012 and 2015 - 2019.Results32 cases of SVN and 34 cases of NSVN were identified. In each group 14 individuals were treated first-line with steroid monotherapy, and 8 with cyclophosphamide. 8 SVN and 9 NSVN cases received steroids plus azathioprine. 15/32 SVN and 13/34 NSVN relapsed after first-line therapy (10/14 and 9/14 on steroid monotherapy, 3/8 and 3/9 on steroids and azathioprine, 2/8 and 1/8 on cyclophosphamide). 10 individuals stabilised with the addition of azathioprine, 13 with cyclophosphamide and 4 with Rituximab.ConclusionThis representative case series suggests that steroid monotherapy is inadequate in the treatment of NSVN and supports an approach akin to that recommended in SVN, even if nerve is the only tissue clinically involved.e.bunting@nhs.net
Pregnancy outcomes in a dimethyl fumarate exposure registry
Authors: Hellwig Kerstin , Rog David , McGuigan Christopher , Chen Kun , Parks Becky , Jones Cynthia C 
Published: May 2022

IntroductionThe delayed-release dimethyl fumarate (DMF) label recommends use during pregnancy only if potential benefit justifies the potential risk. Given limited pregnancy data, United Kingdom (UK) and Ireland are enrolling DMF-exposed pregnant women into an ongoing international registry assessing pregnancy outcomes. Pregnancies end in live birth (62%), abortion (22%), and fetal loss (16%) in general, with similar rates in MS patients.MethodsPregnant women with MS exposed to DMF since the first day of their last menstrual period prior to conception/during pregnancy were included. The UK/Ireland Coordinating Centres liaise directly with patients and HCPs.ResultsAs of April 2019, 263 patients (14 patients from UK/Ireland) were enrolled. Of the 214 pregnancy outcomes (12 UK/Ireland) reported to date, 197(92%) were live births (12 UK/Ireland) and 17(8%) foetal loss. Of infants with known gestational age (n=197), 176(89%) births were full-term (12 UK/Ireland) and 18(9%) premature (<37 weeks). There were 16 spontaneous abortions (1 ectopic pregnancy), and 1 foetal death at ≥28 weeks of gestation. No molar pregnancies or infant or maternal deaths were reported. Seven(4%) infants (1 UK/Ireland) had confirmed birth defects.ConclusionNo safety signal was observed, consistent with MS and general populations. Support: Biogen; disclosures detailed on poster.david.rog@srft.nhs.uk
104  Acute mononeuritis multiplex in a patient with plasma cell leukaemia
Authors: Poole Olivia , Midgley Laura , Siddiqui Sarah , Flores Lorena , Delaj Laura , Hadden Robert , Alkufri Fadi 
Published: May 2022

A 74 year old male with a history of plasma cell leukaemia, treated with VMP (bortezomib, melphalan, prednisolone) presented with a 2 week history of lumbar back pain and weakness of the hands and ankles.Clinical examination confirmed asymmetric weakness in the hands and ankles. Sensory examination was initially normal, reflexes preserved and plantars mute. Other than the known IgG paraproteinaemia and longstanding hyponatraemia, bloods, including a vasculitis screen, were unremarkable. MRI brain and spine were non-contributary. CSF examination revealed paired bands consistent with the presence of an IgG paraprotein, but was otherwise bland. Nerve conduction studies showed a severe sensorimotor axonal neuropathy.The patient was treated with plasma exchange followed by IV methylprednisolone but continued to progress developing more proximal weakness and sensory loss to the knees and elbows, with loss of deep tendon reflexes within 2 weeks. Sural nerve biopsy showed axonal degeneration but no vasculitis or malignant infiltration. The patient became increasingly fatigued and cachectic and the decision was made jointly with the haematologists to palliate.Plasma cell leukaemia is a rare and aggressive subtype of multiple myeloma with a poor prognosis which has been associated with malignant nerve infiltration. Bortezomib may also cause a peripheral neuropathy.o.poole@nhs.net
105  Broadening the clinical spectrum of bortezimib induced peripheral neuropathy: 4 illustrative cases
Authors: Grundy Kristina , Keh Ryan , Power Rachael , Gosal David , Lavin Tim 
Published: May 2022

Bortezomib is a proteasome inhibitor, used in the treatment of multiple myeloma. Bortezimib induced peripheral neuropathy (BIPN) is classically a painful, sensory predominant, length dependent axonal neuropathy [1]. Atypical presentations including demyelinating neuropathies can occur, though rarely (2].We identified 4 patients from the Manchester Centre for Clinical Neuroscience with atypical BIPN. All 4 had multiple myeloma and developed symptoms within 2 cycles of intravenous treatment.Case 1 and 2 developed proximal and distal motor weakness and neuropathic pain. Neurophysiology confirmed mixed demyelinating/axonal neuropathy in both. Cerebral Spinal Fluid analysis confirmed albuminocytological dissociation. Immunomodulatory treatment with IVIg and steroids had minimal effect.Case 3 developed left hand weakness, predominantly affecting the radial musculature with motor conduction block on neurophysiology.Case 4 developed whole body paraesthesias, ataxia and thoracic radicular pain after 2 cycles, neurophysiology confirmed a sensory neuronopathy.Case 2 died due to disease progression, the other 3 cases improved on withdrawal of Bortezimib.ConclusionBIPN can cause neuropathy phenotypes including sensory neuronopathy, motor neuropathy with conduction block and severe demyelinating polyradiculoneuritis. Immunogenic, as well as toxic mechanisms may have a role in the pathogenesis of BIPN.1. Chaudhry V, Cornblath D, Polydefkis M, Ferguson A, Borrello I. Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. Journal of the Peripheral Nervous System. 2008;13(4):275–2822. Thawani S, Tanji K, De Sousa E, Weimer L, Brannagan T. Bortezomib-Associated Demyelinating Neuropathy—Clinical and Pathologic Features. Journal of Clinical Neuromuscular Disease. 2015;16(4):202–209tim.lavin@srft.nhs.uk
126  Headache recognition and management in acute traumatic brain injury patients – a service audit
Authors: Lichtblau Nicole , Griffin Colette 
Published: May 2022

BackgroundHeadache is one of the most frequent immediate and long-term consequences following head injury. No standardised guidelines on management of post-traumatic headache exist and for non- neurologists treatment can be challenging. Inappropriate analgesia prescription can cause medication- overuse headache.MethodsWe audited all head injury related admissions to St. George’s Hospital within a two-month period. We assessed documentation of post-traumatic headache, immediate management and long-term advice to patients and General Practitioners.ResultsWe audited 91 head injury related admissions to surgical and medical wards. 65% of patients suffered traumatic brain injury (TBI) (26.7% mild; 73.7% moderate-severe). Even though 60% of all patients received regular analgesia in hospital, a clear documentation of headache was found in only 5% of them. Only 7.7% of patients discharged with regular analgesia received written advice about headache management in the discharge summary.22% of patients with a TBI were reviewed by the TBI specialty team which diagnosed post-traumatic headache in 50% of reviewed cases and initiated change of headache management in 90% of reviewed cases.ConclusionsOur data shows that post-traumatic headache is not well documented and managed. Wider awareness and education on headache management among all specialities needs to be raised.nicole.lichtblau@nhs.net
129  Network controllability and regional gene expression explain visual hallucinations in Parkinson’s
Authors: Zarkali Angeliki , McColgan Peter , Ryten Mina , Reynolds Regina , Leyland Louise-Ann , Lees Andrew J , Rees Geraint , Weil Rimona S 
Published: May 2022

Visual hallucinations are common in Parkinson’s (PD) and associated with poorer prognosis. Imaging studies have shown white matter and functional changes in PD-hallucinations1 2but the biological factors underlying selective vulnerability of brain regions are unknown.We performed diffusion-weighted imaging in 100 PD patients (81 without hallucinations [PD-non-VH], 19 with hallucinations [PD-VH]) and 34 controls. We used network-based statistics to identify structural con- nectivity changes in PD-VH and performed an analysis of controllability, an emerging technique that allows quantification of influence across the rest of the network. We used the Allen brain atlas to identify regional gene expression patterns associated with affected areas of the network.We identified a subnetwork of reduced connectivity in PD-VH. Within this network, PD-VH showed reduced controllability (influence over other brain regions), than PD-non-VH (U=526, p=0.014) and controls (U=176.5, p=0.003). This subnetwork appears to be critical for brain integration, as even in controls, nodes with high controllability were more likely to be within the subnetwork (U=572.5, p<0.001). Gene expression analysis revealed downregulated genes related to mRNA metabolism and upregulated genes related to membrane localisation.Our findings provide insights into how hallucinations are generated, with breakdown of a key structural subnetwork that exerts control across distributed brain regions.ReferenceShine,et al. The role of dysfunctional attentional control networks in visual misperceptions in Parkinson’s disease. HumBrainMapp;2014.a.zarkali@ucl.ac.uk
138  Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane systematic review and meta-analysis
Authors: Mbizvo Gashirai , Chandrasekar Bharath , Nevitt Sarah , Dixon Pete , Hutton Jane , Marson Anthony 
Published: May 2022

ObjectiveTo evaluate the effectiveness of adjuvant levetiracetam in drug-resistant focal epilepsy. This is an update to the 2001 and 2012 reviews.MethodsThe search included the Cochrane Register of Studies and MEDLINE to 09/2018 for randomised, placebo-controlled trials of add-on levetiracetam in drug-resistant focal epilepsy. Two authors indepen- dently performed study selection, data extraction, and risk of bias assessments. Outcomes included≥50% reduction in seizure frequency (response) and adverse effects. We performed Mantel-Haenszel meta-analyses for risk ratios (RR), with 95% CI (99% for adverse effects). We assessed heterogeneity using I².ResultsThis update includes 14 trials (three more than the previous update), assessing 2,452 participants (296 children). Risks of bias were predominantly low. There were important levels of heterogeneity across multiple comparisons. There were two new findings: 1) Levetiracetam at either 500 mg/day or 4000 mg/day did not perform better than placebo for response (500 mg: RR 1.60, CI 0.71–3.62; 4000 mg: RR 1.64, CI 0.59–4.57). Levetiracetam was significantly better than placebo at all other individual doses (1000–3000 mg). 2) Odds of achieving response were increased by nearly 40% (odds ratio 1.39, CI 1.23–1.58) for each 1000 mg increase in dose of levetiracetam. Somnolence remained the most common adverse effect, and changes in behaviour were negligible overall.ConclusionsIt seems reasonable to continue using levetiracetam in drug-resistant focal epilepsy,10a2lthough a 500-mg dose may be no more effective than placebo.mbizvogkm@gmail.com
139  Can processed EEG improve our ability to monitor status epilepticus?
Authors: Gimson Amy , Smith Matthew 
Published: May 2022

Processed electroencephalogram (EEG) is being increasingly used in operative anaesthetic practice for monitoring depth of anaesthesia. This potentially provides a frequently available, cost effective and simple to interpret method for monitoring status-epilepticus. This is important as continuous formal EEG monitoring (the NICE gold standard) is not available in most critical care environments. We undertook a systematic review of the evidence for using processed EEG for this indication.Literature was available for many of the processed EEG systems now available, with most concerning the Bispectral Index (BIS) device. This equipment provides a numerical value indicative of extent of burst suppression, which correlates to burst suppression observed on standard EEG recordings. Multiple case reports and eight prospective studies report the use of BIS for optimisation of burst suppression in patients with status-epilepticus at the bedside. Further reports suggest the ability of processed EEG to detect the presence of non-convulsive status-epilepticus. Evidence also exists from prospective studies performed during electro-convulsive therapy, providing a predictable model for examining the utility of processed EEG interpretation. We conclude that processed EEG may be helpful in monitoring clinical response in the treatment of status epilepticus, however additional prospective studies are required to provide a robust evidence base.a.gimson@nhs.net
140  How can we maximise discovery potential from sparse clinical information?
Authors: Lewis-Smith David , Galer Peter D , Ganesan Shiva , Ellis Colin A , Thomas Rhys H , Helbig Ingo 
Published: May 2022

Collaborative studies exploit large data sets to discover new associations with diseases. However, analyses of clinical features struggle with big data. Beyond sheer volume, the challenge is in harmonisation of terminology and the level of detail of information provided for analysis by different sources; in epilepsy this is most pertinent to seizures.We applied two ontologies (representations of the relationship between different types of seizure) to the same sparse details from 82 individuals. We compared the amount of information imputed using the Human Phenotype Ontology (HPO, a reference of clinical phenotypes widely used by geneticists) and an ontology of seizures created by the Epilepsiome Task Force of the International League Against Epilepsy Genetics Commission (based upon ILAE classifications).We translated each individual’s seizure descriptions into 2 terms (median) from each ontology. Imputa- tion generated 2 additional terms per individual using the HPO and 4 using the Epilepsiome ontology. The Epilepsiome ontology was able to increase the amount of information available for analysis by two- thirds compared to the HPO.Well-designed ontologies can be used to impute descriptions of complex clinical features at multiple less specific levels of precision, addressing a major limiting step in harmonisation of data for collabora- tion or re-use.rhys.thomas@ncl.ac.uk