bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical inactivity: productivity losses and healthcare costs 2002 and 2016 in Sweden
Authors: Bolin Kristian
Published: October 2018

Objectives

To estimate the costs associated with physical inactivity in Sweden for the year 2016.

Methods

The costs associated with insufficient physical activity was calculated employing population attributable fractions (PAFs) and register information on healthcare utilisation, mortality and disability pensions. The PAFs were calculated using information on exercise habits and morbidity-specific relative risks. The healthcare cost components were calculated based on registry data on inpatient-care, outpatient-care and primary care utilisation. Registry data on cause-specific mortality and granted disability pensions were used to calculate the productivity loss components. Costs associated with pharmaceutical utilisation were not included due lack of data.

Results

Physical exercise habits improved somewhat between 2002 and 2016. Thus, the associated morbidity-specific PAFs decreased over the same time period.

Conclusions

The economic costs attributable to insufficient physical activity decrease between the year 2002 and 2016. Healthcare costs attributable to insufficient physical activity as share of total healthcare expenses increased from 0.86 % in 2002 to 0.91 % in 2016.
WED 016 A service evaluation of the acute neurology clinic
Authors: Ray Wynford-Thomas , Ann Johnston
Published: October 2018

Rationale

Neurological symptoms are a common presentation in primary care and emergency medicine. The acute clinic provides a rapid access service, aimed at reducing unnecessary admissions, outpatient waiting times, inappropriate investigations and achieving a prompt diagnosis. Data on service utilisation will inform future service design and delivery.

Aim

To evaluate the acute neurology clinic service and training experience in the University Hospital of Wales.

Method

Data was collected prospectively on acute referrals over 6 months.

Results

52 patients were seen; 51% were referred from primary care. The median slots filled per clinic was 3 (range 1–6). Median time from referral to review was 3 days (range 1–7). The most common presenting symptom was headache (38%), followed by limb weakness (25%). The commonest clinical syndrome was a myelopathy (15%) and 62% had abnormal neurological signs. 75% of patients were investigated, 10% admitted and 7% discharged. In retrospect, 56% of patients warranted urgent referral.

Conclusion

The acute neurology clinic provides a useful service to primary care. This data suggests it is presently under-utilised and that similar clinics and novel strategies could be enlisted to help reduce admissions and waiting times, and help manage patients with neurological symptoms in primary care.
WED 209 A case report of hyperhomocystinemia due to homozygous MTHFR mutation
Authors: Saadia Afzal , Tom Hayton , Piers Newman , Charlotte Dawson , Mary O’Driscol
Published: October 2018

Homocycteine is metabolized via two pathways, remethylation or trans-sulfuration. The former requires 5-methyltetrahydrofolate reductase (MTHFR) and Vitamin B12, the later requires cystathione–beta-synthetase and Vitamin B6. Mutations in the MTHFR genes affect the enzyme activity to various degree and manifestations can be neuropsychiatric, vascular and neurodegenerative. Here we report a case of severe homocysteinemia secondary to two homozygous MTHFR gene mutations.

32 year old pregnant female initially presented in 2014 with grand mal seizure. After being seizure free on antiepileptics, she was admitted again to hospital in January 2017 with headaches, confusion, slurred speech and neuropathic pain in feet. She developed spastic paraparesis and her condition remained critical for several weeks due to refractory seizures and low GCS.

She was on warfarin for recurrent DVTs and had family history of mental health problems. Homocysteinemia was discovered when he was screened for metabolic causes and leucodystrophies. MRI of the brain showed cerebral, cerebellar and brain stem atrophy. Neurophysiological studies were normal. Genetic testing found her to be homozygous for 2 MTHFR mutations. She was commenced on calcium folinate and parenteral B12, to which she responded really well.

Thorough history, targeted investigations and systematic approach are keys for diagnosis of rare metabolic disorders.
THUR 215 Lessons in the diagnosis and management of poems syndrome
Authors: Kerala Adams-Carr , Stephen Keddie , Michael Lunn
Published: October 2018

We present the case of a 46 year old man who developed a rapidly progressive sensorimotor neuropathy and skin changes. He was diagnosed with Guillain-Barré Syndrome, and subsequently CIDP, but his condition continued to progress despite IVIG treatment and plasma exchange. On transfer to the National Hospital of Neurology and Neurosurgery, six months after the onset of illness, he had profound lower limb weakness with power 0 distal to his knees, and upper limb involvement to the elbows. Deep tendon reflexes were absent, and vibration and joint position sense were reduced peripherally. Nerve conduction studies identified a length-dependent demyelinating polyneuropathy with secondary axonal loss, and blood tests demonstrated thrombocytosis, endocrine dysfunction, and a raised VEGF. Two FGD-avid mixed sclerotic and lytic bone lesions were identified on PET-CT. Biopsy of these lesions demonstrated plasmacytomas with lambda light-chain restriction, and bone marrow biopsy revealed 4% plasma cells, with polytypic light chain staining. A diagnosis of POEMS syndrome was made, and he was initiated on lenalidomide and dexamethasone treatment. With reference to this case we will discuss the challenges in the diagnosis of POEMS syndrome. Additionally, we will outline the therapeutic options available; providing an algorithm to simplify the treatment selection process.
THUR 219 Myopathic manifestations in haematological conditions
Authors: Vinojini Vivekanandam , H Devine , J Holton , Z Jaunmuktane , C Turner , P Machado , H Manji , C McNamara , S D’Sa , A Carr
Published: October 2018

Neurological complications of haematological malignancies are wide ranging but isolated myopathy as a presenting complaint is rare.

Cases: 63 year-old lady with progressive proximal upper then lower limb weakness over 7 years to wheelchair-dependence and hoist-transfers. Muscle biopsy revealed nemalin rods, HIV negative, IgG kappa paraprotein=6 g/L. Late-onset nemalin rod myopathy was diagnosed; function is stable 6/12 post-autologous bone marrow transplant.

56 year-old lady with limb-girdle weakness leading to immobility over 2 years and IgG lambda MGUS. Re-examination of muscle biopsy revealed amyloid deposition, SAP scan negative for systemic AL amyloid. Treated with velcade and dexamethasone but died from amyloid cardiomyopathy 6/12 later.

73 year-old man with painless deltoid weakness. Muscle biopsy revealed plasma cells infiltrate and lightchain deposition with matched lightchain restriction in bone marrow, IgG kappa paraprotein=8 g/L. Cyclosporin and dexamethasone were recommended for infiltrative multifocal, myopathic plasmacytoma.

28 year-old female with pain, fatigue and pelvic-girdle weakness was diagnosed with haemophagocytic lymphohistiocytosis without systemic lymphoma or connective tissue disease. Muscle biopsy demonstrated T-cell and macrophage infiltration. Muscle symptoms are responding to steroids, mycophenolate, cyclosporine and etopiside. An allogenic bone marrow transplant is planned.

We describe four cases of progressive myopathic weakness as the primary manifestation of an underlying haematological disorder.
WED 240 An audit of unplanned admissions in myasthenia gravis patients
Authors: M Talaei , G Burke
Published: October 2018

Background

Unplanned admissions of neuromuscular patients adversely affect patients and NHS. Muscular dystrophy UK designed an audit of unplanned admissions of neuromuscular patients in 2012 and 2017.

Aim

We aimed to compare unplanned admissions amongst myasthenia gravis (MG) patients, in two different hospitals in Wessex, Southampton general hospital (SGH) and Queen Alexandra service (QAH).

Methods

Data was collected from patients attending neurology clinics in conjunction with hospital database.

Results

240 adult patients were included in the audit. 60 unplanned hospital admissions were identified, but only 22 (37%) were judged to be potentially avoidable. 8 admissions were due to myasthenia relapse, 8 occurred in patients with severe myasthenia on dual immunosuppression. 9 admissions were due to pneumonia in elderly patients with multiple comorbidities but well controlled myasthenia. 2 admissions were anxiety related and 3 were due to falls and fracture despite appropriate bone protection.

Conclusion

Our preventable admission rate for MG patients is less compared to MDUK data (37% vs 68.7% and 59.4% in 2012 and 2017). Pneumonia is common in elderly myasthenic patients who have other comorbidities. Fragility fractures can occur despite bone protection and falls advice is necessary during consultation.
WED 253 An atypical presentation of sneddon syndrome
Authors: Cleaver Jonathan , Renowden Shelley , Teo Mario , Clatworthy Philip
Published: October 2018

A 50-year-old female was admitted following a subacute and increasing headache, numbness in both hands and feet, generalised weakness and confusion.

An MRI brain revealed an acute left temporal infarct with multi-focal established infarcts. MR angiography demonstrated marked occlusive disease affecting terminal internal carotid artery and both middle cerebral and posterior cerebral arteries, in a potential Moyamoya pattern.

Lumbar puncture, extensive blood tests and echocardiography were unremarkable. A skin biopsy showed intimal thickening of the deep dermal arteries compatible with a diagnosis of Sneddon Syndrome. Livedo reticularis was absent and antiphospholipid antibodies negative. Antiplatelet therapy only was commenced given her seronegativity and Moyamoya.

Discussion

Sneddon syndrome is an uncommon disorder, characterised as generalised livedo reticularis with stroke (Sneddon, 1965). It is an increasingly recognised cause of ischaemic stroke in young adults, however, its clinical course remains poorly defined in the literature (Boesch et al. 2003). It is increasingly associated with Moyamoya syndrome, posing a challenge in terms of anticoagulation in these patients (Fierini et al. 2015). To our knowledge, this is only the second reported case without livedo reticularis (Marianetti et al. 2011) - highlighting the importance of skin biopsy - and the first with this clinical and radiological combination.
WED 255 SSRIS and risk of intracranial haemorrhage
Authors: Jensen Melanie P , Ziff Oliver J , Banerjee Gargi , Ambler Gareth , Werring David J
Published: October 2018

The abstract has also been presented as an oral presentation at the ESOC conference.

Background and aims

Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRI). We sought to clarify the impact of SSRI on ICrH, accounting for study methodology.

Method

A comprehensive search of Medline, Embase and Cochrane from 1960 to December 2017 comparing SSRI with control. ICrH was meta-analysed using a random-effects model and the review was prospectively registered (PROSPERO:CRD42017084513).

Results

25 observational studies, but no randomised trials, were available for meta-analysis, with a combined total of 4,843,857 patient-years follow-up. Those treated with SSRI were more likely to have depression (p<0.001) and be female (p=0.04). Compared to control, SSRI were significantly associated with first-ever ICrH (RR: 1.31; 95% CI: 1.15 to 1.49); however, in survivors of ICrH there was no association between SSRI and recurrence (0.95, 0.83–1.09). Sensitivity analyses revealed a greater association between SSRI and ICrH in studies with a high risk of bias (p<0.001) than those with a lower risk of bias (p=0.10).

Conclusion

SSRI are associated with increased risk of first-ever ICrH, but not with recurrence. These findings, based solely on observational data, should be taken with caution due to fundamental differences in patients receiving treatment, highlighting the need for randomised trials.
WED 260 Time to scan: barriers to imaging outside normal working hours
Authors: Jennifer Hosty , Jonathan Bunn , Rachel Bainbridge , Geoffrey Dunn , Keith Endean , Kirsty Harkness
Published: October 2018

SSNAP measures quality and organisation of stroke care. Domain 1.1 looks at the number of patients scanned within 1 hour of arrival at hospital; local trust performance is 57.4% (national average 51.3%), with the specialist stroke unit at 79.2%. This is in part related to ‘direct to scan protocols’ in extended working hours, but we currently lack equivalent medical staffing and radiographer support during this time. We aimed to explore which factors impacted on scanning time out of hours. An initial consecutive 14 day sample identified delays in approval of scan request by the duty radiologist. A new Standard Operating Procedure allowed specialist stroke nurse practitioners (SNPs) to request CT head scans directly with the duty radiographer, eliminating need for liaison with the radiologist. A repeat 14 day analysis identified additional factors resulting in delays, including delays in scan request and in-hospital competing emergency clinical scanning requirements, meaning no significant improvement in percentage of patients scanned within 1 hour was observed. The mean time from arrival to scan performance was 52 min, but 21.8% of patients did not undergo a CT head within 1 hour of arrival. Further strategies are required to maximise patients meeting this target.
THUR 264 Multimodal intervention to improve lumbar puncture
Authors: Vanessa Tobert , James Allen , Evan Edmond
Published: October 2018

Introduction

Lumbar puncture (LP) is a routine procedure performed for diagnostic and therapeutic indications for more than 120 years.1 For as long, post-dural puncture headache (PDPH) has been a complication that can be persistent and severe.2 Finer gauge needles and ‘atraumatic’ needle designs3 significantly reduce the incidence of PDPH.4–6

Methods

A multimodal intervention consisting of teaching session on atraumatic needle usage, simulation training with 25G Sprotte needles, and electronic LP proforma was introduced in October 2017.

Records for all patients having LP in the Neurology day-case unit at the John Radcliffe Hospital, Oxford, in the months of November 2016 and Nov/Dec 2017 were retrospectively reviewed for documentation and atraumatic needle usage.

Results

39 records were reviewed from Nov/Dec 2017 and 16 from November 2016. Documentation was significantly improved across all criteria assessed except for documentation of informed consent. Atraumatic needle usage increased from none documented pre-intervention to 38% (n=11 out of 29 where atraumatic needle indicated) post intervention.

Conclusion

Proforma use was associated with improved LP documentation. Atraumatic needle usage increased significantly post-intervention. These results are consistent with previous studies on changing behaviour in LP technique in neurology.7 Large scope for further improvement exists.

Abstract THUR 264 Figure 1

References

1. Quincke H. Die Lumbalpunction des Hydrocephalus -Heinrich Quincke -Google Books 1891. Klin. Wochenschrist. pp. 929–965.

2. Greene HM. Lumbar puncture and the prevention of postpuncture headache. JAMA J. Am. Med. Assoc 1926;86:391.

3. Hart JR, Whitacre RJ. Pencil-point needle in prevention of postspinal headache. J. Am. Med. Assoc 1951;147:657.

4. Vallejo MC, Mandell GL, Sabo DP, Ramanathan S. Postdural puncture headache: A randomized comparison of five spinal needles in obstetric patients. Anesth. Analg 2000;91:916–20.

5. Thomas SR, Jamieson DR, Muir KW. Randomised controlled trial of atraumatic versus standard needles for diagnostic lumbar puncture. BMJ 2000;321:986–90.

6. Halpern S, Preston R. Postdural puncture headache and spinal needle design. Metaanalyses. Anesthesiology 1994;81:1376–83.

7. Davis A, et al. Change practice now! Using atraumatic needles to prevent post lumbar puncture headache. Eur. J. Neurol 2014;21:305–11.
WED 270 Optician’s diagnosis of papilloedema impact hospital admissions
Authors: Sarah Williamson , David Whiteside , Thomas Coysh , Vinod Metta , Fatima Geranmayeh , Alex Everitt , Carolyn Gabriel , Barry Seemungal , Joanna Ball , Richard Nicholas
Published: October 2018

Background

In a landmark case in August 2016 an optometrist was found guilty of missing papilloedema. We examined the current referral pathway for managing papilloedema to determine whether initial assessment by an optician impacted resource use.

Methods

Discharge summaries from St Marys Hospital (SMH) between 1/1/17 and 16/5/17 the referral centre for the Western Eye Hospital (WEH) accident and emergency (A and E) were searched to identify subjects with suspected papilloedema. Analysis of the patients journey was performed.

Results

Of 76 patients identified, 26 were excluded either due to being<18 years old or were treated elsewhere. Of the 50 included, 25/50 were seen by an optician prior to a WEH A and E ophthalmologist, 75% of these were referred for urgent hospital assessment with an admission rate of 45.8%. Of 19/50 assessed by WEH A and E only there was a significantly lower urgent assessment referral rate (75% vs 52.6%, p=0.02) and admission rate (45.8% vs 21%, p=0.02). Of the 6/50 patients finally found to have normal discs, 5 were initially referred by opticians.

Conclusion

Referral by optician prior to ophthalmology A and E assessment is more likely to result in rapid referral for urgent hospital assessment and inpatient admission.
276 A new face for an old foe?
Authors: Gavinda Sangha , Anthony Bron , Michael Donaghy , Cerys Evans , Alison Hardcastle , Kevin Talbot
Published: October 2018

Background

Mutations in the protein gelsolin result in hereditary systemic amyloidosis, characterised by onset of corneal lattice dystrophy in the third decade, a slowly progressive cranial neuropathy and cutis laxa. To date four dominantly inherited gelsolin mutations have been identified, two mutations resulting in the classical syndrome and two mutations resulting in renal-predominant amyloidosis.

Methods

We identified a family in which four individuals in three generations presented with corneal lattice dystrophy and neurological symptoms. Detailed clinical neurological and ophthalmological assessment and investigations including neurophysiology and imaging were performed. Whole exome sequencing was undertaken in three family members.

Results

Whole exome sequencing revealed a novel variant in the gelsolin gene (c. G1738A; p. E580K), dominantly inherited and predicted to be pathogenic. Examination, neurophysiological testing and imaging revealed the presence of distal upper limb weakness and wasting, corneal lattice dystrophy and cervical myelopathy in all affected family members.

Conclusion

The E580K mutation described in this family is in a conserved calcium-sensitive actin-binding domain that displays sequence homology with other actin-depolymerising proteins. Mutations in this domain may result in abnormal gelsolin-actin interactions and changes in calcium sensitivity may render the protein susceptible to the same aberrant proteolytic cascade as with other known mutations.
277 Disentangling corticobasal syndrome from corticobasal degeneration
Authors: Ruth Lamb , Jonathan Rohrer , Steven Lubbe , Rimona Weil , Tammaryn Lashley , Janice Holten , Tamas Revesz , Andrew Lees , Huw Morris
Published: October 2018

Mutations in the TANK-binding kinase (TBK1) gene have been shown to cause frontotemporal dementia (FTLD) and amyotrophic lateral sclerosis (ALS). The phenotype is highly variable and has been associated with behavioural variant FTD, primary progressive aphasia and pure amyotrophic lateral sclerosis. We describe the clinical, anatomical and pathological features of a patient with onset of a corticobasal syndrome (CBS)/primary progressive aphasia overlap aged 59. The patient presented with progressive speech difficulties and later developed an asymmetric akinetic-rigid syndrome. Neuroimaging showed asymmetrical frontal atrophy, predominantly affecting the right side. There was a strong family history of neurodegenerative disease with 4/7 siblings developing either dementia or ALS in their 50’s-60’s. Following death at age 71, post mortem examination revealed FTLD TDP-43 type A pathology. Genetic screening did not reveal a mutation in the progranulin, microtubule-associated protein tau or C9orf72 genes. However exome sequencing revealed a novel E703X mutation in the TBK1 gene. Although segregation data was not available, this loss of function mutation is highly likely to be pathogenic. In conclusion, we show that TBK1 can be a cause of an atypical parkinsonian syndrome and screening for TBK1 should be considered in CBS patients with a family history of dementia, ALS or CBS.
288 Challenges in reducing hospital deaths in multiple sclerosis
Authors: Richard Nicholas , Emma Nicholas , Jonathan Koffman
Published: October 2018

Introduction

Fifty-five percent of people with multiple sclerosis (pwMS) will die in hospital, above the national average. This study aimed to determine factors that impact place of death for pwMS.

Methods

Retrospective sequential notes review from the UK MS Tissue Bank.

Results

Thirty notes were reviewed from 18/06/12% to 08/09/16. 53% died in hospital, 23% in nursing homes, 13% at home and 10% in hospices. Health interventions increased in year of death versus year prior to death in community (p=0.0369) and primary care (p=0.002) but not in secondary care but were not associated with a non-hospital death (NHD). Recognition of dying (73%, p=0.0024) and having an advanced care plan (ACP) (67%, p=0.0003) were associated with NHD. Family involvement was associated with recognition of dying (p=0.0146) but not with NHD. Multivariable analysis found recognition a person is dying and having an ACP were independently predictive of NHD (R2=0.52, p=0.034). The mean time prior to death of having an ACP (9.6±8.1 months) was months prior from when dying was recognised (17.4±27 days, p=0.0004).

Conclusion

Having an ACP and recognition a pwMS is dying are key factors to achieving a NHD. This study highlights the challenges to reducing hospital deaths in MS.
293 Autoimmune autonomic ganglionopathy: the NHNN experience
Authors: Shiwen Koay , Bethan Lang , Gordon Ingle , Merete Hagen Ellen , Christopher Mathias , Laura Watson , Michael Lunn , Fion Bremner , Angela Vincent , Valeria Iodice
Published: October 2018

Background

Autoimmune Autonomic Ganglionopathy (AAG) is a rare, immune-mediated condition characterised by subacute pandysautonomia. 50% have auto-antibodies to the ganglionic nicotinic acetylcholine receptor (gAChR), affecting synaptic transmission at autonomic ganglia.

Methods

We describe 13 patients (5 female, median age 47) presenting with widespread autonomic failure, confirmed on cardiovascular, sudomotor and pupillometry testing at the National Hospital for Neurology and Neurosurgery (NHNN), and high gAChR antibody levels (>200 pm) measured by radioimmunoprecipitation assay at Oxford University.

Results

Of the 13 patients, 8 had other autoimmune conditions, 3 had antecedent infection and 3 were paraneoplastic. All had orthostatic hypotension, gastro-intestinal and urinary symptoms, 11 had documented pupillary abnormalities (9 mixed sympathetic and parasympathetic deficits, 2 subclinical sympathetic deficits), 11 had secretomotor dysfunction, 8 had generalised/partial anhidrosis, 8 had sexual dysfunction and 7 had evidence of small fibre dysfunction on neurophysiology.

Ten received immunomodulatory treatment; 6 plasma exchange and 4 combination treatment including intravenous immunoglobulin, mycophenolate and rituximab. Earlier treatment was associated with greater clinical response.

Discussion

Patients with AAG and high gAChR antibody levels have widespread dysfunction of the autonomic nervous system, which can respond dramatically to immunomodulation. Further research is needed to develop robust clinical biomarkers to guide treatment and monitor response.
294 Neurofilament light protein as a biomarker for huntington’s disease
Authors: Lauren Byrne , Filipe Rodrigues , Eileanoir Johnson , Rana Solyu Kucharz , Sarah Gregory , Rachael Scahill , Maria Björkqvist , Henrik Zetterberg , Sarah Tabrizi , Edward Wild
Published: October 2018

Background

Neurofilament light protein (NfL), a component of the axonal cytoskeleton, has been shown to be increased in cerebrospinal fluid (CSF) and blood and to respond to successful treatment in several neurological diseases. We set out to investigate NfL as a potential biomarker for Huntington’s disease (HD).

Methods

We studied NfL in plasma from 298 participants, in plasma and CSF in 37 participants, and in the R6/2 HD mouse model.

Results

NfL concentration was increased in plasma at every stage of HD including premanifest mutation carriers, rose with progression and had a striking relationship with HTT CAG repeat length. In premanifest HD, baseline plasma NfL predicted subsequent motor onset even after adjustment for age and CAG repeat length. NfL predicted clinical, cognitive and neuroimaging progression, and CSF and plasma levels were strongly associated (Byrne et al, Lancet Neurology 2017). VBM analysis revealed that NfL level predicted atrophy throughout the white matter and in the occipital grey matter (Johnson et al, Neurology 2018). In the R6/2 mouse model, NfL was increased in plasma and CSF and associated with brain volume and clinical measures (Soylu Kucharz et al, Scientific Reports 2017).

Conclusions

NfL is a promising clinical and translational biomarker for HD.
WED 027 Acute neurology in glasgow
Authors: M Brennan , A Tyagi , JP Leach
Published: October 2018

Provision of acute liaison in-patient neurology reduces demand on neurology out patient services, reduces unnecessary investigations and use of medical beds by patients waiting on in-patient neurology review and allows speedier access to necessary neurological services for those with a neurological illness.

The pressure on acute neurology beds at QEUH Glasgow is immense and there is considerable delay in patients waiting for admission to the ward. An audit of the acute on call service in mid 2015 showed a 100% increase in the number of phone calls received by the on call registrar when compared to a similar audit in 2008. The number of requests for ward visiting to review medical inpatients at the Queen Elizabeth University hospital increased by more than 100% over the previous year.

In June 2016 an Acute Neurology rota was introduced whereby a Consultant Neurologist supervised and delivered patient care for the acute neurology wards, referrals from medical wards and acute receiving, as well as twice a week acute neurology clinics. This has led to a significantly improved care for patients referred with neurological problems as perceived by trainees, consultants and referring medical physicians, as evident on a survey carried out in 2017.
WED 033 Minimum prevalence of non-compliance recorded in an audit of antenatal care in a district general hospital joint obstetric epilepsy
Authors: C Smyth , A Gornall , J Bowen
Published: October 2018

Epilepsy is among the leading indirect causes of death in pregnancy. A retrospective case review of 143 DGH patients with seizures (50 Idiopathic Generalised, 72 Focal 19 Dissociative) seen in a joint obstetric neurology antenatal clinic from 2015–2017 was undertaken. Systematic data collection was not possible owing to the retrospective nature of the audit, however, salient findings were: Of the cohort of 143, 25 were not taking any AED at booking (around 12 weeks). Of those on AEDs over 80% were on lamotrigine or Levetiracetam monotherapy. Most (87/143) had been seizure free pre-conception for at least 1 year. 11 of this group had breakthrough seizures. AED levels were checked on 57 patients (Lamotrigine – 48:Levetiracetam 9) and were undetectable in 10/57 (17.5%) at booking. Reasons for AED testing refusal and non-concordance (when present) were unknown. Of 11 patients losing seizure control during pregnancy 3 were non-concordant at booking.

Conclusion

Non concordance at booking was documented in 1 in 6. Loss of previous seizure control occurred in 11/87 (12.6%) of previously seizure free patients of whom 3/11 were nonconcordant. AED monitoring revealed significant non-concordance and may relate to subsequent loss of seizure control. A prospective study is planned.
THUR 002 An unusual presentation: two aetiologies for the price of one!
Authors: Katie Yoganathan , Alexander Stevenson , Sanam Khoylou , Ronald Pearce
Published: October 2018

70-year-old female receptionist presented with acute onset lower back pain whilst sitting down. She tried to weight bear but felt her left leg ‘gave way’. There were no sensory complaints and no sphincter disturbance. Positive examination findings in her left lower limb include reduced tone, power 2/5 throughout, and left extensor plantar. In addition, she had absent knee and ankle reflexes bilaterally and loss of pinprick and temperature sensation on the right side up to L1 dermatome, with preservation of vibration and proprioception. She had a normal sensory examination of her left lower limb and rectal examination was unremarkable. Clinically, she has an atypical form of Brown-Séquard syndrome with weakness in the left lower limb and sensory loss in the right lower limb with a sensory level. MRI lumbar/sacral spine showed L3 slipped anteriorly with L3/4 disc bulge resulting in cauda equina syndrome. She was re-scanned five days later including thoracic spine and found to have an acute left hemi-cord infarct at T8/9. This case demonstrates the importance of scanning the relevant sections of the cord and to keep a broad differential in mind, as there can be two aetiologies at work which might misguide the clinician at first glance.
THUR 058 Eslicarbazepine acetate as monotherapy in clinical practice
Authors: Rob McMurray , Norman Delanty , Vicente Villanueva
Published: October 2018

Purpose

To assess eslicarbazepine acetate (ESL) as monotherapy in everyday clinical practice.

Method

Euro-Esli was a pooled analysis of 14 European studies. In a subanalysis, data were compared for patients treated initially with ESL monotherapy versus adjunctive therapy, and for patients treated at last visit with ESL monotherapy versus adjunctive therapy.

Assessments included responder rate (≥50% seizure frequency reduction), seizure freedom rate (seizure freedom at least since prior visit) and incidence of adverse events (AEs).

Results

ESL was used as monotherapy in 88/2045 and 229/1340 patients initially and at last visit, respectively. At 12 months, responder and seizure freedom rates were significantly higher in patients treated initially with ESL monotherapy versus adjunctive therapy (responder: 94.1% versus 74.8%; seizure freedom: 88.2% versus 39.0%), and in patients treated at last visit with ESL monotherapy versus adjunctive therapy (responder: 93.2% versus 70.4%; seizure freedom: 77.4% versus 25.9%). Overall incidence of AEs was similar in patients treated initially with ESL monotherapy and adjunctive therapy (29.4% versus 34.4%), and in patients treated at last visit with ESL monotherapy and adjunctive therapy (27.1% versus 30.8%).

Conclusion

ESL was significantly more effective when used as monotherapy compared with adjunctive therapy; safety/tolerability was generally comparable.

Supported by Eisai
WED 063 Eslicarbazepine acetate switch from carbamazepine or oxcarbazepine
Authors: Jukka Peltola , Rob McMurray , Vicente Villanueva
Published: October 2018

Purpose

To investigate eslicarbazapine acetate (ESL) in patients transitioning from carbamazepine or oxcarbazepine in clinical practice.

Method

Euro-Esli was a pooled analysis of 14 European studies. Data were analysed for patients transitioning from carbamazepine and oxcarbazepine to ESL due to lack of efficacy or poor tolerability. Responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit) were assessed after 3, 6 and 12 months of ESL treatment, and at last visit. Safety/tolerability analysis evaluated adverse events (AEs) and ESL discontinuation due to AEs.

Results

Euro-Esli included 2058 patients; 233 (11.3%) transitioned from carbamazepine and 134 (6.5%) transitioned from oxcarbazepine. After 12 months, responder and seizure freedom rates for patients transitioning from carbamazepine due to lack of efficacy (n=163) were 70.0% and 30.9%, respectively. Corresponding values for patients transitioning from oxcarbazepine due to lack of efficacy (n=90) were 57.1% and 25.0%, respectively. Among patients who transitioned from carbamazepine (n=64) and oxcarbazepine (n=61) due to poor tolerability, 26.6% and 39.5% experienced AEs; 8.3% and 6.8% discontinued ESL due to AEs, respectively.

Conclusion

ESL may be a useful option for patients experiencing intolerable AEs or not achieving adequate control with carbamazepine or oxcarbazepine.

Supported by Eisai.
THUR 090 Idiopathic intracranial hypertension – towards a streamlined pathway
Authors: Vivek Vijay , Laura Grant , Anindyt Nagar , Anish Bahra
Published: October 2018

Recent studies have yielded the first evidence-based treatments for idiopathic intracranial hypertension (IIH) and shed light on many aspects of this condition, providing an opportunity to streamline the assessment and management of patients with IIH.

This study highlighted the inefficiency of most patient pathways, especially when via outpatients, with resulting delays in diagnosis and /or management. Of note, 37% of patients did not have venography. Up to a third of patients with cerebral venous sinus thrombosis present with isolated signs of elevated intracranial pressure, thus clinically mimicking IIH and emphasising the importance of venography acutely.

Acetazolamide was appropriately commenced but rarely titrated to the maximum dose of 4 g/day as supported by the IIHTT. Over 40% of our cohort had a diagnosable co-morbid primary headache disorder which persisted and required additional headache-specific medication in almost half of these. This is in keeping with studies showing that headache is unrelated to raised intracranial pressure in IIH patients, and headache-specific management is a key aspect to the management of IIH patients.

In summary, this study highlights significant delays and missed investigations when not performed acutely, emphasising the importance of implementing a clear and visible pathway for the assessment and management of IIH patients.
THUR 103 Chorea associated with atrial myxoma
Authors: Sarah Healy , Booth Ellis Richard James , Malcolm Steiger
Published: October 2018

Background

Chorea is a hyperkinetic movement disorder characterised by involuntary, unpredictable muscle contractions and is associated with a broad range of primary and secondary aetiologies.

Case

A 73-year-old gentleman presented with a 12 month history of progressive behavioural change and involuntary movements. His family had become concerned about periods of erratic behaviour and confusion. He appeared agitated and restless. On examination he had choreiform movements predominantly affecting his upper limbs. An abnormal diastolic heart sound was detected on auscultation.

MRI brain and CSF analysis were normal; ASO titre, paraneoplastic, anti-NMDAr antibodies and Huntington’s genetics were negative. A blood film was normal. Transoesophageal echocardiogram demonstrated a variegated mobile mass within the left atrium.

An immune-mediated mechanism was suspected. Intravenous immunoglobulins and oral corticosteroids were trialled with initial major benefit but he relapsed several months later and did not respond to a further trial. The atrial mass was resected and histological analysis confirmed an atrial myxoma. The chorea and cognitive symptoms significantly improved after surgery and he remains well.

Discussion

Atrial myxoma is the most common primary tumour of the heart and is rare with an incidence of 0.5/1,000,000 population/year. There has only been one other case in the paediatric literature.
THUR 005 Two atypical presentations of pres?
Authors: Andrew Lowry , Joyutpal Das , Siân Price
Published: October 2018

Posterior reversible encephalopathy syndrome (PRES) is characterised by acute neurological symptoms with vasogenic oedema typically in parieto-occipital lobes. PRES involving atypical locations is becoming increasingly recognised. Here we report two atypical cases.

An 83-year-old male with ureteric carcinoma presented with confusion, headache and high blood pressure (170/80). MRI revealed symmetrical temporal lobe T2-hyperintensities with no mass-effect or restricted diffusion. He was treated for presumed viral encephalitis. CSF was negative. Seizure was treated with Levetiracetam. Three weeks later MRI showed worsening of temporal lobe T2-hyperintensities with mild mass-effect and one small area of restricted diffusion. Despite no treatment for hypertension, six weeks later MRI showed significant improvement. Gradient echo demonstrated multiple microhaemorrhages consistent with hypertension.

A 69-year-old female presented with discitis, sepsis, fluctuating consciousness and high blood pressure (180/90). Patient reported hearing a song recurrently which could represent ‘musical hallucination’ associated with seizure. CSF was normal. She was treated with Levetiracetam. MRI showed symmetrical fronto-temporal lobe T2-hyperintensities with no mass-effect and small area of restricted diffusion. Although hypertension was not treated, one week later MRI improved significantly.

In summary, MRI appearances improved in both with minimal intervention. The underlying aetiology may remain elusive, but could these be atypical presentations of PRES?
WED 109 Computer vision: a smartphone camera can ‘see’ bradykinesia
Authors: Stefan Williams , Hui Fang , Rami Qahwaji , Paschal O’Gorman , Parisa Patel , D Graham Christopher , Jane Alty
Published: October 2018

The core clinical feature of Parkinson’s disease is bradykinesia. However, the most common method of clinical assessment, finger tapping, has poor inter-rater reliability, even among movement disorder specialists. Many technologies have been devised to objectively measure finger tapping, but virtually all involve specialised equipment, which may explain why none are in widespread use. One method involves patients tapping a smartphone screen, but this cannot detect tapping amplitude or decrement (key features of bradykinesia assessment).

Computer vision takes static or moving images from a camera, and then applies computing algorithms to automatically extract useful information. It is widely used in commercial applications, such as facial detection and recognition of facial expression. Crucially, the only hardware required is a simple camera with a computer processor, and such items are ubiquitous, e.g. smartphones. We report a computing method, including the technique of ‘optical flow’, which uses video from a smartphone to detect the pixels of the hand and track their movement during finger tapping. It has the potential to detect and measure bradykinesia without the need for specialised equipment. We present striking videos and early results comparing computer vision measurements of finger tapping with clinical ratings for Parkinson’s patients and controls.
THUR 120 Postprandial hypotension in MSA and PD with autonomic failure
Authors: Ekawat Vichayanrat , Gordon Ingle , Merete Hagen Ellen , Christopher Mathias , Valeria Iodice
Published: October 2018

Introduction

Postprandial hypotension is often reported in Parkinson’s disease with autonomic failure (PD+AF) and Multiple System Atrophy (MSA). However there has been no study directly comparing this feature between these two disorders. The aim of this study was to evaluate cardiovascular autonomic responses before and after standard liquid meal ingestion in PD+AF and MSA.

Methods

Patients underwent a liquid meal challenge using a previously described protocol. Blood pressure (BP) and heart rate (HR) were measured at intervals. All participants remained supine for 45 min after the liquid meal ingestion. They underwent 10 min head-up tilt (HUT) to 60° before and 45 min after the meal.

Results

22 MSA and 11 PD+AF patients were identified. Supine post-prandial hypotension was significantly more common in PD+AF compared to MSA (73% vs 36%; p<0.05). Both groups had orthostatic hypotension during pre-meal tilt, with no significant difference in BP and HR when tilted post-meal between PD+AF and MSA (p>0.05).

Conclusion

Despite the similar degree of orthostatic hypotension on supine and HUT, postprandial hypotension is more commonly present in patients with PD+AF compared to MSA. The increased tendency to post-prandial hypotension even while supine reflects the nature of post-ganglionic sympathetic denervation in PD.
THUR 121 Identifying participants with parkinson’s disease in uk biobank
Authors: Kathryn Bush , Kristiina Rannikmae , Christian Schnier , Timothy Wilkinson , John Nolan , Michael Bennett , Jingjie Cheng , Cathie Sudlow ,   et al
Published: October 2018

Background

Linkage to routinely collected NHS data from primary, secondary care and death certificates enables identification of participants with Parkinson’s Disease (PD) within the UK Biobank cohort of 5 00 000 adults. Validation of the accuracy of this data is required prior to their use in research studies.

Method

In this validation study participants (n=125) with a code indicating PD were identified from a sample of 17 000 participants in the cohort. Diagnoses were validated by expert adjudicators, based on free text electronic medical records. Positive predictive values (PPV,% of cases identified that are true cases) were calculated.

Results

Primary care diagnostic codes identified 93% of PD cases, with a PPV of 95%. Combined secondary care and death data identified 42% of PD cases with a PPV of 84%.

Combining diagnostic and medication codes identified more participants, but did not increase the PPV.

Conclusions

This study suggests that linkage to routinely collected healthcare data is a reliable method for identifying participants with PD in the UK Biobank cohort.

Primary care diagnostic codes identified the highest proportion of participants and had the highest PPV, demonstrating the value of using primary care data to identify cases of disease in large population based cohort studies.
WED 128 Care and unmet needs in late-stage parkinsonism: a qualitative study
Authors: Joy Read , Sarah Cable , Charlotte Löfqvist , Susanne Iwarsson , Gergely Bartl ,   CLaSP consortium, Anette Schrag
Published: October 2018

Aim

To explore experiences and views about care needs and service use by people with late-stage Parkinsonism.

Method

Ten participants at Hoehn and Yahr stage 4 or 5 were interviewed using semi-structured open ended questions and qualitative content analysis.

Findings

Despite severe disability, participants expressed their desire to maintain normality of activities and interests in their lives. Many perceived that even though health care was provided by professionals they could do nothing more for them. Participants experienced having to ‘fit-in’ to service structures that did not always accommodate their complex needs. The quality of relationships with health care professionals and formal carers shaped perception of service provision and mediated adaptation. Informal support and knowledge on disease management were key factors in their perceived ability to remain in control and to enable normal functioning. There was common reluctance to discuss, and uncertainty about, future plans. For example, moving to a residential nursing home was perceived an undesirable but potentially necessary only option for future care.

Conclusion

Addressing these findings including greater flexibility of healthcare structures and better future planning could increase ability of patients with late-stage parkinsonism to remain at home and improve quality of life of patients in this late disease stage.
THUR 132 Neuroschistosomiasis: complication of a neglected tropical disease
Authors: Dorothy Joe , Thomas Boyle , Amit Roy , Guy Leschziner , Matthew Evans
Published: October 2018

Neuroschistosomiasis is an under-recognised complication of one of the world’s most prevalent, yet neglected parasitic diseases, which if left untreated can result in severe disability. Although schistosomiasis is most commonly found in the tropics, neurologists in developed countries must have a low index of suspicion in the appropriate clinical setting.

We describe a 17 year old previously fit and well Guinean lady presenting with subacute, progressive, symmetric lower limb hyperaesthesia and urinary retention. Neurological examination was consistent with a myeloradiculopathy. Initial tests revealed an eosinophilia and raised ESR. CSF and imaging findings supported the clinical diagnosis of myeloradiculopathy secondary to schistosomiasis. She responded well to empirical steroids and praziquantel with complete resolution of sensory and urinary symptoms over several weeks. Serology later confirmed the diagnosis.

Transverse myelitis and myeloradiculopathy affecting the conus medullaris and/or cauda equina are the most common presentations associated with neuroschistosomiasis. Symptoms are principally due to an inflammatory response to the retained schistosome eggs. This case details the differential diagnosis of a subacute myeloradiculopathy and highlights the importance of a thorough travel history. In the appropriate clinical context, neuroschistosomiasis should be included in the differential diagnosis of a subacute myeloradiculopathy, enabling prompt diagnosis and optimal management.
WED 139 Gene expression regulation in CD4+ t-cell dysfunction in ms
Authors: James Hrastelj , Nicholas Bray , Nigel Williams , Neil Robertson
Published: October 2018

Background

Genetic risk variants for complex disorders such as multiple sclerosis (MS) rarely encode protein. Growing evidence suggests risk variants regulate gene expression in specific disease-relevant cells by altering regulatory genetic sequences. This can be explored by correlating genotype at risk loci with expression of nearby genes (cis-regulation), with greatest sensitivity demonstrated in the most relevant cell types. Identifying genes under regulation by the MS risk variants could be a crucial step in identifying novel therapeutic targets.

Aims

1) Interrogate MS risk loci for cis-regulatory effects using allele-specific expression (ASE) analysis. 2) Establish a publicly available resource of genome-wide RNA-seq expression data in CSF-derived CD4 +T lymphocytes. 3) Correlate gene expression data with longitudinal clinical data to seek biomarkers of prognosis.

Method and progress

We have extracted RNA from FACS-sorted CSF-derived CD4 +T lymphocytes from over 100 individuals. cDNA library preparation and sequencing for each sample is underway.

Data analysis

ASE analysis makes use of a pre-selected transcribed SNP to differentiate maternal and paternal transcripts of each gene of interest. When an individual is heterozygous at an additional functional regulatory locus the ratio of maternal: paternal expression will deviate from 1:1. Each MS risk locus will be interrogated for this effect.