bluuebunny/crossref_metadata_2025 huggingface dataset:
WED 244 CSF cytology alone is unable to predict CNS neoplastic process
Authors: Alex Osborne , Channa Hewamadduma
Published: October 2018

Incidence of both primary and secondary central nervous system (CNS) malignancies are increasing, yet detection and diagnosis of which remains challenging. Neurological examination, CSF cytology and neuroimaging each offer diagnostic value, however, individually, each method has relatively low sensitivity. CSF cytology is often routinely requested as part of the diagnostic work-up. Therefore, we reviewed the value of CSF cytology in predicting CNS neoplastic process.

We systematically analysed 296 patients who had had CSF cytology. All consecutive patients over the last 2 years were included. The 12 patients positive for CSF cytology were also found to have concurrent; clinical findings (92%), radiological findings (92%), or both (83%). In no patient CNS malignancy was identified by CSF cytology alone. Additionally, only 7 of the 12 CSF positive cases were collected by means of lumbar puncture, the rest were carried out during neurosurgical procedures.

We conclude that if there is neither clinical findings nor abnormal neuroimaging, assessing CSF cytology does not contribute towards diagnosis of CNS malignancy. Yield of CSF cytology is high when both clinical and radiological evidence are present. Where neuroimaging is normal but suspicion remains, the low sensitivity of the CSF-cytology would make it a weak corroborator to exclude malignancy.
WED 261 Stroke scan agnosia – what radiologists do not see
Authors: Mark McCarron , Jacqueline McKee , Carrie Wade , Ferghal McVerry
Published: October 2018

Background

Neuroimaging helps clinicians make accurate diagnoses. Most stroke patients have their imaging reported by general radiologists.

Methods

As part of a quality assurance program a database for neurological patients with second opinion reporting from neuroradiologists was searched from 2008 to 2016 to identify patients in whom stroke lesions were missed at initial reporting by general radiologists. Patient demographics, scanning modality, stroke type, location and laterality were recorded.

Results

36 patients, 18 men, 18 women, mean age 59.0 (SD 13.8) years were identified in whom a stroke lesion was not detected on initial reporting. The lesions included cerebellar infarcts in 14 patients (bilateral in 3), pontine ischaemia/infarction (n=6), supratentorial infarction (n=9), vessel abnormality (n=6 – dense middle cerebral and basilar arteries, dissection and cerebral venous sinus thrombosis), and spinal infarction (n=1). In 9 (24%) patients the missed lesions occurred solely on CT brain scanning. The missed lesions were acute presentations in 8 (22%) patients.

Conclusion

Stroke lesions can be missed with both CT and MRI. The posterior fossa and dense artery signals (middle cerebral artery and basilar artery) are prone to detection errors.
THUR 265 Complaints from patients with functional disorders
Authors: Clare Bolton , Paul Goldsmith
Published: October 2018

Objective

To evaluate the nature of complaints from patients with functional neurological disorders and understand the reaction of UK neurology consultants to receiving complaints from this patient group.

Methods

A voluntary anonymised online retrospective survey was advertised to UK consultant neurologists. Questions asked about the nature of the complaint, how it was dealt with, how it affected their emotional wellbeing, attitude to work, and whether it influenced their clinical practice. The frequency of total responses was analysed. Respondents were given opportunities to add comments.

Results

Responses from 58 clinicians were included. The majority of complaints stemmed from patients not agreeing with their diagnosis. Respondents felt that complaints from patients with functional disorders tended to be more involved and personal than other complaints. Lack of awareness about functional conditions among non-specialists was also a common theme. For many respondents, the complaint adversely affected their emotional wellbeing. Following the complaint, defensive practice was more common, and working patterns were altered.

Conclusions

Complaints from patients with functional neurological disorders appear more difficult to resolve than other complaints, and clinicians who deal with them often become the ‘second victim’ in the process leading to potentially adverse effects on patient care. Strategies to tackle these issues are discussed.
WED 268 Improving junior doctors induction: queen square junior doctors handbook
Authors: Talal Al-Mayhani , Aytakin Khalil
Published: October 2018

Introduction

All junior doctors joining Queen Square undergo an induction package delivered along with the Queen Square Junior Doctors’ Handbook (QS-H). QS-H is supposed to provide general guidance to daily medical jobs in addition to useful clinical information, contact details and hints.

Aim

The aim of this quality improvement project (QIP) was to update, and improve, the quality of QS-H. The idea was that better and more informative induction can make carrying out daily jobs easier, increase the efficacy/effectiveness of medical staff and, ultimately, impact positively on patients care.

Methods

In this QIP a participatory assessment approach was employed where the opinions of the beneficiaries (junior doctors) were sought to screen for the strengths/weaknesses of the old version of QS-H, and to assess, later on, the new version.

Results and conclusion

Most junior doctors highlight the length of QS-H and the outdated information of its contents. Based on their suggestions a new, brief and practical version was drafted and was well received with some comments that led to additional round of improvement. Distributing hardcopies of QS-H around the wards further improved the junior doctors’ accessibility, efficiency, effectiveness and satisfaction.
WED 273 Wessex healthlines: neuroline
Authors: Pauline Lillistone , Rachel Chappell , Charlie Dukes , David Higenbottam , Christopher Kipps
Published: October 2018

Background

The ability to provide timely signposting to patient with neurological conditions seen in clinic is crucial, but information resources are not always available or updated. Individuals wishing to participate in clinical trials may find it difficult to locate research opportunities, and busy clinicians may not be aware of local clinical research studies. We sought to develop a means of collating, organizing and displaying information on neurological conditions and research trials in an easily accessible form online.

Methods

Over 350 local support groups, information resources and websites dealing with neurological conditions relevant to neurological patients in Wessex were identified. These were then displayed via a website that maps these resources, and offers a summary with a link to the primary source.

Results

Over the past year, the Wessex HealthLines site has been visited by over 2300 users, with the NeuroLine pages (wessexhealthlines.nhs.uk/neuroline) accessed by over 750 users. The site has now been expanded to include neurological research trials running in the region (ResearchLine).

Discussion

The Wessex HealthLines website (NeuroLine, ResearchLine) makes use of multiple resources to support information signposting in neurological conditions, and to clinical trials, across Wessex. Other regions interested in quality improvement projects may find this approach useful.
275 Poster: acute neurology care model – ‘the neuro network’
Authors: Fletcher Nick
Published: October 2018

The neuro network is a well-developed model in North West England and North Wales, hosted by the Walton Centre Liverpool. It is based on the principle of an equitable, locally accessible service taking responsibility for a regional population, rather than one based on a single unit or small area.

Centralised tertiary activity is based in Liverpool – for patients requiring specialised diagnostic or therapeutic intervention and care; particularly neurosurgery, thrombectomy, neurological ITU or frequent review of complex acute neurological disorders.

Acute neurological support is delivered to 12 acute sites across the region using a combination of consultant visits and ward liaison sessions (typically 3–4 days each week), telemedicine video consultations (presently being developed at pilot sites), 24/7 telephone advice and a weekday consultant advice line for GP’s. Patients are then treated, whenever possible, by a local medical team (or HASU) supported by a neurology management plan (and subsequent on-site or remote review if necessary) or by transfer to the centre if clinically appropriate.

The model offers acute neurology provision to a wide area, by the most effective, resilient and equitable deployment of limited resources.
278 Inspector norse
Authors: Amy Ross Russell , Luke Massey , Imogen Williams , Mark Fabian , James Nicoll , Efrem Eren , Emmanuela Pelosi , Martin Prevett , James Hell , Haider Katifi
Published: October 2018

A 26 year old, Caucasian, female student nurse presented with facial pains and vesicular rash, and over the following three days developed focal faciobrachial twitches. She was febrile, with an erythematous rash. Neurological examination was normal. MRI showed a non-enhancing lesion in the right medulla. CSF was normal with negative viral PCR. EEG demonstrated no seizure activity.

A month earlier she was treated with steroids and antibiotics for acute liver injury and maculopapular rash, of presumed allergic aetiology. On that admission, deficiency of Immunoglobulins A and G was noted prompting diagnosis of Common Variable Immune Deficiency, treated with IVIg.

Her conscious level deteriorated rapidly, requiring ventilation 10 days after admission. Repeat MRI showed a new subcortical inflammatory lesion. EEG showed new background slowing, and progressed to electrographic status, which continued despite six anticonvulsants, IV Propofol and Midazolam. Sequential imaging showed progressive deterioration with widespread inflammation and oedema, and consequent herniation. Life-support was withdrawn one month after presentation.

Post-mortem demonstrated T-lymphocytic inflammation with inclusion bodies suggesting viral encephalitis. Electron microscopy demonstrated filamentous viral particles. Measles PCR was positive in brain tissue and CSF, diagnosing Measles Inclusion Body Encephalitis. Serum measles IgM, previously reported as negative, was re-evaluated and tested positive.
279 Apraxia and the temporal lobe in action: a role for biological motion
Authors: Elisabeth Rounis , Gloria Pizzamiglio , James Kolasinski , Jane Riddoch , Dante Mantini , E Passingham Richard
Published: October 2018

Limb apraxia is a syndrome that affects the ability to perform skilful actions, despite intact elementary motor and sensory systems. Using voxel-based lesion symptom mapping in a large cohort of 387 stroke patients we determined the neuroanatomy of three tasks traditionally used to study praxis skills in patient populations: these included a meaningless gesture imitation task, a gesture production task involving pantomime of transitive and intransitive gestures and a gesture recognition task, involving recognition of these same categories of gestures. Lesions associated with reduced performance in these tasks involved an integrated network previously described in biological motion, with input areas comprising left pre-striate and occipital regions, left superior temporal sulcus and motor output areas comprising left premotor area, left striatum and the white matter underlying the left primary motor cortex. This study confirms a role for the left hemisphere in limb apraxia and supports the hypothesis it is a white matter disconnection syndrome, whilst shedding new light into the nature of the behavioural deficits described in the disorder comprising parts of an integrated network of brain areas described in biological motion.
282 Skull base dural AVF mistaken as cervical myelitis: a series
Authors: Dan Whittam , Saif Huda , Richard Pulicino , Arun Chandran , Mani Puthuran , Anu Jacob
Published: October 2018

Background

Cervico-medullary spinal cord lesions are usually inflammatory (or rarely neoplastic). Dural arteriovenous fistula (DAVF) is considered very unlikely in the cervical cord, particularly if the history is of an acute myelopathy.

Method

Case note review of five patients with skull base DAVF.

Results

All were men aged 60–69 years. Four were symptomatic for a month or less, followed by acute deterioration over hours-7days, mimicking myelitis. MRIs showed extensive T2-hyperintensity and swelling in the cervico-medullary region. Worsening after corticosteroids occurred in 3/4 patients and one needed ventilation. Conspicuous and unambiguous cord-surface vessels were present in only one patient. Clinical suspicion prompted digital subtraction angiography (DSA) in the other four patients. Median time from initial MRI to diagnostic DSA and embolization was 28 days (7–91 days). All patients survived with good clinical recovery.

Systematic retrospective review of MRIs showed lack of gadolinium enhancement in 4/5. CSF examination (n=4) showed normal leucocyte count in all cases and elevated protein concentration in 3/4 (0.6–1.2 g/L).

Conclusion

Skull base DAVF can mimic acute cervical myelitis. Steroids may prompt life-threatening clinical deterioration mistaken for ascending myelitis. A low threshold for angiography in the context of non-enhancing lesions and acellular CSF will facilitate earlier diagnosis and improve outcomes.
WED 026 ‘creating a neurological exam template for acute medical admissions’
Authors: Kieran McMullan , Janice Redmond
Published: October 2018

Introduction

There is sub optimal documentation of neurological exam findings in patient’s hospital records. Documented Neurological findings are often incomplete, omitted or scattered in various places in the clinical notes. This is important in the setting of acute neurological emergencies, where accurate documentation is vital in gauging potential deterioration/improvement in a patient’s condition.

Method

A chart review was performed on 80 patients referred to the Neurology consult service in St James’s Hospital between January-February 2018. All aspects of the Neurological exam findings documented in these charts were noted. A gold standard template for accurate recording of Neurological exam findings was then created and circulated to all Hospital NCHD’s. A repeat chart review was performed on 80 patients referred to Neurology Consults between March-May 2018 (following the circulation of this template) and results were compared.

Discussion

Record keeping varied according to different clinical parameters, being lowest for speech at just over 20% and highest for muscle power at over 70%. Globally there was a small but significant improvement (P Value<0.001) in the documentation rates of neurological exam parameters following circulation of the template. We plan to apply this template to all acute medical admissions in St James’s Hospital.
297 Genetic associations of ICD in parkinson’s disease
Authors: Richard Rees , Leon Hubbard , Yoav Ben-Shlomo , Donald Grosset , Nigel Williams , Huw Morris
Published: October 2018

Introduction

Impuse Control Disorders (ICD) are a potentially devastating side-effect of dopaminergic therapy in Parkinson’s disease (PD). We explore the genetic factors associated with ICD in Tracking Parkinson’s/PRoBaND – a UK-wide cohort of early-stage PD.

Methods

Participants were diagnosed with PD within 3 years and had longitudinal assessment including the Questionnaire for ICD in Parkinson’s (QUIP) for up to 5 years. We defined cases as having any positive response to the QUIP (lax criteria) or 2 positive responses in any domain (strict criteria). We performed a candidate-gene analysis based on systematic review, followed by a genome-wide association study. We used age at onset, gender, and three significant principle components as covariates.

Results

After clinical and genetic quality control steps, we analysed 1602 participants. Prevalence was significantly affected by classification criteria (strict/lax): ICD – 26.8%/11.1%, IRB 29.3%/27.2%, any 31.7%/41.9%. Six SNPs in dopamine, glutamate and adreno- receptor genes achieved nominal significance (p<0.05) in the candidate study. We have identified several SNPs in the GWAS that approach genome wide significance (p<5 × 10–7).

Conclusions

This work is the first genome-wide study of genetic determinants of ICD. Our findings support the hypothesis of genetic determinants of ICD in Parkinson’s and further work will allow understanding of the biology of ICD.
299 Immune-dysregulation in late onset myasthenia gravis
Authors: Girija Sadalage , Saiju Jacob , Paul Maddison
Published: October 2018

Introduction

The aim of our study was to establish if there were any clinical and immunological differences between early (EOMG) and late onset myasthenia gravis (LOMG).

Methods and results

We recruited 150 patients with myasthenia gravis making this the largest prospective cohort study in MG to date. Most (74%) patients have LOMG. Of these, 8 (5.33%) are seronegative. Most (88%) are positive for AChR Abs, 4% have MuSK, 2% LRP4 and 10% are double positive to AChR and MuSK Ab on CBA.

The incidence of LOMG is higher than EOMG. There is a statistically significant fall in AChR titre levels on serial measurement (p <0.0001). LOMG pts have higher AChR titres at recruitment compared to EOMG (p=0.0498) with higher MG composite scores (p=0.0287). Significantly higher numbers of LOMG pts are positive for AChR Ab on RIA in generalised MG compared to EOMG. A third of the pts with Early Onset Generalised MG are positive for MuSK Abs on CBA. There is no significant difference in clinical presentation between single seropositive pts Vs double seropositive pts. AChR Ab titres are lower in ocular EOMG versus ocular LOMG and titres in ocular patients are lower than in generalised patients.Flow cytometric analysis of PBMCs showed a significantly reduced percentage of Treg cells in our patient cohort compared to healthy controls (p<0.0001) and a significant difference in the levels of TNFa, IL10 and IL17 produced.

Conclusion

Our study has shown that there are clinical and immunological differences between early onset and late onset myasthenia gravis, both respond well to treatment with an improvement in composite scores and a fall in antibody titres. We are continuing to study this cohort of MG patients with extended follow-up.
WED 031 Neuro hot clinics: direct access clinic for acute medical patients
Authors: Z Clifford , P Morrish , C Strait , S Hinze
Published: October 2018

20% of acute medical patients present with neurological symptoms, yet are often managed by non-specialist acute physicians. This district general hospital (DGH) introduced a direct access neurology clinic, to reduce hospital admissions and improve access to neurological expertise for vulnerable patients. Patients would otherwise have been admitted to await ward consultation.

20 ‘Hot’ clinic appointments each week were allocated by administration prior to discharge from the medical admissions unit. All appointments were within 48 hours. Common diagnoses were migraine, first seizure, and non-epileptic attack disorder and rarer presentations included 5 with transverse myelitis, 1 with cerebral vasculitis, and 1 with Hepatitis E related encephalomyelopathy.

243 patients were seen by a Consultant Neurologist in 9 months in this hot clinic, thus saving at least 243 bed days and £73 000. Only 4 of these patients were readmitted. The hot clinic required 4PAs of consultant time split across weekdays, at an estimated cost of £30 000 per annum.

This neurology acute clinic successfully provided front door neurological input, a vital service for GPs and patients, and made approximate annual saving of £70 000. Evidently, every DGH should consider implementing neurology ‘hot’ clinics.
THUR 056 Juvenile myoclonic epilepsy in a tertiary centre – a database review
Authors: Marc Edwards , PEM Smith , Khalid Hamandi
Published: October 2018

Background

Juvenile myoclonic epilepsy (JME) is generally thought to respond well to first line treatment but many patients continue to suffer with seizure activity. This study reviews JME patients managed in a tertiary epilepsy centre.

Methods

A JME patient cohort with data on medication and seizure frequency was sourced from an epilepsy database at University Hospital of Wales, Cardiff.

Results

168 patients (18–84 years old) were identified with a diagnosis of JME and a clinic appointment in the past 5 years. There was a female predominance of 2.8:1. The average age at onset was 13.

56% patients were free of generalised tonic-clonic seizures with 40% free of all seizure types. Of those with frequent seizure activity, 66% were on at least 2 anti-epileptic drugs (AEDs). Levetiracetam was the most common therapy (48%). 32 women of childbearing age (32%) were taking Valproate with 71% under regular follow-up.

Conclusion

Whilst JME is considered to respond well to AEDs a significant proportion in our tertiary cohort were deemed drug refractory. However, this may show bias when compared to community samples. The number of women taking Valproate highlights the benefit of the drug and the need for careful monitoring and shared clinical decision making.
THUR 004 Foramen magnum decompression for tonsillar herniation secondary to meningoencephalitis
Authors: Barbara Wysota , Fardad Afshari , Michelle Oswall , Gordon Mazibrada , Edward White
Published: October 2018

Tonsillar herniation and coning is a rare complication of meningoencephalitis and is associated with poor neurological outcome. Our patient presented unresponsive with radiological evidence of tonsillar herniation secondary to meningoencephalitis. She underwent an emergency foramen magnum decompression and C1 laminectomy with full recovery.

16 years old female presented to her local ED with headache, vomiting, hallucinations, photophobia and neck stiffness. Her CT head was normal. She was commenced on acyclovir and ceftriaxone on the same day and clinically improved. LP performed 24 hours later showed WBC of 226 (200 lymphocytes, 6 polymorphs), protein 1.2 g/L, negative MC and S, negative viral PCR, negative TB PCR. CSF glucose was not sent. In light of a predominantly lymphocytic CSF and presumed viral meningitis antibiotics were stopped. Three days later acutely deteriorated. MRI head showed evidence of tonsillar herniation. She was restarted on antibiotics and was transferred to tertiary centre. She underwent emergency insertion of an EVD, foramen magnum decompression and C1 arch laminectomy. She made a full recovery with no residual neurological deficit.

The mainstay treatment of meningoenecephalitis is intravenous antibiotics. However, in cases complicated by tonsillar herniation with reactive pupils, foramen magnum decompression should be considered.
WED 094 Diagnostic error rates in diagnosing idiopathic intracranial hypertension
Authors: Sangeeta Scotton , Anthony Liczkowski , P Mollan Susan , J Sinclair Alexandra
Published: October 2018

Objective

To quantify the rate of diagnostic error amongst patients with IIH. Additionally to identify factors contributing to diagnostic error.

Methods

Sequential patients referred with a diagnosis of IIH to the Birmingham tertiary neuro-ophthalmology IIH clinic were prospectively included (October 2013- February 2017) A diagnostic error taxonomy tool was applied to cases referred as ‘definite’ or ‘possible’ IIH. Discrepancy between referred and final diagnosis were recorded.

Results

212 patients were referred, (96.2% female), 138/212 (65%) with definite IIH and 74/212 (35%) with possible IIH. Of those diagnosed with definite IIH 25% were not IIH and out of those diagnosed with possible IIH 57% were not IIH. Reasons for diagnostic error included incorrectly identifying papilloedema where in fact pseudopapilloedema existed and diagnosing IIH following an isolated lumbar puncture (LP) pressure >25 cmCSF (but in the absence of other diagnostic criteria for IIH). Misdiagnosis lead to 43% receiving unnecessary acetazolamide (or other diuretics) and 14% having multiple LPs.

Conclusions

We noted a high diagnostic error rate amongst IIH patients referred to a tertiary centre for ongoing management. Where there is doubt about the presence of true papilloedema early specialist review may reduce unnecessary treatment and LP’s.
WED 106 Unilateral abnormal dat scan: early indicator of parkinson’s disease
Authors: Nicholas Heng , Ying Chin Mei , Clare Monaghan , John Davidson , Tom Gilbertson , Miratul Muqit
Published: October 2018

Introduction

Dopamine transporter (DaT) scans are used in the investigation of clinically uncertain Parkinsonian syndromes (CUPS). Presently, bilateral abnormal DaT scans are diagnostic of Parkinson’s disease and degenerative Parkinsonism, while normal scans suggest non-degenerative causes. However, the clinical significance of unilateral abnormal scans remains ambiguous. Therefore, we aimed to determine their relevance in CUPS, and hypothesised that they may presage Parkinson’s disease and degenerative Parkinsonism.

Methods

A retrospective analysis was performed for patients with CUPS within a tertiary institution who had undergone DaT scans. Demographic data, clinical features, imaging and diagnoses were collected. In patients with unilateral scans, follow-up assessments, further imaging and diagnostic changes were also recorded.

Results

A total of 200 DaT scans were performed from 1 January 2008 to 1 January 2017. There were 100 (50.0%) with normal scans, 77 (38.5%) with bilateral scans, and 23 (11.5%) with unilateral scans. Of the latter group (n=23), 8 (34.8%) underwent follow-up DaT imaging in a mean period of 31.9±12.6 months from baseline, with 4 (17.4%) now reported as bilateral, although 2 (8.7%) remained unilateral and 2 (8.7%) were reported as normal.

Conclusion

Unilateral DaT scans can serve as a predictive factor for development of Parkinson’s disease and degenerative Parkinsonism.
THUR 117 The L-DOPA response in pathologically confirmed parkinson’s disease
Authors: Pitz Vanessa , Malek Naveed , Grosset Katherine A , Grosset Donald G
Published: October 2018

Background

l-dopa is the standard treatment for Parkinson’s disease, but the response is variable.

Aim

Systematic review of papers reporting the l-dopa response (motor response and/or complications) in pathologically confirmed Parkinson’s disease.

Results

467 cases of pathologically confirmed Parkinson’s were identified: 60.2% male, age at disease onset 63.3 years (SD 10.3), age at death 76.7 years (SD 7.8). Data on a graded l-dopa response were available in 411 cases (88.0% of 467). The motor response was excellent in 148/411 cases (36.0%), good in 179/411 (43.6%), moderate in 51/411 (12.4%) and poor/absent in 33/411 (8.0%). Data about motor complications were available for 161 patients: 71/161 (44.1%) had motor fluctuations and 89/161 (55.3%) had dyskinesia. Comorbid brain pathology was evaluated in 251/411 cases (61.1%), and was present in 148/251 (59.0%): cerebrovascular in 65/148 (43.9%), Alzheimer’s in 55/148 (37.2%), amyloid angiopathy in 18/148 (12.2%), and diffuse Lewy body disease in 10/148 (6.8%). Data linking the graded l-dopa response to comorbid pathologies were available in only 17 cases, of whom 8/17 (47.1%) had a good/excellent response.

Conclusion

There is variation in the l-dopa response in pathologically confirmed Parkinson’s disease. The limited available information suggests a possible association of motor response to comorbid brain pathology.
WED 130 Designing a care pathway for high risk parkinson’s patients
Authors: Chloe Tam Lok Yee , Dominey Thea , Pearson Emma , Murphy Fiona , Carroll Camille
Published: October 2018

Objective

To inform pathway design for patients at high risk of an adverse outcome at 5 years post-Parkinson’s disease (PD) diagnosis.

Background

In our service, all newly diagnosed patients follow a 12 month new patient pathway, which includes assessment with PDQ-39, NMS Quest and MOCA. Use of a prognostic calculator1 allows for refinement of the pathway according to patient need. Patients are classified as low (0–0.3), medium (0.31–0.79) or high (0.8–1) risk of an adverse outcome at 5 years (postural instability, dementia, death).

Aim

We aim to evaluate whether assessments in the newly diagnosed pathway identify additional care needs in higher risk patients.

Methods

An evaluation was carried out of our new patient database. Individuals who had the prognostic indicator performed (n=52) were included in the evaluation.

Results

Patients in the high risk groups were found to be older and more cognitively impaired than lower risk patients (p<0.05). MOCA scores negatively correlated with NMS Quest (r=−0.44, p<0.001) and PDQ-39 (r=−0.51, p<0.001) suggesting as cognition becomes impaired, NMS burden increases, and quality of life is reduced.

Conclusions

Additional care needs were identified in high-risk patients. These findings highlight additional resources are required in this patient cohort to ensure needs are met.

Reference

. Velseboer DC, et al. Development and external validation of a prognostic model in newly diagnosed Parkinson disease.
THUR 134 Isolated CNS histoplasmosis in an immunocompetent patient
Authors: Fatima Jaffer , Stephen Glass , Eli Silber , Naomi Sibtain , Tihana Bicanic , Lina Nashef
Published: October 2018

A 26-year-old Bolivian man presented with a 3 year history of occipital headaches and bilateral papilloedema. MRI showed communicating hydrocephalus and leptomeningeal enhancement. CSF analysis revealed an opening pressure of 32cmH2O, lymphocytic pleocytosis, protein 1.9 g/dL and CSF glucose 0.4 mmol/L. CSF AFB, bacterial and fungal culture, TB-PCR, 18S rDNA PCR, serum b-d glucan, and HIV were all negative. Serum ACE was normal. Steroids and methotrexate were commenced for probable neurosarcoidosis.

He had readmissions with recurrent headache, meningism, symptoms of raised intracranial pressure and development of limb spasticity and brisk reflexes. Repeat imaging demonstrated stable hydrocephalus. Despite immunosuppression and empirical TB treatment, he remained symptomatic with a persistently active CSF: maximum opening pressure 36cmH2O, protein 3.9 g/dL, WCC 205 lymphocytes and low CSF-to-serum glucose ratio on repeated therapeutic LPs.

After re-evaluation and positive CSF b-d glucan, a diagnosis of Histoplasma meningitis, without systemic dissemination, was confirmed by positive serological and CSF tests: positive immunodiffusion; yeast CFT 1:16; CSF EIA antigen 0.85 ng/ml.

He was treated with AmBisome, followed by oral itraconazole, with complete symptom resolution and improvement on interval imaging.

We discuss challenges in reaching a diagnosis of isolated histoplasmosis, its neurological manifestations and diagnostic pathway in evaluating patients with suspected CNS fungal infection.
WED 141 Pathological correlates of age at death in multiple sclerosis
Authors: Ruth Geraldes , Margaret Esiri , Jacqueline Palace , Gabriele DeLuca
Published: October 2018

Introduction

Few studies have investigated which pathological features, including systemic vascular disease (VD), associate with younger age at death in multiple sclerosis (MS) and this constitutes the aim of the present study.

Methods

A post mortem MS brain autopsy tissue was studied for 1)systemic VD scores 2)% brain plaque area and activity from a)frontal plus occipital white matter(WM), b)pons, and c)basal ganglia(BG), 3)frontal plus occipital cortex. These pathology measures, sex, disease duration (DD), and cause of death, were fitted into a regression model to explain age at death.

Results

34 MS cases (mean age 61.6±13.05 years, 58.8% females, DD 20.2±13.45 years) were included. Age at death decreased with increasing WM+pons+ BG (r=−0.382, r=0.02) and cortical (r=−0.299, p=0.03) demyelination, and WM+pons+ BG active plaques (r=−0.326, p=0.011) but increased with DD(r=0.298, p=0.016) and VD(r=0.329, p<0.0001). In the regression model only cortical demyelination (b=−0.39, p=0.014), DD (b=0.36, p=0.009) and VD (b=0.64, p=0.001) persisted.

Conclusion

Higher cortical demyelination associated with younger age at death. Systemic VD did not associate with younger age at death in this MS cohort.
WED 143 Chronic relapsing inflammatory optic neuritis (CRION) in the neuroinflammatory clinic
Authors: Oliver Cousins , Hina Khan , Sreedharan Harikrishnan
Published: October 2018

CRION is a rare cause of optic neuritis. It is usually bilateral, painful and associated with profound visual loss. Significant response to corticosteroid treatment is typical but relapse is common when treatment is withdrawn. We present 2 cases of possible CRION and discuss the diagnostic and management considerations.

Case 1: 50-year-old woman presented with right optic neuritis which spontaneous recovered. A year later she had left painful visual loss which improved with a short course of corticosteroids. MRI neuroaxis revealed left optic nerve enhancement. Non-specific, faint unmatched OCBs were detected. AQP4-IgG was negative. Nine months later she had further visual loss in her left eye. Prednisolone and azathioprine were commenced.

Case 2: 55-year-old woman with bilateral, painless visual acuity deterioration over two weeks. Investigations revealed negative anti-aquaporin 4 antibodies (AQP4-IgG), normal MRI of the neuroaxis, negative oligoclonal bands (OCBs) and visual evoked potentials showed bilateral delay. Serum ACE was slightly elevated. She was started on a tapering course of steroids and had significant visual acuity improvement.

The diagnosis of CRION involves the exclusion of other causes of optic neuritis, particularly multiple sclerosis (MS), Neuromyelitis Optica (NMO) and sarcoidosis. Correct diagnosis is important as aggressive and long-term immunosuppression is required.
THUR 149 ANCA/MPO vasculitis presenting with bilateral ischaemic optic neuropathy
Authors: Dwij Mehta , Charles Wade
Published: October 2018

An 80 year old gentleman presented with bilateral, sequential ischaemic optic neuropathy. He initially developed progressive loss of vision in left eye with loss of colour vision and subsequently developed similar symptoms in the right eye with headaches, weight loss, malaise and lethargy. His visual acuity dropped to 6/12 on the right and counting fingers on the left. He had a dense central scotoma in left eye with left-sided RAPD but no other focal neurological deficits.

Blood tests revealed an ESR of 107 with an MPO ANCA titre of 19. MRI brain with contrast showed prominent meningeal enhancement and infiltration with ischaemic changes in the brain. CSF analysis revealed WCC of 24 (95% lymphocytes), RCC 22 and protein 0.4 g/L with negative bacterial culture. Temporal artery biopsy was normal.

He was treated initially with IV methylprednisolone and 6 cycles of IV cyclophosphamide and subsequently put on methotrexate. His systemic symptoms have resolved completely and his visual acuity continues to gradually improve.

MPO-ANCA vasculitis can mimic temporal arteritis and should be considered in patients presenting with an ischaemic optic neuropathy. It is also a treatable cause of meningeal disease.
THUR 171 Natalizumab effectiveness and safety in top uk patients
Authors: Richard Nicholas , Karen Rosales , Stephanie Licata , Feisal Syed Farooq Syed , Caroline Smethurst
Published: October 2018

Introduction

The TYSABRI® Observational Program (TOP) is an ongoing, global open-label study enrolling natalizumab-treated relapsing-remitting multiple sclerosis patients in real-world settings. Country-specific data can provide information on natalizumab’s benefit-risk in local clinical practice.

Methods

Clinical outcomes in UK and rest of world (ROW) TOP patients were compared.

Results

As of May 2016, 134 UK and 5793 ROW patients were enrolled in TOP. Mean baseline Expanded Disability Status Scale (EDSS) score was 4.27 in the UK and 3.45 in ROW. Mean years on natalizumab was 3.52 in the UK and 3.04 in ROW. Annualized relapse rate (ARR) decreased by 89.7% (from 2.21 pre-natalizumab to 0.23 post natalizumab initiation; p<0.0001) in the UK and by 89.0% (from 1.99 to 0.22; p<0.0001) in ROW. In both cohorts, ARR decrease by baseline EDSS score was 91.0%–93.2% for <3.0 and 87.3%–88.9% for ≥3.0; mean EDSS score change from baseline over 6 years was <1.0. Overall, 9 of 134 UK patients (6.7%) experienced ≥1 serious adverse event.

Conclusions

Natalizumab demonstrated similar effectiveness in the UK and ROW cohorts. Safety in the UK cohort was consistent with natalizumab’s established safety profile.

Support

Biogen

Disclosures

RN: grant/travel support from Biogen; KR, SL, SFSF, CS: Biogen employees.
WED 183 Cladribine tablets effects on t cell subsets in patients with early ms
Authors: Stuve Olaf , Soelberg-Sorensen Per , Leist Thomas , Hyvert Yann , Damian Doris , Boschert Ursula
Published: October 2018

Background

Because of the durable clinical effects of cladribine tablets 3.5 mg/kg (CT3.5) in patients with multiple sclerosis, the influence of treatment on cells with regulatory immune function is of interest.

Objective

Examine effects on central memory; effector memory; and naturally occurring regulatory (nTregs) CD4 +T cells after first administration of CT3.5 in ORACLE-MS.

Methods

Peripheral blood T-lymphocytes were immunophenotyped at baseline, and Weeks 5, 13, 24, 48 in CT3.5 treated patients (n=41). Absolute numbers and proportions of central memory (CD4+RO+CCR7+), effector memory (CD4+RO+CCR7-), Th1-type (CD4+CXCR3+), nTregs (CD4+CD25+CD127-), including naïve-like and memory-like nTregs were measured.

Results

Greatest median reductions in absolute numbers occurred at Week-13 for effector memory cells (−54%); Week-24 for central memory (−63%) and Th1-type cells (−51%); with similar/slightly increased levels at Week-48. There was ~5% reduction in proportion of central memory cells, but no change in proportions of effector memory and Th1-type cells. Absolute numbers of nTregs (−48%), naïve-like (−67%) and memory-like nTregs (−42%) decreased by Week-48. nTregs and naïve-like nTregs proportions were unchanged. Proportions of memory-like nTregs slightly increased up to 48 Weeks.

Conclusion

CT3.5 administration has a comparable effect on CD4+ T cell subpopulations, with no dramatic shifts in proportions.

Disclaimer

http://medpub-poster.merckgroup.com/ABN2018DISC_ORACLE.pdf
WED 190 Teriflunomide pregnancy registry: design and enrolment
Authors: David Rog , Christine Lebrun-Frenay , Nicola Seferta , Myriam Benamor , Susan Colilla , Philippe Truffinet , Angelo Ghezzi
Published: October 2018

Introduction

Teriflunomide is contraindicated in pregnancy, based on developmental toxicity in rats and rabbits. During clinical development, despite requirements for contraceptive use, some pregnancies occurred. There were no signs of structural or functional deficits in newborns.

Methods

The multinational, prospective, observational International Teriflunomide Pregnancy Exposure Registry is enrolling teriflunomide-exposed pregnant women with MS. Signed informed consent is obtained prior to enrolment. In the UK, healthcare professionals submit information to the National Coordinating Centre (Manchester, UK). Infants are followed until 1 year old. Pregnancy outcomes, including birth defects and infant characteristics, are collected. Target recruitment: 196 women to achieve 104 live births, providing 80% power to detect 3.95-fold increase in risk of birth defects associated with teriflunomide exposure vs the European Surveillance of Congenital Anomalies (EUROCAT) network.

Results

As of 26/04/2017, 14 patients have been recruited from 7 European countries (none in the UK). Six healthy babies have been born to date. One patient had an elective termination not motivated by abnormal prenatal test results or concerns regarding potential birth defects.

Conclusion

This registry aims to provide data on pregnancy outcomes and infant development from teriflunomide-exposed women, which may help physicians provide better patient advice.

Study supported by Sanofi.
THUR 192 Yearly lymphopenia rates in cladribine tablets-treated rms patients
Authors: Cook Stuart , Comi Giancarlo , Giovannoni Gavin , Rieckmann Peter , Soelberg-Sorensen Per , Vermersch Patrick , Dangond Fernando , Hicking Christine
Published: October 2018

Background

Cladribine tablets 3.5 mg/kg (CT3.5) demonstrated efficacy in RMS patients in CLARITY/CLARITY-Extension. Lymphopenia was common (CT3.5: mechanism of action).

Objective

Evaluate whether lymphopenia persists following treatment/re-treatment with CT3.5 in CLARITY/CLARITY- Extension.

Methods

Lymphopenia by grade for patients randomised to CT3.5 throughout CLARITY/CLARITY-Extension (7 mg/kg cumulative 4 year dose; n=186) are reported. Patients with Grade 0 (G0) lymphopenia (≥1.0 × 109 cells/L) before the first course of CT and G0/1 (≥0.8 × 109 cells/L) before subsequent treatment in Years 2 (Y2), 3 and 4 were analysed.

Results

176 patients were G0 at the start of CLARITY (167 were G0/1; CLARITY-Extension). G3 lymphopenia was observed in 1% patients (Week-13, Y1), and in 7%, 11% and 12% patients at Week-12 in Y2, 3 and 4. In each year, G3 lymphopenia was observed in 1%, 4%, 4% and 4% patients (Week-24), in 1%, 2%, 2% and 2% patients (Week-36), and in 1% patients (Week-48) in Y2 only. G3 lymphopenia was reported in <18% patients at any time-point. No patients had G4 lymphopenia at the end of each treatment year.

Conclusions

In patients meeting treatment/re-treatment guidelines, no G4 lymphopenia occurred at the end of any treatment year; G3 lymphopenia was uncommon. Lymphocyte-based re-treatment criteria minimised the incidence of severe, sustained lymphopenia during 4 years’ treatment with CT.

Disclaimer

http://medpub-poster.merckgroup.com/ABN2018DISC_Year1-4.pdf
Assessing the risk of preterm birth for newborns with congenital heart defects conceived following infertility treatments: a population-based study
Authors: Tararbit Karim , Lelong Nathalie , Goffinet François , Khoshnood Babak
Published: October 2018

Objectives

To quantify the risk of preterm birth (PTB) for newborns with congenital heart defects (CHDs) conceived following infertility treatments, and to examine the role of multiple pregnancies in the association between infertility treatments and PTB for newborns with CHD.

Methods

We used data from a population-based, prospective cohort study (EPICARD EPIdémiologie des CARDiopathies congénitales) including 2190 newborns with CHD and excluding cases with atrial septal defects born to women living in the Greater Paris area between May 2005 and April 2008. Statistical analysis included logistic regression to take into account potential confounders (maternal characteristics, invasive prenatal testing, CHD prenatal diagnosis, medically induced labour/caesarean section before labour, birth year). The role of multiple pregnancies was assessed using a path-analysis approach, allowing decomposition of the total effect of infertility treatments on the risk of PTB into its indirect (mediated by the association between infertility treatments and multiple pregnancies) and direct (mediated by mechanisms other than multiple pregnancies) effects.

Results

PTB occurred for 40.6% (95% CI 28.7 to 52.5) of newborns with CHD conceived following infertility treatments vs 12.7% (95% CI 11.3 to 14.2) for spontaneously conceived newborns (p<0.001). After taking into account potentially confounding factors, infertility treatments were associated with a 5.0-fold higher odds of PTB (adjusted OR=5.0, 95% CI 2.9 to 8.6). Approximately two-thirds of this higher risk of PTB associated with infertility treatments was an indirect effect (ie, due to multiple pregnancies) and one-third was a direct effect (ie, not mediated by multiple pregnancies).

Conclusion

Newborns with CHD conceived following infertility treatments are at a particularly high risk of PTB, exposing over 40% of them to the ‘double jeopardy’ of CHD and PTB.
Characterisation of circulating biomarkers before and after cardiac resynchronisation therapy and their role in predicting CRT response: the COVERT-HF study
Authors: McAloon Christopher J , Barwari Temo , Hu Jimiao , Hamborg Thomas , Nevill Alan , Hyndman Samantha , Ansell Valerie , Musa Anntoniette , Jones Julie , Goodby Julie , Banerjee Prithwish , O’Hare Paul , Mayr Manuel , Randeva Harpal , Osman Faizel
Published: October 2018

Aims

Cardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome.

Methods

A prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6  weeks and 6  months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6  min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486).

Results

A total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5  ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6  m, MLHFQ=46.4±21.3  and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3  and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response.

Conclusion

No specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study.

Trial registration number

NCT02541773.
Cannabis and epilepsy
Authors: Thomas Rhys H , Cunningham Mark O
Published: October 2018

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The one-third of people who do not gain seizure control through current treatment options need a revolution in epilepsy therapeutics. The general population appears to be showing a fundamental and rapid shift in its opinion regarding cannabis and cannabis-related drugs. It is quite possible that cannabidiol, licensed in the USA for treating rare genetic epilepsies, may open the door for the widespread legalisation of recreational cannabis. It is important that neurologists understand the difference between artisanal cannabidiol products available legally on the high street and the cannabidiol medications that have strong trial evidence. In the UK in 2018 there are multiple high-profile reports of the response of children taking cannabis-derived medication, meaning that neurologists are commonly asked questions about these treatments in clinic. We address what an adult neurologist needs to know now, ahead of the likely licensing of Epidiolex in the UK in 2019.