bluuebunny/crossref_metadata_2025 huggingface dataset:
INDOMETHACIN TEST USAGE AT UNITED KINGDOM TERTIARY CENTRES OVER 20 YEARS-AN AUDIT
Authors: Bose Pyari , Palethorpe DG , Marin J , Nesbitt A , Lowe J , Goadsby PJ
Published: October 2015

Background

Indomethacin-responsive trigeminal autonomic cephalalagias (TACS), paroxysmal hemicrania (PH) and hemicrania continua (HC), are unique, important syndromes to understand.

Aim

Evaluation of the role of the placebo-controlled indomethacin test (P-Indotest) in the diagnosis of primary headache disorders.

Method

Patients notes, clinic letters and headache diaries of patients under our care (PJG) over a 20 year period across various UK Neurology tertiary care centres were examined to obtain data against an audit collection tool. A pre-determined set of data were extracted, and the test procedure reviewed for compliance against a standard with minimum data set requirement by an unblinded observer. The original test score was noted, and prospectively re-scored by a blinded observer.

Results

Patients (n=7; 4 female) were aged from 24 to 51 years. The majority (85%) had side locked headache. P-Indotest was positive in 78% of the cases with patients having either HC or PH. Of all patients tested, 42% had unilateral photophobia and phonophobia and all these cases had a positive response. No serious adverse events were noted. Sleepiness was often reported on the active treatment as was transient worsening of headache in unilateral chronic migraine. Further data is being compiled.

Conclusion

The P-IndoTest is a reliable and safe test and should in the diagnosis of patients with possible indomethacin sensitive TACs. While far from ideal, a positive indomethacin test does identify a particular biology and should be retained as a diagnostic marker of PH and HC until its basis is understood.
A FRAMEWORK FOR MANAGING AND MONITORING NEUROLOGY REFERRALS
Authors: Ng Melissa J , Anderson Jane M , Joannides Alexis J
Published: October 2015

Objectives

Management of emergency referrals is an important component of neurology inpatient practice. On this background, we have developed and implemented a robust electronic framework for referral recording and analysis.

Design

Codes representing all possible referral outcomes were defined and refined in response to user feedback. Further datasets for presenting symptoms, candidate anatomical syndrome and working diagnosis were developed to enable further epidemiological analysis.

Methods

Aggregate referral data from the first year of implementation (1/7/13 to 30/6/14) were analysed with respect to demographics, underlying pathology and management outcome.

Results

A total of 1896 referrals were recorded during the study period, with a mean of 5.9±0.22 per day and a constant activity level throughout the year. Weekly and daily variations were observed, with lower levels of activity outside working hours. Age distribution showed a peak at 50–69 years. The commonest diagnostic categories included cerebrovascular pathology, epilepsy/loss of consciousness, and headache/facial pain, which together represented 49.8% of referrals. Of these, headache-related disorders most often required further neurological management (61% of cases), thus representing a greater area of clinical activity.

Conclusions

Overall, our results demonstrate the feasibility of efficient referral analysis through structured electronic data capture, with potential implications for service evaluation and epidemiological research.
USING NHS PRIMARY CARE DATA TO IDENTIFY UNDIAGNOSED DEMENTIA
Authors: Jammeh Emmanuel , Carroll Camille , Pearson Stephen , Escudero Javier , Anastasiou Athanasios , Zajicek John , Ifeachor Emmanuel
Published: October 2015

Background

Up to 50% of patients with dementia may not receive a formal diagnosis, limiting access to appropriate services. It may be possible to build a picture of ‘underlying undiagnosed dementia’ from a profile of symptoms recorded in routine clinical practice.

Aim

To develop a machine learning tool to identify patients who may have underlying dementia but have not yet received formal diagnosis from analysis of routinely collected NHS data.

Method

Routinely collected NHS READ-encoded data were obtained from 18 consenting GP surgeries across Devon, UK, totalling 26,483 patient records of those aged >65 years. 539 Patients were identified as having dementia within the 2 year study period (June 2010 to June 2012). We determined other codes assigned to these patients that may contribute to dementia risk. The dataset was used to train a supervised classifier (Naives Bayes) to discriminate between patients with underlying dementia and healthy controls using a ten-fold cross-validation approach.

Results

The model obtained a sensitivity of 72.31% and a specificity of 83.06% for identifying dementia.

Conclusion

Routinely collected NHS data can be used to identify patients who are likely to have undiagnosed dementia. This type of methodology is promising for increasing dementia diagnosis within primary care.
DURAL AVF CAUSING A TREATABLE CJD LIKE COGNITIVE DYSFUNCTION
Authors: Randall Anna , Ellis Richard James Booth , Hywel Brython , McCoy Christopher Andrew , Davies Rhys , Eldridge Paul Richard , Putharan Mani , Radon Mark , Alusi Sundus
Published: October 2015

A 67-year-old woman presented with a seven-month history of progressive psychiatric disturbance and sub-acute cognitive decline mimicking Creuztfeldt-Jakob Disease.

She presented initially to Psychiatry with worsening anxiety, depression, lassitude, impaired concentration and insomnia. She was given a diagnosis of agitated depression.

She subsequently experienced episodes of disorientation, indecision and inability to complete routine, learned tasks as well as visual hallucinations. Initial investigations for causes of subacute dementia were unremarkable including a non-diagnostic MRI. However, five months into her presentation, there was further rapid deterioration with fluctuating consciousness and deteriorating mobility. She became bedbound, incontinent and cortically blind. She had right hemiparesis, hemineglect, extrapyramidal features, and extensor plantars.

A 4D computerised tomography angiogram demonstrated a dural arteriovenous (AV) fistula with retrograde filling of superior sagittal sinus and cortical venous congestion. She underwent emergency Onyx embolisation. Over a few weeks, there was gradual improvement in her anxiety, cognition and mobility. She had a mild residual right hemiparesis.

Intracranial dural AV fistulae can present with a spectrum of neurological symptoms, including cognitive decline. A lowhigh index of suspicion combined with close liaison between Neuroradiology, Neurology and Neurosurgery ensures prompt diagnosis and maximises the potential for cognitive recovery.
CONFUSION IN CLINICAL TRIALS OF ALZHEIMER'S DISEASE
Authors: Hobart Jeremy , Cleanthous Sophie , Zajieck John , Cano Stefan
Published: October 2015

Background

Neurology clinical trials frequently use clinical outcome assessment instruments (COAs) as outcome measures. We question the extent to which measurement limitations of COAs contribute to clinical trials failures in Alzheimer's disease.

Objectives

We conducted a series of literature reviews to: identify the concepts assessed in AD clinical trials, and how these concepts were defined and measured; identify which COAs have been used in AD clinical trials, and on which grounds they were selected. We examined published measurement properties of COAs used in AD clinical trials in accordance with FDA guidance.

Results

A set of literature reviews identified >6500 publications from PUBMED/EMBASE inception. In the extracted 850 articles, 984 uniquely named concepts were assessed and 1283 COAs were used. However, few trials provided definitions of the concepts they measured; very different COAs were used to measure the same (named) concepts; the same COAs were used to measure different concepts; COA selection was rarely justified or evidence-based. Further reviews of COA development papers (n=174) indicated most fail to meet recommended criteria.

Conclusions

Findings imply substantial measurement confusion in AD clinical trials and suggest they have provided weak evaluations of treatment effectiveness. Findings were replicated in Parkinson's disease (n366 articles).
MINI-ADDENBROOKE'S COGNITIVE EXAMINATION (M-ACE): PRAGMATIC STUDY
Authors: Larner Andrew
Published: October 2015

Objective

To test diagnostic accuracy of the mini-Addenbrooke's Cognitive Examination (m-ACE) compared to the MMSE for the diagnosis of dementia and MCI in consecutive referrals to a dedicated cognitive disorders clinic.

Results: Of 135 consecutive new outpatients seen over 6 months (June–November 2014) administered the mini-ACE (F:M=64:71, 47% female; age range 18–88 years, median 60), 24 were diagnosed with dementia (DSM–IV–TR criteria) and 39 had MCI (Petersen criteria). Using the cutoffs defined in the index paper (≤25/30 and ≤21/30), m-ACE was sensitive (1.00, 0.92) but not specific (0.28, 0.61) for dementia diagnosis; it also proved useful for MCI diagnosis (sensitivities 1.00, 0.77; specificities 0.43, 0.82). Area under the ROC curve was 0.86. Effect size (Cohen's d) for m-ACE for dementia vs. no dementia was 1.53 (large) and for MCI vs no cognitive impairment was 1.59 (large); for MMSE the corresponding figures were 1.56 and 1.26. Weighted comparison suggested a small net loss for m-ACE vs MMSE for dementia diagnosis (–0.13) but a large net benefit for MCI diagnosis (0.38).

Conclusions: In this pragmatic study, m-ACE proved quick, easy to use, and acceptable to patients, with metrics comparable to MMSE for dementia diagnosis and better for MCI diagnosis.
DOES UNDERSTANDING BASIC NEUROSCIENCE CURE NEUROPHOBIA?
Authors: Charalambous Nicholas , Goh Adrian , Los Ferenc , Sharma Kanch
Published: October 2015

Introduction

Neurophobia – ‘a fear of the neural sciences and clinical neurology’1 is an established phenomenon amongst medical students and physicians.1–3 Conclusions from previous studies indicate a need for more neurology teaching,2 3 with basic neuroscience felt to be extremely useful.2 This study examines whether a concise, focused tutorial integrating basic neuroscience with clinical neurology helps overcome neurophobia.

Methods

Students from the University of Bristol (n=56) were surveyed using quantitative and qualitative questions pre/post/1 month after a 15 minute tutorial on neurological examination, integrating the relevant anatomy and physiology with clinical findings.

Results

Analysis was performed using Wilcoxon signed ranks and Freidman testing. Comparing pre and post surveys there was a statistically significant improvement (p<0.05) in knowledge, confidence and understanding of clinical signs. Importantly this increased confidence persisted when students were re-surveyed 1 month later. Responses to difficulties faced when learning neurology include the following themes (1) complex/overwhelming subject, (2) lack of teaching, (3) inability to correlate neuroanatomy with clinical presentation.

Conclusion

When teaching students (or even clinicians) with “neurophobia”, always commence with a review of basic neuroscience as a foundation on which to build an understanding of neurological function in health and disease.
SAFETY AND EFFICACY OF ESLICARBAZEPINE ACETATE IN ELDERLY PATIENTS
Authors: Costa R , Lopes N , Gama H , Sousa R , Nunes T , Soares-da-Silva P
Published: October 2015

Purpose

To evaluate the safety/tolerability and efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy in elderly patients with partial-onset seizures (POS).

Method

Phase III, multicentre, open-label, non-controlled study in patients aged ≥65 years with ≥2 POS during an 8-week baseline and treated with 1–2 antiepileptic drugs. Following baseline, patients entered a 26-week maintenance period. ESL was initiated at 400 mg once-daily and adjusted (400–1200 mg/day) based on individual response. Safety/tolerability evaluations included treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiogram and physical/neurological examinations. Efficacy evaluations included change in standardised seizure frequency (SSF; seizure frequency/4 weeks).

Results

Of the 72 patients included, 47 (65.3%) experienced 152 TEAEs; most commonly, dizziness (12.5%), somnolence (9.7%), fatigue (8.3%), convulsion (8.3%) and hyponatraemia (8.3%). Three patients died of cardiac failure, glioblastoma multiforme and ischaemic stroke (relationship unlikely/not related). Overall, 16 (22.2%) patients discontinued due to TEAEs. Incidence of clinically significant findings was low for vital signs, electrocardiogram and physical/neurological examinations. SSF decreased from 2.9 at baseline to 1.2 during the maintenance period (median relative change: –54.1%).

Conclusion

Once-daily ESL (400–1200 mg) as adjunctive therapy in elderly subjects with POS did not raise major safety concerns and was efficacious. Supported by Bial.
ADJUNCTIVE PERAMPANEL RCT FOR PGTC SEIZURES
Authors: French Jacqueline , Krauss Gregory , Wechsler Robert , Wang Xuefeng , DiVentura Bree , Brandt Christian , Trinka Eugen , O'Brien Terence , Laurenza Antonio , Patten Anna , Bibbiani Francesco
Published: October 2015

We assessed efficacy and safety of perampanel (selective noncompetitive AMPA receptor antagonist) for primary generalised tonic-clonic (PGTC) seizures. Patients ≥12years with confirmed IGE; ≥3 PGTC seizures/8 weeks prior to randomization; receiving 1–3 concomitant AEDs were recruited. Trial consisted of 4–week screening; 4–8 week Baseline, 1:1 Randomization (perampanel titrated over 4 weeks to 8mg or highest tolerated dose versus placebo), 13–week Maintenance, 4–week Follow-up and Extension Phases. 164 patients were randomized; full analysis set included 81 patients each on perampanel and placebo. Median percent change in PGTC seizure frequency/28 days during Titration/Maintenance versus Baseline was –76.5% with perampanel versus –38.4% placebo; P<0.0001. 50% PGTC seizure responder rate was 64.2% with perampanel versus 39.5% placebo; P=0.0019. During Maintenance, 30.9% of perampanel patients were free of PGTC seizures versus 12.3% placebo. Treatment-emergent AEs (TEAEs) occurred in 82.7% of perampanel and 72.0% placebo patients; most common dizziness, fatigue, headache, somnolence, irritability. Serious TEAEs occurred in 6 (7.4%) perampanel and 7 (8.5%) placebo patients (one death in the perampanel group [accidental drowning; not treatment-related],one with placebo). In conclusion, adjunctive perampanel treatment up to 8mg improved seizure control in PGTC seizure patients, with almost 1/3 free of PGTC seizures during Maintenance. Perampanel was well tolerated. Study sponsor: Eisai Inc.
EPILEPSY IN THE ELDERLY: GETTING TO THE HEART OF THE MATTER, A CASE REPORT
Authors: Jones Lliwen , Johnston Ann
Published: October 2015

A 77-year old man presented following two episodes of altered awareness, with facial and hand automatisms. He had been seizure-free for 23 years, taking phenytoin following excision of a meningioma.

A diagnosis of symptomatic temporal lobe focal seizures was made and phenytoin substituted with carbamazepine. A 12-lead electrocardiogram (ECG) revealed prolonged PR interval of 288 milliseconds. MR imaging revealed a residual right temporal lobe cystic lesion with focal enhancement. Following discussion at the epilepsy-cardiology multidisciplinary meeting (MDT) and anticipating a neurosurgical/anaesthetic work-up, a 24-hour ECG was performed, which demonstrated high grade atrioventricular block with 6.5 seconds of ventricular standstill.

He was admitted as an emergency, during which he collapsed with further ventricular standstill. He underwent pacemaker insertion, remaining seizure-free.

This case illustrates the challenges of epilepsy consultations and management in the elderly with dual pathology. The urgency here was not the potential re-occurrence of the brain lesion, but the conduction abnormality which unmasked serious cardiac pathology. Careful evaluation of the ECG is vital in all patients presenting with episodes of altered consciousness however the pursuit of a recognised benign cardiac conduction abnormality may in the elderly just prove life-saving. The value of a dedicated epilepsy-cardiology MDT therefore cannot be underestimated.
SCREENING FOR DEMENTIA: IS 1 SIMPLE QUESTION THE ANSWER?
Authors: Aji Baba , Larner Andrew
Published: October 2015

Objective

To examine the diagnostic utility of the dementia screening question from the DoH Dementia CQUIN document (2012) in consecutive patients in a dedicated epilepsy clinic, individuals in whom memory complaints are common.

Results

100 consecutive outpatients (M:F=61:39, median age 44.5 years) were asked ‘Have you been more forgetful in the past 12 months to the extent that it has significantly affected your life?’, as advocated in the Dementia CQUIN document. There was a 48% yes response. No patient was adjudged to have dementia. Comparing the yes/no groups, there was no difference in sex ratio, age, seizure type, or use of antiepileptic drugs (monotherapy versus polytherapy). Those answering yes were more likely to be follow-up than new patients. Intergroup difference in epilepsy duration showed a trend to longer duration in the yes group. The most common examples of memory problems volunteered were forgetting to attend appointments, take medications, or switch off appliances, suggestive of attentional rather than mnestic problems.

Conclusions

These data suggest that the Dementia CQUIN screening question has very low specificity, and hence will identify many false positives, with risk of overdiagnosis of dementia in individuals with purely subjective memory impairment.
A NOVEL LGI1 VARIANT IN LATERAL TEMPORAL LOBE EPILEPSY
Authors: Pickrell WO , Hope CHD , Higgins AT , Mullins JGL , Smith PEM , Rees MI , Chung SK
Published: October 2015

Background

We identified a family with autosomal dominant lateral temporal lobe epilepsy (ADLTLE). Given that LGI1 mutations account for around 50% of families with ADLTLE, we screened family members for LGI1 variants.

Method

We sequenced all exonic regions of LGI1 and used in-silico analysis tools to assess the potential affect of the novel variant. We screened 106 control samples for the variant and assessed the structural effect of the variant using a protein modelling platform.

Results

The proband's seizures consist of an unilateral ‘buzzing’ sensation which progresses to unilateral limb numbness and secondarily generalised seizures. Some noises can provoke seizures. Her mother also has epilepsy with identical seizure semiology. We identified a novel heterozygous missense LGI1 variant in the proband and her mother which was not present in other family members or control samples. This variant is close to the splice site region of LGI1 exon 4 and is predicted to be deleterious. Protein modelling suggests that the variant causes conformational structural changes.

Conclusion

We present a family with ADLTLE caused by a novel variant in LGI1. This variant is predicted to be deleterious, alters protein function and adds additional evidence for the role of LGI1 in ADLTLE.
THE INSULA: ISLAND OF REIL
Authors: Wynford-Thomas Ray , Powell Rob
Published: October 2015

Just as ‘no man is an island’, despite its misleading name, the insula is not an island. Sitting deeply within the cerebrum, the insular cortex and its connections play an important role in both normal brain function and seizure generation. Stimulating specific areas of the insula can produce somatosensory, viscerosensory, somatomotor and visceroautonomic symptoms, as well as effects on speech processing and pain. Insular onset seizures are rare, but may mimic both temporal and extra-temporal epilepsy and if not recognised, may lead to failure of epilepsy surgery. We therefore highlight the semiology of insular epilepsy by discussing three cases with different auras. Insular onset seizures can broadly be divided into three main types both anatomically and according to seizure semiology:

1. Seizures originating in the antero-inferior insula present with laryngeal constriction, along with visceral and gustatory auras (similar to those originating in medial temporal structures).

2. Antero-superior onset seizures can have a silent onset, but tend to propagate rapidly to motor areas causing focal motor or hypermotor seizures.

3. Seizures originating in the posterior insula present with contralateral sensory symptoms.
FRONT DOOR NEUROLOGY: THE GP EXPERIENCE
Authors: Binks Sophie , Green Liz
Published: October 2015

Introduction

Neurological symptoms are common in primary care and may represent 10% of consultations. With fewer neurologists in the UK compared to other European nations, the RCGP encourages GP engagement with neurological disease. This project sought to delineate neurological presentations to a large Brighton GP practice.

Method

During a four-month GP placement, an FY2 doctor recorded details of patients presenting with neurological symptoms. In tandem, six months of neurology referrals by the permanent GPs were analysed.

Results

Common symptoms among 29 FY2 neurologically-oriented appointments included headache (n=8), paraesthesiae (n=4) and funny turns (n=3). Significant new diagnoses included right LACS, post-concussion syndrome and cervical radiculopathy. Most (65%) of patients were managed in GP. Those referred included two to TIA clinic, one to A&E and one to headache service. Of 12 GP referrals reviewed, no neurological examination was documented in 25%, and six provisional diagnoses were in agreement with neurological opinion. After neurology outpatient review, two patients were assessed as having no neurological problem.

Conclusions

Headache forms a large component of primary care neurology, but a variety of cases is seen. Acute presentations may be referred to TIA clinic or A&E. Where stated, GP opinion was frequently in line with neurology review.
CEREBRAL FAT EMBOLISM: SUSCEPTIBILITY-WEIGHTED IMAGING IS USEFUL AND PROGNOSIS CAN BE GOOD
Authors: Datta Sayan , McIntosh Catriona , Craven Ian , Macmullen-Price Jeremy , Jung Agam , Lily Oliver
Published: October 2015

We present two cases of cerebral fat embolism. Both patients were 21-years old, male and involved in high impact road traffic collisions with no immediate neurological deficits.

Patient A underwent intra-medullary nailing of right tibia/fibular fractures within 12 hours, and had external fixation for bilateral distal femoral fractures. Post-operatively, GCS was 6. Subsequent intracranial MR imaging showed widespread cerebral hypointense punctate foci on SWI (susceptibility-weighted imaging), some with associated restriction on DWI (diffusion-weighted imaging). Despite initial period of coma lasting weeks and inpatient admission over 5 months, he has been discharged to a neuro-rehabilitation unit and continues to show physical and cognitive improvement (MRS score of 3).

Patient B underwent intra-medullary nailing for a femoral shaft fracture within 24 hours. Post-operatively, GCS was 9, he developed a petechial rash and became hypoxic. MR brain showed bilateral centrum semiovale DWI restriction, and again, widespread SWI punctate abnormalities. He was discharged within weeks and currently lives at home with his parents (MRS of 2).

These cases show the spectrum of radiological abnormalities, the utility of SWI, and highlight that although neurological injury may be severe, there is potential for significant recovery.
WHAT IS THE NIN TELLING US?
Authors: Morrish Paul
Published: October 2015

Data collected by the Health and Social Care Information Centre and Public Health England is throwing light on the way neurology services are needed and delivered in England. GP recorded epilepsy prevalence varied between CCG's, from 456 to 1115 people with epilepsy per 100,000 population. Community spending on anticonvulsant drugs varied between £210,000 and £690,000 per 100,000 population. Percentage of epilepsy patients with 12 months seizure freedom varied between 45% and 74%. Admissions due to epilepsy ranged between 2 and 17 admissions per 100,000 residents. Community spending on headaches and migraine varied between £69,000 and £12,000 per 100,000 residents whilst admissions due to headache and migraine varied between 8 and 134 admissions in 2012–3. Admissions with Parkinson's disease varied between 2 and 21 per 100,000 residents whilst community spending on this illness varied between £183,000 and £36,000 per 100,000. In 2012–3 there was a sevenfold difference between CCG's in neurology appointments provided, from 809 to 5,633 appointments per 100,000 population. 46 CCG's provided no new neurology appointments in their own area, whilst 14 CCG's provided over 90% of new appointments in their own area. 4.86% of all neurology appointments in England were provided by one hospital trust.

These sample headlines show how data are being collected and can be analysed to prompt questions and research, to inform commissioners and providers and to improve the quality of care for patients with neurological illness in England.
MITOCHONDRIAL CYTOPATHY PRESENTING WITH CEREBELLAR ATAXIA
Authors: Pegg Emily , Dodd Katherine , Shaunak Sandip
Published: October 2015

A previously fit and well 59 year old man presented with a 3 year history of slowly progressive decline in mobility with increasing unsteadiness and falls. He also reported clumsiness of both hands and his wife noted poor memory. There was no family history of note, including deafness and diabetes. He drank alcohol occasionally. On examination he had signs consistent with a cerebellar and pyramidal syndrome with subcortical cognitive impairment.

An MRI scan of the brain and spine showed significant generalised cerebral atrophy. CSF protein was 0.80g/L, with normal cell count and no oligoclonal bands. Blood tests were normal or negative for antineuronal antibodies, vitamin E, coeliac disease, autoimmune screen. Genetic tests for spinocerebellar ataxias, Freidreich's, fragile X syndrome and DRPLA were also negative. Muscle biopsy revealed mitochondrial aggregation with COX negative fibres, in keeping with a mitochondrial disorder. Genetic testing found a novel mtDNA variant (p.GLY46Asp) at low levels within the MT-CO3 gene.

He has subsequently developed myoclonus and generalised tonic clonic seizures but there is no evidence of other system involvement.

Mitochondrial disorders should be considered in the differential diagnosis of cerebellar ataxia, even in the absence of multisystem involvement or a significant family history.
URINARY, BOWEL AND SEXUAL FUNCTION IN PATIENTS WITH FRIEDREICH'S ATAXIA
Authors: Lad Meher , Parkinson Michael , Rai Myriam , Pandolfo Massimo , Murphy Sinead , Emmanuel Anton , Panicker Jalesh , Giunti Paola
Published: October 2015

Background

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder leading to ataxia, weakness, peripheral neuropathy, diabetes and cardiomyopathy. Although patients also report urinary, bowel and sexual symptoms these have barely been described in the literature.

Methods

59 Patients seen in a research clinic in a year were included. Questionnaire scores measuring urinary, bowel and sexual symptoms were compared with validated measures of disease severity.

Results

Urinary symptom scores correlated significantly (p=0.021) with duration of disease symptoms and spasticity scores (p=0.045). Quality of life measures of patients with urinary symptoms correlated with ataxia rating scales (SARA) (p=0.036) and non-ataxic symptoms (INAS) (p=0.003). Neurogenic Bowel Disease scores correlated with severity of ataxic symptoms (SARA) (p=0.024) and activities of daily living (ADLs) (p=0.001). Sexual symptom scores did not correlate with any established measures of disease severity and disease duration.

Conclusions

Urinary and lower gastro-intestinal symptoms can have a severe impact on patients with FRDA although they are under-recognised. They impact on quality of life and correlate with established measures of disease severity.
DURAL AVM AS A CAUSE OF RAISED PRESSURE SYMPTOMS IN TREATED CVST
Authors: Abdel-Aziz Khaled , Mirza Nasir , Mbizvo Gashirai , Putharan Mani , Krishnan Anita
Published: October 2015

Case:

A 56 year old man presented with new onset headaches with visual symptoms. Physical examination was normal apart from asymmetrical papilledema and reduced visual acuity 6/9 bilaterally. CSF opening pressure was 26 cm H2O. CTV showed partially recanalised thrombosis in the superior sagittal sinus and the right sigmoid and transverse sinuses which appeared chronic. His headaches initially improved with propranolol but he continued to complain of visual symptoms; repeat CSF opening pressure was 31 cm H2O and repeat CTV was reported as, ‘more occlusive’. He was therefore anti-coagulated and treated with acetazolamide.

Six weeks after starting treatment, ophthalmological assessment found worsening visual fields despite reduction in disc swelling on OCT. CSF pressure remained elevated at 30 cm H2O. Repeat CTV and 4D CTA identified a type IIB occipital dural AV fistula around the thrombosed venous sinuses, causing occipital lobe congestion; the likely cause of the visual field defects.

The patient underwent cerebral angiogram with embolisation of the dural fistula. Following embolization his headaches and papilledema resolved, and visual acuities and fields normalised.

Conclusion

Neurologists should be aware of dural AV fistula as a complication of cerebral sinus thrombosis which may cause persistent raised pressure symptoms in treated patients.
FAMILIAL MIGRAINE LIMB PAIN SYNDROME (MLPS): THREE GENERATIONS AND SEVEN YEAR FOLLOW-UP
Authors: Angus-Leppan Heather , Guiloff Roberto Jaime
Published: October 2015

We describe a family with migraine-limb pain syndrome (MLPS) in children and adults over three generations, in an autosomal dominant pattern.

MLPS is intermittent pain occurring in any limb, temporally related to a migraine episode, cluster headache or cluster migraine. It is usually ipsilateral to the headache, but can alternate and may spread with a migrainous march over 20 minutes or more. Body or chest pain (corpalgia) is also described. Limb or body pain may not coincide with headache at presentation. The association may be misdiagnosed as radiculopathy, thoracic outlet syndrome or arthritis.

There is one previous report of a family with childhood limb pain, followed by migraine in adulthood, in a pattern suggesting autosomal dominant inheritance.

We report a second family with three generations of MLPS starting in childhood or adulthood, with variable duration, commencing in any limb. All the patients with limb pain had concurrent or associated migraine with aura. Pain intensity in the previous family was mild, but poorly responsive to treatment. In our family the symptom was treatment responsive with variable intensity.

Convergence of nociceptive input from the trigeminovascular system in the cervical spinal cord, brainstem, thalamus and cortex is a possible physiological basis for MLPS.
CHARACTERISTICS OF FUNCTIONAL AND ORGANIC STROKE MIMICS
Authors: Gargalas Sergios , David Anthony , Khan-Bourne Najma , Shotbolt Paul , Weeks Robert
Published: October 2015

Aim

To establish whether the groups of patients with conditions that mimic Stroke display certain characteristics which differentiate them from patients with true Stroke.

Methods

All admissions to King's College Hospital's Hyper–Acute Stroke Unit (HASU) over 12 months were reviewed using SINAP data. Subgroups of functional stroke mimics (FSM) and medical mimics (MM) were identified through consensus between experts. Statistical analysis comparing these subgroups to Stroke admissions was performed using Chi2, Kruskal–Wallis and Mann–Whitney methods.

Results

FSM patients (N=98) were younger (mean age 49, p<0.001) and mostly females (63.27%, p=0.003). They had the shortest stay on HASU and were more likely to have had MRI during admission. Compared to MM (N=198), FSM were more likely to have had history of Asthma, Back Pain, Migraine or Depression (p=0.001). FSM presented later compared to Strokes (N=904) (latency FSM 4.57 hrs vs. Stroke 2.17 hrs, p<0.001) and were less likely to present with cortical features (Visual disturbances, Dysphasia or Neglect, p<0.001) or facial weakness or numbness. MM were much more likely to present with altered consciousness (MM 15.34% vs. FSM 4.08% vs. Stroke 1.99%, p<0.001).

Conclusion

Both functional and medical stroke mimics appear to have distinct features that could aid the diagnostic process.
THE MANAGEMENT OF MIGRAINE IN PRIMARY CARE
Authors: Ralston Katherine
Published: October 2015

Migraine is a common and debilitating neurological disorder. This study aimed to audit the management of adults with migraine in a Newcastle GP practice against NICE guidelines (2012) on the acute and prophylactic treatment of migraine.

A search of practice records for patients with a new diagnosis of migraine between December 2013–14 identified 38 patients. Medical records were reviewed to determine if their management was consistent with NICE guidance.

Acute treatment was indicated in 35 patients, with 27 (77%) receiving correct treatment. 1 patient (3%) received unrecommended treatment, while 7 (20%) received no treatment. Prophylactic treatment was given to 11/13 (85%) patients where it was indicated. Of these, 6 (55%) received first line treatment, 1 (9%) second line treatment and 4 (36%) unrecommended treatment. All patients should be followed up after treatment initiation. This occurred or was planned in 14/35 (40%) acute patients and 6/11 (55%) prophylactic patients.

The majority of patients with migraine received the correct acute treatment, however over one third of patients received unconventional preventative medication and follow up was sporadic. A template prompting the correct management of migraine has been incorporated into the computer system following this audit to improve patient care.
THERAPEUTIC EFFECT OF INTRANASAL EVAPORATIVE COOLING IN PATIENTS WITH MIGRAINE. A REPORT OF THE RESULTS OF THE COOL HEAD I, PILOT STUDY
Authors: Vanderpol Jitka , Bishop Barbara , Matharu Manjit , Glencorse Mark
Published: October 2015

Background

Intranasal evaporative cooling due to vascular anatomy, allows the transfer of venous blood from nasal and paranasal mucous membranes to the dura mater, providing an excellent anatomical basis for the cooling processes. The aim of this study was to ascertain whether it may be an effective intervention in an acute migraine attack.

Methods

We conducted a prospective, open-label, observational, pilot study. A total of 20 treatments were administered in 15 patients who satisfied the ICHD 2 diagnostic criteria for migraine. All patients provided pain and migraine-associated symptoms severity scores.

Results

Immediately after the treatment, 8 treatments (40%) resulted in pain and symptoms freedom, a further 10 treatments (50%) resulted in partial pain and symptoms relief. At 2 hours, 9 treatments (45%) provided full pain and symptoms relief, with a further 9 treatments (45%) resulting in partial pain and symptoms relief. In summary 13 patients (87%) had benefit from the treatment within 2 hours that was sustained at 24 hours; without significant side effects.

Conclusions

Intranasal evaporative cooling was safe and gave considerable benefit to patients with migraine. An adequately powered randomised controlled study will be required to confirm the potential of this application in the treatment of migraine.
THE KNOWN UK CASES OF ATAXIA TELANGIECTASIA-LIKE DISORDER (ATLD)
Authors: Westwood Katy , Ealing John , Taylor Malcolm , Worth Paul , Nemeth Andrea
Published: October 2015

Ataxia telangiectasia-like disorder (ATLD) is a very rare autosomal recessive disease with only 25 patients recognised worldwide. ATLD is likened to Ataxia telangiectasia (A-T) due to an overlap of clinical presentations and cellular characteristics. The clinical hallmark of A-T and ATLD is progressive young onset cerebellar ataxia. Variably present characteristics include dysarthria, oculomotor apraxia, ocular telangiectasia, immunodeficiency, spontaneous chromosome abnormalities and a predisposition to malignancy. In contrast to A-T, ocular telangiectasia is absent. Furthermore, ATLD patients tend to have a later onset and slower progression of neurological signs than A-T. The ATM gene, that has a key role in genome stability, is mutated in A-T resulting in an increase cancer predisposition. In ATLD, gene MRE11 is mutated leading to deficient activation of ATM. A functional consequence of the MRE11 mutation is raised chromosomal radiosensitivity because functional ATM kinase is required to rejoin chromosome breaks. This poster/presentation will describe the clinical features and genetic analysis of the ATLD cases with progressive ataxia known in the UK.

Undergraduate Prize Winner 2015
DIGGING DEEPER
Authors: Witherick Jonathan , Bovill Begoña , Dong Anni , Albur Mahableshwar , Bosnell Rose
Published: October 2015

Background

Multiple ring-enhancing brain lesions have a wide differential. We report a case with a rare cause that was successfully treated.

Case report

An 18 year old presented with a short history of headache, dry cough and fevers. His past medical history included Aspergers, childhood epilepsy and bilateral hearing loss (with identified chromosomal translocation) and a recent diagnosis of trans-bronchial biopsy-positive sarcoidosis for which he was taking prednisolone. Radiology showed left upper zone consolidation; despite initial improvement with piperacillin-tazobactam, his headaches intensified and contrast-enhanced brain imaging demonstrated multiple ring-enhancing lesions; lesions were also identified in the liver and spleen. CSF analysis confirmed active inflammation but cultures (including liver biopsy) were negative. Subsequently liver tissue 16S rDNA rtPCR analysis identified rDNA of the pseudomonas genus with a 99% sequence homology for P.luteola and P.zeshuii. These soil-dwelling organisms may have been acquired by the patient whilst working on his grandfather's allotment. The patient was successfully treated with Meropenem.

Conclusion

This case involved input from multiple clinical specialties and highlights the collaboration needed to diagnose and manage such a rare organism. The case highlights unusual pathogens that may cause opportunistic infection in the immunocompromised host and the importance of a thorough occupational history.
IS THE APPLAUSE SIGN USEFUL FOR DIAGNOSIS OF DEMENTIA AND MCI?
Authors: Bonello Michael , Larner Andrew
Published: October 2015

Objective

To examine the diagnostic utility of the applause sign for dementia and MCI in consecutive referrals to cognitive disorders clinic.

Results

Over a 10–month period (January–November 2014) 243 consecutive new outpatients (F:M=124:119; age range 18–91 years, median 61) were administered the applause test (“clap 3 times”). Of the 240 with interpretable results, 46 were diagnosed with dementia (DSM–IV criteria), 66 with MCI (Petersen criteria), and 128 with no cognitive impairment. Using the categorization of applause sign from Luzzi et al. (2011), the percentage of patients with any cognitive impairment who clapped 3–10, and >10 times was 38.9, 60, 70.8, and 87.5 respectively. The null hypothesis that the proportion of patients with cognitive impairment did not differ significantly between groups was rejected (χ2=21.4, df=3, p<0.001). Abnormal scores (>3 claps) had sensitivities for dementia, MCI, and any cognitive impairment of 0.52, 0.24, and 0.36 respectively, and specificities of 0.84, 0.88, and 0.88.

Conclusions

This pragmatic study confirms and extends the results of a previous smaller study (n=100) of applause sign in the cognitive clinic, showing the applause sign to be a high specificity low sensitivity test for cognitive impairment.
Designing Redundancy-Free XML Schema: A Smallest Closure Approach
Authors: Mok Wai Yan , Fong Joseph , Wong Kenneth
Published: October 2015

XML has too many low-level details that hinder high-level conceptual design. We therefore propose DTD graphs and XSD graphs as a mean for conceptual modeling of XML applications. Similar to document type definitions (DTDs) and XML schema definitions (XSDs), DTD graphs and XSD graphs are trees, and as such they can easily be mapped to DTDs and XSDs for implementation. Unlike DTDs and XSDs, DTD graphs and XSD graphs capture various high-level data semantics such as cardinality, ISA, participation, aggregation, categorization, and n-ary relationship. Furthermore, this paper also presents transformation rules between DTDs and a large class of XML Schemas and an algorithm that inputs users’ requirements and outputs a DTD graph that has a minimum number of redundancy-free fragments. As a result of these good properties, the resulting DTD or XSD facilitates query processing and update.
Diagnosis of Obstructive Sleep Apnea in Parkinson’s Disease Patients: Is Unattended Portable Monitoring a Suitable Tool?
Authors: Gros Priti , Mery Victoria P. , Lafontaine Anne-Louise , Robinson Ann , Benedetti Andrea , Kimoff R. John , Kaminska Marta
Published: October 2015

Purpose.Obstructive sleep apnea (OSA) is frequent in Parkinson’s disease (PD) and may contribute to nonmotor symptoms. Polysomnography (PSG) is the gold standard for OSA diagnosis. Unattended portable monitoring (PM) may improve access to diagnosis but has not been studied in PD. We assessed feasibility and diagnostic accuracy in PD.Methods.Selected PD patients without known OSA underwent home PM and laboratory PSG. The quality of PM signals (n= 28) was compared with matched controls. PM accuracy was calculated compared with PSG for standard apnea hypopnea index (AHI) thresholds.Results.Technical failure rate was 27.0% and airflow signal quality was lower than in controls. Sensitivity of PM was 84.0%, 36.4%, and 50.0% for AHI cut-offs of 5/h, 15/h, and 30/h, respectively, using the same cut-offs on PM. Specificity was 66.7%, 83.3%, and 100%, respectively. PM underestimated the AHI with a mean bias of 12.4/h. Discrepancy between PM and PSG was greater in those with more motor dysfunction.Conclusion.PM was adequate to “rule in” moderate or severe OSA in PD patients, but the failure rate was relatively high and signal quality poorer than in controls. PM overall underestimated the severity of OSA in PD patients, especially those with greater motor dysfunction.
AngiomiRs: Potential Biomarkers of Pregnancy’s Vascular Pathologies
Authors: Rodríguez Santa Laura María , González Teshima Laura Yuriko , Forero Forero Jose Vicente , Castillo Giraldo Andres Orlando
Published: October 2015

In recent years, microRNAs (miRNAs) have been the focus of research for their role in posttranscriptional regulation and as potential biomarkers of risk for disease development. Their identification in specific physiological processes, like angiogenesis, a key pathway in placental vascular development in pregnancy, suggests an important role of miRNAs that regulate angiogenesis (angiomiRs). Many complications of pregnancy have in common placental vascular alterations, involving an imbalance in the angiogenesis process in the development of conditions such as preeclampsia, intrauterine growth restriction, and gestational diabetes, complications with the highest rates of morbimortality in pregnancy. Many studies have identified angiomiRs with differential expression profiles in each of these diseases; however, this evidence requires further studies focused on evaluating their potential as biomarkers of risk for the angiomiRs detected, to establish correlations between placental tissue and serum/plasma expression profiles. Therefore, the objective of this review is to highlight the best angiomiRs detected in placental tissue and serum/plasma in each of these three pathologies to show the current data available for potential biomarkers and to propose future research strategies on this topic.
Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis
Authors: Bowen Timothy , Meran Soma , Williams Aled P. , Newbury Lucy J. , Sauter Matthias , Sitter Thomas
Published: October 2015

Hyaluronan (HA) is a ubiquitous extracellular matrix glycosaminoglycan composed of repeated disaccharide units of alternating D-glucuronic acid and D-N-acetylglucosamine residues linked via alternatingβ-1,4 andβ-1,3 glycosidic bonds. HA is synthesized in humans by HA synthase (HAS) enzymes 1, 2, and 3, which are encoded by the correspondingHASgenes. Previous in vitro studies have shown characteristic changes in HAS expression and increased HA synthesis in response to wounding and proinflammatory cytokines in human peritoneal mesothelial cells. In addition, in vivo models and human peritoneal biopsy samples have provided evidence of changes in HA metabolism in the fibrosis that at present accompanies peritoneal dialysis treatment. This review discusses these published observations and how they might contribute to improvement in peritoneal dialysis.
Analysis and Design of a Novel Multiband Antenna for Mobile Terminals
Authors: Yao Yuan , Chen Wanzhong , Chen Xiaodong , Yu Junsheng
Published: October 2015

A multiband planar terminal antenna with a compact size of 40 mm × 24 mm is proposed in this paper. This antenna consists of a monopole patch with two slots on it and a meandering strip loaded on the top. Two parasitic stubs and a branch on the ground are used to adjust and widen the impedance bandwidth of the antenna. Simulations and measurements are carried out to study the antenna performances in terms of impedance matching, efficiency, gain, and radiation patterns. Both of simulation and measurement results are shown to illustrate the good performance of the proposed antenna. The antenna can operate at 450–474 MHz, 860–1040 MHz, 1705–2428 MHz, and 2500–2710 MHz. These operating bandwidths cover GSM900, DCS, PCS, UMTS, LTE2500, and LTE’s low frequency band (450–470 MHz). It is very suitable for multifunctional terminal applications in wireless communication systems.
The Role of Interferon in the Management of BCG Refractory Nonmuscle Invasive Bladder Cancer
Authors: Correa Andres F. , Theisen Katherine , Ferroni Matthew , Maranchie Jodi K. , Hrebinko Ronald , Davies Benjamin J. , Gingrich Jeffrey R.
Published: October 2015

Background. Thirty to forty percent of patients with high grade nonmuscle invasive bladder cancer (NMIBC) fail to respond to intravesical therapy with bacillus Calmette-Guerin (BCG). Interferon-α2B plus BCG has been shown to be effective in a subset of patients with NMIBC BCG refractory disease. Here we present a contemporary series on the effectiveness and safety of intravesical BCG plus interferon-α2B therapy in patients with BCG refractory NMIBC.Methods. From January of 2005 to April of 2014 we retrospectively found 44 patients who underwent induction with combination IFN/BCG for the management of BCG refractory NMIBC. A chart review was performed to assess initial pathological stage/grade, pathological stage/grade at the time of induction, time to IFN/BCG failure, pathological stage/grade at failure, postfailure therapy, and current disease state.Results. Of the 44 patients who met criteria for the analysis. High risk disease was found in 88.6% of patients at induction. The 12-month and 24-month recurrence-free survival were 38.6% and 18.2%, respectively. 25 (56.8%) ultimately had disease recurrence. Radical cystectomy was performed in 16 (36.4%) patients.Conclusion. Combination BCG plus interferon-α2B remains a reasonably safe alternative treatment for select patients with BCG refractory disease prior to proceeding to radical cystectomy.
Ongoing Pregnancies following Cosmetic Micromanipulation of Preimplantation Embryos in Patients with Implantation Failure
Authors: Halvaei Iman , Khalili Mohammad Ali , Safari Somayyeh , Esfandiari Navid
Published: October 2015

Cosmetic micromanipulation is defined as fragment and coarse granulation removal from preimplantation embryos. We report two cases of pregnancies in patients with implantation failure following cosmetic micromanipulation.