bluuebunny/crossref_metadata_2025 huggingface dataset:
A LOCAL SURVEY AMONGST 92 PATIENTS WITH MULTIPLE SCLEROSIS: WHAT CAN WE LEARN ABOUT THIS POPULATION'S DISEASE MANAGEMENT? HOW SATISFIED ARE PATIENTS WITH OUR SERVICE?
Authors: Bashford James , Silber Eli
Published: October 2015

In order to better inform local clinical practice, we collected primary data from our local MS population. We addressed important aspects concerning relapse management, bone health, mental health, sphincter dysfunction, symptom burden, recognition of comorbidities and pharmacological treatment. An emphasis was placed on discovering the extent of patient satisfaction with the local service.

An 11-page patient questionnaire was distributed to consecutive consenting patients attending the MS clinic. A supplemental questionnaire was provided to those patients on regular natalizumab therapy. In total, 92 full and 22 natalizumab questionnaires were completed.

Two particular areas highlighted for improvement with regards to patient management and patient education were bone and mental health:

1. Only 26% of respondents confirmed having had a dual-energy X-ray absorptiometry (DEXA) scan. When asked if reduced ability in MS is an important risk factor for osteoporosis, only 44/92 patients confirmed they thought this was true.

2. In the last year, 41% and 58% of respondents have suffered from depression and anxiety, respectively. Despite this, only a third of these patients received any treatment (pharmacological or non-pharmacological) for anxiety, depression or both.

Encouragingly, 95% of those surveyed would recommend our MS service to a friend or family member.
SEASON OF GLANDULAR FEVER AS A RISK FACTOR FOR MULTIPLE SCLEROSIS
Authors: Downham Christina , Visser Elizabeth , Vickers Mark , Counsell Carl
Published: October 2015

Background

Glandular fever (GF) is a known risk factor for multiple sclerosis (MS) but it is unclear if the risk varies by season due to vitamin D-related variations in immune responses.

Methods

Patients with MS diagnosed between 16–60 yrs were identified from the Clinical Practice Research Datalink (CPRD) along with up to six controls per case, matched by age, gender, general practice and duration of observation in CPRD prior to the date of diagnosis (index date). The numbers of patients and controls with a coded diagnosis of GF prior to the index date were identified and the date of GF diagnosis noted. Multivariable logistic regression analysed whether cases were more likely than controls to have GF in winter rather than summer, adjusted for age, gender and region.

Results

9247 cases (118 with GF) and 55033 controls (483 with GF) were included. GF was more common in MS cases than controls (odds ratio [OR] 1.77, 95% CI 1.53–2.05) but winter exposure was not associated with a higher risk of MS than summer (OR 1.09, 95% CI 0.72–1.66).

Conclusions

Glandular fever in winter as opposed to summer does not appear to be associated with a greater risk of developing MS.
REGIONAL EFFICACY OF NATALIZUMAB TREATMENT IN RELAPSING-REMITTING MULTIPLE SCLEROSIS (RRMS)
Authors: Doshi Anisha , Voysey Zanna , Bunting Eva , Malik Muzaffar , Rashid Waqar
Published: October 2015

Natalizumab is an established treatment for highly active Relapsing-Remitting Multiple Sclerosis (RRMS). Two-year efficacy in the AFFIRM trial showed No Evidence of Disease Activity(NEDA) – no relapses, no disability progression, no new MRI lesions – in 37% of patients compared with 7% in the placebo group. NEDA is increasingly used as a treatment goal in RRMS.

Methodology

We performed a retrospective analysis of Natalizumab treatment in RRMS patients in our centre. We assessed the proportion of patients achieving NEDA in a typical clinical setting with at least 1 year treatment duration and analysed for predictors of response.

Results

Mean age was 41.44 (13–62), 77% (51) of patients were female. 56 out of 66 patients had been on Natalizumab for >1year and were analysed. 55.36% patients achieved NEDA at 1 year. No statistically significant predictors (age, gender, starting disability and relapse rate) of response were identified.

Discussion

The data confirms in a typical UK clinical setting good treatment response was achieved in highly active RRMS patients using Natalizumab. No additional factors were found which could predict treatment response suggesting within the limitations of power and length of this study that Natalizumab is effective in a broad range of highly active RRMS patients.
THE PHYSICAL, SOCIAL & ECONOMIC EXTENT OF MULTIPLE SCLEROSIS IN SUSSEX
Authors: Howells Jacob , Rashid Waqar
Published: October 2015

Background

Multiple sclerosis (MS) is the most common disabling illness of young adults in the UK causing significant social and economical cost. The aim of this study was to ascertain further detail of the characteristics of the MS population in an area of Sussex representing about 25% of the whole region.

Methods

The following was obtained from community databases: (a) demographics; (b) employment status; (c) DMT use; (d) walking aid use and (e) utilisation of social care.

Results

N=665. The mean (SD) age was 54 (13.2) years; Relapsing-Remitting MS 51%, Secondary Progressive MS 29% and Primary Progressive MS 15%. Of participants <65 years: 56% were unemployed, 44% worked part or full-time; 57.8% of participants required walking aids to mobilise, 23.3% were on a DMT, 35.1% required informal care and 20.2% required external social care. We found associations (at α level=0.05) between unemployment and: SPMS, walking aid use, informal care and external social care.

Discussion

This study highlights the needs of people with MS in Sussex. Of note is the impact on employment and the need for walking aids and additional care associated with MS. This knowledge will allow us to better develop services for people with MS with commissioners.
PARTIAL INDEPENDENCE OF FINGOLIMOD EFFECT ON DIFFUSE VS. FOCAL DAMAGE
Authors: Constantinescu C , Stefano N De , Kappos L , Radue EW , Sprenger T , Meier D Piani , Häring D , Tomic D
Published: October 2015

Objective

To investigate if the effects of fingolimod 0.5mg on brain volume loss are mediated through effects on focal disease activity (FD) or independent-reduction of diffuse damage (DD).

Methods

FREEDOMS and FREEDOMS-II data was pooled and analyzed post-hoc. Assessment of the percent brain volume change (PBVC) at M12 and 24, in patients with no evidence of FD, (absence of new Gd+ T1-lesions and/or new/enlarging T2-lesions) and clinical relapses. Regression analysis of the intent-to-treat (ITT) population to quantified whether the extent of the treatment effect was maintained for patients with new/active lesions and relapses

Results

Of the 1383 patients included, 808 patients (placebo=142; fingolimod=666) showed no FD at M12 and 573 patients (placebo=79; fingolimod=494) at M24 showed no FD. Fingolimod significantly reduced PBVC by 52% and 42% vs. placebo, over 12M and 24M respectively. In the pooled ITT population, fingolimod reduced 49% of PBVC (p<0.001)vs placebo over 24M. This effect was still evident when adjusting for new-active lesions and relapse activity (28% reduction vs placebo, p<0.001). The regression model suggests 57% of fingolimod effect on PBVC is FD-independent. Fingolimod effect on DD is partly independent of its treatment effect on FD, suggesting fingolimod impacts both inflammatory and neurodegenerative components.
EARLY PREDICTION OF LONG-TERM RESPONSE TO NATALIZUMAB IN MULTIPLE SCLEROSIS
Authors: Raffel Joel , Gafson Arie , Dahdaleh Samer , Nicholas Richard
Published: October 2015

Introduction

In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict poor prognosis. However, this association has not been studied in those receiving natalizumab.

Methodology

Data were collected on early relapses and new MRI activity from an observational cohort of 161 patients on natalizumab, with long-term follow-up. Two outcome measures were used. The first – ‘Clinical Activity Years 1–3’ – defined non-responders as those with relapses or EDSS progression at years 1–3 post-treatment, versus baseline. The second – ‘Disability Progression Years 3+’ – defined non-responders as those with EDSS progression at 3–7 years post-treatment, versus baseline.

Results

‘Clinical Activity Years 1–3’ was strongly predicted by early relapses (Odds Ratio (OR) 8.4, p<0.0001), and by a combined score of early relapses and MRI activity (Modified Rio Score 1: OR 4.9, p<0.001. Modified Rio Score 2: OR 19.0, P<0.01). In contrast, ‘Disability Progression Years 3+’ was not predicted by early relapses or MRI activity.

Conclusions

Relapses and new MRI activity within the first year of starting natalizumab predict short-term outcomes, but not long-term disability outcomes. This requires further validation in other cohorts.
EFFECT OF TERIFLUNOMIDE ON LYMPHOCYTE AND NEUTROPHIL COUNTS
Authors: Weller Belinda , Comi Giancarlo , Freedman Mark , Kappos Ludwig , Miller Aaron , Olsson Tomas , Wolinsky Jerry , Benamor Myriam , Truffinet Philippe , O'Connor Paul
Published: October 2015

Introduction

Teriflunomide is an immunomodulator known to decrease the proliferation of stimulated lymphocytes via inhibition of dihydro-orotate dehydrogenase. Lymphocyte/neutrophil counts were assessed in pooled data from one phase 2 and three phase 3 (TEMSO, TOWER, and TOPIC) placebo-controlled studies.

Methods

Patients were randomized to receive once-daily teriflunomide 14mg (n=1002), 7mg (n=1045), or placebo (n=997). Blood samples were collected throughout the studies.

Results

Mean baseline lymphocyte and neutrophil counts were similar across groups. Small decreases in mean lymphocyte and neutrophil counts occurred within the first 12 weeks (lymphocytes) or 6 weeks (neutrophils) of treatment, and stabilized within the normal range for most patients thereafter. Patients with neutrophil counts <1×10^9^/L were to discontinue treatment; 11 (1.1%; 14 mg), 8 (0.8%; 7 mg), and 1 (0.1%; placebo) patients discontinued due to neutropenia or neutrophil count decrease as per protocol requirements. Neutropenia was reported as a serious adverse event (SAE) in 7 (0.7%; 14 mg), 2 (0.2%; 7 mg), and 3 (0.3%; placebo) patients; there were no lymphopenia SAEs. No link between neutrophil or lymphocyte count decreases and infection was observed.

Conclusions

These data demonstrate that teriflunomide has small, reversible effects on lymphocyte/neutrophil counts, with no increase in infection risk observed. (Study supported by Genzyme, a Sanofi company).
EARLY RELAPSES IN PATIENTS WITH HIGHLY ACTIVE MULTIPLE SCLEROSIS COMMENCED ON FINGOLIMOD; THE LEEDS TEACHING HOSPITAL EXPERIENCE
Authors: Weerasinghe Kalani Chisha , Shanmugarajah Priya , Russell Melanie , Ford Helen
Published: October 2015

Fingolimod is the much anticipated oral disease modifying treatment for patients with highly active Multiple sclerosis. A total of 42 patients were commenced on Fingolimod from December 2012 to June 2014 in Leeds Hospitals NHS Trust.

Four patients discontinued treatment due to patient choice, consecutive severe relapses and hepatotoxicity. No other severe side effects were noted in these 42 patients. A total of ten relapses were seen in nine patients. Of which eight out of ten relapses occurred within the first two months. Of the nine patients who experienced relapses, five (55%) were previously treated with Natalizumab, as opposed to four on injectable Disease Modifying Treatments (45%).

The five patients previously treated with Natalizumab all underwent a three month wash out period prior to commencing Fingolimod. The relapses all took place within the first two months following initiation of Fingolimod.

Early relapses in a patient group with highly active disease would suggest that a period of three months without disease modifying treatment could be too long. Currently this period has been shortened to four weeks and it remains to be seen if this will result in fewer early relapses in patients commencing Fingolimod.
HYPERSENSITIVITY PNEUMONITIS FOLLOWING ALEMTUZUMAB TREATMENT FOR MULTIPLE SCLEROSIS
Authors: Willis Mark , Cossburn Mark , Ingram Gillian , Pickersgill Trevor , Barry Simon , Robertson Neil
Published: October 2015

Alemtuzumab has recently been licensed in several countries for relapsing multiple sclerosis. Despite its marked clinical efficacy it is associated with acquired autoimmune disease with a particular predilection for the thyroid gland. Despite the recognition and surveillance mechanisms that exist to monitor patients treated with alemtuzumab, vigilance must be maintained to monitor for less common immune-related disorders. We present two patients diagnosed with hypersensitivity pneumonitis following alemtuzumab therapy for multiple sclerosis. Both patients presented with a sub-acute pulmonary illness characterized by cough and breathlessness with interstitial pulmonary infiltrates subsequently demonstrated on chest x-ray and computed tomography of the thorax. Both patients responded well to oral prednisolone and in the case of one patient for whom serum avian precipitins had been strongly positive, removal of a pet parrot. There has been no recurrence of respiratory disease following treatment. Autoimmune disease post-alemtuzumab treatment tends to be due to an aberrant humoral immune response such as that seen in Grave's disease. However, these cases highlight that cell-mediated autoimmunity disorders may also occur and underline the importance of long term surveillance for immune complications in patients treated with this drug.
CLINICAL AND ELECTROPHYSIOLOGICAL CHARACTERISTICS OF 103 PATIENTS WITH SENSORY NEURONOPATHY
Authors: Lavin Timothy , Al-Bachari Sarah , Gosal David Yunus
Published: October 2015

Sensory Neuronopathy (SN) represents a distinct peripheral nervous system disorder associated with degeneration of the Dorsal Root Ganglia. We present our retrospective review of 103 patients with an electro-clinical diagnosis of SN.

Average age of onset was 54 yr. Aetiologies included Sjogrens (21%), Probable Inflammatory (16%), Idiopathic (29%), Inherited (20%), Toxic (5%) and paraneoplastic (9%).

Of those with inherited SN (n=21); CANVAS syndrome 2/21, mitochrondrial cytopathy 9/21 with 4 confirmed POLG1 mutations, 3/21 presumed HSANIIb, Frederich's Ataxia 1/21 and 6/21 unidentified phenotypes.

Clinically, acquired causes commonly presented with pain (62%), asymmetrical/non-length dependent sensory disturbance (91%) as compared to the inherited group who are more likely to present with gait disturbance without prominent sensory symptoms (52%).

Of the cohort with presumed inflammatory disease, 29 patients were immunosuppressed with 12 patients responding to a combination of steroids and Mycophenolate. IVIG was not found to be beneficial with no sustained benefit in 7 patients.

Paraneoplastic causes (n=9) included Breast (n=2), Neuroendocrine tumours (n=2), Carcinoid (n=2), Bowel (n=1), SCLC (n=1) and unknown primary (n=1) with only 4 Hu positive

Conclusions

Sensory neuronopathy is clinically and aetiologically pleomorphic. In cases with a suspected inflammatory cause it is worthwhile considering a trial of immunomodulatory treatment.
SCREENING FOR RESPIRATORY FAILURE IN ALS USING CLINICAL QUESTIONING, RESPIRATORY FUNCTION TESTS AND TRANSCUTANEOUS CARBON DIOXIDE: WHICH IS THE BETTER TOOL?
Authors: Rafiq Muhammad , Proctor Alison , McDermott Christopher , Shaw Pamela
Published: October 2015

Background

Screening patients regularly for evidence of respiratory failure is an important facet in the management of ALS.

Objectives

To evaluated the relative value of symptom history, forced vital capacity (FVC) and day time transcutaneous carbon dioxide (Ptc CO2) monitoring in early detection of respiratory failure in ALS.

Methods

This is a prospective observational cohort study consisting of 50 consecutive patients with ALS. The participants underwent 3 monthly assessments for symptoms of respiratory failure, FVC and Ptc CO2 monitoring.

Results

Symptoms of respiratory failure were the most powerful tool, alerting the physician to the possibility of respiratory failure. All the patients where respiratory failure was confirmed on overnight capnometry had symptoms of respiratory failure. Shortness of breath was the most common symptom reported by the patients, present in 74% of the patients with confirmed respiratory failure. 37% of these patients had FVC of >50% predicted and only 15% had day time hypercapnia (Ptc CO2>6.0 kPa). None of the patients had day time hypercapnia without any other marker of respiratory failure. There was statistically significant difference between the day time Ptc CO2 and median overnight Ptc CO2 (p=0.0002).

Discussion

This study has emphasised the importance of symptom history in detection of respiratory failure in ALS.
PERIPHERAL NERVE BING-NEEL SYNDROME
Authors: Carr Aisling , D'Sa Shirley , Arasaretnam A , Boyd K , Johnston R , Jaunmuktane Zane , Brandner Sebastian , Marafioti T , Koltzenburg Martin , Lunn Mike
Published: October 2015

Background

Bing-Neel syndrome (BNS) is a rare manifestation of Waldenstrom's Macroglobulinaemia (WM) due to direct infiltration of the central nervous system. Isolated peripheral nerve infiltration has not been described but as the blood-nerve-barrier has similar characteristics to the blood-brain-barrier, CNS-penetrating chemotherapy would be required.

Case

A 43 year-old man was diagnosed with WM after presenting with constitutional symptoms; IgMk paraprotein (34.6 g/L) and lymphoplasmacytoid cells in the bone marrow. He received R-CVP (Rituximab, Cyclophosphamide, Vincristine, and Prednisolone) with good partial haematological response and minimal distal sensory vincristine-related neuropathy. Ten months later he developed a rapidly progressive, symmetric sensorimotor deficit in all four limbs with impairment of walking and hand clumsiness, MRC sum score=61/70. Electrophysiology showed a non-length dependant axonal neuropathy with patchy slowing. Sural nerve biopsy revealed a patchy infiltrate WM cells. He tolerated 4 cycles of blood-nerve-barrier penetrating multi-agent chemotherapy, IDARAM (idarubicin, dexamethasone, cytosine arabinoside, methotrexate, cytosine arabinoside plus intrathecal methotrexate). A marked improvement was seen during treatment and by 3 months later MRC score was 70/70. No electrophysiological difference was detectable at this stage.

Discussion

Peripheral BNS is not a recognised neurological manifestation of WM but with appropriate treatment a good outcome may be achieved.
THE NEUROPATHY SPECTRUM IN WALDENSTRöM'S MACROGLOBULINAEMIA
Authors: Carr Aisling , Jaunmuktane Zane , Brandner Sebastian , Kothari J , Blake Julian , D'Sa Shirley , Lunn Mike
Published: October 2015

Background

UK WM Guidelines recognise 2 mechanisms of nervous system involvement either direct tumour invasion of the CNS or antibody mediated damage to peripheral nerves. We present 5 cases illustrating an extended diversity of PNS involvement in WM with implications for treatment and outcome.

Cases

A 73 year-old man (IgMκ WM) developed progressively disabling tremor with stable WM. Neurophysiology was demyelinating with disproportionate DMLs; anti-MAG antibodies were strongly positive. He was treated with DRC with symptom stabilisation.

A 64 year-old woman (IgMκ) with typical anti-MAG neuropathy developed severe episodic foot pain and ulceration. Skin biopsy confirmed leucocytoclastic vasculitis. She was treated with DRC but died from sepsis.

A 43 year-old man (IgMκ WM) with rapidly progressive sensorimotor neuropathy had lymphplasmacytoid cellular infiltrate in sural nerve. He was successfully treated with IDARAM.

A 59 year-old man (IgMλ WM) developed small then large fibre axonal neuropathy with autonomic symptoms within 2 years. A SAP scan showed moderate kidney uptake. MRI neurography directed biopsy and confirmed amyloid. Palliative treatment was offered.

A 70 year-old woman (IgMλ WM) developed severe burning pains in her feet and became ataxic 2 months later. Sural nerve biopsy confirmed endoneurial amyloid. DRC was given.

Discussion

These cases highlight the importance of accurate diagnosis in WM-associated neuropathy. We propose a novel diagnostic algorithm.
CNS RELAPSE OF NHL MASQUERADING AS MILLER FISHER SYNDROME
Authors: Dharia Sonali , Harrower Timothy
Published: October 2015

A 60 year old man with previous history of NHL (Non Hodgkin Lymphoma) presented with progressive dysphagia and dysarthria over two weeks.He had bilateral lower motor neuron facial weakness, diplopia on lateral gaze and nystagmus on examination. Working diagnosis was Miller Fisher syndrome and he was commenced on intravenous immunoglobulins. Subsequently he developed shortness of breath due to inability to maintain airway secondary to bulbar dysfunction. Review of MRI brain revealed enhancement of basal meninges with contrast suggestive of entrapment of cranial nerves. CSF showed 760 lymphocytes and elevated protein at 1.2 g/L. Immunophenotyping revealed the lymphocytes to be of Natural Killer (NK) cell origin leading to diagnosis of relapse of lymphoma involving CNS. He was diagnosed ten months ago with extranodal nasal NK/T cell lymphoma involving paranasal sinuses which is a rare subtype of NHL and is associated with Epstein-Barr virus. He was treated with four cycles of SMILE chemotherapy and local radiotherapy and had achieved complete remission as evidenced by a negative PET CT scan three months ago. This case stresses the importance of considering CNS relapse as a differential in patients presenting with neurological symptoms and history of lymphoma even though CNS relapse is rare for NHL (2.8%).
AUDIT OF CSF CYTOLOGY AT THE WEST MIDLANDS NEUROSCIENCE CENTRE
Authors: Evans William , Carey Martyn , Dunne Fiona , Nagaraju Santhosh , Hayton Tom
Published: October 2015

Cerebrospinal Fluid (CSF) cytology is thought to be the gold standard for diagnosing neoplastic meningitis. The accuracy of this test is important since it may determine whether or not a patient is given intra-thecal chemotherapy. Previous studies indicate that >10.5ml of CSF should to be collected in order to achieve a false negative rate of ≤3% and European Guidelines on CSF analysis recommend that this be the minimum volume collected.

275 consecutive CSF cytology samples from the West Midlands regional clinical neuroscience and haemo-oncology centre were audited to see how many met this standard.

The median volume of CSF sent for cytology was 2 ml (IQR1 to 5 ml). In fact only 2 (<1%) of the samples met the standard of >10.5 ml, though a further 22 (8%) of samples were close at 10 to 10.5 ml.

A re-evaluation is needed of the way in which neoplastic meningitis is diagnosed in the West Midlands. If newer techniques are sufficiently sensitive to allow an acceptable false positive rate with a lower volume of CSF, local guidelines should be drawn up which take this into account, otherwise the doctors collecting the samples need to be educated and monitored to ensure they meet the established standard.
DOES HIPPOCAMPAL DAMAGE EXPLAIN MEMORY LOSS IN VASCULAR COGNITIVE IMPAIRMENT?
Authors: Hosseini Akram , Meng Dewen , Simpson Richard , Auer Dorothee
Published: October 2015

Introduction

Cognitive impairment (CoI) is common in old age and following cerebrovascular disease. The contribution of acute and chronic cerebral infarcts and hippocampal integrity to various domains of CoI remains unclear.

Methods

100 patients with recent cerebrovascular ischaemic events and >30% carotid artery stenosis (age: 75.4±9.2, 40% female) received brain MRI. Addenbrooke's cognitive examination was used for assessment. Acute and chronic ischaemic volume was identified on diffusion tensor and FLAIR images. Total ischaemic lesion load (TILL), and mean diffusivity (MD) of bi-hippocampi were calculated. A statistical cognitive prediction model was build using age and vascular risk factors between cognitively impaired subgroup against the normal cognition. Next, TILL and then hippocampal MD were added to the relevant risk factors. AUC for each model was compared.

Results

51% were cognitively impaired, particularly the eldest (P=0.002). Age and TILL were independently associated with CoI (P=0.03), specifically executive dysfunction. Hippocampal MD was significant predictor of overall cognition, particularly memory, after adjusting for age and infarction volume (P=0.001). AUC of model prediction confirmed superior predictability of hippocampal MD for cognition.

Conclusion

In vascular cognitive impairment, hippocampal integrity independently contributes to anterograde, long recall and recognition memory, whilst volume of brain infarcts correlates with executive dysfunction.
INVESTIGATION OF MOTOR LEARNING IN PARKINSON'S DISEASE USING AN ACTION ACQUISITION TASK
Authors: Fearon Conor , Newman Louise , Quinlivan Brendan , Butler John , Lynch Tim , Reilly Richard
Published: October 2015

Movement learning is complex, involving multiple structures including cortex, cerebellum and the basal ganglia. In idiopathic Parkinson's disease (PD) there is initial loss of dopaminergic innervation to the caudal putamen, which governs habitual movement. With disease progression, however, this spreads to involve more anterior regions of the basal ganglia involved in goal-directed behaviour.

Given the loss of phasic dopamine signaling in these areas we expect motor learning to be impaired in PD. The goal of this study is to investigate movement learning in PD and healthy controls using a computer-based action acquisition task.

A cohort of PD patients and age-matched healthy controls were asked to repeatedly manipulate a joystick in order to move an unseen cursor on a computer screen, initially to a seen target (task 1) and then to an unseen target (task 2). By examining how these movements are refined in order to locate the target from task 1 to task 2 (which requires action selection by the basal ganglia) we quantify the rate at which movements are learned.

The results show differences in parameters associated with the execution of the action acquisition task for the PD cohort when compared to healthy controls, supporting impaired motor learning in PD.
THE PREDICTIVE VALUE OF DIFFERENT MOTOR FEATURES IN PARKINSON'S
Authors: Macleod Angus , Counsell Carl
Published: October 2015

Background

Other than tremor dominance (TD) or the postural instability-gait disorder phenotype (PIGD), little is known about what baseline motor characteristics influence prognosis in Parkinson's disease (PD).

Methods

We analysed data from the PINE study, a prospective, community-based incident cohort of PD in Aberdeen, Scotland, recruited between 2002–09, with long term follow-up. Baseline motor features derived from the UPDRS part 3 scale were assessed as independent predictors of four outcomes: death, dependence (Schwab & England <80), “death or dependence”, and progression to Hoehn & Yahr stage 3 (H&Y3) using Cox regression adjusting for age.

Results

198 patients were analysed (median 6.1 years follow-up). In univariable analyses, bradykinesia score, axial score, limb score, axial/limb ratio, dopa-responsive signs, and dopa-non-reponsive signs were significant predictors of all outcomes. In univariable analyses, asymmetry predicted dependency and death or dependency and TD/PIGD only predicted H&Y3. In multivariable analyses bradykinesia and axial/limb ratio were independent predictors of death and death or dependency and axial score and dopa non-responsive symptoms were predictors for dependency and H&Y3.

Discussion

Different motor characteristics were independent predictors of different outcomes. However, a variable relating to severity of axial signs was a common theme across three of these outcomes. Thus, at diagnosis, axial motor features appear to be important predictors of prognosis, perhaps stronger than the TD/PIGD classification and deserve further study.
SUSCEPTIBILITY WEIGHTED IMAGING TO DETECT NIGRAL IRON ACCUMULATION IN PARKINSON'S DISEASE
Authors: Martin-Bastida Antonio , Politis Marios , Loane Clare , Lao-Kaim Nicholas , Valle-Guzman Natalie , Kefalopoulou Zenovia , Gesine Paul , Foltynie Thomas , Barker Roger , Piccini Paola
Published: October 2015

Introduction

Dopaminergic neuron loss in substantia nigra (SN) in patients with PD is associated with deposits of iron. Susceptibility weighted imaging (SWI) is a high-resolution MR-based imaging technique for quantifying iron depositions in vivo. SWI may be a robust biomarker for clinical characterization of PD.

Methods

Forty-two patients with PD were studied with SWI imaging. Average phase shift (radians) and percentage iron deposition of the SN were analysed using SPIN software. SWI data were also compared between PD patients with early (4.0±0.5 PD duration) vs. established PD (7.7±1.9), and according to low (21.2±4.5) vs. high (41.3±8.7) UPDRS-III-assessed motor symptoms severity. Data were interrogated using analysis of covariance (age), relative to healthy controls, and using post hoc univariate tests.

Results

PD patients had higher phase shift values (p<0.01) and iron deposition percentage (p<0.001) in the SN bilaterally, compared to healthy controls. Phase shift values were significantly higher in patients with established PD compared to those with early PD (p<0.05) and higher UPDRS-III motor scores (p<0.05).

Conclusions

PD patients show higher levels of deposits of iron in SN compared to healthy controls, and increased iron levels in SN are associated with prolonged disease and increased motor disability
A CASE OF ATRAUMATIC CONVEXAL SUBARACHNOID HAEMORRHAGE DUE TO UNUSUAL CAUSE
Authors: Zaidi SAH , Agrawal Amit , Davey Richard
Published: October 2015

Objective

To describe a rarely described case of severe internal carotid artery stenosis presented as convexal subarachnoid haemorrhage (SAH) in the setting of acute ischemic stroke.

Case report

A 52 year old female, smoker, presented with right sided numbness, slurred speech and difficulty in walking. Neurological observation revealed mild expressive dysphasia and subtle right sided weakness. Brain imaging showed left cortical sulcal SAH with ischemia in the left corona radiata. Carotids ultrasound showed 90% stenosis of left internal carotid artery that was later confirmed by magnetic resonance angiogram. She was treated conservatively for acute ischemic stroke and later underwent left carotid endarterectomy.

Conclusions

This case shows that ICA stenosis can cause convexal SAH and it should therefore be added to the differential diagnosis of atraumatic SAH. The association is under recognised and can be missed due to the unusual location of the blood and failure to image the extra cranial carotid arteries.
NETWORK DYSFUNCTION IN POST-STROKE APHASIA
Authors: Geranmayeh Fatemeh , Wise Richard
Published: October 2015

Recovery of language function after aphasic stroke is the product of activity in domain-general and domain-specific distributed brain networks. These may include left and right fronto-temporo-parietal, cingulo-opercular, and default mode networks.

This functional MRI study investigated the effects of a previous left hemisphere stroke on brain activity during speech production in fifty-three patients. The results were related to twenty-four healthy participants. The analyses investigated not only local activity, but also functional connectivity both within and between distributed networks.

Although activity within individual networks was not predictive of speech production, the relative activity between networks was a predictor of both within-scanner and out-of-scanner performance, over and above that predicted from lesion volume and various demographic factors. The specific imaging predictors were the differential activity between the default mode network and both the left and right fronto-temporo-parietal networks, respectively activated and deactivated during speech. These networks also showed altered between-network functional connectivity in patients.

Therefore the systems neuroscience of recovery of function after focal lesions is not adequately captured by notions of brain regions ‘taking over’ lost domain specific functions, but is best considered as the interaction between what remains of domain-specific networks and the domain-general systems that regulate behaviour.
CADASIL IN NORTHERN IRELAND: A RETROSPECTIVE CLINICAL, NEUROIMAGING AND GENETIC STUDY
Authors: McMacken Grace , McKenna Eugene , McKee Shane , McConville John
Published: October 2015

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial cerebral small vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. Characteristic features include migraine with aura, recurrent subcortical ischaemic events, cognitive impairment and mood disturbances. The disorder is often overlooked or misdiagnosed, and true population prevalence and disease burden is still undetermined. We identified NOTCH 3 mutation positive CADASIL patients from the Northern Ireland genetics databases. We assessed neuroimaging where available and reviewed medical records.

21 gene positive patients were identified within this population. Two mutations accounted for 7/9 pedigrees (arg 182 cys and arg141cys). Mean age of diagnosis was 46 years (range 28–65 years). 10/21 patients had a known family history of CADASIL at time of genetic testing. 19/21 patients were symptomatic: migraine with aura (61%); stroke (52%); TIA (43%); dementia (29%); mood disturbance (29%); seizures (14%). MRI features were highly variable but showed striking similarities within families; some exhibiting changes considered classical of CADASIL and others demonstrating only non-specific white matter changes. One patient exhibited vasculitic type changes on MR angiogram. This study demonstrates the wide variability in the phenotype and MRI features of CADASIL.
THE ZEBRA SIGN
Authors: Patel Bhavini , Nagendran Arjuna , Khan Usman
Published: October 2015

A 65 year old female was transferred to the Hyperacute Stroke Unit after a routine L5/S1 laminectomy. She suffered a small dural tear. 3 hours post procedure, her GCS dropped to 3. CT scan showed a bi-cerebellar haemorrhage and MRI brain the next day revealed a convexity subarachoid haemorrhage. Imaging was reviewed with neuroradiologists and neurosurgeons. They recognised this as a typical case of post-dural puncture remote cerebellar haemorrhage. In surgical literature there are many cases reported since 1981 of “the Zebra sign”. Patients can become obtunded up to 72 hours after the injury. The mechanism of the haemorrhage is not fully understood. There are no cases reported after a lumbar puncture, which suggests a rapid loss of CSF is required for the pressure shift. Sudden caudal shift of brain with traction of arachnoid matter and venous structures on brain surface during ‘cerebellar sag’ may result in venous bleeding and sometimes infarction. Usually bleeding is bilateral near upper vermis and cerebellar sulci in close proximity to cerebellar draining veins giving rise to the ‘Zebra sign’. Remote cerebellar haemorrhage is an unknown known for a neurologist but with the increased access to stroke services, we are likely to see more cases.
THE IMPACT OF TRAUMATIC BRAIN INJURY ON PATIENT-REPORTED PHYSICAL AND MENTAL HEALTH
Authors: Gorgoraptis Nikos , Zaw-Linn Joanna , Feeney Claire , Jimenez Carmen Tenorio , Niemi Mari , Malik Aysa , Ham Timothy , Baxter David , Goldstone Anthony , Sharp David
Published: October 2015

Traumatic Brain Injury (TBI) is a major cause of disability, with staggering social consequences, but little is known on what determines the impact of TBI from the patient's perspective.

In an audit of 240 patients (172 males, median age: 42 years, range: 20–89 years) who attended our multidisciplinary TBI clinic, we examined the impact of cognitive function, depression, sleep, history of substance abuse, age, injury severity (172 moderate-severe, 68 possible-mild TBI) and time since injury (median: 4 months, range: 20 days–28 years) on two patient-reported measures of quality of life: SF–36 Health Survey and Nottingham Health Profile (NHP).

Worse outcomes in NHP and both Mental and Physical sub-scores of SF–36 were associated with poorer cognitive performance, as measured by ACE–R. Depression, examined using BDI–II, showed a strong negative correlation with both quality of life measures. Sleep-related symptoms were also strongly associated with worse patient-reported outcomes. Patients reported poorer outcomes in both SF-36 and NHP when examined at a later time since their injury, and this effect could not be attributed to older age.

Impairments in cognition, mood and sleep following TBI may have a significant impact on patients' perception of their physical and mental well-being.
ACQUIRED PENDULAR NYSTAGMUS IN STARGARDT'S SYNDROME SUPPRESSED BY ALCOHOL
Authors: Ahmad Hena , Arshad Qadeer , Patel Mitesh , Roberts Richard , Bronstein Adolfo
Published: October 2015

Stargardts disease is the most common inherited form of juvenile macular degeneration leading to progressive visual loss. We describe a case of female twins aged 47 with Stargardt's Type III (rare autosomal dominant form) who, aged 7, developed blurred vision leading to identical progressive macular dystrophy and deterioration in visual acuities (both 1/60). Pendular nystagmus, presumably secondary to visual deprivation, was observed 4 years ago in both although only one twin (AW) described worsening horizontal oscillopsia, reportedly improving following alcohol consumption. Here, we report measurements of eye movements using 3D video-oculography at baseline and post alcohol ingestion (Blood alcohol concentrations: pre <10 mg/dl, post AW=66 mg/dl and HW=49 mg/dl). Analysis software was used to determine the amplitude and frequency of the pendular nystagmus. In AW peak-to-peak horizontal amplitude decreased from 5° (3.13 Hz) to 0.8°, and vertical amplitude from 2.9° (3.13 Hz) to 0.5°. In HW, peak horizontal amplitude reduced from 4.2° (3.22 Hz) to 1.5° and vertical amplitude from 1.9° (6.25 Hz) to 1.7°. In AW the oscillopsia resolved completely post-alcohol with modified oscillopsia scale scores reduced by 50%. (21/28 to 10/28). The findings demonstrate the potential effects of alcohol in suppressing pendular nystagmus and oscillopsia which may guide pharmacological treatments with alcohol-mimetics.
THE CHANGING FACE OF ACUTE NEUROLOGY: EXPERIENCE FROM TWO DECADES OF THE CAMBRIDGE NEUROLOGY EMERGENCY CLINIC
Authors: Axinte Laura , Sawcer Stephen , Stacpoole Sybil
Published: October 2015

Acute neurological presentations are a common problem, accounting for around 17% of GP consultations, 10% of A&E visits and around 20% of the medical take. There is an increasing appreciation of the need to reconfigure neurological services to meet this need, but the challenge is to provide a service for those who most need it with an under-resourced specialty. The Royal College of Physicians 2012 Consultant Physician Survey reported that there were 716 neurology consultants in the UK, resulting in 1 per 90,000 population, significantly lower than the recommended RCP minimum of 1 consultant per 70,000, every day of the week. One solution to the evident need is providing rapid access ambulatory pathways. Here we report on the Cambridge experience of nearly two decades provision of an emergency neurology clinic at Addenbrooke's Hospital. We show how the service has evolved and the changing patterns of presentation, management and outcomes of the patients seen. Annualised attendance data demonstrates increasing demand, whilst the proportion of patients presenting with headaches (now 40%) has escalated dramatically. By contrast, the number of patients referred with problems related to established chronic neurological diseases has fallen considerably, no doubt related to the development of specialist nurses and clinics.
ULTRASOUND ASSISTED LUMBAR PUNCTURE; THE NOT-SO-STEEP LEARNING CURVE
Authors: Weerasinghe Kalani Chisha , Sharma Anupama , Weerasinghe Asoka , Tung Patrick
Published: October 2015

Lumbar puncture is a frequently undertaken procedure in Neurology and Acute Medical settings. It can at times be challenging requiring several attempts causing patient discomfort and anxiety.

Ultrasound assisted Lumbar Puncture/Epidurals are currently undertaken by Anaesthetists trained in the technique but not by Neurologists or Medical Physicians in the United Kingdom.

Our goal was to train non-Anaesthetic doctors to use ultrasound to assist lumbar punctures through a short training course. The Sonography Assisted Lumbar puncture Training (SALT) course was conducted at Mid Yorkshire Hospitals NHS trust which consisted of 80 minutes of didactic teaching and 160 minutes of supervised scanning.

A total of 31 candidates of which 35.48% (n=11) were Neurology trainees and consultants undertook this course. The end of course assessment revealed that 87.09% were able to stabilize the probe and optimize the ultrasound image independently, whereas 93.54% were able to identify the relevant sonoanatomy independently. The remaining candidates demonstrated these skills with minimal prompting.

Ultrasound assisted lumbar puncture is a useful technique, which improves the success rate in difficult lumbar punctures. This study shows that it can be taught in a controlled environment through a focussed short training programme.
ABNORMAL SOUND AND MUSIC REWARD PROCESSING IN DEMENTIA: A BEHAVIOURAL AND NEUROANATOMICAL ANALYSIS
Authors: Fletcher Phillip , Schott Jonathan , Rossor Martin , Warren Jason
Published: October 2015

Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music (‘musicophilia’) occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens, implicated in reward processing. Our findings suggest that abnormalities of auditory hedonic processing are associated with abnormal behavioural symptoms in dementia.
THE MAN WHO MISTOOK THE FRIDGE FOR A DOOR: AN ATYPICAL PRESENTATION OF DEMENTIA WITH LEWY BODIES
Authors: O'Dowd Sean , Munteanu Tudor , Hardiman Daniel , Sheehy Niall , Redmond Janice
Published: October 2015

A 61-year old engineer was referred for a fourth opinion regarding visual symptoms. He had a recent history of depression, and was taking fluoxetine. He reported an eight-year history of progressive visual symptoms, manifest particularly as difficulty judging distances and depth. He acknowledged visual misperceptions and rare visual hallucinations; his reading had deteriorated; he complained of loss of mathematical skills. There had been episodic topographical disorientation. Memory and insight were preserved. There were no extrapyramidal symptoms. Examination (see video) revealed evidence of significant parietal and some frontal dysfunction. Visuospatial and visuoperceptual impairments were particularly marked. There was no evidence of parkinsonism. A diagnosis of posterior cortical atrophy (PCA) syndrome was made. Structural imaging was reported as normal but SPECT imaging revealed bilateral presynaptic dopaminergic denervation and FDG-PET demonstrated significant parieto-occipital hypometabolism. CSF tau and beta-amyloid levels were normal. A diagnosis of probable dementia with Lewy bodies (DLB) was made. PCA is a relatively rare and often under-recognised neurodegenerative syndrome, most frequently associated with Alzheimer pathology. The clinical and paraclinical findings in this case suggest a Lewy body process, which very rarely presents as PCA. The challenges pertaining to the accurate diagnosis of PCA and the implications for management are discussed.
THE SPECTRUM OF MIGRAINE IN 306 PATIENTS WITH CADASIL
Authors: Tan Rhea , Markus Hugh
Published: October 2015

Migraine is often the first manifestation of CADASIL, the commonest monogenic cause of stroke. We aimed to determine the pattern of migraine, and its relationship with other features of CADASIL. Of 314 patients seen in a national referral clinic, 71.6% reported migraines. Migraine was the first feature of CADASIL in 67.6% of symptomatic individuals. Females (81.7%) were more likely to develop migraine than males (66.9%), and suffered migraine at an earlier age (27.0±12.7 vs 32.3±13.2 years, p=0.004).

89.8% of migraneurs experienced aura. Where aura occurred it was visual in 69.7% sensory 58.7%, dysphasic 30.3%, confusional 17.9%, motor 15.9% and sensorimotor 9.95%.

A self-limiting encephalopathy occurred in 33 patients (10.8%); 72.7% of these evolved from a migraine episode. Patients with confusional migraines were more likely to develop encephalopathy (OR=3.93, 95% CI=1.51–9.73, p=0.0024).

Non-migraneurs had a higher cumulative risk of stroke than those migraneurs (HR 2.13, 95% CI 1.53–2.96, p=6.8×10−6).

In conclusion, the spectrum of migraine in CADASIL differs from that in the general population. Acute encephalopathy is a common feature of CADASIL and usually evolves from a migraine episode. Non-migraneurs have a higher risk of developing stroke, however the reasons for this are not well understood.
PATIENT SATISFACTION WITH MEDICAL ENCOUNTERS IN NEUROLOGY OUTPATIENT CLINICS
Authors: Reuber Markus , Toerien Merran , Wiseman Hannah , Shaw Rebecca , Duncan Rod
Published: October 2015

Aim

Recent public policy documents have emphasised the need for healthcare practitioners to give patients choice. As part of a larger qualitative project investigating how neurologists give patients choices, we explored whether evidence of patient choice is associated with higher patient satisfaction.

Method

Fourteen neurologists and 223 patients were recruited in neurology outpatient clinics in Glasgow and Sheffield. All participants completed post-appointment questionnaires assessing whether choice was offered or perceived. Clinicians also rated the extent to which symptoms were medically explained. Patients completed the Medical Interview Satisfaction Scale-21 (MISS-21).

Results

Two dominant factors contributed to the total MISS-21 scale, ‘rapport’ and ‘distress-relief’. Regression analysis showed that the extent to which symptoms were medically explained predicted most of the variance on both subscales and the total MISS-21 score. Spearman's rho correlations showed greater patient satisfaction if symptoms were medically explained and if no choice had been offered or perceived.

Conclusion

There was no evidence that giving patients choices in interaction increased patient satisfaction with clinical encounters. Our findings suggest that patient satisfaction is most strongly influenced by the extent to which neurologists perceive symptoms as medically explained.