bluuebunny/crossref_metadata_2025 huggingface dataset:
SAFETY AND TOLERABILITY OF TERIFLUNOMIDE IN CLINICAL STUDIES
Authors: Barnes David , Leist Thomas , Freedman Mark , Olsson Tomas , Miller Aaron , Wolinsky Jerry , O'Connor Paul , Benamor Myriam , Truffinet Philippe , Comi Giancarlo
Published: October 2015

Introduction

Teriflunomide, approved for the treatment of relapsing-remitting multiple sclerosis, has a well-characterized safety profile based on individual clinical studies. We report pooled safety and tolerability data from four, double-blind, placebo-controlled trials of teriflunomide. Post-approval updates on hair thinning and pregnancy outcomes, sometimes concerns for patients initiating teriflunomide, are reported.

Methods

Data were pooled from phase 2 (NCT01487096) and phase 3 TEMSO (NCT00134563), TOWER (NCT00751881), and TOPIC (NCT00622700) studies. Patients were randomized to receive teriflunomide 14 mg, 7 mg, or placebo. Safety analyses were performed for all patients exposed to teriflunomide.

Results

The pooled dataset included 3044 patients. Commonly reported adverse events (AEs) were in accordance with individual clinical studies, most being transient and mild-to-moderate in intensity. Incidence of hepatic AEs was higher in teriflunomide groups; however, serious hepatic AEs were similar across groups (∼2–3%). Hair thinning was higher in teriflunomide than placebo groups, but typically resolved on treatment without intervention and led to discontinuation in <2% of patients. No structural or functional abnormalities were reported in 42 newborns from teriflunomide-exposed parents.

Conclusions

These data from >6800 patient-years of teriflunomide exposure were consistent with individual studies and no new, unexpected safety signals were observed. (Study supported by Genzyme, a Sanofi company).
DISEASE MODIFYING TREATMENT UTILISATION IN MULTIPLE SCLEROSIS
Authors: Williams Owain H , Harding Katharine E , Willis Mark , Pickersgill Trevor , Wardle Mark , Robertson Neil P
Published: October 2015

Background

The number of disease modifying treatments (DMT) for multiple sclerosis continues to expand, although there is limited data concerning their long term use and utilisation in clinical practice.

Objective

Descriptive analysis of historic and current DMT utilisation in relation to treatment pathways, course length and discontinuation reasons in real practice.

Methods

A subset of a population-based cohort of MS identified 270 patients with prospective data on DMT utilisation, reasons for discontinuation were classified. Descriptive and survival analysis were conducted.

Results

498 drug initiation events were identified in 270 patients. 2nd line treatment was initiated in 39%, 3rd line=9%, 4th line=3%, 5th line=0.4%, 6th line=0.4%. Commonest DMT initiated was Interferon (67%) followed by Alemtuzumab, with proportional increase in prescription with each line of treatment escalation (1st=19%, 2nd=26%, 3rd=36%). Persistence on first DMT was a median of 1.7 (1.4–2.3) years for Interferon and 2.7 (0.8–5.1) years for Copaxone, excluding fixed course DMTs. Discontinuation occurred on 307 occasions, with the commonest reason being intolerance of side effects in 57%.

Conclusion

The greatest limitation to drug efficacy will be its course length and its appropriate utilisation, thus a greater understanding of drug indication and discontinuation will be of benefit in clinical practice.
CASE REPORT: A PRESUMPTIVE DIAGNOSIS OF ACUTE DISSEMINATED ENCEPHALOMYELITIS
Authors: Al-Ansari Aseel , Hill Marguerite
Published: October 2015

A 42-year old previously well man presented with a ten-day history of a flu-like illness, headache, back pain and urinary retention. He deteriorated in hospital with pyrexia and agitation and developed acute respiratory compromise necessitating intubation. MR imaging of the neural axis demonstrated enhancement of the leptomeninges, the splenium of the corpus callosum and patchy enhancement of the cervical and thoracic cord. CSF analysis revealed a white cell count of 211 (95% lymphocytes), protein 2.96 g/L and glucose 3.2 mmol/L (serum glucose 9.6 mmol/L).

Initial working diagnosis was of a meningoencephalitis with a transverse myelitis and given the clinical presentation and CSF findings an infectious aetiology was strongly considered. Treatment with anti-bacterial, anti-viral, anti-fungal and anti-tuberculous agents was initiated. Repeated CSF testing yielded negative PCR and culture results for a range of bacterial and viral causes, including tuberculosis. HIV was negative. Aquaporin-4 and MOG antibodies were negative.

A neuro-inflammatory cause, most probably post-infectious, was considered, and steroids initiated. This patient showed a good response to high dose oral steroids, improving over a number of weeks from complete quadriparesis with facial paralysis and ophthalmoplegia to regaining excellent facial and upper limb strength.
ABNORMAL PAIN AND TEMPERATURE PROCESSING IN DEMENTIA
Authors: Fletcher Phillip , Rohrer Jonathan , Schott Jonathan , Rossor Martin , Warren Jason
Published: October 2015

Psychiatric symptoms including somatisation are increasingly recognised in frontotemporal lobar dementia (FTLD), especially in conjunction with the recently discovered mutation in the C9orf72 gene. However, the neuroanatomical basis of these symptoms remains to be evaluated. Here we used voxel-based morphometry to analyse the neuroanatomical basis of symptoms of disrupted pain and temperature processing in a cohort of patients with FTLD (n=58, including pathogenic mutations in the C9orf72 and MAPT genes) and Alzheimer's disease (AD, n=20). Symptoms were particularly prevalent in behavioural-variant FTD (71% cases) and semantic dementia (65% cases) and in association with C9orf72 mutations (6/6 cases), but also developed in AD (45% cases). Responses were more blunted in behavioural variant FTD and exaggerated, occurring in conjunction with somatisation behaviour, in semantic dementia. Within the FTLD cohort, symptoms were associated with grey matter loss in a right-lateralised network (posterior thalamus, posterior insula and anterior temporal cortex), key areas implicated in homeostatic processing, and specifically associated with posterior thalamic atrophy in the C9orf72 mutation cohort. We propose a candidate model of how differential disruption to a sensory processing hierarchy can result in abnormal behaviours with the evolution of psychiatric symptoms in neurological disease. The clinical implications of this are discussed.
GLYCINE RECEPTOR ANTIBODY—A MARKER FOR NMO/ NON-MS DEMYELINATION?
Authors: Hamid Shahd , Elsone Liene , Waters Patrick , Woodhall Mark Woodhall , Mutch Kerry , Rafferty Cahal , Tang Lisa , Solomon Tom , Vincent Angela , Jacob Anu
Published: October 2015

Background

Antibodies against glycine receptors (GlyR Ab) have been strongly linked to progressive encephalomyelitis with rigidity and myoclonus (PERM). Their association with other neurological disorders is poorly understood.

Methods

We looked retrospectively at all patients who were tested for (GlyR Abs) in the Walton Centre between 2010–2014.

Results

138 patients were tested. The pre-test diagnoses (n) were transverse myelitis (34), NMO (22, (7 AQP4 IgG+ve and 15 AQP4 IgG-ve), optic neuritis (17), MS (22), ADEM (4), other atypical demyelination (4), encephalitis (11), epilepsy (4), dementia (4), parkinsonism (3), functional disorders (3) and others (10). 53.6% (74) had a relapsing course

6/138 (4%) were positive for GlyR Ab. The diagnoses (n) were optic neuritis (2) one of which was AQP4 IgG+ve, NMO-AQP4-IgG negative (1), transverse myelitis (1), tumefactive demyelination (1) and undiagnosed spastic ataxic syndrome with normal imaging (1). 5/6 had a relapsing course and are on immunosuppressants.

Conclusion

Antibodies against GlyR are not common and seem to be associated with some non-PERM inflammatory CNS diseases, with a relapsing course. Larger studies are required to understand the clinical and prognostic significance of these early findings.
HASHIMOTO'S ENCEPHALOPATHY PRESENTING AS REFRACTORY HYPOTHERMIA
Authors: O'Sullivan Oliver , Sturrock Aaron , Jacob Saiju
Published: October 2015

Hashimoto's encephalopathy (HE) is a neuropsychiatric condition characterised by elevated thyroid autoantibodies and an exquisite responsiveness to steroids. Patients may present with acute encephalopathic, chronic psychiatric, ataxia, CJD-like and limbic encephalitis symptoms. We report here, for the first time, a case of HE presenting with profound, refractory and recurrent hypothermia.

A 58-year-old lady was admitted following an episode of slurred speech. At presentation GCS was 15, with a temperature of 28C and pulse of 35–45 bpm. She later developed progressive slurring dysarthria, and worsening paranoid ideation and delusions. Despite active warming with bear huggers, she remained hypothermic. 11 days after admission, her GCS dropped to 5, so was intubated and ventilated.

The TPO antibody was raised at 507IU (normal 0–59IU). A diagnosis of HE was made and she responded dramatically to IV methylprednisolone. While rehabilitating on the ward one month later, her temperature fell to 33.5C and within 24 hours she was paranoid and agitated. A relapse of the HE was suspected. After a further course of IVMP, her temperature normalised, and confusion resolved within 36 hours.

This case further expands the clinical phenotype of Hashimoto's encephalopathy. Furthermore it bears clinical similarities to disorders of hypothalamic dysfunction both traumatic, chronic inflammatory, and that after clonidine toxicity suggesting a possible target for future investigations.
CLINICAL FEATURES AND TREATMENT RESPONSE IN A LARGE UK COHORT OF STIFF PERSON SYNDROME PATIENTS
Authors: Sadalage Girija , Karim Abid , Jacob Saiju
Published: October 2015

Stiff Person syndrome (SPS) is a chronic autoimmune neurological disorder causing muscle stiffness, excessive startle and pain. Patients often have anti-GAD and occasionally anti-amphiphysin antibodies (especially in the paraneoplastic forms). There is no clear age, sex or race predilection clearly identified. Immunomodulatroy therapy with plasma exchange and IVIg is often beneficial in most patients.

We systematically looked at patients with a diagnosis of SPS with positive antibodies. 12 of these patients were evaluated in detail for their clinical features, concomitant illness and immunological status. We also evaluated the treatment response of these patients using a locally developed rating scale combining the functional activity and quality of life scores (BRIT scale– submitted as another abstract). Many patients had a long delay between the onset of symptoms and the final diagnosis. It was also noted that a good proportion of patients had certain behavioural and personality changes which could well be attributed to the disease, rather than by chance. More than 80% of patients had significant response to immunomodulatory therapy, although the duration of remission/response was variable.

This is one of the largest cohorts of SPS patients looked after in a single centre, which gives an insight into the clinical characterstics and immunological response of this rare neuroimmunological disorder.
PSYCHIATRIC PRESENTATIONS OF AUTOANTIBODY-MEDIATED ENCEPHALITIS
Authors: Matthews Rachael , Hackett Richard , Jones Matthew
Published: October 2015

Background

Antibody-mediated limbic encephalitis refers to a spectrum of inflammatory neurological disease. Patients typically have a syndrome consisting of disorientation, amnesia, seizures and behavioural change. Autonomic disturbance and movement disorders are also observed. There has been recent interest in the potential role of autoantibodies in patients with psychosis without the other clinical features of limbic encephalitis.

Aims

To characterise the clinical phenotype of patients presenting to a neuropsychiatry clinic with predominant psychosis and positive autoantibodies. We also aimed to determine if a standardised approach was being taken to their assessment.

Methods

Retrospective case note review using a standardised proforma.

Results

20 patients were identified with prominent psychosis and positive autoantibodies (9 NMDAr, 7 VGKC, 3 GAD, 1 TPO). 7 patients had psychiatric symptoms only. 5 patients had additional clinical symptoms to suggest a diagnosis of limbic encephalitis. 8 patients had prominent psychosis symptoms and only very mild other associated neurological problems making them hard to classify. There was variability in the assessment that patients received.

Conclusions

Pure psychiatric presentations in patients with positive autoantibodies are observed and further study is required to elucidate the role of such antibodies in the pathogenesis of these disorders.
CEREBRAL VASCULITIS HISTOPATHOLOGY IN RELAPSING POLYCHONDRITIS
Authors: Mbizvo GK , Ellis RJB , Michael BD , Rathi N , Doran M , Crooks D
Published: October 2015

Central nervous system (CNS) involvement in relapsing polychondritis (RPC) is rare and presumed to be the result of either a vasculitic or an encephalitic process, although there is little in the way of histopathological evidence for these. Understanding the underlying pathological process is important because cognitive decline can be halted or reversed with tailored immunosuppression.

We describe here the histopathological features of RPC with CNS involvement in a 65-year-old gentleman that presented with rapidly progressive cognitive decline, fevers and ataxia over six weeks. He had bilateral auricular inflammation with cartilage destruction, but relative lobe sparing, ocular inflammation, and a symmetrical small-joint polyarthropathy.

The cerebrospinal fluid showed lymphocytic pleocytosis. Diffuse sub-cortical white matter abnormalities were seen on magnetic resonance imaging. A clinical diagnosis of RPC was made on the basis of McAdam criteria.

Routinely stained histological brain sections showed scattered foci of vasculitis associated with multinucleated giant cells (MNGC), T-lymphocytes, neutrophils and eosinophils. The leptomeninges were oedematous and thickened by an increase in loose collagenous tissue, vascular proliferation and inflammatory infiltrate of neutrophils, lymphocytes and plasma cells. PAS staining did not reveal any infective organisms. Auricular histology showed central erosion of the cartilage and mild non-specific inflammation of the skin consistent with clinical impression of RPC.

In the context of the clinical diagnosis, our findings help further refine the histopathological understanding of RPC involving the CNS, suggesting a vasculitic rather than encephalitic process. Our histology also showed giant perivascular multinucleated cells as part of the vasculitic process, and this not been described before in the literature.
PILOCYTIC ASTROCYTOMA: A CASE OF NOT SO BENIGN INTRACRANIAL HYPERTENSION
Authors: Appleton Jason Philip , Hayton Tom , Williams Adrian
Published: October 2015

Idiopathic intracranial hypertension (IIH) is a condition of raised CSF pressure without any apparent structural lesion or problem with venous drainage. We present a lady who was initially diagnosed with IIH, but was later found to have an unusual brain tumour.

A 30 year old lady presented in 2012 with a three month history of headaches, nausea and vomiting, two weeks of blurred vision and one week of double vision on looking left. Visual acuity was 6/6 on the right and 6/9 on the left with a left relative afferent pupillary defect, bilateral papilloedema and left lateral rectus palsy. MRI showed ventriculomegaly. Lumbar puncture revealed normal constituents with an opening pressure of 60 cm H2O. In the absence of a space occupying lesion or venous occlusion a diagnosis of IIH was made. A ventriculoperitoneal shunt was inserted and she was discharged but didn't attend follow-up. She re-presented in May 2014 with headaches and intermittent left arm and leg numbness. An MRI revealed widespread CSF pathway infiltration, leptomeningeal enhancement, tonsillar descent and an extensive cervical syrinx. She underwent posterior fossa decompression and biopsy, which was histologically confirmed as pilocytic astrocytoma.

Ventriculomegaly is not a feature of IIH. This case illustrates the wide differential of raised CSF pressure and that careful assessment of brain imaging and CSF constituents is required prior to making what is, in effect, a diagnosis of exclusion.
OCKHAM'S RAZOR OR HICKAM'S DICTUM? THE DIAGNOSTIC JOURNEY OF A PATIENT WITH PROXIMAL MYOPATHY
Authors: O'Dowd Sean , Munteanu Tudor , Hardiman Daniel , Langan Yvonne , Brett Francesca , Redmond Janice
Published: October 2015

A 39-year old Congolese native presented with a ten-year history of myalgia and progressive muscle weakness. He had a known tissue diagnosis of pulmonary, mediastinal and hepatic sarcoidosis, as well as latent tuberculosis. Family history was unavailable. Examination revealed deformity of the distal joints; shoulder girdle and proximal lower limb atrophy; proximal muscle weakness and a waddling gait. CK was 2560 IU/l (normal <290). Plain films of the hands revealed cystic bony change. EMG demonstrated features consistent with a necrotising myopathy. MRI of proximal muscle groups revealed abnormal high signal consistent with myositis. Biopsy of quadriceps was abnormal but failed to demonstrate features consistent with inflammation. A second biopsy targeted the deltoid- again no convincing evidence of inflammation was present; no granulomata were detected; the possibility of an underlying inherited myopathy was queried. The patient continued to experience progressive muscle symptoms. A third muscle biopsy of the contralateral deltoid was ultimately diagnostic, demonstrating a number of non-caseating granulomata.

Symptomatic sarcoid myopathy is rare, although the literature suggests high rates of asymptomatic muscle involvement. Securing an accurate diagnosis in this case was essential in order to guide appropriate use of immunosuppression. The clinical features and management of sarcoid myopathy are reviewed.
TIMELINESS OF MOTOR NEURONE DISEASE CARE– DIAGNOSIS TO SERVICE ACCESS
Authors: Shanmugarajah Priya Devi , Tuttle Linda , Jung Agam
Published: October 2015

Background

MND is a rapidly progressive incurable neurodegenerative condition. The unpredictable rate of deterioration poses challenges to timely seamless co-ordinated care delivery. We performed an audit mapping time intervals of the patient's journey at the Leeds MND Centre to inform local service development.

Objectives

Evaluate the time period from symptom onset to referral, diagnosis and access to multidisciplinary services.

Method

Retrospective medical records review for newly diagnosed patients between 2010–2012. Time intervals were compared with MNDA Standards of Care and King's MND pathway.

Results

33 case notes were analysed. Median symptom onset to neurology referral was 36 weeks. Diagnosis was confirmed within 5 weeks. Post diagnosis nurse specialist review was within 2 weeks; however MDT review and consultant follow-up did not meet standards.

Discussion

This audit identified the lack of a standardised diagnostic and referral pathway. It resulted in significant service review and redesign. Measurement of specific time intervals can be a practical and relevant measure for assessing variation in quality of care. The limitations of a modest sample size and limited time frames can be overcome by a national prospective audit. This will identify delays in both diagnosis and multidisciplinary team access thus ensuring equitable provision of services for patients.
ANALYSIS OF AN ADULT DUCHENNE MUSCULAR DYSTROPHY POPULATION: TEN YEARS ON
Authors: Wu Kit , Rigaudy Axelle , Christodoulou Loucas , Okello Aren , Ballard Emily , Hart Nicholas , Howard Robin
Published: October 2015

Background

Duchenne muscular dystrophy (DMD) is a progressive, multi-systemic condition, management of which has benefitted from improvements in research and healthcare.

Aim

1. To review the multidisciplinary management of a late adolescent and adult DMD population attending the Lane Fox Respiratory Unit. 2. To compare the findings to those of an audit conducted 10 years previously (Parker et al, QJM. 2005.), so to identify areas of improvement and issues that require further input.

Method

We studied 30 patients with DMD referred to an adult neuromusclular clinic over a ten-year period. Clinical details were obtained from case notes or direct observations.

Results

The age for our cohort ranged from 19 to 49 years, all of whom became symptomatic before ten years old. Nine patients died during the study period. 25 patients were wheelchair bound in their mid-teens. Over the last ten years, areas of improvement include provision of non-invasive ventilation, provision of aids, and access to education (9/30 of our cohort attended university or college, and three patients are in active employment). Areas of care that need further input are management of mood, bowel hygiene, fatigue and pain.

Discussion

Despite improvements in several areas, there is still a need for a consistent and multi-faceted approach to management of DMD.
PARANEOPLASTIC NMO AND REVIEW OF MRI FINDINGS IN 18 NMO PATIENTS
Authors: Mistry Niraj , Jacob Saiju
Published: October 2015

A 79-year-old lady was admitted with rapid onset weakness in both legs with a mid-throacic sensory level. She had a preceding history of viral upper respiratory infection. She was recently treated for breast cancer 12 months' previously. Within 24 hours she developed complete paraplegia and the MRI scan revealed extensive T2W high signal changes throughout the spinal cord with discrete contrast enhancement and expansion of the cord. CSF showed 7 mononuclear cells with low CSF glucose (vs serum) and high CSF protein. Investigations revealed positive aquaporin-4 antibodies and she rapidly improved after a course of intravenous steroids followed by oral steroid taper. Extensive screen for an underlying malignancy was negative. Given the temporal relationship with cancer, a diagnosis of possible paraneoplastic syndrome was made as per established criteria (Graus et al. 2004).

We took this opportunity to review the MRI findings in 18 of our recent NMO patient cohort (15 aquaporin-4 antibody positive, 1 anti-MOG positive and 2 seronegative). We compared this against the established radiological criteria (Miller DH et al, 2008) for NMO.

We discuss the possibility of NMO being a rare paraneoplastic phenomenon and review the radiological findings in our cohort of NMO patients against established criteria.
LUNG CANCER BRAIN METASTASES: FACTORS ENHANCING TUMOUR CELL ADHESION
Authors: Gutowski N , Rai S , Whatmore J
Published: October 2015

Metastatic lung cancer cell arrest along brain microvasculature maybe mediated by interactions between ligands on circulating tumour cells and E-selectin adhesion molecules on brain endothelial cells, which are shielded by a dense endothelial glycocalyx layer. We previously identified proteins, including vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-α), in A549 and SK-MES-1 lung tumour conditioned media, which enhance tumour cell adhesion to human brain microvascular endothelial cells (HBMECs).

Aim

To examine whether increased lung tumour/HBMEC adhesion is a consequence of VEGF and TNF-α-induced brain endothelial glycocalyx degradation subsequently enhancing E-selectin exposure.

Methods

Following treatment with 0.2 ng/ml VEGF and 160 pg/ml TNF-α, endothelial glycocalyx changes were measured by binding of fluorescein isothiocyanate-linked wheat germ agglutinin (WGA-FITC). E-selectin levels were quantified by ELISA.

Results

Both VEGF and TNF-α significantly reduced WGA-FITC staining of HBMEC glycocalyx by more than 20% to 74±5.2% and 77±3.8%, respectively compared to control (100%) (p≤0.05, n=6). After 30mins, enhanced E-selectin levels were also observed (VEGF: 146±41.0% and TNF-α: 122±11.2%) (p=0.037, n=3).

Conclusion

Lung tumour cell secreted VEGF and TNF-α enhance lung tumour cell adhesion to HBMECs by inducing endothelial glycocalyx degradation revealing previously ‘hidden’ E-selectin.
LYMPHOMATOSIS CEREBRI: A TREATABLE CAUSE OF RAPIDLY PROGRESSIVE DEMENTIA
Authors: Samani Amit , Davagnanam Indran , Cockerell Oliver Charles , Ramsay Alan , Patani Rickie , Chataway Jeremy
Published: October 2015

We describe a case of lymphomatosis cerebri (LC), an extremely rare variant of Primary Central Nervous System Lymphoma (PCNSL) characterised by diffuse infiltration of brain parenchyma by a non-cohesive mass of malignant lymphocytes.

A 50 year-old lady presented with rapidly progressive cognitive decline. Neuropsychometric testing showed global cognitive deficits with magnetic resonance imaging of the brain showing diffuse T2-weighted white matter hyperintensity. Initial impression included metachromatic leukodystrophy however after a series of normal investigations, and clinicoradiological deterioration, a decision was made to proceed to brain biopsy which showed LC. Following chemoradiotherapy she regained the ability to ambulate independently and her cognitive state improved.

PCNSL typically presents as discrete gadolinium-enhancing T2 hyperintense lesions. Very rarely it presents as LC, usually manifest as rapidly progressive cognitive decline and leukoencepahlopathy. Complete remission of LC has been achieved with steroid use followed by radiotherapy, cisplatin or methotrexate. Although there are many causes of rapidly progressive leukoencephalopathy, rapid progression of structural change, perhaps combined with new foci of enhancement, should prompt thoughts of an underlying neoplastic process and the need for biopsy. This case highlights the diagnostic (and potential therapeutic) importance of early consideration of brain biopsy in patients with rapidly progressive atypical neurological syndromes
USING TRANSCRANIAL MAGNETIC STIMULATION (TMS) TO PROBE EFFECTS OF VISUAL MOTION ADAPTATION ON PRIMARY VISUAL CORTEX (V1) EXCITABILITY IN BILATERAL VESTIBULAR FAILURE (BVF) PATIENTS
Authors: Ahmad Hena , Roberts Richard , Arshad Qadeer Arshad , Patel Mitesh , Bronstein Adolfo
Published: October 2015

Background and aim

Patients with BVF report oscillopsia due to a defective vestibulo-ocular reflex causing retinal slip. No previous studies have probed visual cortical excitability using TMS and visual motion processing in these patients. We investigated the effects of visual motion adaptation on V1 cortical excitability in BVF patients and correlated this with psychophysical parameters.

Methods

12 BVF patients (7 males) aged 29–65 (mean=54.5) and 12 controls (6 males) aged 42–73 (mean=55) were recruited. Biphasic TMS pulses were applied at V1 and phosphene threshold (PT) was estimated. 3 measurement phases were (1) Stationary (2) Motion with optokinetic stimulation (OKS) Adaptation: OKS rightwards for 5 minutes 3) Post adaptation during viewing motion. All subjects completed questionnaires prior to the experiment. Results were analysed offline by calculating the probability of phosphene perception.

Results

Baseline phosphene thresholds were significantly higher in BVF patients (p=0.024) reflecting reduced visual cortical excitability. Lower oscillopsia scores correlated with reduced baseline V1 excitability (p=0.009).

Conclusions

This novel finding acts as a neurophysiological correlate for clinical observations of adaptive visual motion perception and is also correlated with psychophysical parameters. These results provide evidence for adaptive mechanisms leading to cortical plasticity following BVF.
FOWLER'S SYNDROME OF URINARY RETENTION: A RETROSPECTIVE STUDY OF CO-MORBIDITY
Authors: Hoeritzauer Ingrid , Stone Jon , Fowler Clare , Elneil Sohier , Carson Alan , Panicker Jalesh
Published: October 2015

Aims

To study the frequency of pain, psychological or functional disorders in patients with Fowler's syndrome.

Methods

We carried out a retrospective chart review of patients with a diagnosis of Fowler's syndrome attending the Uro-Neurology centre at the National Hospital for Neurology and Neurosurgery between 2009–2013 looking at triggering events, physical and psychological comorbidities.

Results

Of 62 patients with clinical and electromyographic diagnosis of Fowler's syndrome, 31 (50%) had unexplained chronic pain syndromes, 12 (19%) of these were taking opiates. 15 (24%) had ‘functional’ neurological symptoms. Abdominopelvic surgery with general anaesthesia was the leading trigger (n=21, 35%).

Conclusions

We found high levels of co-morbidity with patients having some form of pain (50%), a probable functional disorder (24%) or psychological symptoms (31%). There are several potential explanations for this association including the effect of developing an apparently unexplained distressing condition, confounding effect of opiate use or referral bias. The findings suggest a need for prospective systematic study of comorbidity for this disabling condition.
BILATERAL INTERNAL CAROTID ARTERY DISSECTION WITH CONFUSION
Authors: Kapoor Ambika , Chinthapalli Krishna , Warner Graham
Published: October 2015

Bilateral internal carotid artery (ICA) dissections are rare. Typical clinical presentation includes cerebral ischaemia, neck/headache, Horner's syndrome & pulsatile tinnitus1.

We present a forty-two year old right-handed man admitted to hospital with a ten day gradual onset headache, altered taste, widespread cognitive impairments, horizontal diplopia and a right Horner's syndrome. There was no history of trauma. Brain magnetic resonance imaging revealed multiple small embolic infarcts in carotid territories of both cerebral hemispheres. Computed tomography angiogram (CTA) of intracranial and extracranial vessels revealed occlusion of the left ICA and attenuation of the right ICA below the skull base.

Symptoms resolved within 3–5 days of starting sub-cutaneous low molecular weight heparin and he was then anticoagulated with warfarin for six months. Repeat CTA at 4 months showed persisting complete left ICA occlusion but complete recanalisation of the right ICA.

This is the first description of cognitive changes following bilateral ICA artery dissections. Whilst ICA dissection presentations are usually explained by embolic phenomena or local effects upon ICA walls, the mechanism here is probably due to cerebral hypoperfusion. Cognitive assessment should be performed in all patients presenting with ICA dissection especially when it is bilateral.
ARE SUBTHALAMICUS NUCLEUS, INTERNAL GLOBUS PALLIDUS AND THALAMUS INVOLVED IN THINKING?
Authors: Minks Eduard , Jurák Pavel , Chládek Jan , Hummelová Zuzana , Halámek Josef , Minksová Alexandra , Bareš Martin
Published: October 2015

Introduction

The aim was to compare evoked potentials (EP) from the P300 paradigm against mismatch negativity (MMN) paradigm, both recorded in the subthalamic nucleus (STN), internal globus pallidus (GPi) and thalamus (Th) and thus electrophysiologically isolate conscious cognition component in these structures.

Methods

We included 8 patients in Deep brain stimulation program and recorded EP (patients with Parkinson's disease, Generalized dystonia, Essential tremor, Epilepsy). The two four-contacts intracerebral electrodes were implanted into the left and right STN, GPi or Th bilaterally. We computed local potentials on the left and right electrode and we studied the latency of cognitive response (from 200 to 400 ms).

Results

In the comparison of infrequent stimuli related P300 and MMN a significant difference was found in 14 from 16 electrodes. Comparing frequent answers we found significant difference in 13 from 16 electrodes.

Conclusion

The difference between evoked potentials of MMN and P300 protocols in 200–400 ms latency suggests that STN, GPi and Th are involved in conscious cognitive processes at the time of stimuli application.
SIMILARITIES IN ARTERIAL ARRIVAL TIME PROLONGATION AND POSTERIOR HYPOPERFUSION IN PATIENTS WITH IDIOPATHIC PARKINSON'S DISEASE AND STROKE
Authors: Al-Bachari Sarah , Vidyasagar Rishma , Silverdale Monty , Emsley Hedley , Parkes Laura
Published: October 2015

The relevance of impaired neurovascular function in idiopathic Parkinson's disease (IPD) is unknown. Furthermore, it is unknown whether any such changes might contribute to, or be the effect of, neurodegeneration, or potentially reflect comorbid cerebrovascular disease (CVD). MRI arterial spin labelling (ASL) is a suitable, non-invasive tool for quantifying cerebral haemodynamics including measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). Prolonged AAT has been attributed to increased collateral circulation, chronic vasodilatation and/or increased tortuosity of vessels.

12 subjects with CVD (mean age 68.9±7.8), 19 tremor dominant (TD) IPD subjects (mean age 67.2±0.6), 17 postural instability and gait dominant (PIGD) IPD subjects (mean age 70.7±6.6) and 23 control subjects (mean age 65.1±5.7) completed a 3T MRI scanning protocol, including ASL. CVD subjects had significantly more cerebrovascular risk factors than the other groups. A significant widespread increase in baseline AAT was seen in IPD (both TD and PIGD) and CVD groups when compared to controls. Voxel-based analysis of CBF revealed significant focal hypoperfusion (predominantly posteriorly) in the TD, PIGD and the CVD groups when compared to controls.

These novel findings suggesting similar alterations in cerebral haemodynamics in IPD and CVD groups merit further study.
FRACTURE RISK IN INCIDENT PARKINSONIAN COHORT VERSUS CONTROLS
Authors: Sleeman Isobel , Che Zhu-Chung , Counsell Carl
Published: October 2015

Background

Postural instability and resultant fractures are common in parkinsonism but no studies have analysed fracture rates in prospective incident cohorts of parkinsonian patients and controls.

Methods

Data from the PINE study (326 incident parkinsonian patients, 261 age-gender matched controls) were used. The study database included prospectively collected data on falls and fractures from annual reviews supplemented by hospital and GP records. Major fractures were defined as skull, long bone or pelvis. Kaplan-Meier curves for time-to-first fracture from diagnosis were analysed by diagnostic groups. Multivariate Cox regression analysis was used to identify factors that independently predicted fractures.

Results

The fracture rates in patients with PD, Parkinson's plus syndromes, dementia with Lewy Bodies and vascular parkinsonism were similar (log rank p value=0.89) and so these groups were combined. The percentage of frequent fallers among the patients (24.2%) was higher than the controls (1.3%). The incidence of any fractures and major fractures was about three times higher in patients (5.51 and 4.25 per 100 patient-years respectively) than in controls (1.96 and 1.42 respectively). Parkinsonism, female gender, frequent fallers and development of dementia were independent predictors of major fractures.

Conclusion

Patients with parkinsonism have a much higher risk of falls and fractures.
PREDICTORS OF INSTITUTIONALISATION IN PARKINSON'S DISEASE
Authors: Macleod Angus , Counsell Carl
Published: October 2015

Background

Institutionalisation (entry to nursing home, or other place of residential care) is an important outcome in PD. We investigated frequency of, and baseline predictors of, institutionalisation in Parkinson's disease (PD).

Methods

We identified all new cases of PD in Aberdeen, UK, over 4.5 years using multiple, community-based ascertainment methods. Age-sex matched community-based controls were also recruited. Participants were seen annually and place of residence at each follow-up or before death were ascertained, together with date of entry to institution. Kaplan–Meier institution-free survival probabilities were plotted. Potential baseline predictors were investigated using Cox regression.

Results

198 PD patients and 260 controls were recruited. One patient and one control were institutionalised before diagnosis. One patient and four controls were lost to follow-up. 44 (22%) PD patients and 19 (7%) controls were institutionalised during mean 6.1 years follow-up. Hazards of institutionalisation were higher in PD than controls (HR 3.72 [2.16–6.39]). Older age (HR 1.05 [1.01–1.09]), lower MMSE score (HR 0.88 [0.79–0.98]), and baseline dependence (HR 2.48 [1.18–5.25]) were independently associated with institutionalisation.

Conclusions

Institutionalisation was higher in PD than controls. Older age, poorer cognition and being dependent at diagnosis led to increased institutionalisation.
MORTALITY IN PARKINSON'S DISEASE AND ATYPICAL PARKINSONIAN DISORDERS
Authors: Macleod Angus , Counsell Carl
Published: October 2015

Background

We evaluated the mortality associated with Parkinson's disease (PD), Lewy body dementia (LBD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and vascular parkinsonism (VP) using a community-based incident cohort.

Methods

All incident parkinsonism cases identified over 4.5 years (2002-4, 2006-9) were tagged to the NHS central register for regular death notifications. Kaplan-Meier survival probabilities were plotted. Standardised mortality ratios (SMRs) and life expectancy, adjusted for age, sex and calendar year, were calculated using regional mortality data.

Results

Until June 2014, 90 deaths occurred in 198 PD patients, and 107 deaths in 117 patients with other syndromes. Median survival in PD, LBD, PSP, MSA, and VP was 7.8 (6.7–9.4), 3.3 (2.3–4.1), 2.6 (1.1–3.8), 5.1 (1.3–NA), 2.1 (1.5–3.4) years, respectively. SMRs were 1.5 (1.2–1.9), 4.2 (3.0–5.9), 3.8 (2.6–5.5), 1.8 (0.9–3.4), 4.2 (3.0–6.0) respectively. In PD, median survival was lower than life expectancy, but more so in under 65s.

Conclusions

Mortality in PD was increased by 50% over expected population mortality. Younger patients have proportionally more to lose. Survival was much poorer in other syndromes.
ABNORMALITIES OF FIXATION, SACCADE AND PURSUIT IN POSTERIOR CORTICAL ATROPHY
Authors: Shakespeare Timothy , Kaski Diego , Yong Keir , Patterson Ross , Slattery Catherine , Ryan Natalie , Schott Jonathan , Crutch Sebastian
Published: October 2015

Background and aims

The clinico-neuroradiological syndrome posterior cortical atrophy (PCA) is the cardinal ‘visual dementia’. We evaluated oculomotor function in patients with PCA.

Methods

20 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 22 healthy controls completed tests of fixation, saccade and smooth pursuit eye movements using an infrared pupil tracking system.

Results

Eye movement abnormalities occur in 80% of PCA patients (compared to 17% tAD, 5% controls). PCA saccades were significantly hypometric, especially for distant targets. PCA patients were slower to reach saccadic targets whose onset overlapped with fixation, consistent with ‘sticky fixation’. Time to reach saccadic targets was also significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, tAD patients showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, whilst PCA patients showed characteristically large saccadic intrusions whose frequency correlated significantly with generalised reductions in cortical thickness. Smooth pursuit was also impaired, with lower gain in both PCA and tAD patient groups compared to controls.

Conclusions

Eye movement abnormalities are near-ubiquitous in PCA, and may help distinguish PCA from tAD. We suggest the PCA oculomotor profile reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. The results have implications for other patients with dementia-related visual impairment.
FEATURES IN IDIOPATHIC RBD MIRROR THOSE OBSERVED IN PD
Authors: Rolinski Michal , Zokaei Nahid , Lawton Michael , Evetts Samuel , Mackay Clare , Quinnell Timothy , Zaiwalla Zenobia , Ben-Shlomo Yoav , Husain Masud , Hu Michele
Published: October 2015

Introduction

Patients with idiopathic RBD have an increased risk of developing a defined neurodegenerative disorder, the majority developing PD. Is it possible to detect features of PD in RBD, before a diagnosis of PD is established?

Methods

Fifty-seven patients with polysomnography-proven idiopathic RBD and seventy-four control and drug-naïve PD subjects were recruited. All participants underwent a thorough motor and non-motor assessment, and were screened for mutations in glucocerebrosidase (GBA) genes. Visual working memory was separately assessed in 21 RBD, 15 drug-naïve PD and 21 controls using a serial order task testing both recall precision and the pattern of impairment.

Results

RBD patients had increased motor and postural impairment compared to controls. Non-motor deficits (hyposmia, constipation, depression, anxiety) were similar between RBD and PD cases. Furthermore, there was a significant deficit of working memory memory recall precision in PD and RBD, with the pattern of deficit being similar in both groups.

Conclusion

RBD is associated with motor and non-motor impairment often seen in early PD. The pattern of visual working memory impairment in RBD is equivalent to that observed in early PD. These results support the hypothesis that idiopathic RBD is representative of prodromal sporadic PD.
KNOWLEDGE OF PRESCRIBING IN PARKINSONISM AMONG JUNIOR DOCTORS
Authors: Bedford Jonathan , Whiteside David , Dassan Pooja
Published: October 2015

Junior doctors are primarily responsible for prescribing medications for patients with parkinsonism attending a district general hospital. We assessed levels of confidence and knowledge of appropriate prescribing in a variety of circumstances among 30 junior doctors at Ealing Hospital, using a 5 part questionnaire. Only 10% felt confident in prescribing a regimen for patients with parkinsonism who are unable to take their usual medications orally. 60% could not select a suitable anti-emetic, and just 2 respondents answered all assessment questions correctly. Confidence in prescribing improved with seniority but overall scores in the assessment section did not.

We have designed a protocol to assist doctors when managing patients with parkinsonism on the ward, and are conducting teaching sessions to improve understanding. The impact of these interventions will be assessed and presented at the Annual Meeting.
THROMBOSED BRAINSTEM DEVELOPMENTAL VENOUS ANOMALY CAUSING HYDROCEPHALUS
Authors: Dodd Katherine , Pegg Emily , Mathur Sachin , Suresh Chhetri
Published: October 2015

Developmental venous anomaly (DVA) is a commonly encountered congenital abnormality of the venous drainage system. Spontaneous thrombosis of DVA is rare. We present a case of thrombosed brainstem DVA leading to venous infarction and oedema within the posterior fossa.

A 49 year old, previously fit gentleman presented to the local hospital with a one day history of headache, slurred speech and incoordination. Examination demonstrated GCS of 13/15, cerebellar dysarthria, horizontal nystagmus to the left, mild right sided pyramidal weakness, right sided cerebellar ataxia and bilateral extensor plantars.

CT venogram revealed a cerebellar DVA with thrombosis of one of the veins. There was surrounding venous infarction and oedema within the posterior fossa, causing compression of the fourth ventricle and dilatation of the lateral ventricles. MRI demonstrated extensive T2 change in the right cerebellar hemisphere, dorsal pons and right cerebral peduncle. No underlying thrombotic tendency was identified. He was treated successfully with intravenous heparin infusion. He improved over the next 3 weeks, and was discharged on warfarin with mild right sided ataxia and cerebellar dysarthria.

Our case demonstrates that DVAs, generally considered as common insignificant anatomical variants, can uncommonly lead to significant complications.
ORAL ANTICOAGULANT PRESCRIBING IN A HYPERACUTE STROKE UNIT
Authors: Samani Amit , Kayani Mahaz , Asokanathan Asaipillai
Published: October 2015

Background

Non-vitamin K antagonist oral anticoagulants provide a valuable alternative option to warfarin for thromboprophylaxis for non-valvular atrial fibrillation. NICE has recently released a national consensus statement which will guide local protocol/guideline development. Currently, their use is often governed by physician preference combined with patient factors. We explored the pattern of prescribing in the pre-guideline era.

Method

Retrospective analysis of admissions from June–October 2014. Student T-test and Fischer's exact test with Bonferroni corrections were used to compare demographics between groups. A creatinine clearance of <60 umol/L defined renal impairment.

Results

61 patients, 37 female, mean age 80.8 years were audited. 35 were prescribed rivoroxaban 20 mg, 7 rivoroxaban 15 mg, 11 apixaban 5 mg and 8 apixaban 2.5 mg. None were prescribed dabigatran. Age, CHADS2 and HAS-BLED scores did not show statistically significant variability between subgroups. Renal impairment was signficantly commoner in the apixaban 2.5 mg group compared to the 5mg group (p<0.001) and the rivoroxaban 15mg compared to the 20mg group (P<0.01). There was no difference between the rivoroxaban and apixaban groups.

Conclusion

Currently, renal impairment is the main determinant for thromboprophylaxis choice. Local guidelines have been created with physician education underway and re-audit planned in 3 months. The authors will present the full data.
PHASE 2 OPEN-LABEL EXTENSION STUDY OF PATISIRAN, AN INVESTIGATIONAL RNAI THERAPEUTIC FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY
Authors: Adams David , Suhr Ole , Conceicao Isabel , Waddington-Cruz Marcia , Schmidt Hartmut , Buades Juan , Campistol Josep , Pouget Jean , Berk John , Coelho Teresa
Published: October 2015

Familial amyloid polyneuropathy (FAP) is a progressive disease. Patisiran is an investigational small interfering RNA (siRNA) targeting TTR. The primary objective of the Phase 2 study is to evaluate the safety of 0.3 mg/kg patisiran administered intravenously once every 3 weeks. Twenty-seven patients were enrolled; the mean duration of treatment was 7 months (range 3–12), with 282 doses administered (median of 11 doses/patient). Chronic dosing with patisiran has been generally well tolerated. Two patients experienced serious adverse events regarded as being unrelated to study drug. Infusion-related reactions were observed in 14.8% of the patients, were mild in severity, and did not result in any discontinuations. Sustained TTR lowering of at least 80% was achieved based on serial TTR measurements for over 9 months, with further nadir of up to 89.6% between doses. Neurologic impairment scores were stable after 6 months of treatment with patisiran. A mean decrease from baseline in mNIS+7 of 0.95 points (N=19) observed in this study compared favorably to the estimated increase of 7–10 points in mNIS+7 at 6 months from prior FAP studies in a patient population with similar baseline NIS values. Dosing continues in all patients, and 12–month results will be presented.
MOTOR NEURON DISEASE: A CASE OF MISGUIDED THERAPEUTIC NIHILISM
Authors: Rossor Alexander , Josifova Dragana , Howard Robin , IsaacsItua Alifa
Published: October 2015

We report the case of a 62 year old gentleman with sensorineuronal hearing loss beginning in the second decade. At the age of 40 he collapsed and was unable to walk more than a few metres. He was admitted to hospital and diagnosed with a motor neuron disease on the basis of an EMG. Examination at the time revealed bilateral deafness, facial weakness, dysphagia, dysphonia and both proximal and distal weakness.

The family history was remarkable for two sisters who died of a similar condition in the second decade. In view of the combination of sensory neuronal deafness and a motor neuronopathy, a diagnosis of Brown Violetta Van Laera (BVVL) syndrome was made.

A PEG tube was inserted and the patient was discharged to a nursing home for palliation. After several months, our patient discharged himself, reintroduced thickened fluids resulting in removal of the PEG tube. His clinical condition has continued to improve although he intermittently requires a wheelchair.

Genetic testing of the SLC52A3 gene revealed two missense mutations (p.Glu36Lys and p.Val413Ala) confirming the clinical diagnosis of BVVL. SLC52A3 encodes a riboflavin transporter and in case series, riboflavin supplementation has halted or reversed the disease.