bluuebunny/crossref_metadata_2025_split huggingface dataset:
047 Creutzfeld-jakob disease with prolonged disease course in two younger patients
Authors: Dhanapalaratnam Roshan , Beran Roy , Buckland Michael , Cappelen-Smith Cecilia 
Published: May 2018

IntroductionSporadic Creuzfeldt-Jakob disease (sCJD) is a rare disease caused by prion proteins and usually presents in the 7th decade of life. sCJD classically presents with a rapidly progressive dementing illness, associated myoclonus and a median time to death of 6 months. Less commonly younger patients are described with a neuropsychiatric presentation and a prolonged disease course. We report two young sCJD patients with neuropsychiatric presentations and slow disease progression admitted to Liverpool Hospital, Sydney (2016–2017).Case 1 A 48 year old Chinese man presented with a 12 month history of depressive symptoms and insomnia. Over the next 5 months, he developed progressive cognitive impairment, disinhibited behaviour, aggression, paranoia and ataxia of gait. Serial EEG and MRI brain scans, cerebrospinal fluid (CSF) testing for 14–3–3 protein and PRNP gene testing were negative or non-contributory. He progressively became mute, bedbound and died at 24 months from symptom onset. Diagnosis was only confirmed with a limited brain autopsy at post-mortem that revealed severe microvacuolar change, gliosis, neuronal loss and status spongiosus. Anti-prion antibody 12 F10 staining showed a diffuse fine synaptic pattern in the frontal cortex and striatum consistent with sCJD.Case 2 A 42 year old Afghani man presented with a 36 month history of emotional lability and progressive social withdrawal followed by auditory and visual hallucinations, cognitive impairment and gait ataxia. Screening for vasculitis, infective (including HIV/syphilis) and autoimmune encephalopathies were negative. EEG demonstrated non-specific slowing, without characteristic periodic sharp-wave complexes. MRI brain was initially normal but progress imaging showed bilateral cortical ribboning, caudate nucleus T2-hyperintensity and associated diffusion restriction consistent with sCJD. CSF 14–3–3 protein analysis was positive. The patient died 38 months from symptom onset. Post-mortem examination was not performed.ConclusionsCJD in younger patients may present as a slowly progressive neuropsychiatric disorder and ante-mortem investigations may remain negative. Post-mortem remains the gold standard for CJD diagnosis.
005 Filling in the gaps: precision MRI reporting in multiple sclerosis clinical practice
Authors: Beadnall Heidi , Barnett Yael , Ly Linda , Wang Chenyu , Billiet Thibo , Ribbens Annemie , Hecke Wim Van , Masters Lynette , Hardy Todd A , Barnett Michael H 
Published: May 2018

IntroductionClinical multiple sclerosis (MS) magnetic resonance imaging (MRI) brain reports provide important information to neurologists. The quantitative data reported varies between centres and radiologists. Structured MRI reporting and formal quantitative MRI (QMRI) analysis may assist clinicians with patient management. The objective is to compare quantitative data derived from standard clinical reports, structured neuroradiologist reviews, local QMRI analyses and fully-automated MSmetrix QMRI analyses, in a longitudinal clinical MS cohort.MethodsClinical brain MRI scans separated by one-year minimum, from the same patient on the same scanner, were evaluated. Quantitative information was extracted from the clinical reports and structured neuroradiologist reviews. MRI scan-pairs were analysed locally by imaging-analysts and centrally by MSmetrix.Results50 MS patients, baseline age 39.02 (9.06) years, disease duration 9.11 (6.88) years and Expanded Disability Status Scale score 1.91 (1.62), were included. Compared to clinical reports, structured neuroradiologist reviews provided increased semi-/quantitative data; baseline T2 and T1 lesion burden (50% vs 100%; 2% vs 100%), baseline brain volume-loss (BVL; 72% vs 100%), new T1 lesions (0% vs 100%), regional brain atrophy (BA; 20% vs 100%). Lesion and brain volumes were not provided in radiology reports/reviews. Comparison of local and central QMRI revealed moderate-strong Pearson correlations for most metrics; Intra-class correlations varied more widely. Statistical consistency existed across all methods in detecting new T2 lesions. Radiologist-identified baseline BVL was associated with lower quantitatively-measured brain volumes. Local QMRI longitudinal BA rates >0.4% and >0.8%, were 48% and 26% respectively. Neuroradiologist review identified BA in 12%.ConclusionStructured neuroradiology review provided additional quantitative information over standard clinical reports. Quantitative data measured using local and MSmetrix pipelines were generally well associated but are not interchangeable. Longitudinal whole brain and regional atrophy is not reliably identified by radiologists and QMRI analysis provides a clear advantage in this regard. Structured reporting, and formal QMRI analysis, provide additional quantitative MRI data that may assist clinical decision-making in MS.
057 Real world evidence (RWE) on long-term persistence of fingolimod in relapsing-remitting multiple sclerosis (RRMS) in australia
Authors: Walker Robert , Schulz Mark , Arora Birendra , Chung Eric , Juneja Prabhjot , Verhaeghe Stephane , Spelman Tim , Broadley Simon 
Published: May 2018

IntroductionThis study aimed to examine and compare patient persistence of fingolimod to all reimbursed disease modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) in Australia.MethodThe Pharmaceutical Benefits Scheme (PBS) 10% sample supplied by the Department of Human Services was used in this study. Eligible patients must have received a script for a reimbursed DMT for RRMS between September 2011 and February 2016. Patient demographics were summarised using mean and standard deviation or frequency percentage. Persistence was defined as a patient that remained on a DMT with a gap in scripts of no longer than 4 months. Individual patients could be included multiple times if they initiated a new DMT during the study period. Persistence was derived using the Kaplan-Meier method and hazard ratios (HR). Persistence to individual treatments was then compared to the average persistence observed across all treatments; p-values were based on the log-rank test.Results720 unique patients were eligible for the study, contributing 1827 observations that for analysis (2.5 new initiations/patient). Overall the median persistence (MP) to therapy was 29.6 months with 67.7% of patients remaining on therapy for 12 months. The only DMT with significantly better persistence compared to the overall average was fingolimod (HR 0.65 (95%CI 0.57–0.73; p<0.001). Patients had an MP of 60 months on fingolimod with 79.5% of patients persistent at 12 months. Patients were significantly less persistent to interferon Beta-1a, interferon Beta-1b, glatiramer acetate and dimethyl fumarate (hazard ratios above 1.27 (p values all≤0.001) whilst the remaining DMTs, teriflunomide and natalizumab, showed no significant difference from the average persistence.ConclusionIn this analysis of PBS sample data, patients were most persistent to fingolimod treatment amongst all DMTs.
059 Teratoma with glycine, NMDA & VGKC antibodies presenting with severe weakness, respiratory failure & corticospinal tract dysfunction
Authors: Swayne Andrew , O’Gorman Cullen , Sheikh Nabeel , Brown Helen , Buck Lyndall , Prain Kerri , Gillis David , Wong Richard , Blum Stefan 
Published: May 2018

IntroductionGlycine antibodies are associated with progressive encephalomyelitis with rigidity and myoclonus (PERM) but have been rarely reported to cause myasthenic-like symptoms.1 We present a single patient seen at a tertiary neurology centre with fatigable muscle weakness and corticospinal tract dysfunction with positive glycine, VGKC and NMDA receptor antibodies, associated with an ovarian teratoma expressing neural tissue.CaseA 32 year old female presented with fatigable muscle weakness. Physical examination was atypical for a disease of the neuromuscular junction with features of exaggerated reflexes and clonus. The weakness progressed over 1–2 weeks leading to respiratory failure. Investigations including MRI brain, repetitive stimulation and acetylcholine-receptor antibody studies were all within the normal limits. Studies for neuronal antibodies against intracellular targets were negative. Further investigation revealed positive autoantibodies against Glycine receptor, NMDA (N-Methyl-d-aspartate) receptor and VGKC (voltage-gated potassium channel) with an underlying ovarian teratoma. Complete clinical resolution was achieved with teratoma resection and 2 g/kg course of intravenous immunoglobulin. Histopathological examination of the tumour revealed a mature cystic teratoma with dystrophic calcification. The teratoma included skin, adipose tissue, intestinal type mucosa, and neuroglial tissue in which nerve fibres and ganglion cells are present. A lymphoid infiltrate was concentrated in areas of neural tissue within the teratoma.ConclusionMuscle weakness, corticospinal tract dysfunction and respiratory failure have previously been reported in the context of anti-glycine antibodies. This is the first case where anti-glycine, anti-NMDA and anti-VGKC antibodies have been found in the context of an ovarian teratoma. The autoimmune nature of this condition is emphasised by the lymphoid infiltrate around the neural tissue expressed within the teratoma.Reference1. Carvajal-Gonzalez A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, … Vincent A. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain2014;137(Pt 8):2178–2192.
067 Efficacy of cladribine tablets in patients with highly active relapsing-remitting multiple sclerosis: analysis of pooled double-blind data from the clarity and onward studies
Authors: Giovannoni Gavin , Montalban Xavier , Rammohan Kottil , Cook Stuart , Comi Giancarlo , Rieckmann Peter , Soelberg-Sorensen Per , Vermersch Patrick , Dangond Fernando , King John , Damian Doris 
Published: May 2018

IntroductionPatients with relapsing MS (RMS) who show an increased rate of relapse or disability worsening can be described as showing high disease activity (HDA). Treatment with cladribine tablets (CT) in the CLARITY study, and with CT added to interferon-β in the ONWARD study demonstrated efficacy vs. placebo (PBO) across a range of patients with active MS. Combining double-blind data from these studies allows assessment of the efficacy of treatment with CT 3.5 mg/kg (CT3.5; cumulative dose). The objective of this post-hoc analysis is to compare the effects of CT3.5 vs. PBO on the proportion of patients achieving no evidence of disease activity (NEDA) status in HDA subgroups identified using two sets of criteria in a pooled cohort of patients from CLARITY and ONWARD.MethodsPatients from CLARITY and ONWARD were retrospectively stratified using 2 sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: high relapse activity (HRA; n=314) and HRA plus disease-activity-on-treatment (HRA +DAT; n=459). Patients treated with CT3.5 or PBO who fulfilled these criteria and achieved NEDA were compared over 2 years using odds ratios (ORs) and 95%CIs.ResultsIn the HRA subgroup, 76.5% of CT3.5-treated patients were relapse-free, 86.7% were T1 Gd +lesion free vs. 50.7% and 35.8%, respectively, for PBO. In the HRA +DAT subgroup, 77.6% were relapse-free and 88.8% were T1 Gd +lesion free with CT3.5 vs. 53.9% and 40.8%, respectively for PBO. In the HRA and HRA +DAT subgroups, 42.7% and 41.3%, respectively, of CT3.5-treated patients were disease activity free compared with 9.7%, (OR 6.94, 95% CI 3.67;13.12, p<0.0001) and 13.7% (OR 4.28, 95% CI 2.62;6.99, p<0.0001) respectively, of PBO recipients. In the overall CLARITY+ONWARD population (including non-HDA patients), the composite NEDA score also favoured CT over PBO (OR 3.95, 95% CI 2.90;5.37, p<0.0001).ConclusionCompared with placebo, treatment with CT3.5 was associated with increased odds of achieving NEDA in HDA patients.
075 Association between intracranial stenosis and extracranial stenosis seen in stroke patients
Authors: Guduguntla Geetha , Ting Cheng Ling , Jain Tarun , Gawarikar Yash , Patel Ronak 
Published: May 2018

IntroductionThe association between intracranial stenosis (ICS) and extracranial stenosis (ECS) using CT angiography (CTA) and the occurrence of ischaemic stroke and TIA has not yet been fully investigated.This study aimed to investigate if there is a clinically significant relationship between ICS and ECS with stroke and its risk factors, including diabetes, hypertension, hypercholesterolemia, atrial fibrillation (AF) and ischaemic heart disease (IHD).MethodsFour hundred and fifteen consecutive patients that presented to Calvary Public Hospital, Bruce were retrospectively analysed, with 158 excluded for incomplete CTA and MRA results. ICS and ECS severity was based on grading used in the WASID and SAMPRISS trials, while the Fazekas scale was used to grade periventricular white matter disease. CTA findings were used to base the presence and absence of stenosis.ResultsICS and/or ECS was present in 80% with ischaemic stroke, 78% with TIAs but comparatively only in 56% of those diagnosed as ‘mimics’ (p<0.05). Univariate analysis demonstrated an association between presence of ICS and AF, hypertension, IHD and diabetes (82%, 73%, 84%, 78%; p<0.001) respectively, while for ECS only with AF, hypertension and IHD (77%, 67%, 81%; p<0.001) respectively. Diabetes was independently associated as single biggest risk factor for ICS. Most steno-occlusive lesions were bilateral for ICS and ECS at 80% and 61%, respectively. There also seems to be an association between the presence of ECS and the presence of ICS, with ECS particularly demonstrating predictive value for ICS (ECS PPV for ICS=0.85, chi-square p-value<0.001).ConclusionThese findings suggest a significant association between the presence of ICS and ECS with the occurrence of ischaemic stroke and TIAs as well as with well-known stroke risk factors. This also indicates that perhaps the underlying pathophysiology for steno-occlusive lesions plays a role in ischaemic stroke and warrants further investigating.
079 Nerve ultrasound cross sectional area does not correlate with electrodiagnostic carpal tunnel severity in the very elderly
Authors: Mulroy Eoin , Pelosi Luciana 
Published: May 2018

IntroductionUltrasound measurement of median nerve cross-sectional area (CSA) at the wrist has emerged as an accurate and useful complement to electrophysiology in the diagnosis of carpal tunnel syndrome (CTS).AANEM, 2012 A number of studies have also shown a positive correlation between median nerve CSA and electrodiagnostic severity. After noting absence of the expected nerve enlargement on ultrasound in some very elderly patients, we sought to correlate nerve ultrasound and electrodiagnostic findings in a very elderly population and to compare this with a population of younger patients.MethodsWe undertook a retrospective review of electrophysiology and ultrasound data collected during routine clinical practice at our institution over a 13 month period. The correlation between electrodiagnostic severity and median nerve CSA at the wrist in patients aged 40–65 years (59 patients, 70 hands) was compared with a population of very elderly patients aged ≥80 years (33 patients, 40 hands). The sensitivity of nerve ultrasound for the detection of CTS was calculated for both groups.ResultsIn the 40–65 years age group, there was a strong positive correlation between electrodiagnostic severity and median nerve CSA (r=0.79, p<0.01). In patients aged over 80 years, there was no significant correlation between the two techniques (r=0.09, p=0.57). Compared to ‘gold standard’ electrophysiologic tests, nerve ultrasound sensitivity for the detection of CTS was 98% in the 40–65 years age group and 62% in the very elderly group.ConclusionThe absence of expected median nerve enlargement in very elderly patients with electrodiagnostic evidence of CTS may reflect a different pathophysiologic response to distal median nerve entrapment in advanced age. Our data also suggests that nerve CSA measurement alone may not be a reliable tool for the detection of CTS in the very elderly. Further studies of its diagnostic accuracy in very elderly patients are warranted.
093 Clinical and imaging discordance in reversible cerebral vasoconstriction syndrome
Authors: Devlin Michael J , Dwivedee Archana , White Richard P 
Published: May 2018

IntroductionReversible cerebral vasoconstriction syndrome (RCVS) is to be suspected in cases of thunderclap headache particularly when associated with convex subarachnoid haemorrhage without cerebral aneurysm. Angiographic changes and clinical state do not always correlate. We present a case report from the Townsville Hospital.CaseA 49 year old female presented to another hospital with recurrent thunderclap headaches first commencing with exercise. The medical history included idiopathic intracranial hypertension in remission, chronic migraine treated with botulinum toxin, and depression treated with amitriptyline and desvenlafaxine. MR imaging revealed cerebral vertex subarachnoid haemorrhage with normal MR angiogram of the cerebral vessels. The patient was transferred to our institution in a confused and restless state for cerebral digital subtraction angiogram, which was normal. A lumbar puncture revealed elevated white cells of 17×106/L with normal CSF protein and opening pressure of 39 cm H2O. Nimodipine that had been commenced before the patient became encephalopathic was ceased. Her confusion and headaches resolved but relapsed after three days. A repeat MR brain revealed multiple T2 hyperintensities in bilateral anterior and posterior circulation territories demonstrating diffusion restriction, and MR angiography revealed new segmental strictures and beading of bilateral middle and anterior cerebral arteries. The patient was diagnosed with overlap RCVS/posterior reversible encephalopathy syndrome; desvenlafaxine was ceased, acetazolamide commenced for raised intracranial pressure and a several week course of nimodipine recommenced. The patient was discharged home after resolution of headache and confusion without neurological deficit.ConclusionThis case highlights the dynamic changes of vasoconstriction and that angiographic findings can be discordant from the clinical status. Serial imaging is required to detect abnormalities of RCVS when the clinical suspicion is high. CSF analysis can be normal, however may reveal elevated protein or pleocytosis. The cause of our patient’s RCVS was thought to be the chronic use of desvenlafaxine.
096 A 47-year old female with slowly progressive cognitive impairment and motor decline
Authors: Vallat Wilson , Kleinig Timothy 
Published: May 2018

IntroductionWe present the case of a woman with an 8 year history of slowly progressive cognitive dysfunction and gait disturbance, and a diagnosis of vanishing white matter disease (VWMD).CaseThe patient struggled at work as an accountant, her hand writing became illegible, she had difficulty judging distances when driving and she had developed gait instability, slowing and falls. Her past medical history was unremarkable save for premature menopause at 35. Examination showed marked cognitive impairment ACE-R 59/100 (attention and orientation – 13/18, memory – 16/26, fluency – 1/14, language – 21/26, visuospatial – 8/16), reduced dexterity of hands, left upper limb ataxia and high- level gait dysfunction. MRI brain showed leukodystrophy with frontal predominance. Relevant investigations – white cell enzymes, very long chain fatty acids, phytanic acid, CSF were normal. In view of the clinical and radiological features genetic testing with leukodystrophy panel was performed which revealed homozygous eukaryotic translation initiation factor B3 (EIF2B3) mutation (p.Ala87Val variant). Adult onset leukodystrophies are rare genetic metabolic disorders of the glial cells. The white matter (WM) degeneration causes disruption of distributed neural networks resulting in variable constellation of cognitive dysfunction, ataxia, pyramidal and extrapyramidal signs. The clinical and radiological phenotypes overlap and there are up to 60 genes that account for adult onset leukodystrophy, which makes diagnosis challenging. Vanishing white matter disease due to EIF2B gene mutation are a group of disorders that result from mutation of any of the EIF2B subunits (1 to 5). Two thirds have associated premature ovarian failure. MRI shows confluent WM T2 high signal, subcortical U Fibre sparing, periventricular WM rarefaction and cerebral atrophy. Management is symptomatic.ConclusionAdult onset VWMD is a rare and devastating condition. When evaluating these patients targeted gene testing guided by clinical and radiological phenotype is likely to provide the highest diagnostic yield. Establishing the diagnosis is important as it has implications on future generations.
100 Autoimmune lambert eaton myasthenic syndrome in young adults
Authors: Winkel Antony , Reardon Katrina , Roberts Leslie 
Published: May 2018

IntroductionLambert Eaton myasthenic syndrome (LEMS) is a neuromuscular junction transmission disorder that is associated with malignancy (most often small cell lung cancer) and antibodies to the voltage gated calcium channel. Rarely, it can occur as a non-paraneoplastic phenomenon. The diagnosis can be difficult, and reduced motor amplitudes on nerve conduction studies can be misattributed to neurogenic or myopathic processes unless the referring physician or neurophysiologist considers LEMS in the differential diagnosis. Two cases of non-paraneoplastic LEMS were identified from testing performed in the Neurophysiology laboratory of St Vincent’s Hospital Melbourne in 2017. The histories, examination findings, investigations, extensive neurophysiological testing and response to treatment are presented.CasesThe two patients identified were aged 18 and 34 years at diagnosis. Both had a history of slowly progressive proximal weakness preferentially affecting the lower limbs over several years, with associated autonomic symptoms. The younger patient had become wheelchair dependent at age 17. Detailed neurophysiological testing demonstrated a pre-synaptic defect of neuromuscular junction transmission. The younger patient showed myopathic features on needle EMG. Voltage gated calcium channel antibodies were positive in both cases. Treatment with intravenous immunoglobulin, 3, 4-diaminopyridine, pyridostigmine, and azathioprine was associated with a definite improvement in strength and function in both patients. The patient with myopathic EMG features has residual moderate weakness but is now ambulant. Extensive screening for malignancies (including whole-body PET) has been negative, but surveillance will be continued for up to 5 years.ConclusionNon-paraneoplastic LEMS is a rare, but treatable, condition that warrants consideration, particularly when neurophysiological testing reveals reduced motor amplitudes. Successful diagnosis requires a threshold of suspicion in the neurophysiologist or referring neurologist.