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Background: The experience of psychological distress is prevalent in people with multiple sclerosis (MS), including high levels of stress, anxiety, and depression. It has been shown that people with MS use less adaptive coping compared with healthy individuals. This study examined the ability of coping strategies to predict maladaptive and adaptive psychosocial outcomes across areas of stress, depression, anxiety, and quality of life (QOL) in people with MS. Methods: 107 people with MS completed measures of depression (Beck Depression Inventory–II), anxiety (State-Trait Anxiety Inventory), QOL (Multiple Sclerosis Quality of Life–54), stress (Daily Hassles Scale), and coping (COPE inventory). Results: Consistent with expectations, depression, frequency of stress, trait anxiety, and mental health QOL were predicted by adaptive and maladaptive coping styles. Severity of stressful events was predicted by maladaptive, but not adaptive, coping styles. Depression and mental health QOL were most prominently connected to coping use. Emotional preoccupation and venting showed the strongest relationship with poorer psychosocial outcomes, whereas positive reinterpretation and growth seemed to be most beneficial. Conclusions: The results of this study highlight the importance of intervention programs targeting specific coping strategies to enhance psychosocial adjustment for people with MS.

This review article aims to provide an evidence-based approach to evaluating the patient who presents with acute prolonged, spontaneous vertigo in the context of the acute vestibular syndrome (AVS). Differentiation of posterior circulation stroke (PCS) presenting as an AVS has been regarded as an important diagnostic challenge for physicians involved in acute care. Current evidence suggests that a targeted approach to history taking and physical examination with emphasis on the oculomotor examination, more specifically the HINTS (Head Impulse/Nystagmus/Test-of-skew) examination battery, yields a higher sensitivity for the diagnosis of PCS than even standard magnetic resonance imaging with diffusion-weighted imaging. However, most studies have only validated the utility of the HINTS examination when performed by experts, who interpret the most powerful component of HINTS, namely the head impulse test (HIT), considerably different to the novice. Several investigations useful in the differentiation of the AVS are becoming more accessible and portable, such as videooculography with Frenzel goggles and video head impulse testing (vHIT), which allows for the quantitative assessment of the HIT. In clinical practice, vHIT has already become accepted as standard of care in the evaluation of AVS.

The experience of cognitive deficits and emotional dysfunction are prevalent in people with multiple sclerosis (PwMS), although research examining their interaction has provided inconsistent findings. The current study examined the ability of executive function to predict psychosocial adjustment in PwMS. One hundred and seven PwMS underwent cognitive assessment and completed measures of stress, depression, anxiety, and quality of life (QoL). There was limited support for a relationship. There was no relationship between objective cognitive tasks and state or trait anxiety, mental health QoL, overall QoL, or stress frequency. The only relationship with depression was found when the Beck Depression Inventory Fast-Screen was used, with a task of planning when the timing element was removed. A measure of error rates on a task of cognitive flexibility predicted physical health QoL, and severity, but not frequency, of stress was predicted by a task of working memory. The results of this study highlight the need for further research into the relationship between cognitive deficits and psychosocial adjustment because of the conflicting findings between studies and call for a common measurement framework for future investigation.

A federal emergency was declared in Flint, Michigan on January 16, 2016 because of elevated lead levels in the city drinking water system. Resulting from a number of technical mistakes and a lack of oversight by the Michigan Department of Environmental Quality, this crisis may have implications for the professional practice of emergency management. This paper explores the relationship between critical infrastructure and disaster theory, reviews the Flint crisis as a representative case study, and presents recommendations for emergency managers to begin to assess the drinking water systems within their own communities. As this is a still-evolving event, the discussion is based on the extent of the information available to both researchers and the public primarily as of late Fall, 2016. Future researchers will need to evaluate records from upcoming court proceedings and file additional FOIA requests after all subpoenas have been lifted in order to analyze how both a large public water system and a state government could allow the omission of corrosion control.

This review article aims to provide an evidence-based approach to evaluating the patient who presents with acute prolonged, spontaneous vertigo in the context of the acute vestibular syndrome (AVS). Differentiation of posterior circulation stroke (PCS) presenting as an AVS has been regarded as an important diagnostic challenge for physicians involved in acute care. Current evidence suggests that a targeted approach to history taking and physical examination with emphasis on the oculomotor examination, more specifically the HINTS (Head Impulse/Nystagmus/Test-of-skew) examination battery, yields a higher sensitivity for the diagnosis of PCS than even standard magnetic resonance imaging with diffusion-weighted imaging. However, most studies have only validated the utility of the HINTS examination when performed by experts, who interpret the most powerful component of HINTS, namely the head impulse test (HIT), considerably different to the novice. Several investigations useful in the differentiation of the AVS are becoming more accessible and portable, such as videooculography with Frenzel goggles and video head impulse testing (vHIT), which allows for the quantitative assessment of the HIT. In clinical practice, vHIT has already become accepted as standard of care in the evaluation of AVS.

Executive function deficits are prevalent in people with multiple sclerosis (PwMS), and PwMS use less adaptive coping than healthy controls. This cross-sectional study assessed whether there is a relationship between executive function and coping in PwMS.One hundred and seven participants with relapsing remitting or secondary progressive MS (n = 83 and 24, respectively; age M = 48.8 ± 11.1 years) completed measures of coping and executive function.A positive relationship was found between verbal fluency and use of active, emotional, and instrumental social support coping, and total executive function and substance abuse coping. There was a negative relationship between coping strategies and core (social support, acceptance, religion, restraint, and total coping), higher order (denial and humor), and total executive function indices (acceptance, religion, behavioral disengagement, denial, and total coping).These directional differences provide support for the importance of specific executive functions in coping strategy utilization. Understanding these relationships will assist psychologists and neuropsychologists with patient psychoeducation, adaptive coping strategy intervention and management for PwMS with reduced executive function ability.

OBJECTIVE: Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude. METHODS: The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak. RESULTS: A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29-53.71, p = 0.028). INTERPRETATION: We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere.

Objectives: The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype. Methods: Information about relapses was collected using MSBase, an international observational registry. Associations between relapse phenotypes and history of similar relapses or patient characteristics were tested with multivariable logistic regression models. Tendency of relapse phenotypes to recur sequentially was assessed with principal component analysis. Results: Among 14,969 eligible patients (89,949 patient-years), 49,279 phenotypically characterised relapses were recorded. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were more frequent in early or non-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women presented more often with sensory or visual symptoms. Men were more prone to pyramidal, brainstem and cerebellar relapses. Importantly, relapse phenotype was predicted by the phenotypes of previous relapses. (OR = 1.8–5, p = 10-14). Sensory, visual and brainstem relapses showed better recovery than other relapse phenotypes. Relapse severity increased and the ability to recover decreased with age or more advanced disease. Conclusion: Relapse phenotype was associated with demographic and clinical characteristics, with phenotypic recurrence significantly more common than expected by chance.

Water issues are a feature of public debate in Australia. The increasing privatisation of water and changes to water allocation systems are resulting in change, often referred to as water ‘wars’ (de Villiers, 1999). The Australian dairy industry uses 25% of the surface irrigation water in Australia. How does a rural industry like dairying negotiate a future? What is the role of broker professions like extension in supporting change in this context? We focus on three critical issues to address these questions: farm-level adaptation; new technologies; and balancing environmental and productive water-use. Two case studies of farm decision-making and advisory practice suggest that managing complexity in water issues requires learning processes at three levels: farmer–advisor; advisors–policy; advisors–other disciplines–policy. We conclude there is a need for a framework to guide an ethical response to water policy, bringing farm adaptation and advisory practice to implement change.

OBJECTIVE: To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis. METHOD: Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging. RESULTS: Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = -0.66). INTERPRETATION: Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss.

Purpose To investigate topographical relationship between amplitude of multifocal visual evoked potentials (mfVEP) and retinal nerve fibre layer (RNFL) thickness following acute optic neuritis (ON). Patients and Methods Fifty patients with a clinical diagnosis of acute unilateral ON between 6 and 36 months prior to the study and 25 age-matched controls underwent mfVEP testing (Accumap V 2.1, ObjectiVision Pty Ltd, Sydney, Australia) and OCT imaging (fast RNFL protocol, Stratus™, software version 3.0, Carl Zeiss Meditec, Inc., Dublin, CA). RNFL thickness and mfVEP amplitude were measured for upper, temporal and lower retinal sectors and corresponding areas of the visual field in affected eyes of ON patients and control eyes. Inter-eye asymmetry coefficients for both RNFL thickness and mfVEP amplitude were calculated for each zone, and corresponding coefficients were correlated between each other. Results There was highly significant reduction of RNFL thickness and mean mfVEP amplitude in all three retinal sectors of the affected eye. Largest reduction of RNFL thickness was noticed in temporal sector and of mfVEP amplitude in corresponding central part of the visual field. RNFL thickness correlated highly with amplitude of the mfVEP derived from corresponding areas of the visual field in all three zones. Conclusions We demonstrated strong topographical associations between structural and functional measures of optic nerve integrity in patients with ON.

In recent decades we have witnessed a diversification of rural communities, where the agricultural sector has had to increasingly compete with other interests and demands on rural land. Land management agencies have recognised that in order to resolve sustainability dilemmas, it is important to bring the diverse stakeholders together to negotiate the sustainable use of land and natural resources. Such collaborative approaches can only be effective if there is some sense of integration between various stakeholders. This paper explores how integration among diverse stakeholders can be facilitated in a way that accommodates and embraces diversity. It does this through an investigation of a project implemented by the Victorian state government that aimed to involve a diversity of stakeholders in the land management process.

Post-modern theorists have challenged the totalizing and unifying ambitions of change management practices. This paper explores how a narrative action research approach may be used to combine our modernist commitment to facilitate change and collaboration in the land management context with a post-modern sensitivity to complexity and difference. It critically examines the way in which this approach was implemented within a Victorian state government project that attempted to instigate a collaborative approach to land management. The narrative action research approach problematized the project team's representations of the project and brought into view the way in which these erased the space for genuine participation by the broader community. However, while the narrative action research approach highlighted some of the ambiguities that existed within the project, it did very little to change the course of the project. The paper identifies ways in which the approach needs to be modified and conclud...

Managing the competing interests of productivity growth, environmental concerns, landscape change and societal expectations presents challenges for agricultural industries. Innovation projects supporting knowledge development to address these challenges often involve partnerships with commercial farms, a methodology which promises much but has inherent challenges as well. This paper will examine the requirements of learning partnerships between farmers, research and extension (as members of innovation projects) to address conditions of complexity. We review designs for the involvement of commercial farms in innovation projects and explore the conditions for effective learning partnerships using two case studies from the Australian dairy industry. Learning partnerships with commercial farms can contribute to addressing the conditions of complexity faced by agricultural industries. Our analysis suggests that the conditions for effective learning partnerships involve the active negotiation of learni...

OBJECTIVE To identify the moderating and mediating relationship of different coping strategies between executive function and stress, depression and anxiety in people with multiple sclerosis (PwMS). METHOD Participants were 107 people with relapsing remitting or secondary progressive multiple sclerosis who were administered tasks of executive function and completed self-report measures of stress, depression, anxiety, and coping. RESULTS An indirect relationship was found between executive function and psychosocial adjustment through maladaptive coping strategies: behavioral and mental disengagement, and substance abuse; adaptive coping strategies: acceptance, active, positive reinterpretation, and growth, as well as for an index of adaptive coping. In general, a relationship was found between better performance on tasks of executive function and psychosocial adjustment when adaptive coping strategies were low, as opposed to high, or maladaptive coping strategies were high, as opposed to low. Some unexpected findings are also discussed. CONCLUSION Executive function and psychosocial adjustment is mediated and moderated by coping strategies used by PwMS. Well-preserved executive function provides relative protection from poorer adjustment in the presence of high maladaptive or low adaptive coping. PwMS who perform poorly on tasks of executive function benefit from using less cognitively demanding adaptive coping strategies to enhance adjustment outcomes and further research in this area would be advantageous to underpin effective intervention strategies.

Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVES To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. METHODS Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. RESULTS Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. CONCLUSIONS Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry. This study was funded by MSBase Foundation, a not-for-profit organisation. The MSBase Foundation receives financial support from Merck Serono, Biogen Idec, Novartis Pharma, Bayer Schering and Sanofi Aventis. The study was also funded by Multiple Sclerosis Research Australia and MSAngels. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Yes

Previous research has suggested that free-ranging mourning doves (Zenaida macroura) may ingest spent lead pellets, succumb to lead toxicosis, and die in a relatively short time (i.e., an acute lead toxicosis hypothesis). We tested this hypothesis by administering 157 captive mourning doves 2–24 lead pellets, monitoring pellet retention and short-term survival, and measuring related physiological characteristics. During the 19- to 21-day posttreatment period, 104 doves that received lead pellets died (deceased doves) and 53 survived (survivors); all 22 birds in a control group survived. Within 24-hr of treatment, blood lead levels increased almost twice as fast for deceased doves compared to survivors (F1,208 = 55.49; P < 0.001). During the first week, heterophil:lymphocyte (H:L) ratios increased twice as fast for deceased doves than with survivors (F1,198 = 23.14, P < 0.001). Posttreatment survival differed (χ2 = 37.4, P < 0.001) among the 5 groups of doves that retained different numbers of pellets, and survival ranged from 0.57 (95% CI: 0.44–0.74) for doves that retained ≤2 lead pellets 2 days posttreatment compared to 0.08 (95% CI: 0.022–0.31) for those doves that retained 13–19 lead pellets on 2 days posttreatment; significant differences existed among the 5 groups. After controlling for dove pretreatment body mass, each additional lead pellet increased the hazard of death by 18.0% (95% CI: 1.132–1.230, P < 0.001) and 25.7% (95% CI: 1.175–1.345, P < 0.001) for males and females, respectively. For each 1-g increase in pretreatment body mass, the hazard of death decreased 2.5% (P = 0.04) for males and 3.8% (P = 0.02) for females. Deceased doves had the highest lead levels in liver (49.20 ± 3.23 ppm) and kidney (258.16 ± 21.85 ppm) tissues, whereas controls showed the lowest levels (liver, 0.08 ± 0.041 ppm; kidney, 0.17 ± 0.10 ppm). For doves dosed with pellets, we observed simultaneous increases in blood lead levels and H:L ratios, whereas packed-cell volume (PCV) values declined. Our results support an acute lead toxicosis hypothesis. Although further research is necessary to investigate the magnitude of lead shot ingestion and toxicosis in mourning doves, we recommend that management agencies initiate development of a long-term strategic plan aimed at implementing a nontoxic shot regulation for mourning dove hunting.

The public policy process in Australia is changing towards a more interactive, collaborative model, where governments seek to develop partnerships with civil society and private sector organisations to manage complex policy challenges. This article discusses research conducted into a project implemented by a Victorian government department that sought to involve stakeholders in addressing natural resource management issues in the agricultural sector. The research revealed that public administration practices associated with the new public management approach impeded the ability of the project to facilitate participation by diverse stakeholders in the decision-making process. The article challenges the view that the discourse of collaboration and community engagement takes public administration down a constructivist path and suggests that agencies need to become reflexive about the way in which public administration practices are constitutive of the community engagement process if they are to facilitate genuine participation of other stakeholders.

Dizziness is a term used to describe a range of symptoms, but is rarely a sign of a serious

Background: The competing interests of preventing recurrent ischemic optic neuropathy (ION) and minimizing medication side effects make corticosteroid dose reduction in giant cell arteritis (GCA) a difficult problem. The authors sought to determine whether any factors were predictive of recurrent ION. Methods: Retrospective review of the records of 100 consecutive patients with biopsy-proven giant cell arteritis diagnosed in two Australian hospitals between 1988 and 1998. Among 67 patients who met inclusion criteria for ION in GCA, seven patients had recurrent ION. We compared the seven patients with recurrent ION to the 60 patients with nonrecurrent ION in terms of age, gender, mode of corticosteroid delivery, initial visual acuity in the affected eye, prevalence of bilateral ION, initial erythrocyte sedimentation rate (ESR) level, and rate of corticosteroid dose reduction. In the recurrent ION group, we documented the timing of the recurrence in relation to corticosteroid dose, elevation in acute phase reactants, and relapse of systemic symptoms. Results: We found recurrent ION in GCA in 10% of our cohort, higher than has been previously reported. Recur- rences, all of which were ipsilateral, occurred from 3 to 36 months (median 8 months) after the initial ION. None of the clinical indicators the authors examined differed between the two groups. Six of seven patients with recurrent ION had elevations in ESR or C-reactive protein or a new headache at the time of ION recurrence, but in only one of these patients were these features recognized as preceding the recurrent ION. One patient had neither an elevation in acute phase reactants nor a relapse in systemic symptoms of GCA at the time of ION recurrence. Conclusions: Recurrent ION in GCA is difficult to predict. Although elevated acute phase reactants or new systemic symptoms consistent with GCA were present in six (83%) of our patients with ION recurrence, in only one patient (17%) did these events occur with enough lead time to allow caregivers to act preemptively. Thus, even very close monitoring of GCA patients with ION may not predict ION recurrence.

Institutions involved in public policy and technological innovation are concerned with processes that influence the behaviour of people. This paper reports on research in the New Zealand dairy industry that is seeking to develop improved process models for managing change in a range of policy, industry and business contexts. The Practice Interplay Model was used to evaluate mediating methods for negotiating environmental and production outcomes within the context of a farm dairy effluent management case study. Significant misalignments between research, farming, extension and policy practitioners' expectations and perceptions of factors required for effective farm dairy effluent management were found. The combination of interactive workshops linked to quantitative verification and testing and follow-up interviews enabled a depth of investigation that was rich in information yet cost-effective in terms of research resources. The process used identified opportunities to change the actions of system...

Ophthalmic artery hypoperfusion is a relatively uncommon clinical entity. This study illustrates the posterior segment findings of ophthalmic artery hypoperfusion in a series of nine patients. Colour photographs and relevant fluorescein angiograms highlighting the findings are shown. The retinal manifestations of ophthalmic artery hypoperfusion in this series of patients include midperipheral haemorrhages, dilated retinal veins, optic disk collaterals, optic disk neo-vascularization, cotton wool spots, grey intraretinal lesions, fundus pallor, optic disk swelling and choroidal infarcts. Recognition of the ophthalmic changes in this condition may lead to detection of carotid artery disease, the surgical and medical treatment of which has important bearing on patient management.

A single case study is presented of an unusual dissociation between the sensory perception of an object and the grasping action towards the same object. The patient IW was found at age 74 to have spent all his life without the left parietal lobe, as a result of a congenital peri-natal insult. IW does not show any signs of sensory dysfunction, but he has a persistent motor bias that arises during movement towards objects. When IW was required to reach and grasp stationary and rotating objects, he consistently grasped the objects to the left side. Thus, it appears that information that is available at a sensory level can nevertheless be unavailable at a motor level. Our findings not only help to clarify the functions of the parietal lobe, but also show that lesions in this area are linked specifically to a process of response performance, which is fundamental for our understanding of visuomotor control.

Rationale Central retinal artery occlusion is a stroke of the eye caused by a blockage of its main blood supply by platelet-fibrin clot. Systemic thrombolysis has been successful in restoring perfusion to ischaemic tissue by fibrin-platelet clot lysis in ischaemic stroke and myocardial infarction. Several open-label studies have demonstrated efficacy of thrombolysis in the treatment of central retinal artery occlusion, with up to 60–70% of treated subjects experiencing an improvement in visual acuity. Most of these are given intraarterially, which is an invasive procedure and not widely applicable to all treatment centres. An alternative is the intravenous infusion of tissue plasminogen activator using existing stroke thrombolysis protocols. A systematic review of all observational studies of intravenous tissue plasminogen activator in acute central retinal artery occlusion showed that 48·5% of subjects had a four line or more visual acuity improvement with an acceptable rate of haemorrhagic complications, creating the equipoise necessary to conduct a randomised controlled trial. Aim To determine the efficacy of intravenous thrombolysis in acute treatment of central retinal artery occlusion. Design A phase II, placebo-controlled, double-blind, randomised controlled trial comparing intravenous tissue plasminogen activator at 0·9 mg/kg to placebo (normal saline) 100 ml in a 1 : 1 block randomisation. Study outcome The primary outcome measure is an improvement of three lines or more on the Snellen visual acuity chart, which signifies a doubling of the visual angle.

Background: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. Objective: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. Methods: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. Results: Of the 3326 included patients, 345–1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b ( p≤0.001). No differences in 12-month confirmed progression of disability were observed. Conclusion: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.

BACKGROUND: Susac syndrome is characterized by the triad of branch retinal arterial occlusions, encephalopathy and cochlear microangiopathy. The underlying process is believed to be a small vessel vasculitis causing microinfarcts in the retina, brain and cochlea. METHODS: Analysis of two male and two female cases of Susac syndrome recognized in Australia. RESULTS: In this series the epidemiology, mode of presentation, ophthalmologic features, neurologic and cochleo-vestibular features, radiologic characteristics, cerebrospinal fluid findings, therapeutic interventions, clinical course and outcome of Susac syndrome is examined. Key ophthalmologic differential diagnoses include systemic lupus erythematosis (SLE), Behcet's syndrome and other vasculitides such as sarcoidosis, tuberculosis, syphilis and lymphoma. Neuro-otologic features are most frequently misdiagnosed as multiple sclerosis. CONCLUSION: Susac syndrome, first described in 1979, is becoming an increasingly recognized condition. Early recognition of the syndrome is important because treatment with systemic immunosuppression may minimize permanent cognitive, audiologic and visual sequelae.

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. Methods Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and Results A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres ( p = 0.68), regions ( p = 0.96) or countries ( p = 0.50). Conclusions Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.

Vestibular rehabilitation programs do appear to play a beneficial role in the treatment of dizziness in patients with vestibular migraine. Anecdotally, however, patients with vestibular migraine may report persistent significant symptoms at the end of a standard treatment period where other non-migrainous patients are accomplishing their treatment goals. Therefore, the objective of this study was to assess the efficacy of vestibular rehabilitation in patients with vestibular migraine compared to patients with vestibular symptoms without migraine. Thirty-six patients (vestibular migraine = 20, vestibular impairment = 16) with significant daily vestibular symptoms received a nine week customized vestibular rehabilitation program. Each subject attended five therapy appointments occurring at initial, two, five, nine and six months. A range of subjective and physical performance outcome measures were taken at baseline, nine weeks and six months. The vestibular migraine group showed poorer subjective performance at the onset of therapy, which was not reflected in the difference in physical performance between the groups. Both groups benefitted equally from rehabilitation. The same degree of improvement was observed in the migraine group regardless of medication regime. This study has validated vestibular rehabilitation as an effective treatment in dizzy patients both with and without vestibular migraine where the use of medication did not preclude benefit from therapy. However, further research is required to clarify the role of specific vestibular suppressant medications and the scheduling of their use in relation to physical therapy.

BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, chi(2) = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.

Traditionally, grade control of iron ores has relied on elemental analysis of sampled materials such as blast cone drill cuttings. This analysis provides a standard elemental suite (Fe, SiO2, Al2O3, P, Mn, S, MgO, CaO and TiO2 along with loss on ignition) that is used in grade control to assign mined material as grade blocks to high grade, low grade or waste destinations. However, the mineralogy of the sample is often not considered or at best inferred from visual geological logging of the sampled material. As such, mineral contaminants such as gibbsite, kaolinite and substituted goethite that cannot be identified visually and/or by chemical analysis alone are often not quantified. To address this issue Rio Tinto Iron Ore (RTIO) has trialled the application of rapid X-ray diffraction (XRD) to grade control in iron ore mining. RTIO provided PANalytical with 110 samples from two of its mine sites, referred to here as deposits A and B. The samples included high grade, low grade and waste materials. All samples were analyzed qualitatively and quantitatively for major phases such as hematite Fe2O3 and goethite FeOOH and minor phases including kaolinite Al2Si2O5(OH)4, gibbsite Al(OH)3, quartz SiO2 and calcite CaCO3. Automated Rietveld quantification was undertaken for all samples to determine the phase composition. Substituted goethite was identified as a discrete phase. The analysis of the resultant mineralogical data was undertaken in three steps: data clustering, phase identification and phase quantification. Once the mineralogy of the samples was established the spatial distribution of the detected minerals was plotted for both deposits. Based on these plots the stratigraphy could be demarcated and mineralogically characterised. The additional information also provided the opportunity to blend and/or isolate these minerals throughout the defined theoretical grade blocks which included high grade, high grade with minor gibbsite, high grade beneficiation, low grade beneficiation, low grade other and waste. As such material with a propensity for higher degrees of beneficiation was identified and domained. Conversely, material with limited upgrade potential could be identified and not submitted to traditional forms of beneficiation. Based on this trial, rapid XRD analysis and associated cluster analysis was shown to offer additional criteria for the definition of theoretical grade blocks in iron ore mining which is potentially advantages compared with definitions based only on chemistry.

Background Axonal loss is a major determinant of disability in multiple sclerosis (MS). While acute inflammatory demyelination is a principal cause of axonal transection and subsequent axonal degeneration in acute disease, the nature of chronic axonal loss is less well understood. In the current study, the relationship between degree of chronic demyelination and axonal degeneration was investigated using optic neuritis (ON) as a model. Method 25 patients with a first episode of unilateral ON, good recovery of visual function and concurrent brain or spinal cord MRI lesions were enrolled. Axonal loss was assessed using change in retinal nerve fibre layer (RNFL) thickness between 1 and 3 years after ON. Optic nerve conduction was evaluated using latency of multifocal visual evoked potentials (mfVEP). The level of mfVEP latency delay at 12 and 36 months was considered indicative of the degree of permanent demyelination. Data from 25 age and gender matched normal controls were used for comparison. Results RNFL thickness was significantly reduced in ON eyes at 12 months compared with controls but remained unchanged in fellow eyes. Average RNFL thickness demonstrated a small but significant reduction between 12 and 36 months for both ON and fellow eyes. Change in RNFL thickness between 12 and 36 months, however, did not correlate with the degree of mfVEP latency delay. Conclusion The results, therefore, show no association between the degree of permanent optic nerve demyelination (as measured by latency delay) and progressive axonal degeneration, at least in the early stages of the disease. The fact that fellow eyes demonstrated a similar degree of progressive axonal loss supports this suggestion.

Trans‐synaptic degeneration could exacerbate neurodegeneration in multiple sclerosis (MS). We aimed to assess whether anterograde trans‐synaptic degeneration could be identified in the primary visual pathway in vivo. Diffusion tensor imaging (DTI) was used to assess the optic radiations in 15 patients with previous optic nerve inflammation and 9 healthy volunteers. A probabilistic atlas of the optic radiations was created from healthy diffusion tractography data. Lengthwise profiles for DTI parameters (axial [λ(||)], radial [λ(⟂)] and mean diffusivity [MD], fractional anisotropy [FA] and the angle of deviation of the principal eigenvector [α]) were analyzed for patients and controls. Patients also underwent multifocal visual evoked potential (mfVEP) assessments to characterize the latency and amplitude of cortical potentials. Correlations were performed between mfVEP latency and amplitude in the left and right visual hemi‐fields and DTI parameters in the contra‐lateral optic radiations. Patients displayed a significant decrease in λ(||) within the body of both optic radiations, which significantly correlated with loss of mfVEP amplitude. Abnormal λ(⟂) and FA were detected bilaterally throughout the optic radiations in patients but the abnormality was not associated with amplitude reduction or latency prolongation of the mfVEP. An abnormal α value was observed in the left optic radiations of patients, and the α value in the body of the optic radiations also correlated with mfVEP amplitude loss. The assocation between bilateral DTI abnormalities within the optic radiations and loss of afferent electrical activity could indicate anterograde trans‐synaptic degeneration occurs following optic neuritis. Hum Brain Mapp 33:2047–2061, 2012. © 2011 Wiley Periodicals, Inc.

Optic neuritis provides an in vivo model to study demyelination. The effects of myelin loss and recovery can be measured by the latency of the multifocal visual evoked potentials. We investigated whether the extent of initial inflammatory demyelination in optic neuritis correlates with the remyelinating capacity of the optic nerve. Forty subjects with acute unilateral optic neuritis and good visual recovery underwent multifocal visual evoked potentials testing at 1, 3, 6 and 12 months. Average latency changes were analyzed. Extensive latency delay at baseline significantly improved over time with rate of recovery slowed down after 6 months. Magnitude of latency recovery was independent of initial latency delay. Latency recovery ranged from 7 to 17 ms across the whole patient cohort (average = 11.3 (3.1) ms) despite the fact that in a number of cases the baseline latency delay was more than 35—40 ms. Optic nerve lesions tend to remyelinate at a particular rate irrespective of the size of the initial demyelinated zone with smaller lesions accomplishing recovery more completely. The extent of the initial inflammatory demyelination is probably the single most important factor determining completeness of remyelination. The time period favorable to remyelination is likely to be within the first 6 months after the attack.

Purpose Acute optic neuritis (ON) is often followed by recovery of visual function. Although this recovery is mainly attributable to resolution of the acute inflammation, the redistribution of ion channels along the demyelinated membrane, and subsequent remyelination, part of it may be the result of neural plasticity. In the present study, the interrelationship was examined between structural (retinal nerve fiber layer [RNFL] thickness) and functional (amplitude of multifocal visual evoked potentials [mfVEPs]) measures of the integrity of the visual pathway in the postacute stage of ON, to determine whether there was any evidence of ongoing neural reorganization. Methods Twenty-five subjects with acute unilateral ON underwent serial RNFL thickness measurement and mfVEP recording. The inter-eye asymmetry of both measures was analyzed. In the period between 6 and 12 months, the subjects were considered free of optic disc edema, and that period was used to analyze the structure-function relationship. Twenty control subjects were also examined. Results There were significant but opposite changes in RNFL thickness and mfVEP amplitude. The average asymmetry of RNFL thickness between affected and fellow eyes increased from 17.5 +/- 11.5 to 21.1 +/- 12.8 microm (P = 0.0003), indicating progressive axonal loss, whereas mfVEP amplitude asymmetry decreased from 46.6 +/- 32.4 to 38.3 +/- 31.1 nV (P = 0.0015), indicating continuous functional recovery. In comparison to the 6-month results, the mfVEP amplitude in the ON eye improved by 17.8%, whereas RNFL thickness decreased by 20.8%. The result remained unchanged regardless of the degree of optic nerve remyelination. Conclusions The finding of structural-functional discrepancy at the postinflammatory stage may support the concept that neural plasticity contributes to functional recovery after acute ON.

Recently, there has been strong interest in the development of imaging techniques to quantify axonal and myelin pathology in patients with multiple sclerosis (MS). Optic neuritis, a condition characterised by inflammatory demyelination of the optic nerve, is one of the commonest sites of MS relapse, and exhibits similar pathological alterations to MS lesions elsewhere in the central nervous system (CNS). Unlike other regions of the CNS, however, the function of the optic nerve can be accurately assessed using clinical measures, as well as electrophysiological techniques such as visual evoked potential recordings. Therefore, optic neuritis is useful for investigating the relationship between abnormalities in optic nerve structure, assessed using magnetic resonance imaging (MRI), and visual dysfunction, assessed clinically and electrophysiologically. The aims of the present study were to assess optic nerve structural abnormalities in patients with a history of unilateral optic neuritis using MRI, and then to identify correlations between abnormalities in optic nerve MRI and visual dysfunction. Ten controls and sixteen patients underwent high resolution optic nerve diffusion tensor imaging (DTI), T2- and T1-weighted MRI. In addition, Snellen visual acuity and the latency and amplitude of multifocal visual evoked potentials (mfVEP) were tested in all patients. Diffusion and volumetric MRI indices were correlated to mfVEP functional indices. Significant abnormalities were detected in MRI and mfVEP measures in patients' affected nerves compared to unaffected optic nerves or optic nerves from healthy controls. Reduced mfVEP amplitude in the affected side significantly correlated with both affected optic nerve atrophy (R=0.58, p=0.02) and reduced fractional anisotropy (FA) (R=0.52, p=0.04). However, atrophy and reduced FA did not correlate with each other. To further investigate this disassociation, we used linear regression analysis with optic nerve atrophy and optic nerve FA as independent variables and mfVEP amplitude as the dependent variable. The resulting linear regression model was highly significant (R=0.819, p=0.001). These results show that, 4 years after unilateral optic neuritis, MRI-based measures of optic nerve structural abnormalities (decreased anisotropy and volume) independently predict visual dysfunction.

To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis.Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging.Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = -0.66).Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss.

This study presents the neuro-otological findings of 523 patients attending a tertiary vestibular clinic with migraine- and nonmigraine-related dizziness. Subjects were categorized into one of 4 groups, definite migrainous vertigo, probable migrainous vertigo, vestibular disorder coexisting with migraine and nonmigraine-related dizziness. No notable relationship was found between the numbers of abnormal findings between the groups for the majority of the neuro-otological tests. However, there was a significant trend in emetic response to caloric testing. The definite migrainous vertigo group were at least 4 times more likely to be nauseous to caloric testing than any other migraine category. This difference was independent of the magnitude of caloric responses between the emetic migraine groups. While further investigation is required, this study has potentially identified that nauseous/emetic response to caloric stimulation may be a distinguishing factor between migrainous vertigo and other vestibular disorders including those with a coexisting history of migraine.