Publications by authors named "Simon A Broadley"

36 Publications

Using eye movements in the dot-probe paradigm to investigate attention bias in illness anxiety disorder.

World J Psychiatry 2021 Mar 19;11(3):73-86. Epub 2021 Mar 19.

The Department of Clinical Psychology and National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing An'Ding Hospital, Capital Medical University, and Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing 100089, China.

Background: Illness anxiety disorder (IAD) is a common, distressing, and debilitating condition with the key feature being a persistent conviction of the possibility of having one or more serious or progressive physical disorders. Because eye movements are guided by visual-spatial attention, eye-tracking technology is a comparatively direct, continuous measure of attention direction and speed when stimuli are oriented. Researchers have tried to identify selective visual attention biases by tracking eye movements within dot-probe paradigms because dot-probe paradigm can distinguish these attentional biases more clearly.

Aim: To examine the association between IAD and biased processing of illness-related information.

Methods: A case-control study design was used to record eye movements of individuals with IAD and healthy controls while participants viewed a set of pictures from four categories (illness-related, socially threatening, positive, and neutral images). Biases in initial orienting were assessed from the location of the initial shift in gaze, and biases in the maintenance of attention were assessed from the duration of gaze that was initially fixated on the picture per image category.

Results: The eye movement of the participants in the IAD group was characterized by an avoidance bias in initial orienting to illness-related pictures. There was no evidence of individuals with IAD spending significantly more time viewing illness-related images compared with other images. Patients with IAD had an attention bias at the early stage and overall attentional avoidance. In addition, this study found that patients with significant anxiety symptoms showed attention bias in the late stages of attention processing.

Conclusion: Illness-related information processing biases appear to be a robust feature of IAD and may have an important role in explaining the etiology and maintenance of the disorder.
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http://dx.doi.org/10.5498/wjp.v11.i3.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953363PMC
March 2021

Worldwide Incidence and Prevalence of Neuromyelitis Optica: A Systematic Review.

Neurology 2021 01 11;96(2):59-77. Epub 2020 Dec 11.

From the Department of Neurology (V.P., Z.I.), Odense University Hospital; Danish Multiple Sclerosis Center (M.M.), Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Neurology (O.A.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (T.B.), Medical University of Vienna, Austria; Menzies Health Institute Queensland (S.A.B.), Griffith University, Gold Coast; Department of Neurology (S.A.B.), Gold Coast University Hospital, Australia; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Fort-de-France, Martinique, France; Department of Neurology (A.J.), The Walton Centre, Liverpool, UK; Cleveland Clinic (A.J.), Abu Dhabi, United Arab Emirates; Departments of Neurology (J.K., J.P.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Nuffield Department of Clinical Neurosciences (M.I.L., J.P.), John Radcliffe Hospital, University of Oxford, UK; Service de Neurologie (R.M.), Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, et Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France; Department of Neurology (K.M.), Kindai University Graduate School of Medicine, Osaka, Japan; Center of Neuroimmunology (A.S., M.S.), Service of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain; Department of Neurology (O.S.), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institute of Clinical Research (Z.I.), University of Southern Denmark, Odense, Denmark; and Institute of Molecular Medicine (Z.I.), University of Southern Denmark, Odense.

Objective: Since the last epidemiologic review of neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), 22 additional studies have been conducted. We systematically review the worldwide prevalence, incidence, and basic demographic characteristics of NMOSD and provide a critical overview of studies.

Methods: PubMed, Ovid MEDLINE, and Embase using Medical Subject Headings and keyword search terms and reference lists of retrieved articles were searched from 1999 until August 2019. We collected data on the country; region; methods of case assessment and aquaporin-4 antibody (AQP4-Ab) test; study period; limitations; incidence (per 100,000 person-years); prevalence (per 100,000 persons); and age-, sex-, and ethnic group-specific incidence or prevalence.

Results: We identified 33 relevant articles. The results indicated the highest estimates of incidence and prevalence of NMOSD in Afro-Caribbean region (0.73/100 000 person-years [95% CI: 0.45-1.01] and 10/100 000 persons [95% CI: 6.8-13.2]). The lowest incidence and prevalence of NMOSD were found in Australia and New Zealand (0.037/100 000 person-years [95% CI: 0.036-0.038] and 0.7/100,000 persons [95% CI: 0.66-0.74]). There was prominent female predominance in adults and the AQP4-Ab-seropositive subpopulation. The incidence and prevalence peaked in middle-aged adults. African ethnicity had the highest incidence and prevalence of NMOSD, whereas White ethnicity had the lowest. No remarkable trend of incidence was described over time.

Conclusion: NMOSD is a rare disease worldwide. Variations in prevalence and incidence have been described among different geographic areas and ethnicities. These are only partially explained by different study methods and NMO/NMOSD definitions, highlighting the need for specifically designed epidemiologic studies to identify genetic effects and etiologic factors.
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http://dx.doi.org/10.1212/WNL.0000000000011153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905781PMC
January 2021

Overlapping central and peripheral nervous system syndromes in MOG antibody-associated disorders.

Neurol Neuroimmunol Neuroinflamm 2021 01 3;8(1). Epub 2020 Dec 3.

From the Inflammatory Neuropathy Group (S. Rinaldi, A.D., J.F.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital; University of Oxford; Department of Neurology (S. Rinaldi, S.R.I.), Oxford University Hospitals NHS Foundation Trust, UK; Department of Neurology (H.N.B., M.H.B.), Royal Prince Alfred Hospital, Sydney; Brain and Mind Centre (H.N.B., T.A.H., M.H.B., S.W.R., F.B., R.C.D.), University of Sydney; Department of Neurology (J.W.), St George Hospital, Sydney; Department of Neurology (T.A.H., S.W.R., S. Ramanathan), Concord Repatriation General Hospital, Sydney; Menzies Institute of Health Queensland (S.A.B.), Griffith University; Department of Neurology (S.A.B.), Gold Coast University Hospital, Australia; Autoimmune Neurology Group (P.W., S.R.I., S. Ramanathan), Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital; University of Oxford, UK; Brain Autoimmunity and Clinical Neuroimmunology Groups (F.B., R.C.D., S. Ramanathan), Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney; Faculty of Medicine and Health (F.B., R.C.D., S. Ramanathan), University of Sydney; School of Medical Sciences (F.B.), Discipline of Applied Medical Science, Faculty of Medicine and Health, University of Sydney, Australia; and TY Nelson Department of Paediatric Neurology (R.C.D.), Children's Hospital at Westmead, Sydney, Australia.

Objective: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody-associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort.

Methods: Using a live cell-based assay, we diagnosed 271 adults with MOGAD (2013-2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement.

Results: We identified 19 adults with MOGAD and PNS involvement without prior TM. All patients had CNS involvement including ON (bilateral [n = 3], unilateral [n = 3], and recurrent [n = 7]), a cortical lesion (n = 1), meningoencephalitis (n = 1), and subsequent TM (n = 4). Clinical phenotyping and neurophysiology were consistent with acute inflammatory demyelinating polyneuropathy (n = 1), myeloradiculitis (n = 3), multifocal motor neuropathy (n = 1), brachial neuritis (n = 2), migrant sensory neuritis (n = 3), and paresthesia and/or radicular limb pain (n = 10). Onset MRI spine was consistent with myeloradiculitis with nerve root enhancement in 3/19 and normal in 16/19. Immunotherapy resulted in partial/complete PNS symptom resolution in 12/15 (80%) (steroids and/or IV immunoglobulin n = 9, rituximab n = 2, and plasmapheresis n = 1). We identified serum antibodies targeting neurofascin 155, contactin-associated protein 2, or GM1 in 4/16 patients with MOGAD PNS compared with 0/30 controls ( = 0.01). There was no binding to novel cell surface antigens using an in vitro myelinating sensory neuronal coculture model.

Conclusions: Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies.
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http://dx.doi.org/10.1212/NXI.0000000000000924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803332PMC
January 2021

Homozygous frameshift mutation of SPG11 as a cause of progressive flaccid paralysis, ataxia and dysphagia.

J Clin Neurosci 2020 Nov 29;81:90-91. Epub 2020 Sep 29.

Gold Coast University Hospital, Southport, QLD 4215, Australia; Menzies Health Institute Queensland, Griffith University, QLD 4222, Australia. Electronic address:

Hereditary spastic paraplegias (HSP) are phenotypically and genotypically diverse. We describe a unique case of autosomal recessive HSP (ARHSP) diagnosed at age 44 in a patient previously described as having "spinal muscular ataxia" [sic]. Predominant lower motor neuron findings and lack of clinical spasticity reduced suspicion for HSP in early life. The identified SPG11 mutation was novel and the presentation was atypical for HSP in general and SPG11 disease specifically.
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http://dx.doi.org/10.1016/j.jocn.2020.09.004DOI Listing
November 2020

Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide.

Front Neurol 2020 26;11:501. Epub 2020 Jun 26.

Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Japan.

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of <1/million population. Among East Asians, the prevalence is higher, at ~3.5/100,000 population, while the prevalence in Blacks may be up to 10/100,000 population. For MOG-antibody disease, hospital-based studies largely do not observe any significant racial preponderance so far. This disorder comprises a significant proportion of NMOSD cases that are AQP4-antibody-seronegative. A recent Dutch nationwide study reported the annual incidence of MOG-antibody disease as 1.6/million population (adult: 1.3/million, children: 3.1/million). Clinical and radiological differences between AQP4-antibody and MOG-antibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibody biomarker. More population-based studies in different geographical regions and racial groups will be useful to further inform the prevalence and incidence of NMOSD and their antibody-specific subgroups. Accessibility to AQP4-antibody and MOG-antibody testing, which is limited in many centers, is a challenge to overcome. Environmental and genetic studies will be useful accompaniments to identify other potential pathogenetic factors and specific biomarkers in NMOSD.
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http://dx.doi.org/10.3389/fneur.2020.00501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332882PMC
June 2020

Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation.

Front Neurol 2020 16;11:537. Epub 2020 Jun 16.

Westmead Clinical School, Westmead Hospital, University of Sydney, Westmead, NSW, Australia.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis ( < 0.001) and area postrema relapses ( = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS ( < 0.001). Prior to age 30 years, attacks of optic neuritis were more common in NMOSD than transverse myelitis. After 30 this pattern was reversed. Relapses in NMOSD were more likely to be treated with acute immunotherapies and were less likely to recover completely. Analysis by month of relapse in NMOSD showed a trend toward reduced risk of relapse in February to April compared to a peak in November to January ( = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD.
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http://dx.doi.org/10.3389/fneur.2020.00537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308484PMC
June 2020

The clinical profile of NMOSD in Australia and New Zealand.

J Neurol 2020 May 31;267(5):1431-1443. Epub 2020 Jan 31.

Department of Neurology, Westmead Hospital, Westmead, NSW, 2145, Australia.

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.
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http://dx.doi.org/10.1007/s00415-020-09716-4DOI Listing
May 2020

PRES-like presentation in MOG antibody-related demyelination (MARD).

J Clin Neurosci 2020 Feb 22;72:453-455. Epub 2020 Jan 22.

Department of Neurology, Gold Coast University Hospital, Southport, QLD 4215, Australia; School of Medicine, Griffith University, Gold Coast Campus, QLD 4222, Australia.

A 33-year-old male presented with a progressive four-week history of frontal headache and left visual field impairment. MRI brain confirmed bilateral, asymmetric, occipital vasogenic oedema, suggestive of posterior reversible encephalopathy syndrome (PRES). Serum testing for MOG antibodies was positive, confirming a diagnosis of MOG antibody-related demyelination (MARD). A similar PRES-like pattern of white matter inflammation has been reported previously in neuromyelitis optica spectrum disorder but has not previously been reported in MARD.
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http://dx.doi.org/10.1016/j.jocn.2020.01.034DOI Listing
February 2020

AQP4 Antibody Assay Sensitivity Comparison in the Era of the 2015 Diagnostic Criteria for NMOSD.

Front Neurol 2019 4;10:1028. Epub 2019 Oct 4.

School of Medicine, Gold Coast Campus, Griffith University, Southport, QLD, Australia.

We have compared five different assays for antibodies to aquaporin-4 in 181 cases of suspected Neuromyelitis optica spectrum disorders (NMOSD) and 253 controls to assess their relative utility. As part of a clinically-based survey of NMOSD in Australia and New Zealand, cases of suspected NMOSD were referred from 23 centers. Clinical details and magnetic imaging were reviewed and used to apply the 2015 IPND diagnostic criteria. In addition, 101 age- and sex-matched patients with multiple sclerosis were referred. Other inflammatory disease ( = 49) and healthy controls ( = 103) were also recruited. Samples from all participants were tested using tissue-based indirect immunofluorescence assays and a subset were tested using four additional ELISA and cell-based assays. Antibodies to myelin oligodendrocyte glycoprotein (MOG) were also assayed. All aquaporin-4 antibody assays proved to be highly specific. Sensitivities ranged from 60 to 94%, with cell-based assays having the highest sensitivity. Antibodies to MOG were detected in 8/79 (10%) of the residual suspected cases of NMOSD. Under the 2015 IPND diagnostic criteria for NMOSD, cell-based assays for aquaporin-4 are sensitive and highly specific, performing better than tissue-based and ELISA assays. A fixed cell-based assay showed near-identical results to a live-cell based assay. Antibodies to MOG account for only a small number of suspected cases.
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http://dx.doi.org/10.3389/fneur.2019.01028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787171PMC
October 2019

Vitamin D for the treatment of multiple sclerosis: a meta-analysis.

J Neurol 2018 Dec 3;265(12):2893-2905. Epub 2018 Oct 3.

School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, QLD, 4222, Australia.

Objective: There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS.

Methods: A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing-remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software.

Results: Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01-0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms.

Conclusion: These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.
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http://dx.doi.org/10.1007/s00415-018-9074-6DOI Listing
December 2018

Incidence and prevalence of NMOSD in Australia and New Zealand.

J Neurol Neurosurg Psychiatry 2017 08 26;88(8):632-638. Epub 2017 May 26.

School of Medicine, Griffith University, Gold Coast, Australia.

Objectives: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry.

Background: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established.

Methods: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases.

Results: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD.

Conclusions: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.
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http://dx.doi.org/10.1136/jnnp-2016-314839DOI Listing
August 2017

Smoking increases the risk of progression in multiple sclerosis: A cohort study in Queensland, Australia.

J Neurol Sci 2016 Nov 28;370:219-223. Epub 2016 Sep 28.

School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, QLD 4222, Australia.

Background: Cigarette smoking has been associated with increased risk of progressive multiple sclerosis (MS). The effect of smoking status on risk and timing of disease progression in patients with MS in Queensland, Australia has not been established.

Methods: A clinical cohort of 646 cases (531 females, 115 males) were followed from first clinic attendance to onset of clinically determined progressive disease. Progression risk was analysed with gender, age, age of onset, exposure to disease modifying therapy, and smoking status as covariates in a Cox proportional hazards analysis.

Results: There were significantly higher risks of secondary progressive disease in males (Hazard Ratio, HR 1.83, 95% CI: 1.3-2.7) and in ever smokers (HR 1.4, 95% CI: 1.0-2.0). Progressive disease occurred approximately 4years earlier in ever smokers. Smoking did not affect age of onset of primary progressive disease.

Conclusions: Cigarette smoking was associated with earlier onset of progressive disease in this large clinical cohort. For patients with relapsing-remitting disease, smoking cessation should be encouraged.
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http://dx.doi.org/10.1016/j.jns.2016.09.057DOI Listing
November 2016

Adopting genetics: motivations and outcomes of personal genomic testing in adult adoptees.

Genet Med 2016 09 28;18(9):924-32. Epub 2016 Jan 28.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Purpose: American adult adoptees may possess limited information about their biological families and turn to direct-to-consumer personal genomic testing (PGT) for genealogical and medical information. We investigated the motivations and outcomes of adoptees undergoing PGT using data from the Impact of Personal Genomics (PGen) Study.

Methods: The PGen Study surveyed new 23andMe and Pathway Genomics customers before and 6 months after receiving PGT results. Exploratory analyses compared adoptees' and nonadoptees' PGT attitudes, expectations, and experiences. We evaluated the association of adoption status with motivations for testing and postdisclosure actions using logistic regression models.

Results: Of 1,607 participants, 80 (5%) were adopted. As compared with nonadoptees, adoptees were more likely to cite limited knowledge of family health history (OR = 10.1; 95% CI = 5.7-19.5) and the opportunity to learn genetic disease risks (OR = 2.7; 95% CI = 1.6-4.8) as strong motivations for PGT. Of 922 participants who completed 6-month follow-up, there was no significant association between adoption status and PGT-motivated health-care utilization or health-behavior change.

Conclusion: PGT allows adoptees to gain otherwise inaccessible information about their genetic disease risks and ancestry, helping them to fill the void of an incomplete family health history.Genet Med 18 9, 924-932.
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http://dx.doi.org/10.1038/gim.2015.192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965328PMC
September 2016

A new era in the treatment of multiple sclerosis.

Med J Aust 2015 Aug;203(3):139-41, 141e.1

Gold Coast University Hospital, Gold Coast, QLD.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system with a multifactorial aetiology and highly variable natural history. A growing understanding of the immunopathogenesis of the condition has led to an expanding array of therapies for this previously untreatable disease. While a cure for MS remains elusive, the potential to reduce inflammatory disease activity by preventing relapses and minimising disease progression is achievable. The importance of early treatment in minimising long-term disability is increasingly recognised. Most of the newer, more effective therapies are associated with risks and practical problems that necessitate an active management strategy and continuous vigilance. While the initiation of these therapies is likely to remain the responsibility of neurologists, other specialist physicians and general practitioners will be involved in the identification and management of adverse effects.
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http://dx.doi.org/10.5694/mja14.01218DOI Listing
August 2015

Longlook: initial outcomes of a longitudinal integrated rural clinical placement program.

Aust J Rural Health 2015 Jun 15;23(3):169-75. Epub 2015 May 15.

School of Medicine, Griffith University, Gold Coast, Queensland, Australia.

Objective: To assess outcomes in terms of academic performance and subsequent career choice in medical students undertaking a longitudinal integrated rural clinical placement.

Design: This was a retrospective, observational, cohort study.

Setting: The 'Longlook' program is a longitudinal integrated rural clinical placement run collaboratively by Griffith University, Queensland Rural Medical Education and Queensland Health as part of the Griffith medical program.

Participants: Participants in this study were students completing years 3 and 4 in the Griffith medical program between 2010 and 2013. Assessment data were available for 683 participants, and internship location was available for all 472 students allocated within Queensland (87% of graduated students).

Interventions: Introduction of Longlook program.

Main Outcome Measures: The primary outcome measures were performance in overall and clinical assessments, and intern location (rural versus urban).

Results: When performance in prior year was taken into account, there were no statistically significant differences in academic performance in year 3 or 4 for rural and urban students. Of Longlook students who have graduated, 31/46 (67%) have undertaken internship at a rural location compared with 63/426 (15%) for urban hospital-based students (odds ratio 11.91; 95% confidence interval 6.08-23.32).

Conclusions: We have demonstrated that it is feasible to implement a parallel longitudinal integrated rural clinical placement in an established conventional postgraduate medical program and provide similar learning outcomes. Initial findings suggest that this experience is translating into positive outcomes in terms of future careers in rural settings. There is a need to reappraise the structure of initiatives aimed at promoting rural careers in medicine.
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http://dx.doi.org/10.1111/ajr.12164DOI Listing
June 2015

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations. MS Neurology Group of the Australian and New Zealand Association of Neurologists.

J Clin Neurosci 2014 Nov 30;21(11):1857-65. Epub 2014 Jun 30.

Department of Neurology, Auckland City Hospital, Auckland, New Zealand.

In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.
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http://dx.doi.org/10.1016/j.jocn.2014.01.017DOI Listing
November 2014

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 1 historical and established therapies. MS Neurology Group of the Australian and New Zealand Association of Neurologists.

J Clin Neurosci 2014 Nov 30;21(11):1835-46. Epub 2014 Jun 30.

Department of Neurology, Auckland City Hospital, Auckland, New Zealand.

Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS.
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http://dx.doi.org/10.1016/j.jocn.2014.01.016DOI Listing
November 2014

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 2 new and emerging therapies and their efficacy. MS Neurology Group of the Australian and New Zealand Association of Neurologists.

J Clin Neurosci 2014 Nov 28;21(11):1847-56. Epub 2014 Jun 28.

Department of Neurology, Auckland City Hospital, Auckland, New Zealand.

In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes.
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http://dx.doi.org/10.1016/j.jocn.2014.01.018DOI Listing
November 2014

Review article: elevated troponin: diagnostic gold or fool's gold?

Emerg Med Australas 2014 Apr;26(2):125-30

School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, Queensland, Australia; Department of Cardiology, Gold Coast University Hospital, Gold Coast, Queensland, Australia.

Troponin is a highly sensitive biomarker of myocardial injury and has been used extensively in everyday clinical practice in the community as well as in hospitals for the diagnosis of acute myocardial infarction (AMI) and for risk stratification of patients with acute coronary symptoms. Dynamic elevations in biomarkers (troponin) are considered fundamental to the diagnosis of AMI. Unfortunately, many clinical conditions can cause troponin elevation in the absence of myocardial ischaemia, and elevated levels sometimes pose a diagnostic dilemma. In some cases, inappropriate diagnosis of 'AMI' based primarily on a raised troponin can have a deleterious impact on an individual, including on driving, insurance and other medicolegal matters. An incorrect diagnosis of myocardial infarction can also lead to the oversight of serious life-threatening alternative causes of troponin elevation (e.g. pulmonary embolism). This article discusses the role of troponin in our everyday clinical practice in the ED.
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http://dx.doi.org/10.1111/1742-6723.12203DOI Listing
April 2014

Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review.

Endocr Pract 2013 Sep-Oct;19(5):821-8

Department of Diabetes and Endocrinology, Gold Coast Hospital.

Objective: The monoclonal antibody alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in multiple sclerosis (MS) patients when compared to β-interferon. The development of autoimmune diseases, including thyroid disease, has been reported in the literature with a frequency of 20 to 30%. In this article, we describe 4 cases of alemtuzumab-induced thyroid disease in patients with MS. We also performed a systematic review of the available literature.

Methods: Four patients who had received alemtuzumab for MS and subsequently developed thyroid dysfunction are presented. We compared our patients' clinical courses and outcomes to established disease patterns. We also undertook a systematic review of the published literature.

Results: All 4 patients presented with initial hyperthyroidism associated with elevated thyroid-stimulating hormone (TSH) receptor antibodies (TRAb). In 2 cases, hyperthyroidism did not remit after a total of 24 months of carbimazole therapy, and they subsequently underwent subtotal thyroidectomy. The third case subsequently developed biochemical hypothyroidism and required thyroxine replacement, despite having a markedly raised initial TRAb titer. Autoimmunity following alemtuzumab therapy in MS appears to occur as part of an immune reconstitution syndrome and is more likely in smokers who have a family history of autoimmune disease.

Conclusion: Management of alemtuzumab-induced thyroid disease is similar to the management of "wild-type" Graves' disease. The use of alemtuzumab in this setting will necessitate close monitoring of thyroid function and early intervention when abnormalities are developing.
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http://dx.doi.org/10.4158/EP13020.RADOI Listing
June 2014

Multiple sclerosis: from molecules to treatment.

Authors:
Simon A Broadley

Int J Mol Sci 2013 Apr 8;14(4):7598-602. Epub 2013 Apr 8.

School of Medicine, Gold Coast Campus, Griffith University, QLD 4222, Queensland, Australia.

The treatment of multiple sclerosis has been radically transformed over the past 20 years and this special issue of IJMS, focusing on the molecular aspects of the disease, highlights the growing conformity of the various investigative approaches. It is a very exciting time to be involved in the research of this disease.
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http://dx.doi.org/10.3390/ijms14047598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645705PMC
April 2013

Role of trigeminal microvascular decompression in the treatment of SUNCT and SUNA.

Curr Pain Headache Rep 2013 May;17(5):332

Department of Neurology, Gold Coast Hospital, 108 Nerang Street, Southport, QLD, 4215, Australia.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are primary headache disorders. Evidence suggests that SUNCT/SUNA have similar pathophysiology to the trigeminal autonomic cephalalgias and involves the trigeminal autonomic reflex. This review provides an overview of microvascular decompression of the trigeminal nerve and other surgical therapeutic options for SUNCT/SUNA. We have undertaken a mini-meta-analysis of available case reports and case series with the aim of providing recommendations for the use of such therapies in SUNCT/SUNA. There is some evidence supporting microvascular decompression of the trigeminal nerve in selected patients who have medically refractory SUNCT/SUNA and a demonstrable ipsilateral aberrant vessel on magnetic resonance imaging (MRI). We also consider what further investigations could be undertaken to assess the role of surgical interventions in the treatment of these often debilitating conditions.
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http://dx.doi.org/10.1007/s11916-013-0332-0DOI Listing
May 2013

Molecular pathogenesis of neuromyelitis optica.

Int J Mol Sci 2012 Oct 11;13(10):12970-93. Epub 2012 Oct 11.

School of Medicine, Gold Coast Campus, Griffith University, QLD 4222, Australia.

Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.
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http://dx.doi.org/10.3390/ijms131012970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497307PMC
October 2012

What do effective treatments for multiple sclerosis tell us about the molecular mechanisms involved in pathogenesis?

Int J Mol Sci 2012 Oct 4;13(10):12665-709. Epub 2012 Oct 4.

Department of Neurology, Royal Melbourne Hospital, Royal Parade, Parkville VIC 3050, Australia.

Multiple sclerosis is a potentially debilitating disease of the central nervous system. A concerted program of research by many centers around the world has consistently demonstrated the importance of the immune system in its pathogenesis. This knowledge has led to the formal testing of a number of therapeutic agents in both animal models and humans. These clinical trials have shed yet further light on the pathogenesis of MS through their sometimes unexpected effects and by their differential effects in terms of impact on relapses, progression of the disease, paraclinical parameters (MRI) and the adverse events that are experienced. Here we review the currently approved medications for the commonest form of multiple sclerosis (relapsing-remitting) and the emerging therapies for which preliminary results from phase II/III clinical trials are available. A detailed analysis of the molecular mechanisms responsible for the efficacy of these medications in multiple sclerosis indicates that blockade or modulation of both T- and B-cell activation and migration pathways in the periphery or CNS can lead to amelioration of the disease. It is hoped that further therapeutic trials will better delineate the pathogenesis of MS, ultimately leading to even better treatments with fewer adverse effects.
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http://dx.doi.org/10.3390/ijms131012665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497294PMC
October 2012

Modelling genetic susceptibility to multiple sclerosis with family data.

Neuroepidemiology 2013 11;40(1):1-12. Epub 2012 Oct 11.

School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, QLD, Australia.

A genetic contribution to susceptibility is well established in multiple sclerosis (MS) and 57 associated genetic loci have been identified. We have undertaken a meta-analysis of familial risk studies with the aims of providing definitive figures for risks to relatives, performing a segregation analysis and estimating the proportion of the overall genetic risk that currently identified genes represent. We have used standard methods of meta-analysis combined with novel approaches to age adjustment to provide directly comparable estimates of lifetime risk. The overall recurrence risk for monozygotic twins was 18.2% and for siblings 2.7%. The recurrence risk for dizygotic twins was significantly higher than for siblings. The overall estimate of sibling relative risk (λ(S)) was 16.8. Risks for older relatives (parents, siblings, aunts, uncles and cousins) show a latitudinal gradient, in line with population risk. No latitudinal gradient for λ(S) was seen. Segregation analysis supports a multiplicative model of one locus of moderate effect with many loci of small effect. The estimated contribution of the 57 known MS loci is 18-24% of λ(S). This meta-analysis supports the notion of MS being in part the result of multiple genetic susceptibility factors and environmental factors.
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http://dx.doi.org/10.1159/000341902DOI Listing
October 2013

The value of [18F]-fluorodeoxyglucose-positron emission tomography/CT scanning in the diagnosis of neurosarcoidosis.

J Clin Neurosci 2012 Oct 11;19(10):1461-2. Epub 2012 Aug 11.

School of Medicine, Gold Coast Campus, Griffith University, Queensland, Australia.

Sarcoidosis is a granulomatous disease of unknown aetiology which primarily affects the lungs, but can affect other tissues including the central nervous system (CNS). In neurosarcoidodis, the CNS is often the only affected site, which makes a tissue diagnosis difficult. Although a clinical diagnosis of neurosarcoidosis can often be made, the wide range of potential differential diagnoses, including other steroid responsive conditions (such as idiopathic lymphocytic meningitis) means that a confirmed diagnosis is invaluable. This is particularly important because neurosarcoidosis has a poor prognosis and aggressive immunosuppressive treatment is generally recommended. We present a man with clinically suspected neurosarcoidosis where attempts to obtain histological confirmation of the disease through skin and meningeal biopsy was unhelpful, but a lymph node biopsy, directed with the use of [18F]-fluorodeoxyglucose-positron emission tomography/CT scanning was diagnostic.
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http://dx.doi.org/10.1016/j.jocn.2012.02.013DOI Listing
October 2012

Case-control study of blink rate in Parkinson's disease under different conditions.

J Neurol 2012 Apr 8;259(4):739-44. Epub 2011 Oct 8.

School of Medicine, Gold Coast Campus, Griffith University, QLD 4222, Australia.

Standard neurology texts list a reduced blink rate as one of the clinical features of Parkinson's disease. However, there are few clinical studies which have quantified this clinical sign. Here we present the results of a quantified study in a cohort of cases and controls using a standard protocol. Cases meeting standard criteria for a diagnosis of Parkinson's disease were studied together with age- and sex-matched controls. Baseline data included age, sex, duration of disease, Hoehn and Yahr stage, mini-mental state examination and treatment. Subjects were videoed undertaking three different tasks: being interviewed, watching a video, and reading from a book. Blink rates were calculated as a mean 'per minute' figure for each of the three tasks. A meta-analysis of previous studies of blink rate was undertaken. A total of 20 cases and 41 controls were studied. A decline in blink rate with increasing age was seen for cases but not controls. A significant reduction in blink rate was seen in cases when compared with controls for each of the test conditions. Blink rates were highest in subjects when being interviewed and were lowest whilst reading a passage in both cases and controls. No effect of disease duration, severity or treatment was observed. We have quantified the reduction in blink rate which has long been recognised as a feature of Parkinson's disease. We have identified factors which determine blink rate within individuals. We have also been able to define normal and abnormal levels for blink rate which may be of value clinically and for future research.
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http://dx.doi.org/10.1007/s00415-011-6261-0DOI Listing
April 2012

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Nature 2011 Aug 10;476(7359):214-9. Epub 2011 Aug 10.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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http://dx.doi.org/10.1038/nature10251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531PMC
August 2011

A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis.

PLoS One 2010 Dec 1;5(12):e14176. Epub 2010 Dec 1.

Centre for Bioinformatics, Biomarker Discovery & Information-Based Medicine, University of Newcastle, and Hunter Medical Research Institute, Newcastle, Australia.

Background: Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls.

Methodology/principal Findings: We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value <3.31E-6; V$CREBP1_Q2, p-value <9.93E-6, V$YY1_02, p-value <1.65E-5).

Conclusions/significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014176PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995726PMC
December 2010

Comparing endurance- and resistance-exercise training in people with multiple sclerosis: a randomized pilot study.

Clin Rehabil 2011 Jan 16;25(1):14-24. Epub 2010 Aug 16.

School of Physiotherapy and Exercise Science, Griffith University, Australia.

Objective: The purpose of this study was to compare adaptations in functional and quality of life measures following endurance- and resistance-exercise training in people with multiple sclerosis.

Design: Cross-over design with an eight-week washout period.

Setting: Community health centre.

Subjects: Sixteen individuals with multiple sclerosis.

Intervention: Subjects completed both an eight-week endurance- and an eight-week resistance-exercise training programme in a randomized order. The exercise training comprised individualized progressive programmes that were completed twice weekly in a supervised group setting.

Main Measures: Grip strength, functional reach, four step square, timed up and go and six-minute walk tests, Multiple Sclerosis Impact and Modified Fatigue Impact Scales, Becks Depression Inventory and the Health Status Questionnaire Short Form-36.

Results: Sixteen of 21 (76%) subjects completed the study. Subjects attended 13.2 ± 1.6 endurance- and 15.8 ± 1.9 resistance-exercise training sessions. No adverse events were reported. No significant differences (P < 0.05) in any outcome measures were observed between the two exercise training programmes either at baseline or following the completion of both training programmes.

Conclusion: Both endurance- and resistance-exercise training were well tolerated and appear to provide similar effects for people with multiple sclerosis, but larger studies are required to confirm these findings.
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http://dx.doi.org/10.1177/0269215510375908DOI Listing
January 2011