this issueDoes diagnosis matter?4–5Two new studies comparing criteria for ME and CFSME/CFS Biobank and Disease Register6–7Funding the next steps in two important infrastructure projectsIs ME/CFS different in elderly people?8–9New ME Research UK-funded research on the effects of age and illnessFunding the breakthrough 10–11Recent projects funded by ME Research UKResearch bites12–15Should ME/CFS patients have vaccinations? Plus, recovery in the PACE trial, theend of the XMRV hypothesis, faecal transplants, cadmium poisoning, and moreOur friends – 101 Donations16–19Fundraising by the Friends of ME Research UK: Simmone’s skydive, birthdayswim, Cardiff half marathon, cross-channel swim, Redcar half marathonSpring 2013 • BREAKTHROUGH • 3
Does diagnosis matter?Two new studies comparingcriteria for ME and CFSOne of the most animated debatessurrounding the diagnosis and treatment ofME/CFS concerns the name of the illnessand how it is diagnosed. At present, a rangeof possible definitions exist (see the tablebelow), but each is different, and today theterms ME, CFS and their various combinationsmean different things to different people.Does this matter? Absolutely –because the different ways of diagnosingpatients (‘diagnostic criteria’ in theparlance) capture different kinds ofpatients, and this in turn influences thetypes of clinical research carried out, thetreatment options that are offered, andthe perception of the illness by employers,benefit agencies and the public generally.4 • BREAKTHROUGH • Spring 2013The Belgian investigation: an experimental studyCurrent definitions of ME and CFSDefinitions of MEME/postviral fatigue syndrome (Ramsay) 1988London criteria (various) 1994+‘Nightingale’ definition (Hyde) 2007International consensus criteria 2011Definitions of CFSCDC definition (Holmes) 1988Australian case definition 1990Oxford case definition 1991CDC definition revised (Fukuda) 1994CDC empirical case definition 2003/2005‘Combined’ definitionsCanadian consensus definition (ME/CFS) 2003NICE guideline clinical criteria (CFS/ME) 2007How did this messy situationcome about? Well, the term myalgicencephalomyelitis (ME) originally referredto potentially chronic illness characterisedby profound, generalised post-exertionalloss of muscle power (fatigability); musclepain that could include tenderness andswelling; a range of neurological or cognitivesymptoms; and a tendency to relapse. Earlyreports dating from 1934 described apparentepidemics of an ME-like illness – such asthe famous 1955 outbreak at the RoyalFree Hospital in London – and the illnessis though to result from a continuing orpersisting viral infection in most cases.After 1988, however, chronic fatiguesyndrome (CFS) arrived on the scene. Thiswas a diagnosisgiven (after otherpossible diagnoseshad been excluded)to patients with sixmonths of fatigueplus a number ofother non-specificsymptoms, suchas sore throatand unrefreshingsleep. Since therewas (and presentlyremains) no specificdiagnostic test forME, and since postexercisefatigue wasone of its prominentsymptoms, peoplewho wouldpreviously have beengiven a diagnosisof ME began to bediagnosed with CFS.Today, theterm CFS hasbeen adopted bydoctors, healthcareprofessionalsand scientificjournals, whileProf. Jo Nisthe term ME is seen largely as a lay termused by campaigning patients’ organisationsand some patients themselves.In recent years, however, there hasbeen a growing recognition that CFS is avery broad diagnostic category that couldwell contain a range of very different kindsof patients. In short, CFS is thought of asan umbrella diagnosis, and probably moreof a holding bay for complex cases ratherthan a final destination. For this reason, arange of alternative definitions have beensuggested, some using combination termsME/CFS and CFS/ME, as the table shows.The two most commonly discusseddefinitions are the 1994 Fukuda definition ofCFS (used in the majority of scientific studies)and the 2003 Canadian definition of ME/CFS (designed by consensus to help healthprofessionals make a diagnosis effectively).In addition, there are various ME criteria inexistence, proposed by individual ME theorists;none are recognised by modern medicineor science today, but may become useful ifproperly operationalised and standardised.In the final analysis, onlyexperimentation is capable of cuttingthrough the suppositions and preconceptionssurrounding the relative effectivenessof this or that diagnostic definition.
ME/CFS Biobank – fundingthe second phaseBiobanks are large collections of biologicalspecimens (tissue, blood, DNA samples, etc.)obtained from patients or healthy peoplewho have volunteered their tissues forresearch. Crucially, every sample is linkedwith comprehensive clinical informationabout the donor, making biobanksparticularly useful for medical research.From the patients’ perspective, theinformation they provide can be used inmany research studies over many years,even though samples and information aredonated once only. From the perspectiveof the scientist, there exists a valuabledatabase of ‘well-characterised’ samples,with individual privacy and confidentiallymaintained, that can be made accessiblefor approved research projects.Over the past decade, a large number ofdisease specific biobanks have been formedacross the world, for illnesses such as cancer,schizophrenia and heart disease. In that time,two biobanks have been created to housesamples from ME/CFS patients: the SolveCFSBioBank (part of the Genetic AllianceBioBank) run by the CFIDS Association ofAmerica, and the Whittemore PetersonInstitute repository. Both are located in theUSA, however, and it was felt that the UKneeded an ME/CFS-specific biobank of itsown, given that around 200,000 of its citizens6 • BREAKTHROUGH • Spring 2013are affected by the illness at any one time.In 2011, a consortium of charities – MEResearch UK, Action for ME and the MEAssociation, with the help of a private donor –joined forces to fund the establishment phase(Phase I) of the UK’s first biobank of humanblood samples for research into ME/CFS.The project is led by Dr ElianaLacerda and Dr Luis Nacul from theLondon School of Hygiene and TropicalMedicine, and the biobank itself is situatedat London’s Royal Free Hospital whereWhat information iscollected about each donor?••Detailed history and clinical measurements••Demographic (age, gender, etc.), socio-economic and other exposure variables••Clinical data (phenotype), including disease severity••Confirmation of an ME/CFS diagnosis (Fukuda, Canadian) according to study criteria••Fatigue Severity Scale and Energy Fatigue Scale••Pain Analogue Scale – pain severity••MOS Short Form-36 data – function and quality of life••General Health Questionnaire-28••Epworth Sleepiness Score••Laboratory tests, including full blood count, blood chemistry, liver function tests,erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, thyroidfunction tests, tissue transglutaminase antibodies, serum vitamin B12, red cell folate,and urine analysisDr Eliana Lacerda and Dr Luis Naculit links with the extensive researchfacilities at University College London.During Phase 1, the researchers achievedtheir target of banking samples from 60well-characterised, clinically assessed ME/CFSpatients and 30 healthy people (controls). Foreach person assessed, the UCL/RFH Biobanknow holds approximately 46 aliquots ofblood sub-products (including whole blood,serum, plasma, red blood cells, peripheralblood mononuclear cells, and preparationsfor RNA extraction), alongside key datainformation (see the box below), anonymisedso that confidentiality is preservedThus, the fundamental infrastructurehas been put in place to underpin adisease-specific biobank for ME/CFS.At the end of 2012, the consortium ofcharities agreed to fund the next, expansionphase of the UCL/RFH Biobank. The aim ofPhase II is to increase the number of storedsamples to 200 (patients and controls),representing around 9,200 aliquots of bloodsub-products available to medical researchersfor specific research studies in the future.In the process, other GP networks willbe recruited, and the researchers will put inplace a procedure so that other scientistscan apply to access the samples for researchpurposes. The hope for the longer term is thatthis vital piece of research infrastructure willbecome a repository for blood and tissuesfrom many thousands of people with ME/CFS.
Expansion of the ME/CFSDisease RegisterDisease registers hold key information onpatients with a particular illness. Unlikebiobanks, which store clinical tissuesand samples, registers generally containinformation alone, and can be very importantreservoirs of demographic and clinical data.As one review has pointed out, inchronic diseases “an accurate wellmaintainedregister is a prerequisiteto providing comprehensive andcoordinated care”. For example,there are twelve CancerRegistries in the UK at present,and these are used to explorepatient follow-up after therapies,to evaluate services, to help withhealth service planning, and toanswer a range of other questions.The ME/CFS DiseaseRegister is the first systematicattempt to develop a populationbaseddisease register for the illness. Ledby Prof. Derek Pheby, it was housed initiallyalongside the ME/CFS biobank at the LondonSchool of Hygiene and Tropical Medicine.At present, the Disease Register containsthe details of over 300 ME/CFS patients;most were originally identified from GPWhat are diseaseregisters?practices in the UK, while others are severelyaffected patients originally on a databaseof housebound and bedbound patients.All patients have had their diagnosisdetermined, and completed a rangeof assessment instruments, includingShort Form-36 (which measures health“An accurate wellmaintained[disease]register is a prerequisite toproviding comprehensiveand coordinated care.”status and quality of life) and visualanalogue scales for pain and fatigue.Importantly, Prof. Pheby and colleagueshave undertaken a pilot project (publishedin BMC Research Notes, 2011) in EastAnglia, East Yorkshire and London, whichconfirmed the feasibility of their approachto case identification, data processing,transmission, storage and analysis.For logistical reasons, the ME/CFS Disease Register is moving to newpermanent premises at BuckinghamshireNew University, from where it can beginexpansion of its operations. A consortiumof charities – ME ResearchUK, Action for ME and the MEAssociation – is sponsoringthis relocation and expansion.As soon as the register hasbedded down, the recruitmentof larger numbers of patientswill begin, and a publication willbe prepared on the experiencesof the most severely ill patients.The expectation is thatthe Disease Register will, fromthese positive beginnings,develop into a repository ofhigh-quality information on many thousandsof patients. In particular, long-term followupdata may be of considerable use toclinicians and researchers, especially whenthey are linked with samples in the ME/CFSBiobank or, ideally, to a post-mortem tissuearchive of pathological specimens.••Disease registers aim to identify, as far as possible, all cases ofa particular disease or condition in a defined population.••In the main, they are used for chronic conditions, such asdiabetes, coronary artery disease, asthma or cancer, whichconsume a high proportion of healthcare resources.••Many hundreds of disease registers now exist in the USA andEurope, where they have a significant record of contributingto medical knowledge and health care.••Their main uses include epidemiological research, healthneeds assessment, and contributing to improvements inpatients care and service quality.••A report commissioned by the UK’s Department of Health in2000, ‘Saving Lives: Our Healthier Nation’ gave a commitmentto “… strengthen the information base on chronic diseases in thepopulation by establishing a series of disease registers in differentparts of the country”.Prof. Derek PhebySpring 2013 • BREAKTHROUGH • 7
Is ME/CFS differentin elderly people?It is estimated that around 9,300 peopledevelop ME/CFS every year in the UK, andthat around 200,000 are living with the illnessat any one time. We also know that mostbecome ill between the ages of 30 and 50,but does age itself make a difference? Forinstance, do people who are older whenthey first become unwell have a differenttype of disease than people whofirst become ill at a younger age?The issue is importantscientifically because there isnow quite good evidence tosuggest that abnormalities of theautonomic nervous and vascularsystems underpin at least some ofthe symptoms of ME/CFS. Theseabnormalities are, however, also acomplication of the ageing processitself, so it is certainly possiblethat older people who develop ME/CFS areat additional risk of these complications,over and above the effect of ageing itself.An ME Research UK-funded studyhas been examining this aspect, and theresults (published in the European Journal ofClinical Investigation, 2013) make interestingreading. For this investigation, patientsaged over 50 years were matched, on acase-by-case basis, by sex and duration8 • BREAKTHROUGH • Spring 2013of illness to a group of younger patients.This matching was particularly importantto disentangle the effects of ageing fromthe effects of illness duration, which itselfcritically affects the type and severity ofsymptoms experienced by patients.Of the 179 consecutive patients who hadattended the Northern Regional CFS Clinical“The effects of ageand illness combine tocreate even more severeautonomic dysfunction”Service in Newcastle between November2008 and June 2011, 52 (29%) were over 50years old. Twenty-five of these patients (agedbetween 51 and 70 years; who had been illfor 93 months on average) were matchedcase-by-case to 25 patients (aged between 16and 29 years; ill for 91 months on average).In addition to a full clinical assessment,the volunteers underwent assessment ofsymptoms, and autonomic nervous systemfunction was tested by measuring heartrate variability as well as the sensitivity andeffectiveness of the baroreflex mechanism,which is involved in blood pressure control.Overall, there was no differencebetween the younger and older patients asregards pain, cognitive function, sleepinessor anxiety. However, older subjects hadmore fatigue, more depression, anda poorer overall quality of life.The most intriguing differencesbetween the two groups were found in themeasurements of autonomic nervous systemfunction. Compared with the younger patients,the older group had significantly increased‘low frequency’ but reduced ‘high frequency’heart rate variability. This suggests animbalance between the two complementaryparts of the autonomic nervous system,the sympathetic (‘quick response’) andparasympathetic (‘rest-and-digest’) divisions.Additional support for the relativeimpairment of parasympathetic functionwas seen in the RR ratio (an indicator ofthe inter-beat interval of the heart) whichwas significantly reduced in the oldersubjects (see the figure opposite). Restingheart rate was significantly lower in olderpatients, who also had an impaired abilityto maintain blood pressure.One of the most interestingfindings concerned the leftventricular ejection time (the timeinterval from the opening to theclosing of the aortic valve in theheart), which was significantlylonger in older than in youngerpatients (286 versus 275 ms).In both groups, however, leftventricular ejection times weremuch shorter than the 374 msmeasured in healthy people by a previousstudy. This supports other findings fromNewcastle University of a reduced leftventricular performance and impairedcardiac function in ME/CFS patients.Now, some of these observed effectsare certainly due to the ageing process itselfbecause autonomic nervous system function,including heart rate variability, is knownto deteriorate with age. However, since
Bringing the evidence togetherFunding a systems approach to modelling symptom dataSince 2006, researchers at NewcastleUniversity have collected a large volumeof clinical, autonomic and symptomdata from patients recruited to studiesfunded by ME Research UK and itspartners, the John Richardson ResearchGroup and the Irish ME Trust.Full sets of data are available for over200 patients to date, and the very largeamount of data available (plus informationcollected from every patient attendingthe Newcastle ME/CFS Clinical Service)represents a very valuable longitudinalresource of clinical and biologicalinformation on people with the illness.While their scientific papers publishedto date have reported key headline findings,Prof. Newton and colleagues recognise thatmining this rich dataset has the potential toreveal even more about the illness, includingthe relationships between demographic,clinical and biological parameters.The power of modern computing and,in particular, a scientific approach called‘systems biology’ allows the developmentof multi-dimensional models of how a largenumber of different measurements link witheach other. Such models might allow theidentification of processes causing diseaseand, crucially, allow formal estimation tobe made of how changes in one or moresymptom might be expected to impact onthe overall burden of disease.Of course, these models can neverreplace studies involving patients, butthey can allow prediction of which patientstudies are most important and indicate thedirection of future research and treatment.An example of such a systemsapproach to a complex clinical problem isthe work on the cell biology of ageing byProf. Kirkwood and colleagues at NewcastleUniversity (Nat Rev Mol Cell Biol, 2003).Their modelling of the interactions betweenmultiple molecular mechanisms believedto contribute to the ageing of cells led to anovel prediction of the interaction betweenmitochondrial dysfunction, oxidative stressand chromosomal erosion in human cells,something that was subsequently confirmedexperimentally.The aim of this new ME ResearchUK-funded investigation, headed by Prof.Newton but involving other colleagues ina cross-discipline collaboration, is to applysimilar computational and mathematicaltools to the rich dataset on ME/CFSpatients which now exists at NewcastleUniversity.There are four elements to the study:identification and phenotyping of the studycohorts; development of the ME/CFSsymptom model; testing of the ME/CFSsymptom model; and indicative applicationof the model in ME/CFS to explore thepossible effects of treatments for fatigue orother symptoms (‘in silico trials’ to identifypotentially valuable interventions for ‘in vivo’testing).The work may yield novel insights andhypotheses that can be tested subsequentlyin clinical or biomarker studies.autonomic dysfunction is a consistent findingin people with ME/CFS of any age, it may bethat the effects of age and illness combine tocreate even more severe autonomic nervoussystem dysfunction in older patients. It is evenpossible that the underlying disease processdiffers between older and younger patients.Overall, the results show that there aredistinct physiological and clinical differencesbetween older and younger people withME/CFS, even though they have had theillness for the same length of time. Notonly do older patients have more fatigueand depression, and a poorer quality of life,but they also have a significantly greaterburden of autonomic dysfunction.The importance of these findings lies inthe fact that a sizeable proportion of peoplewith ME/CFS present with symptoms forthe first time aged over 50, and a significantproportion are aged over 60. It is importantto be aware that the combination ofunderlying ME/CFS disease mechanisms andthe normal physiological effects of ageing mayresult in a greater disease impact (particularlyon the cardiovascular system) in thesepeople who are older when they become ill.Parasympathetic function isreduced in older patientsRR ratioYoungOldSpring 2013 • BREAKTHROUGH • 9
Funding thebreakthroughProf. Julia NewtonProf. Jonas BlombergThe primary aim of ME Research UK isto fund biomedical research into ME/CFS, to find its cause, to develop effectivetreatments, and ultimately to discover a cure.We have invested more than £950,000in 34 specific biomedical projects basedin the UK or overseas; some of themost recent are listed here, and fullerdetails, including the resulting scientificpapers, can be found on our website.Money is the platform which supportsall biomedical research. But it is expensive:one clinical trial can cost half a millionpounds, while a major programme ofresearch can last for years and costmillions of pounds. So, unravelling thecauses and finding cures for ME/CFS willrequire big money over a long time.Major central funders like the MRCin the UK or the NIH in the USA can help,but the money they have available is thinlyspread across all types of research into alldiseases. Even the £1.65 million recentlyprovided by the MRC for ME/CFS researchis only a small part of the biomedicalactivity needed to set the field alight.In fact, a significant proportion ofresearch funding for all illnesses comesfrom charitable sources – if the charitysector did not exist, scientific research intoall medical conditions would be much thepoorer and discoveries far less frequent.Across the board, UK charitiesspent £1,137 million on research in2011/12 – an astonishing figure. In thesame period, the income of CancerResearch UK alone was £492,627,000.Much of the income for research intocancer and other illnesses comes directly orindirectly from public donations. We have todo the same for ME/CFS. As most patients aretoo ill to fundraise themselves, our strategyhas to be to raise awareness of the needfor biomedical research into the illness, toensure that our organisations are worthy ofthe trust and support of patients and thewider general public, and keep the researchcommunity on-side for the long march ahead.Dr Gwen KennedyDr Derek PhebyLong-term researchprogrammes are vitalFunding one-off investigations is usefulsince these can provide pilot data forsubsequent grant applications, or sparkoff interest in other researchers. But inmodern science real breakthroughs comeat the end of a programme of painstakingwork by a specialist group of researchers.One of the few examples of sucha programme on ME/CFS, anywhere inthe world, is the work at the VascularDiseases Research Unit, Universityof Dundee, which has received anumber of grants from ME ResearchUK and its funding partners.In a step-by-step progressioninvolving both adults and young peoplewith the illness, the group has uncovered:• unusual sensitivity of bloodflow responses to acetylcholine(a neurotransmitter),• increased levels of isoprostanes (agold standard marker of oxidativestress in the bloodstream),• an unexpected increase in dying(apoptotic) white blood cells, consistentwith an activated inflammatoryprocess or persistent infection,• increased cardiovascular risk factorswith arterial stiffness in patients, and• biochemical anomalies inchildren mirroring those foundin adults with the illness.Such a progression – whethertowards positive findings or awayfrom negative ones – is the normfor scientific investigation.The burning need in this illness isfor there to be many groups undertakingprogrammes of research across a rangeof basic and clinical sciences fields sothat a ‘critical mass’ of investigators canproduce a ‘critical mass’ of biomedical data.10 • BREAKTHROUGH • Spring 2013
Recent projects fundedby ME Research UKLymphocyte phenotype and cytokine productionDr Clive Carter, Leeds Teaching Hospital NHS TrustME Disease Register: transfer and implementationDr Derek Pheby, Buckinghamshire New University(co-funded with the ME Association and Action for ME)The sensitized brain: experiments using laser-evokedpotentials and cerebral blood flowProf. Jo Nijs, Vrije Universiteit Brussels, BelgiumDr Faisel KhanDevelopment of a rational diagnostic system based on microbiological biomarkersProf. Jonas Blomberg, Uppsala University Hospital, SwedenDePaul Symptom Questionnaire: evaluation in the ME Research UK cohortProf. Julia Newton, School of Clinical Medical Sciences, University of NewcastleAssessment of visual functionDr Claire Hutchinson, Vision and Language Group, University of Leicester(co-funded with the Irish ME Trust)Establishment of the UK ME/CFS BiobankDr Luis Nacul and Dr Eliana Lacerda, London School of Hygiene and Tropical Medicine(co-funded with the ME Association and Action for ME)Dr Les Paul & Dr Lorna PaulAdopting a systems approach to modelling symptom dataProf. J Newton, School of Clinical Medical Sciences, University of NewcastleComparison of criteria for ME and CFS: neurocognitive,physical and autonomic manifestationsDr J Van Oosterwijck and Prof. Jo Nijs, Artesis University College Antwerp, BelgiumMuscle bioenergetic abnormalitiesProf. David Jones, Institute of Cellular Medicine, University of NewcastleDr Jo NijsXMRV in Swedish patientsProf. Jonas Blomberg & Prof. Carl-Gerhard Gottfries, Uppsala University Hospital, Sweden(co-funded with the Irish ME Trust)Vitamin D supplementation and cardiovascular disease riskDr Faisel Khan, Institute of Cardiovascular Research, University of DundeeAutonomic nervous system dysfunction – a clinical cohort studyProf. Julia Newton, School of Clinical Medical Sciences, University of Newcastle(co-funded with the Irish ME Trust and the John Richardson Research Group)Biochemical and blood flow aspects in childrenDr Gwen Kennedy, University of Dundee(co-funded with The Young ME Sufferers Trust and Search ME)Evaluation of pain and therapeutic interventionsDr Lorna Paul and Dr Les Wood, Glasgow Caledonian UniversityDr Claire HutchinsonSpring 2013 • BREAKTHROUGH • 11
Research bites fromaround the worldAnd they implicate specific immune cells,plasmacytoid dendritic cells, in the process.It is far too early to say what thisnovel ‘observational’ finding really means, ifanything – particularly as measurementswere made on surplus clinical biopsiesand unmatched control specimens. As theauthors say, HERV protein expression mighthave a central role in the pathology of ME/CFS, but it might also be common to manyinflammatory diseases. And the association ofHERV with autoimmune diseases might turnout to be a blind alley. We await replicationby other research groups… watch this space.Source: De Meirleir et al., In Vivo, 2013NETHERLANDSThe vaccinationquestionWhether or not ME/CFS patients shouldhave vaccinations has been a hot topic formany years. The question is reasonablesince if the illness involves immunedysfunction, as we suspect, then patients’responses to vaccination might be verydifferent from those of healthy people.At Radboud University, Nijmegen,researchers have been investigating ME/CFS patients’ responses to the seasonalflu jab. Overall, the influenza vaccinationfulfilled its function: patients were able tomount a protective antibody response anda cellular immune response seven daysafter a single shot. The degree of protectionagainst flu was similar in patients and healthycontrols, leading the authors to concludethat “Standard seasonal influenza vaccination…when indicated, should be recommended…”So, is that the end of the story? Well, theauthors report no follow-up assessmentsof clinical outcomes, such as adverseeffects on symptoms or even relapses, inthe days and weeks after the flu jab. This isimportant because some patients say thatvaccinations, including for flu, significantlyworsen their condition. In one review ofpatients’ experiences of vaccinations, 20%of patients said that the flu jab provoked amarked flare-up in their symptoms, whileother respondents reported a variety ofreactions to other vaccines, although mostreported little or no adverse effects.Ideally, for a more complete picture,research studies on vaccination and ME/CFS should include both immunologicaloutcomes and clinical outcomes over time.Source: Prinsen et al., BMC Immunology, 2012NEVADAHuman endogenousretrovirusesHuman endogenous retroviruses (HERVs)are remnants of ancient retroviralinfections, and are thought to beinvolved in autoimmune diseases such asmultiple sclerosis and systemic lupus.As ME/CFS involves symptomsthat overlap with autoimmune diseases,including gastrointestinal problemswhich affect 80 to 85% of patients, couldHERVs be involved in this illness too?Researchers at the University ofNevada, Reno have just reported finding‘immunoreactivity’ to HERV proteins in thegut (duodenal) biopsies of 8 out of 12 peoplewith ME/CFS, but in none of 8 healthy people.BELGIUMPersonalitydisorders nota factorCDSM-IV axis II personality disordersinvolve ‘maladaptive personality traits’, suchas obsessive–compulsive disorder. A studyfrom Belgium reports no increase in suchpersonality disorders in ME/CFS patientscompared with people in the community(prevalence 16.3% in each group, in contrastwith 58.7% in a comparison group ofpsychiatric patients). No surprise therethen, particularly as the results accordwith a previous study in 2009 (prevalence12% in both patients and controls).The interesting thing is that both ofthese ‘negative’ investigations used theADP-IV questionnaire to assess personalitydisorder, whereas other ‘positive’ studies(reporting moderate differences betweenME/CFS patients and controls) have tendedto use the PDQ questionnaire which, asthe authors point out, gives high ratesof false positives and overestimates theprevalence of personality disorder. Suchmatters are important, particularly when theresults of research studies affect the livesof real people, and impact on healthcareprofessionals’ views of the illness!Source: Kempke et al., Int J Behav Med, 201212 • BREAKTHROUGH • Spring 2013
BOSTONQualitative studyof the lightningprocessThere are many views about the LightningProcess (LP) as an alternative treatmentfor ME/CFS, and the internet hosts a rangeof patients’ anecdotes – some reportinglightning cures, some reporting no success atall. So, it was refreshing to see some publishedinformation from Harvard University, Bostonon the experiences of young people with LP.Nine youngsters, members of theAssociation of Young People with ME,answered a call to share their experiences ofLP with researchers. As the authors report,“The experience of effectiveness split the youngpersons in roughly three categories: instant healing,gradual improvement, and no improvement at all.”A qualitative interview study likethis cannot tell us anything about clinicaleffectiveness, yet its 8,000 words certainlythrow a spotlight on the youngsters’experience of illness. The positive aspectsof LP, as reported by the children, includepositive and encouraging staff, practicalassignments, the one-to-one setting,and the setting of specific goals.The negative aspects included thesecrecy surrounding LP, the high cost, theapparent lack of honesty about truesuccess rates, and the perception thatpatients can be left feeling guilty andblamed if the treatment is not a success.As this article points out, LP aims toaddress dysregulation of the central nervoussystem by breaking the ‘adrenaline loop’that keeps the systems’ stress responseshigh. The core scientific question is whetherthis rationale stands up to scrutiny – andonly experimentation can answer it.Source: Reme et al., British Journal of Health Psychology, 2012NEWCASTLEA patient’s journeyThe British Medical Journal publishesoccasional articles by patients about theirexperiences that offer lessons for doctors.The latest is by Matilda Hale inconjunction with Professors Julia Newton andDavid Jones of Newcastle University. Matildahas primary biliary cirrhosis, an autoimmuneliver disease with fatigue as a prominentsymptom, and some elements of her journeywill be recognised by ME/CFS patients,particularly the day-to-day struggle and thescepticism of GPs and hospital doctors.It was Prof. Newton and Prof. Jones’experiences of primary biliary cirrhosis as anillness and its effects on patients like Matildathat sparked off their interest in fatigue asan overarching symptom common to manydifferent illnesses. This, in turn, led to theirinvolvement in ME/CFS, which they haveshown to involve far higher levels of totalfatigue than other comparable conditions.For example, the investigationshave shown that ME/CFS has a totalfatigue impact score of 102, comparedwith 41 in primary biliary cirrhosis and18 in primary sclerosing cholangitis.Source: Hale, Newton & Jones, British Medical Journal, 2012ITALYCadmium poisoning?Heavy metal exposure, such as with mercuryin dental amalgam, has been suggested asa cause of ME/CFS in some people. A newhypothesis paper suggests that cadmium (awidespread occupationaland environmental pollutant)might be involved in theillness, based on thesimilarity between theneurological symptomsand the known effects ofcadmium on the human body.For instance, brain greymatter has been shown to bedecreased in ME/CFS patientscompared with healthy people,and cadmium is said to induceneuronal death in corticalneurons in the brain. Again,ME/CFS has been associatedwith reduced cerebralblood flow, and cadmiumhas disruptive effects on thecreation of new blood vessels.This is all speculation,of course, but if high levelsof cadmium were indeedmeasured in these patients,the hunt would be on fortherapies capable of limiting orreversing cadmium exposure.Source: Pacini et al., MedicalHypotheses, 201214 • BREAKTHROUGH • Spring 2013
ME or CFS diagnosisRecovery of participants in the PACE trialPercentage of PACE participants who ‘recovered’Adaptive pacing CBT GET Standard medical careOxford criteria (i.e. all participants) 8 22 22 7CDC empirical case definition (2005) 9 19 22 6London ME criteria (1994) 11 21 21 10LONDONBiomedicalresearch comesinto its ownIn 2012, the UK’s Medical Research Councilallocated £1.65 million for biomedical projectsinto ME/CFS – to widespread congratulationsfrom patients and charities. But several yearsbefore, it had funded two large, expensiveclinical trials (FINE and PACE) of cognitivebehavioural approaches for ME/CFS, andthe consequences are still reverberating.The FINE trial found that ‘pragmaticrehabilitation’ of severely affected patients hadsome benefits in the short-term, but thesewere not maintained after one year, and thecost-benefits of treatment were minimal (BMCFamily Practice, 2013).When the PACE trial was finallypublished in the Lancet in 2011, it reportedimprovements in fatigue and physicalfunctioning in some ME/CFS patients aftercognitive behavioural therapy (CBT) orgraded exercise therapy (GET), comparedwith medical care alone. Overall, around10 to 15% of patients benefitted over andabove the beneficial effects of standardmedical care – an unsurprising finding sincewe already know from surveys that somepatients can be helped by non-specifictherapies. For instance, the ME Association’ssurvey of 2010 found GET to “improve/greatly improve” symptoms in 22.1% ofrespondents (906 responses), while theequivalent figures were 25.9% for CBT (997responses) and 53.7% (1675 responses)for meditation or relaxation techniques.Now a second report, this time inPsychological Medicine, has been publishedon the numbers of people who ‘recovered’from illness after treatment in the PACEtrial. ‘Trial recovery’ was defined as occurringwhen a patient was in the normal rangesfor fatigue and physical function, no longermet the Oxford case definition of CFS, andhad ratings of ‘very much’ or ‘much’ betteron the Clinical Global Impression scale.As the table above shows, around 15% ofparticipants derived extra benefit from CBTand GET over and above standard medicalcare, reiterating the previous findings.But what about the 85% of patientswho did not derive this additional benefitfrom the therapies, or the 90% or moreof patients who had not recovered fromME/CFS after 12 months of basic care?The authors themselves recognisethis problem when they say, “Therelatively small proportion of recoveredpatients…should also spur us on both toenhance currently available therapies andto develop new and better treatments.”Exactly. Patients with chronic illnessessuch as ME/CFS have a variety of useful nonspecificpsychological approaches available tothem. However, these cannot substitute forthe whole clinical and therapeutic armouryrequired to treat and (ultimately) curethe underlying disease, and this is wherebiomedical research comes into its own.Source: White et al., Psychological Medicine, 2013MARYLANDHuman herpesvirusHuman herpesvirus 6 is thought to playa role in several neurological diseases. Arecent technical report from the NationalInstitutes of Health, Bethesda describesthe development of novel techniquescapable of detecting antibodies to HHV-6infection, and the use of these techniquesto examine blood serum samples fromME/CFS patients and healthy controls.Overall, seropositive HHV-6A antibodyresponses were found in 13.5% of controlsamples and 9.7% of ME/CFS samples, whilethe equivalent figures for HHV-6B were 76and 75%, respectively. There was, therefore,no evidence of increased infection with (orserum antibodies directed against) HHV-6 inCFS patients compared with healthy people,although immune responses to HHV-6B werehighly prevalent in the general population.Does this mean that we can excludeHHV-6 as a causal or maintaining factor inME/CFS? Well, no – we’re still far from thatstage. Results of studies can differ dependingon whether testing is for active infection,for the presence of antibodies only, or forreactivation of latent infection. In fact, thereal importance of HHV-6 might lie inhow it associates with other co-infectingviruses, such as parvovirus B19, to impair theimmune function of the patient, as Latvianresearchers suggested earlier this year.Source: Burbelo et al., Am J Transl Res, 2012Spring 2013 • BREAKTHROUGH • 15
Our FriendsDONATIONSRecent fundraising for ME research9,000 framesStevie Laws, a second-year animation studentat the University of Central Lancashire, wasdiagnosed with ME recently, and says that ather worst she barely has the energy to eatand drink.Determined to help ME ResearchUK, she set herself the task of animatinga 6 minute film – quite a task, since everysecond of film consists of 25 separate framesof animation. “I know I can’t run a marathonor swim the channel but I still want to make adifference, and this is my way of doing that.”In total, Stevie aims to complete the9,000 frames needed within a year – 25frames per day for the next 360 days! Sheset her initial goal at a modest level, askingher Facebook friends to donate £1 eachfor the first 100 frames. Her first milestonehas been reached, and she is now askingfriends to help her reach her target frame byframe, with each frame raising funds for us.She has created a blog so peoplecan track her progress and see clipsof the final animation – have a lookat 9000frames.tumblr.com.Simmone’s skydiveTaking support for ME Research UK tonew heights (13,000 feet, in fact), SimmoneBell and friends from the Newry &Mourne ME/FMS Support Group leapt atthe challenge to skydive to raise funds. Abig hug to all who took part in the event,hosted by the skydive centre in Garvagh.As Joan McParland, one of thefounder-organisers of the group, said, “Wewere delighted with the turn-out, and allvery proud of Simmone’s bravery in jumpingfrom that plane. Simmone says that theinstructor tells you to SHOUT as you jumpout of the plane. I think I would be screamingall the way down and that’s only if my heartdidn’t stop. Brave girl, our Simmone!”The complete DVD of the fall showsSimmone laughing and smiling the rest of the16 • BREAKTHROUGH • Spring 2013 2012way down… wow! Our thanks to everyonein the group, who helped raise almost £3,000.Walk for MEFor this year’s ME Awareness Week (6–12May 2013), ME charity supporters havelaunched a ‘Walk for ME’ campaign. The hopeis that as many people as possible, especiallythe family and friends of patients, will do asponsored walk no matter how small, and itneed not be over ME Awareness Week either!As they say, “We hope this will be a funbut poignant event. The whole idea is that thefriend or family member is doing somethingthat their loved one would like to do but can’t.”There is a dedicated web page whereyou can choose which charity to walkfor, so please visit walkforme.co.uk andchoose ME Research UK as your charity.75th birthday swimGues what Janet Baker did to celebratereaching the age of 75? Shortly after herbirthday, she swam 75 lengths for MEResearch UK, simply because she believes thatbasic research into ME is urgently needed, andthat something should be done to help.Janet says, “I have chosen ME ResearchUK as one of my charities as my daughterHeather has ME and very little is known aboutit. Even though at least 200,000 people sufferfrom it in the UK very little research has beendone into what causes it and what is actuallyhappening in the body. Until it is better understood,there is scant chance of finding a cure.”
Cardiff HalfMarathonBeth Whittingham was supposed to runthe Cardiff Half Marathon in support of MEResearch UK, but sustained a stress fractureof her femur and so was unable to take part.But all was not lost because her brother Tomtook up the cudgel and ran instead.Tom did absolutely brilliantly andfinished in 1 hour 34 minutes, with Bethcheering him on at the 2 and 7-milepoints and again at the finish line.As Beth said, “I certainly couldn’t haveasked for a better replacement and I’m reallyproud of him, and pleased with what we haveboth managed to raise for ME Research UK.”You can still donate using their JustGivingpage.Life with ArtLife With Art is a charity which works withlocal communities and organisations providingfree workshops in art, photography anddrama – and ME Research UK is one of theorganisations it has chosen to support.For a few weeks, its extensivephotographic exhibition was open to thepublic in Dundee at The Vision Buildingnear the centre of town. We were therewith an information display to meet visitorscoming to view the exhibits, which included70 photos (including the one picturedbelow) from two shows about the invisiblenature of ME: ‘A diagnosis of exclusion’ and‘Unpredictable patters’ by photographicartist Juliet Chenery-Robson.Life with Art has ambitiousplans to launch Juliet’s show in arange of other venues round theUK – all inside empty offices andbusinesses. The other charitiesin the exhibition are the Ridingfor the Disabled Associationand the Teenage Cancer Trust.Stranger andStrangerMany thanks to Robert McMullen,author of ‘Stranger and Stranger’who has very generously donatedhis Kindle royalties from the saleof his book to ME Research UK.As our own residentreviewer said, “The arrival ofa mystery e-mail sparks an exchange thatilluminates a dark place but takes up hisavailable energies and has an emotional cost.“Like the illness ME itself, the story takesunexpected turns, with quizzes, challengesand quotations, and the outcome is a mostsurprising one, leaving a questioning reader.”The Kindle Edition is available onAmazon but please remember to shopthrough our website to help us even more.Public talk by DrVance SpenceOur Chairman, Dr Vance Spence, has givenover sixty public talks over the years, andhis most recent took place at the endof 2012, in the Soutar Theatre, Perth.Entitled, ‘ME/CFS – 21st CenturyIssues and Challenges’, his wide-rangingdiscourse was accompaniedby a PowerPoint presentation,and he discussed a range ofresearch findings, highlighting inparticular the research projectsthat ME Research UK has funded.The afternoon ended with astimulating Q&A session.Many thanks to the PerthME Support Group, whichmeets on the first Tuesdayof every month in Perth, forjointly organising this event.Particular thanks go tomember Alison Ferguson whoencouraged her colleagues atPerth & Kinross Council todonate the money raised fromtheir Dress-Down-Friday, andalso held a cake and candy stall,raising £300 in the process.Spring 2013 • BREAKTHROUGH • 17
Cross-ChannelswimUnfazed by bad weather, Sam Stevensand friends Jon Bury, James Goymourand Dave Glasgow completed the 35-mile cross-Channel swim in support ofME Research UK in 13 hours and 13minutes. Even more amazingly, they did itall without wetsuits in the cold water.Sam’s friend, Martin, who was a fellowstudent at Reading University, has beenfighting ME/CFS for the past four years.As Sam says, “I share Martin’s loveof all things connected with the ocean, sothought it was fitting that my friends andI should raise some money for researchby swimming the English Channel!”The guys had to complete a two-hourqualifying swim in Dover harbour, but theirtraining paid off – and what can we say exceptcongratulations and thank you for raisingover £8,000 for our biomedical programme.Redcar HalfMarathonGemma Wilson and running partner Laura Iles(pictured below) successfully ran the RedcarHalf Marathon for us, with great smiles andenthusiasm, albeit with aching legs afterwards.Before the race, Gemma said, “I’ll berunning 13 miles, that’s more than I’ve everwalked, and facing more pain than I’ve everbeen in… and I’ve had to give up Dominoespizza! If you know me, you know that thisis a massive deal for my inactive, unsportingbody and I’m having to work really hard. ButI’m determined to do it without walking, andfinish in an un-embarrassing time, and raiseas much money as possible on the way.”In fact, Gemma and Laura completedthe course in a very respectable time,raised a grand total, and learned one keylesson: to wear thicker socks next time!Read with MEAmy Christian is encouraging people tosponsor her to read or listen to as manybooks as possible, or to undertake theirown sponsored read over a 3-monthperiod. In her blog, Amy gives full details ofhow to join in, and there is a specific MEResearch UK JustGiving page too. Amy says,“As someone with ME/CFS, I’m not able to domany physical activities, but one thing I enjoyand which makes me feel better is reading.”Our own Dr Neil Abbot is helpingAmy’s campaign by reading his first Millsand Boon romance, Beneath the Major’sScars. As the cover says, “Major DominicCoale’s formidable manner is notorious, butZelda shows no signs of fear…” Phew!18 • BREAKTHROUGH • Spring 2013
Standing Order FormTo allow us to press ahead with our mission to Energise ME Research, please consider setting up a Standing Order bycompleting this form and sending it to ME Research UK, The Gateway, North Methven Street, Perth PH1 5PP.NameAddressPostcodeTelephoneE-mail addressTo the Manager, Bank/Building SocietyBranch addressPostcodeName of account holder(s)Account number ___________________________________________ Branch sort codePlease arrange to debit my/our account with the sum of £ __________ on the __________ day of each month until further noticeStarting on _______________________________Pay to: Clydesdale Bank, 23 South Methven Street, Perth PH1 5PQ, UKAccount: ME Research UK, Account no: 50419466, Branch code: 82-67-09Tick if you would like us to treat this, any future donations to ME Research UK, and all paymentsin the previous 4 financial years, as Gift Aid donations until you notify us otherwise. You confirmyou have paid or will pay an amount of UK Income Tax and/or Capital Gains Tax for each tax yearthat is at least equal to the amount of tax that all the charities or CASCs which you donate towill reclaim on your gifts for that particular tax year – 28p of tax on every £1 given up to 5 April2008 and 25p of tax on every £1 thereafter. Please inform us of changes in your tax status.Signature ___________________________________________________________ DateThank you for your supportShop at Amazon for ME Research UKCan there be any easier way to earn money for our charity? If you are buying from Amazon,then just click through the link on the Amazon page on our website, and 5% or more ofyour purchases could be making its way back to ME Research UK. It really is that simple.Whether it’s books, electronics or toys, Amazon has it all. Provided that you connect toAmazon via one of our links, your shopping will qualify. The amount we get varies according tothe type of product and the type of link followed. It won’t cost you a penny more, and you won’tlose out on other discounts, so please help us by shopping via ME Research UK’s Amazon link.Visit our website for more details: www.meresearch.org.uk/support/shopping.html.Read about more Friends’ activities and ideas for your ownfundraising at our website www.meresearch.org.uk/supportSpring 2013 • BREAKTHROUGH • 19