Lancet neurology.
`v. 9, no. 1 (Jan . 2010)
`General Collection
`W1 LA453U
`2010-01-20 10:15:24
`
`ET Neuro~ogy
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`Articles
`
`Review
`
`Review
`
`Assessment of brain tissue injury after
`moderate hypothermia in neonates with
`hypoxic-ischaemic encephalopathy
`Seep.1gc39
`
`Diagnosis and management of
`ihy, part 1
`Duchenne muscular dv
`Seep,1gc77
`
`Sporadic ataxia with adult onset:
`classification and diagnostic criteria
`Sccpagc94
`
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`THE LANCET Neurology
`
`Volume 9 • Issue 1 • January 2010
`
`Articles
`39 Assessment of brain tissue injury after moderate
`➔ @\ hypothermia in neonates with hypoxic-ischaemic
`encephalopathy: a nested substudy of a randomised
`controlled trial
`M Rutherford and others
`46
`Efficacy of community-based physiotherapy
`➔@ networks for patients with Parkinson's disease:
`a cluster-randomised trial
`M Munneke and others
`55
`An outbreak of neurological autoimmunity with
`➔ @ polyradiculoneuropathy in workers exposed to
`aerosolised porcine neural tissue: a descriptive study
`DH Lachance and others
`67 Antibodies to the GABA, receptor in limbic encephalitis
`➔@\ with seizures: case series and characterisation of the
`antigen
`E Lancaster and others
`Review
`77
`Diagnosis and management of Duchenne muscular
`@\ dystrophy, part 1: diagnosis, and pharmacological and
`psychosocial management
`K Bushby and others
`Sporadic ataxia with adult onset: classification and
`diagnostic criteria
`r Klockgether
`105 Medical complications after stroke
`S Kumor and others
`Personal View
`119 Hypothetical model of dynamic biomarkers of
`the Alzheimer's pathological cascade
`C RJockJrand others
`
`94
`
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`Covtr
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`(srep.uJen)
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`2
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`4
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`6
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`7
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`9
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`13
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`Leading Edge
`A new voice for global neurology?
`1
`Round-up
`Stroke: more protection for patients with atrial
`fibrillation
`GWA/bers
`Alzheimer's disease: progress in prediction
`RC Petersen
`Movement disorders: advances in cause and treatment
`A H V Schapiro
`Multiple sclerosis: predicting risk and delaying
`progression
`EA Yeh, 8 Weinstock-Guttman
`Epilepsy: insights into causes and treatment dilemmas
`SF Berkovic
`11 Headache: spreading from molecules to patients
`J Srhoenen, G Coppola
`Paediatric neurology: brain development at an interface
`between genetics, the environment, and the immune
`system
`M Tordicu
`14 Neurological infections: the year of PML and innuenza
`JR Berger, SA llouf(
`17 Neuro-oncology: new hope for patients with gliomas
`LM llrAngclis
`Reflection and Reaction
`19
`@
`20
`@
`
`Is MRI still cool after hypothermia?
`)Neil
`Time for comprehensive care networks for Parkinson's
`disease
`CJ I/ass, M S Okun
`22 A hazardous vapour trail from abattoir to
`neuropathy clinic
`@
`II J Wrllison, fl C Wraith
`24 Autoimmune limbic encephalitis: an expanding concept
`@
`Jllonnorat
`25
`Promoting palliative care in dementia
`JC l/11ghrs
`27 Definition of refractory epilepsy: defining
`the indefinable?
`@
`I' Kwan, M J Brodie
`Erratum
`29
`Correspondence
`30 Randomised trials of endovascular treatment of stroke
`arc needed
`A (icwnr, R Stmi; A-M Schott; M Moziqhi on,/ others
`Neurology training around the world: asking the
`trainees
`K R.-jd"k om/ otl,m
`In Context
`Cuts in Sp,1in fall heavily 011 the brain:
`the Cllll:HNED plight
`Allwtt111
`l'rofill'
`l.m1is C1pl,111: bedside neurologist
`RW11/11um
`
`32
`
`34
`@
`
`37
`31
`
`]8
`
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`This material wsas copied
`
`\ Srt•www.tht~l.mn•t.com forWrb[x tr.i content
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`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Review
`
`Diagnosis and management of Duchenne muscular
`dystrophy, part 1: diagnosis, and pharmacological and
`psychosocial management
`
`Katharine Bushby, Richard Finkel, David) Birnkrant, Laura E Case, Paula R Clemens, Linda Cripe, Ajay Kaul, Kathi Kinnett, Craig McDonald,
`Shree Pandya, James Poysky, Frederic Shapiro, Jean Tomezsko, Carolyn Constantin, for the DMD Care Considerations Working Group*
`
`Duchenne muscular dystrophy (DMD) is a severe, progressive disease that affects 1 in 3600-6000 live male births.
`Although guidelines arc available for various aspects of DMD, comprehensive clinical care recommendations do not
`exist. The US Centers for Disease Control and Prevention selected 84 clinicians to develop care recommendations
`using the RAND Corporation-University of California Los Angeles Appropriateness Method. The DMD Care
`Considerations Working Group evaluated assessments and interventions used in the management of diagnostics,
`gastrocntcrolo1-,,y and nutrition, rehabilitation, and neuromuscular, psychosocial, cardiovascular, respiratory,
`orthopaedic, and surgical aspects of OM D, These recommendations, presented in two parts, are intended for the wide
`range of practitioners who care for individuals with OM D. They provide a framework for recognising the multisystem
`primary manifestations and secondary complications of DMD and for providing coordinated multidisciplinary care.
`In part 1 of this Review, we describe the methods used to generate the recommendations, and the overall perspective
`on care, pharmacological treatment, and psychosocial management.
`
`Introduction
`D11chcnnc m11srnlar dystrophy (DMD; Online Mendelian
`Inheritance in Man [OMIM] reference 310200) is an
`X-li11kcd disease that afTi~cts I in 3600-6000 live male
`births.' ' Affected i11divid11als can have mildly delayed
`motor milestones and most arc unable to nm and jump
`properly due to proximal m11sclc weakness, which also
`rcs11lts in the use of the classic Gowers' manoeuvre when
`arising from the floor. Most patients arc diagnosed at
`approximately 5 years of age, when their physical ability
`diverges markedly from that of their peers.' Untreated,
`m11sclc strength deteriorates, a11d boys require the use of
`a wheelchair before their teens. Respiratory, orthopaedic,
`and cardiac complications emerge, and without
`intervention, the mean age al death is around 19 years.
`Non-progressive cognitive dysfimclion might also be
`present.''
`DMD ocC11rs as a result of m11lali0t1s (mainly deletions)
`in the dystrophin gc11e (DMD; lorns Xp21.2). Mutations
`le:1d to an ahse11ce ofor defect in the protei11 dystrophin,
`which
`res11lts
`i11 progressive 11111scle degeneration
`leading to loss of indepe11dent ambulation by the age of
`J 3 years.'· Variable phenotypic expression relates mainly
`to the type of mutation and its effoct on the production
`of dystrophin. Milder allelic forn1s of the disease also
`exist, including intermediate 11111sC11!:ir dystrophy and
`Becker m11srnlar dystrophy, which c:111st•
`loss of
`ambulation at 13-1(, years or ovl'r 1(, y<'ars, respectively.
`With the use of cortirnsll'roids to prolo11g a111hulatio11,
`thl'Sl' boundaries :ir<' less distinrt. I lowl'vn, that thl'sl'
`ph<'11otypl's l'xist is i111porta11l, a11d
`if' prowl'ssio11 is
`111ildl'T tha11 expccl\'ll for Dl\11), ;1sst•ss1111·11t for thl'sl'
`:ilt<•rnativt• for111s should hl' doll<', So1111• p:1ti<'11ts with
`dystrophi11 n1utatio11s also h:1\'(' an isol:itl'd c:inli:K
`plH'11otypt•.' " Approximall'ly 10'.':, of' li•111alt• rarril'rs
`show so111l' disl':ISl' n1:111ili·stalio11s that might i11d11dt•
`
`or even exclusively affect cognitive and/or cardiac
`function." " Although the disorder in affected girls is
`usually much milder than in boys, a few cases do have
`disease severity similar to that seen in affected boys.n•"
`Apart from a few cases associated with chromosomal
`rearrangements, most girls are assumed to be affected
`as a result of skewed X inactivation.
`The molecular basis of DMD has been known for over
`20 years."'" Many promising therapeutic strategies have
`since been developed in animal models." Human trials
`of these strategics have started, leading to the hope of
`definitive treatments for this currently incurable disease."
`Although specific treatments for DMD have not yet
`reached the clinic, the natural history of the disease can
`be changed by the targeting of interventions to known
`manifestations and complications. Diagnosis can be
`swiftly reached;
`the family and child can be well
`s11pportcd, and individuals who have DMD can reach
`their full potential
`in education and employment.
`Corticosteroid, respiratory, cardiac, orthopaedic, and
`rehabilitative interventions have led to improvements in
`ti111ction, quality of life, health, and longevity, with
`childrc11 who arc <liag11oscd today having the possibility
`ofa life expectancy into their fourth decade.'''"
`Advocacy organisations report variable an<l inconsis(cid:173)
`tl'nt health care for individuals with DMD. Although
`anticipatory :111d prevcntivl' clinic;il management ofDM D
`is csse11tial, n•commcmlations exist in only a few are:1s.
`!Hldrcssi11g thl' 111a11y co111plicatio11s of' DMD
`in a
`rnmprl'hl'nsivl' and rn11sisll'11t way is crncial for pla11ning
`11111lticcnlre
`trials, as well as
`for
`improving care
`worldwide.
`The dl'Vl'lop111e11l a11d i111ple111t•ntalion of standardised
`r:1rl' n•rnn1111t'llllatio11s were i11itially emphasised by
`sl:tkl'holdl'rs
`i11
`the DMD co111111t1nily,
`i11cl11ding
`g0Vl'rn1n1•nl :1ge11cies, clinicia11s, scientists, volunteer
`
`wwwlhPl.11111•! 1rnn/11,•111111oqy Vol 9 J.rnu.uy 1010
`
`Th is mate-ria I was copied
`at the NLM and ma y b-e
`Seubject US Copyright Laws
`
`Lancet Neurol 2010; 9: 77-93
`
`Published Online
`November 30, 2009
`DDl:10.1016/51474·
`4422(09)70271-6
`
`See In Context page 37
`
`Sec Online/RC'view
`DOl:10.1016/51474·
`4422(09)70272- 8
`
`'Members listed at end of paper
`
`Institute of Human Genetics,
`Newcastle University,
`Newcastle upon Tyne, UK
`(K Bushby MD); Division of
`Neurology (R Finkel MD) and
`Divisions of Pulmonary
`Medicine and
`Gastroenterology, Hepatology,
`and Nutrition (J Tomezsko PhD),
`Children's Hospital of
`Philadelphia, Philadelphia, PA,
`USA; Division of Pediatric
`Pulmonary Medicine,
`MetroHealth Medical Center,
`Case Western Reserve
`University, Cleveland, OH, USA
`(D J Birnkrant MD); Division of
`Physical Therapy, Department
`of Community and Family
`Medicine, Duke University,
`Durham, NC, USA
`(LE Case DPT); Department of
`Neurology, Molecular Genetics
`and Biochemistry, University of
`Pittsburgh, and Department of
`Veteran Affairs Medical Center,
`Pittsburgh, PA, USA
`(PR Cll'lllC'llS MD); Division of
`Cardiology (L Cripe MD,
`K Kinnett MSN) and Division of
`Pediatric Gastroenterology,
`Hepatology, and Nutrition
`(A K,1ul MD), Cincinnati
`Children's Hospital Medical
`Center, Cincinnati, OH, USA;
`DepMtment of Physical
`Medicine and Reh.,bilitation,
`Univrrsity of C.1liforni.,, O.wis,
`CA, USA (C Mdlon.,ld MIJ);
`D<"partment of Nl•urolo9y,
`Univl•rsityof Roch<'st<'r,
`Rochester, NY, USA
`(S l',rndy,1 l'f); School of Allied
`He,,lth Sciences, R.,ylor College
`of Mrdicinr, Houston, TX, USA
`IJ l'oy, ky l'hll); DepMtnwnt of
`Orthop,,edic Surgery, Children's
`llospit,,I Ooston, Bm.ton, MA,
`
`77
`
`I •
`
`I ..
`
`' ..
`
`:..
`
`i,.
`
`

`

`Review
`
`USA (F Shapiro MD); National
`Center on Birth Defects and
`Developmental Disabilities,
`Centers for Disease Control and
`Prevention, Atlanta, GA, USA
`(C Constantin PhD)
`
`Correspondence to:
`Katharine Bushby, Newcastle
`University, Institute of Human
`Genetics, International Centre
`for Life, Centre Parkway,
`Newcastle upon Tyne NEl 3BZ,
`UK
`kate.bushby@newcastle.ac.uk
`
`For OMIM see http://www.ncbi.
`nlm.nih.gov/omim/
`
`For the Muscular Dystrophy
`Association see http://www.
`mda.org/
`
`For Parent Project Muscular
`Dystrophy see http://www.
`parentprojectmd.org/
`
`For TREAT-NMD see http://
`www.treat-nmd.eu/
`
`See Online forwebappendix
`
`health agencies, and advocacy organisations such as the
`Muscular Dystrophy Association and Parent Project
`the Muscular
`the USA,
`Muscular Dystrophy.
`In
`Dystrophy Community Assistance, Research, and
`Education Amendments of 2001 directed increased
`research and public health initiatives towards the
`muscular dystrophies.n Development of these care
`recommendations are part of these activities. In Europe,
`a European Union-funded Network of Excellence
`(EC036825), TREAT-NMD, received funding to advance
`the treatment and care for neuromuscular diseases,
`with standardisation of care in DMD as one of their
`priorities. The US Centers for Disease Control and
`Prevention (CDC) has facilitated the development of
`these care recommendations as a collaborative effort
`among these stakeholders.
`TI1c aim of this Review is to present rccornrncndations
`for DMD management based on analysis of independent
`expert ratings of assessments and interventions. These
`recommendations focus attention on the many positive
`areas promoting efficient diagnosis and eflectivc
`management in DMD. They arc intended for the wide
`range of health-care providers who work with individuals
`who have DMD and their families, from primary care to
`the multidisciplinary
`team. The purpose of these
`is
`to provide a framework
`for
`recommendations
`recognising the primary manifestations and possible
`complications and for planning optimum treatment across
`different specialties with a coordinated multidisciplinary
`team. In the first part of this Review, we describe the
`methods used, and provide
`recommendations
`for
`diagnosis, pharmacological treatment, and psychosocial
`management. In the second part," we will discuss the
`implementation of multidisciplinary care.
`
`Methods
`Very few large-scale randomised controlled trials (RCls)
`have been done in DMD. In areas in which such trials
`exist (cg, for the use of corticosteroids), the evidence that
`can be derived from these studies has been emphasised.
`For most of the other recommendations, the CDC chose
`the RAND Corporation-University of California Los
`Angeles Appropriateness Method (RAM) to guide their
`development." RAM combines scientific evidence with
`the collective judgment of experts to determine the
`appropriateness and necessity of clinical assessments
`and interventions. Unlike consensus-driven methods,
`RAM preserves the integrity of individual expert opinion
`through anonymous and independent ratings, allowing
`areas of agreement, as well as areas of disagreement and
`uncertainty, to be revealed.,·,
`experienced
`An
`international
`coalition of 84
`practitioners, who represent the specialties involved in
`the delivery of DMD care, were nominated by their peers,
`and selected by the CDC and steering committee to serve
`on one or more panels. Experts independently rated
`interventions and assessments used in DMD rnan;1g<'·
`
`ment for appropriateness and necessity based on clinical
`scenarios presented in a matrix format. The matrices
`were developed from an extensive literature review for
`articles pertaining to interventions and assessments for
`DMD, augmented by expert opinion. Of the 1981 articles
`reviewed, the CDC used 489 articles in its final literature
`review. On completion of the literature review, the CDC
`and the expert panellists identified signs and symptoms
`that trigger the use of an assessment tool or intervention,
`and any clinical factors that should be taken into account.
`On the basis of expert input, the CDC organised the
`clinical factors and signs or symptoms into a matrix
`format. Each matrix addressed a particular assessment or
`intervention and included a clinical question, objective,
`or major presenting sylllptom (sec webappendix for
`clinical scenarios reviewed).
`The experts then rated the matrices in three rounds or
`ratings: two for appropriateness and one for necessity. In
`round
`each
`expert
`anonymously
`rated
`the
`I,
`appropriateness of using a particular assessment tool or
`intervention in specific clinical scl'narios 011 an ordinal
`scale of 1-<J. An intervention or assessment tool was
`designated as "appropriate" if the expected health benefit
`outweighs the anticipated risk, irrespective of financial
`implications.'' The CDC tabulated and analysed median
`ratings for each scenario according to RAM guidelines.
`During in-person meetings, the expert panels discussed
`the results and edited the matrices for round 2 for
`appropriateness. Alier round 2, the CDC categorised the
`asscsslllents
`and
`interventions
`as
`"appropriate",
`identified any
`"inappropriate", or "uncertain", and
`disagreernent alllong the experts.
`In round .!, the experts rated th<' assessments and
`interventions deemed
`appropriate without panel
`disagn·<'lllt'nt in round 2 for necessity on a silllilar
`1-<J scale. Experts rnuld rate an intervention or assess(cid:173)
`ment tool as "n<·u·ssary" if it met tire following four
`criteria: (I) intt·rvt·ntion or ass<'ss11w11t tool was rated
`it would he
`"appropriat<'" without disagreement: (2)
`irnproper not to offi•r tire intervention or assesslllcnt tool
`under tire clinical scenario proposed; (3) there is a
`reasonable chance that tire intervention or assessment
`tool will benefit the patient; and (4) tire magnitude of the
`expected benefit is not small.,·, See webappendix for
`examples of matrices, analyses, and results. After three
`rounds of independent ratings, the expert panellists
`to develop
`the
`reviewed and
`interpreted
`the data
`recommendations into a clinically relevant document.
`This two-part Review concentrates on those assess(cid:173)
`to he
`ments and
`interventions
`that were
`found
`"necessary", "appropriate", and "inappropriate",
`:rs
`defined by RAM. Areas of disagreement or urllertainty
`are underscored if particularly pertinent to pr;1ctice.
`These reco111111e11datio11s are therefore k1sed 011
`the
`RAM results except in cases in which llinical trial
`evidence exists, in partirnhr RCT data. Wt· h;1\'l' noted
`tire ran· inslann·s in which tlrl're is RCI' l'Vid1·1H1' lo
`
`78
`
`This material wascopcied
`at th.e N LM and may b.e
`~u bject USCopcyright Laws
`
`www tlwl.11ul't lo111/111•111oloqy Vol CJ J.mu.uy 1010
`
`

`

`►
`
`Review
`
`support the recommendations. During the development
`of the recommendations, the expert panels identified
`clinical questions not covered in the original matrices. If
`indicated, RAM results were supplemented by literature
`and expert opinion to provide a comprehensive picture of
`recommended care for DMD.
`
`The multidisciplinary team and the toolkit
`Each panel defined the toolkit of assessments and
`interventions applicable to DMD management (figure 1).
`The multidisciplinary approach to caring for patients
`with DMD and the range of expertise required are key
`features of this process. The patient and family should
`actively engage with
`the medical professional who
`
`coordinates clinical care. Depending on the patient's
`circumstances, such as area/country of residence or
`insurance status, this role might be served by, but is not
`limited to, a neurologist or paediatric neurologist,
`rehabilitation
`specialist, neurogeneticist, paediatric
`orthopaedist, paediatrician, or primary-care physician.
`This physician must be aware of the potential issues and
`be able to access the interventions that are the foundations
`in DMD. These
`include health
`for proper care
`maintenance and proper monitoring of disease
`progression and complications to provide anticipatory,
`preventive care and optimum management. Input from
`different specialties and the emphasis of interventions
`will change as the disease progresses (figure 2).
`
`Neuromuscular and skeletal management
`
`Tools
`(r(',1tine kin.1se
`Genetic testing
`Musde biopsy
`
`Interventions
`Genetic counsrlling
`Family support
`
`Assessments
`ClinicJI ev,1luJtion
`Strength
`Function
`ROM
`
`Considerations
`Age of patient
`St.1ge of disease
`Risk factors for
`sidr-rffrcts
`Available GC,
`ChoicC' of regimen
`Side-effect monitoring
`and prophylaxis
`Dose altrrJtion
`
`Tools
`Upp1•r and low,•r
`GI invt•stirJ<lti,mc;,
`A11tlm1ponwtry
`
`Interventions
`DiPt control ,md
`sup1,lrmrntJtion
`(;,1.,lr0\l1irny
`l1l1,1rn1.1t1,l11cJicJI
`111,111,HJ('lll('fll of CJ,1\lric
`reflux Jnd con-:.tip,1tion
`
`Assessments
`ROM
`Strength
`Posture
`Function
`Alignment
`Gait
`
`Interventions
`Stretching
`Positioning
`Splinting
`Orthoses
`Submaximum exercise/activity
`Seating
`Standing devices
`Adaptive equipment
`Assistive technology
`Strollers/scooters
`Manual/motorised wheelchairs
`
`Interventions
`Tendon surgery
`Posterior spinal fusion
`
`Tools
`Assessment of ROM
`Spinal assessment
`Spinal radiograph
`Bone age (left wrist
`and hand radiograph)
`Bone densitometry
`
`Assessments
`Coping
`Neurocognitive
`Speech and language
`Autism
`Social work
`
`Interventions
`Psychotherapy
`Pharmacological
`Soci,11
`Education.ii
`Supportive care
`
`Tools
`Spironwtry
`Puhr oxi111Pl1y
`( ,1JlllO<Jf,1phy
`l'C f, Mll'/MII', AIIG
`
`lntrrventions
`V<iltHlH' f('(r!Jitllll'llt
`Vl•1111l,1tc,r\/i11tl1ff,1rt.'\
`T r,H IH•11\I rnny tul>t'\
`Mt•t h.mi,,11 im11f!l,1tm/
`l')(\tJltl,ll(lf
`
`ldu,
`lloli,•r
`
`lnterv('ntions
`ACE inhibitors
`µ blmkers
`Other lw.ut failure
`nwdic,1tion
`
`rigure l: lntrrdisciplin.uy m.rn.19ement of IJMIJ
`( 011rdi11,11ion of dinir,,l l,11t' i, ,1 urn L,I llllllpnn,·nt ol thr 111,1t1,1tJPllh'l11 of llMll. 1 hi\ c.111• i\ hP,t pmvi1h•d in ,1 rn11lt idi'llipli11,uy t,lll1 Sl'tlinq in whic.h tlw individ11,1I and f.1111ily can ,lCU'SS rxpt>rtise frn
`1h" n•quin•d 11111hi.,y.,trm m,rn,H11•11w11t ol ()Mil in ,1111ll.1hor,1l1v1• 1•lh1rt. A lnrndi11,11l•d llink,1I L,111 1 roll' r,m lw p1nvidl•d by ,1 widl' r,lll<Jl' of lw,11th-c,Hl' prufL•s\ion,11\ dqwnding on local services,
`irn hidinq (11111 11ot lir11il1•d to) llf'tllnlnq1\h 01 p.wd1,1t1it. 111•111ol11qi\l\ 11·h.1liihl.1tion \pl'ti,,li\l\, 111•u1oq1•rwtiL hi\, p,H'di,1lrili,lll\ ,llHI p1im,uy r,1n• pliy,id,111\. It is cruci,11 th,1t tlw person respor1,ible for
`tlw 1onrd111,1ti()ll oft 111111 ,11 t ,111• i, ,1w,111• ol tlu• ,1v,1tl,1hh• ,1\\t'\\IIH'llh, tool\, ,111d inlt•1v1•111iom lo )llO,H tiv1•ly 111,111,HJt' ,111 polL'llli,1I i\\lll'\ involvinq DMD. ABG-..a,lllt'ri,1I blood g,l<;. A(Ex 11ngio!t'll\ill•
`(1HlVP!lt11q 1•111y1111·. llMD-lhu lw111w llH">t 1,l.11 dv,11opliy I I ho-1·1 lui1,11d1nqr.1111. I ( (,-l'lt•t t1ot,1tdioq1,1111. C1C-qhJt.ntrntiulith, (.l .. q,1..,tmintt•stin,1I. MEP.am,1ximum expiratory prcsstne.
`MW-111.1x111111111 irr,p11,1trny Jlll'\\t1ll'. I'( I -p,•,1~ 11111qh tl11w l~