review open access consensus-based care ......review open access consensus-based care...
TRANSCRIPT
REVIEW OPEN ACCESS
Consensus-based care recommendations foradults with myotonic dystrophy type 2Benedikt Schoser MD Federica Montagnese MD Guillaume Bassez MD PhD Barbara Fossati MD
Josep Gamez MD PhD Chad Heatwole MD James Hilbert MS Cornelia Kornblum MD
Anne Kostera-Pruszczyk MD PhD Ralf Krahe PhD Anna Lusakowska MD PhD Giovanni Meola MD
Richard Moxley III MD Charles Thornton MD Bjarne Udd MD PhD and Paul Formaker on behalf of the
Myotonic Dystrophy Foundation
Neurology Clinical Practice August 2019 vol 9 no 4 343-353 doi101212CPJ0000000000000645
Correspondence
Paul Formaker
LeahHellersteinmyotonicorg
AbstractPurpose of reviewMyotonic dystrophy type 2 (DM2) is a rare progressive multi-system disease particularly affecting the skeletal muscle A causaltherapy is not yet available however prompt appropriate symp-tomatic treatments are essential to limit disease-related complica-tions Evidence-based guidelines to assist medical practitioners inthe care of DM2 patients do not exist
Recent findingsThe Myotonic Dystrophy Foundation (MDF) previously workedwith an international group of 66 clinicians to develop consensus-based care recommendations for myotonic dystrophy type 1 Following a similar approach theMDF recruited 15 international clinicians with long-standing experience in the care of DM2patients to develop consensus-based care recommendations The single text procedure wasadopted This process generated a 4-page Quick Reference Guide and a comprehensive 55-pagedocument that provides care recommendations for DM2 patients
SummaryThe resulting recommendations will help standardize and improve care for DM2 patients andfacilitate appropriate management in centers without neuromuscular specialists
Myotonic dystrophy type 2 (DM2) also known as proximal myotonic myopathy is a raremulti-systemic disease similar to but distinct from myotonic dystrophy type-1 (DM1) DM2has a later onset usually milder phenotype and lacks the severe congenital form seen in DM1The gene defect in DM2 is an unstable CCTG repeat expansion in the cellular nucleic acid-binding protein gene (cellular nucleic acid-binding proteinmdashformerly known as ZNF9 gene)1
Like DM1 DM2 has an autosomal dominant inheritance pattern and expansion lengths of 75repeats or longer are considered pathogenic1
Ludwig-Maximilians- Universitat (BS) Friedrich-Baur-Institut (FM) Munich Germany Institut deMyologie (GB) Paris France UO Neurologia (BF) IRCCS Policlinico SanDonato MilanItaly Vall drsquoHebron University Hospital (JG) Barcelona Spain University of Rochester (CH JH RM CT) Rochester NY University Hospital of Bonn (CK) Germany Medical University ofWarsaw (AK-P) Poland University of Texas (RK) MD Anderson cancer center Medical University ofWarsaw (AL) Poland Department of Biomedical Sciences for health (GM) Universityof Milan Italy Tampere University (BU) Finland Myotonic Dystrophy Foundation (PF) San Francisco
Funding information and disclosures are provided at the end of the article Full disclosure form information provided by the authors is available with the full text of this article atNeurologyorgcp
The Article Processing Charge was funded by the Myotonic Dystrophy Foundation
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 40 (CC BY-NC-ND) which permits downloadingand sharing the work provided it is properly cited The work cannot be changed in any way or used commercially without permission from the journal
Copyright copy 2019 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology 343
The CCTG-expansion is extremely unstable It increases withage and shows marked heterogeneity in length within differenttissues of the same subject2 Unlike DM1 there is no clearcorrelation between the length of the CCTG expansion andclinical severity Symptoms in DM2 patients usually begin inthe third to fifth decades of life No congenital or infantile caseshave been reported Muscular symptoms are usually the majorcomplaints that cause patients to see a physician Howeverextramuscular manifestations such as cataracts may precedethe muscular complaints Muscle weakness andor myalgia arethe most common symptoms at onset whereas about40ndash50 of patients initially complain of myotoniamusclestiffness34 As the duration of DM2 increases many organs andsystems may be affected hence the patientrsquos managementshould include screening for heart diseases (cardiomyopathyarrhythmias) diabetes mellitusinsulin resistance thyroiddysfunctions cataract gastrointestinal disturbances respiratoryinvolvement mild cognitive disorders and tumors5ndash8 Symp-tom severity widely varies among patients even within mem-bers of the same family Age-dependent worsening of muscularsymptoms and an increase of the multi-systemic complicationshas been observed4
Because of the low diagnosed prevalence of DM2 patientsworldwide and the relatively recent discoveryof this disease thereis a lack of rigorous evidence regarding the care andmanagementof patients For this reason evidence-based guidelines cannotcurrently be developed Consensus-based clinical care recom-mendations can serve as a support and guide for clinicians notfamiliar with the heterogeneous nature of DM2 enabling qualitystandardized patient care for those living with DM2
MethodologyThe Myotonic Dystrophy Foundation (MDF) recruitedclinicians from the United States and Europe who have ex-perience in the treatment of patients with DM2 to developconsensus-based care recommendations
The project included a total working group of 15 clinicalprofessionals MDF provided project design developmentand management support A complete list of working groupmembers and authors is provided below
The principles of the single text procedureweremainly adoptedto steer the consensus-building process9 The single text pro-cedure employs the use of a single document as a starting pointto incorporate the input and contributions of stakeholders In
this approach stakeholders add subtract and refine a draft textthat becomes the foundation for a final ratified document
This consensus-building model was selected because it could beeffectivewithin the contextof the limited clinical caredata availablefor DM2 the clinical content already available and the com-plexities of working across a large international group of experts
Having already developed consensus-based care recom-mendations for DM110 and given the similarity of system in-volvement and management between DM1 and DM2 MDFcreated a draft document for DM2 based on DM1-consensuscare recommendations (for further methodological detailsrefer to the Consensus-based Care Recommendations forAdults with Myotonic Dystrophy Type 1 2018 myotonicorgclinical-resources)
MDF circulated the draft document toworking groupmemberswho read the draft content and provided their recom-mendations MDF aggregated all the revisions and suggestionsinto a single updated document Recommendations in conflictwere circulated within the group for discussion and resolvedthrough serial conference calls
These efforts led to the final consensus-based care recom-mendations and Quick Reference Guide for DM2 which werecompleted inmid-2018 TheQuick Reference Guide content isprovided as an appendix and the full document is availableonline (appendix e-1 linkslwwcomCPJA88) Both featureflowcharts and other infographics for ease of use
ResultsSee full recommendations at Neurologyorgcp
Life-threatening symptomsmdashClinicalcare recommendations Cardiovascular management
DM2-related cardiac pathophysiology although affect-ing all myocardial tissues preferentially targets thecardiac conduction system Conduction system defectsare progressive and although initially asymptomaticincrease the risk for symptomatic arrhythmias
DM2 has a later onset usually milder
phenotype and lacks the severe
congenital form seen in DM1
Consensus-based clinical care
recommendations can serve as
a support and guide for clinicians not
familiarwith theheterogeneousnature
of DM2 enabling quality standardized
patient care for those living with DM2
344 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
Significant cardiac involvement that subsequentlyleads to adverse cardiac events is often asymptomatic
At diagnosis check for cardiac symptoms performa 12-lead ECG and consider a 24-hour Holter ECG
Conduction abnormalities on a standard 12-lead ECGincluding sinus rate lt 50 beats per minute PR intervalgt 200 ms QRS duration gt 100 ms left anterior orposterior fascicular block abnormal Q-waves atrialtachycardia fibrillation or flutter and ventriculararrhythmias are indicative of cardiac involvement
Refer patients with cardiac symptoms abnormalannual 12-lead ECG indicative of cardiac involvementand patients older than 40 years without previouscardiac evaluation to a cardiologist for furtherevaluation
See Flowchart figure 1 in Quick Reference Guide(appendix linkslwwcomCPJA87)
See full recommendations at myotonicorgclinical-resources
Respiratory management Some DM2 patients have significant breathing
problems that can result from muscle weakness ofthe diaphragm abdominal and intercostal musclesand myotonia of these muscles leading to poorventilatory force and resulting in low blood oxygenand elevated blood carbon dioxide levels
Clinicians must look for respiratory symptoms inDM2 patients
In asymptomatic patients a pulmonary functionassessment every 2 years is recommended
Refer DM2 patients with respiratory symptoms in-cluding ineffective cough (normal peak expiratorycough flow rate is gt270 Lmin) respiratory in-sufficiency recurrent pulmonary infections prominentsnoring and maximal inspiratory pressure lt60 cmH2Oor forced vital capacity values of 50 less thanpredicted normal values to a pulmonologist knowl-edgeable in neuromuscular disorders
Vaccinate for pneumonia and flu treat respiratoryinfections quickly and use cough assistance andmechanical ventilation as needed along with obtainingconsultations from respiratory therapy and pulmonarymedicine groups
Some patients will eventually require nighttimeventilator support Most patients with chronic re-spiratory insufficiency respond to noninvasive venti-latory support (NIV)
For chronic respiratory insufficiency use supplemen-tal oxygen with caution and in conjunction with NIV
If surgery is planned reassess clearance capacity ifneeded possible adaptation to NIV or cough assistance
See Flowchart figure 2 in Quick Reference Guide(appendix linkslwwcomCPJA87)
See full recommendations at myotonicorgclinical-resources
Severe symptomsmdashClinicalcare recommendations Pain control
Muscle pain can occur in the neck back shoulders hipflexors and lower limbs Statin-induced myopathy isoften accompanied by muscle pain
Treat with conventional pain medications which maybe useful in treating the painful aspects of myotonicdystrophy (eg Ibuprofen)
Opioids can be used but should be avoided if possible Ifimplemented low doses should be used with closemonitoring for side effects (see Anesthesia and surgery)
Other remedies such as massage nerve blocks heatice or chiropractic can be used Some patients havereported that cannabis cannabinoids or phytocanna-binoids ease pain however this needs to be proven incontrolled clinical trials
Refer to Physical Therapy or Occupational Therapy ifconventional treatment is not successful
See full recommendations at myotonicorgclinical-resources
Skeletal muscle weakness and rehabilitationSkeletal muscle weakness and myalgia are major featuresof DM2 Initial weakness is in proximal hip girdle and neck
(flexors gt extensors) muscles Axial muscle weakness isfrequent in DM2 and may result in lower back pain
The progression is relatively slow 1ndash3 percent peryear
Mild ptosis might be occasionally present Calfhypertrophy may occur
Myalgia can be the most prominent clinical feature in theearly stages and may severely affect occupationalperformance
Impacts to employment and activities of daily livingoccur because of the proximal and axial muscleweakness (eg climbing stairs and standing up fromthe floor)
Treat with moderate- or low-intensity aerobic andresistance exercise orthoses or braces It is advised toobtain a cardiac evaluation before starting a new exerciseroutine
See full recommendations at myotonicorgclinical-resources
Skeletal muscle myotonia Myotoniamdasha sustained muscle contraction and diffi-
culty in relaxing musclesmdashmay occur and be symp-tomatic in DM2 patients
Myotonia can contribute to muscle stiffness painprolonged hand grip speech and swallowing difficultiesand gastrointestinal issues
Mexiletine may be considered in select patients formyotonia treatment of the hands with appropriatecardiac monitoring
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 345
See full recommendations at myotonicorgclinical-resources
Ocular symptoms Major and clinically relevant eye manifestations in DM2
can include the following cataracts eyelid ptosis andincomplete eyelid closure retinal changes and changes inintraocular pressure
Bilateral eyelid ptosis is a rare feature of DM2 but canoccur in some patients
See full recommendations at myotonicorgclinical-resources
Gastrointestinal symptoms Limited information is available and manifestations are
less severe than in DM1 Ask about problems with chewing swallowing
drooling reflux bloating abdominal pain bowelmovement frequency and characteristics diarrheaand incontinence
Physical examination should include abdominal pal-pation including around gall bladder and rectalexamination for anal sphincter spasm and dyssynergicdefecation for symptomatic patients
DM2 patients are at risk for pseudo-obstruction andexperience other problems that may cause actualobstruction of small or large intestine includingendometriosis acute gallbladder inflammation rup-tured ovarian cysts and sigmoid volvulus Monitorpotential obstructions to determine whether they arepseudo or actual and treat accordingly
Nonmedical interventions High-fiber diet for diarrhea or constipation increasewater intake
Nutritional supplement for weight loss weight gainor dysphagia
Dysphagia therapy referral for oral pharyngealdysphagia
Possible medical interventions Loperamide for diarrhea control Laxatives for constipation
First-line therapy Miralax Senna Ducosate orLinaclotid
Second-line therapy Bisacodyl Lubiprostone orLinaclotide Metoclopramide for gastroparesis pseudo-obstruction reflux
Antibiotics for bacterial overgrowth-induced diar-rhea (based on breath testing)
Enteral feeding only for recurring pneumonia orsevere dysphagia causing weight loss or causinginability to swallow safely without recurrentaspiration
Mexiletine may be considered to treat diarrhea orconstipation in DM2 however its use for theseindications requires further study
See full recommendations at myotonicorgclinical-resources
Neuropsychiatric symptoms Advise patients that DM2 is also a ldquobrain disorderrdquo that
can involve cognitive deficits and changes in cognitionover time
Include psychiatric and behavioral examination atbaseline and during regularly scheduled follow-upappointments or when symptoms appear
Refer patients with psychiatric or behavioral disordersand patients with cognitive complaints to a mentalhealth care professional for testing and follow-uppatients may have limited insight into these issuesmdashconsider input from partners and family members asappropriate
Treat with psychostimulants if apathy is associated withan impairing level of fatigue or excessive daytimesleepiness (EDS) (see Excessive daytime sleepiness) orantidepressant medication (cardiac examination beforestarting treatment including a 12-lead ECG)
See full recommendations at myotonicorgclinical-resources
Excessive Daytime Sleepiness symptoms EDS is very rare in DM2 but can be a life-altering
symptom In contrast fatigue is relatively common inDM2 and may be seriously disabling
Assess for EDS with Epworth Sleepiness Scale orsimilar standardized questionnaire instrument pre-scribe sleep study if sleep disturbance is suspected
Monitor periodic limb movements (muscle activityduring sleep) as well as EEG and respiratory measuresduring sleep study to assess possible obstructive sleepapnea and CNS-mediated sleep apnea
Refer to pulmonologist andor sleep specialist if EDSscores are positive on scales
Question patients regarding alcohol or caffeineconsumption medications and sleep habits forcontribution to EDS
Evaluate effect of possible respiratory muscle weakness(forced vital capacity value sitting and supine) onpresence of EDS
If nocturnal or daytime hypoventilation is suspectedconsider noninvasive positive pressure ventilationand refer to a pulmonologist with experience inneuromuscular diseases regarding possible need forNIV
Consider modafinil for treatment if coexisting CNSalteration is suspected as the cause for EDS
Consider cognitive behavioral therapy or behavioraltherapy for apathy also help treat fatigue psychostimu-lant treatment can be considered if apathy is associatedwith an impairing level of fatigue or EDS
See full recommendations at myotonicorgclinical-resources
346 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
Endocrine and metabolic symptoms Follow criteria from American Diabetes Association
regarding the type of initial testing to obtain typicallyfasting blood glucose or HbA1c and if symptomaticdiabetes is suspected
Consider formal glucose tolerance testing to monitorglucose control in patients request serial measure-ment of HbA1c and fasting plasma glucose annuallyand coordinate care with diabetes specialist asnecessary
Consider treating insulin resistance with lifestylechanges in diet and exercise
Measure liver and bilirubin levels at baseline andannually chronic liver enzyme elevation is typical anddoes not necessarily indicate the need for obtaininga liver biopsy
Request thyroid-stimulating hormone (TSH) andcirculating thyroid hormone (TSH and Free T4) leveltests at baseline and at least every 3 years morefrequently if indicated
Test for hyperlipidemia using serum blood lipidlevels at baseline and every 3 years more frequentlyif indicated Treat hyperlipidemia per currentpractice
Gender-specific recommendations Women Inquire about painful or irregular mensesovarian cysts endometriosis reproductive history
Men Inquire about erectile dysfunction considerfurther workup and medications to treat erectiledysfunction Consider possible cardiovascularrisksmdashside effects associated with some erectiledysfunction medications (over the counter andprescribed)
Inquire about infertility and family planning See full recommendations at myotonicorgclinical-
resources
Tumors Follow general population cancer screening guidelines
particularly for breast testicular cervical and coloncancer
Evaluate suspicious new CNS abdominopelvic andthyroid symptoms for possible cancer consider cancersof the brain uterus and ovary
See full recommendations at myotonicorgclinical-resources
Pregnancy and obstetric management The effects of DM2 on both smooth and striated
muscle can complicate pregnancy labor and deliveryand increase myotonia
Prenatal and preimplantation genetic diagnosis canallow for termination of the pregnancy or selectiveimplantation of unaffected embryos if desired
See full recommendations at myotonicorgclinical-resources
Surgery anesthesia and pain Although a higher incidence of adverse reactions to
medications used for anesthesia and analgesia has beenreported for DM1 (about 8) it is yet not clearwhether similar risks occur also in DM2 patientsHowever given this uncertainty and the potentiallyserious complications reported in some DM2 patientsour advice is to adopt similar anesthesia guidelines assuggested for DM1
See MDFrsquos Practical Suggestions for the AnestheticManagement of a Myotonic Dystrophy Patient (myo-tonicorgclinical-resources) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia
See full recommendations at myotonicorgclinical-resources
ConclusionsThese consensus-based care recommendations for patientswith DM2 are the product of an international group of ex-perienced clinicians They are intended to lead to more in-formed and prepared clinical professionals and more readilyavailable and high-quality care for affected families
AcknowledgmentThis project would not have been possible without the majorcommitment made by the 15 international professionalsinvolved in its development MDF team leads included PaulFormaker Leah Hellerstein and Molly White
Study fundingMyotonic Dystrophy Foundation
DisclosureB Schoser serves on the scientific advisory boards of andreceived funding for travel from Sanofi-Genzyme BiomarinAmicus Therapeutics and Audentes Therapeutics serves onthe editorial boards of Neuromuscular Disorders and Journal ofNeuromuscular Disorders and as a Section Editor for CurrentOpinion in Neurology F Montagnese served on a scientificadvisory board organized by Lupin Europe GmbH for theapproval of mexiletin for the treatment of myotonia G Bassezserves on the scientific advisory boards of Lupin pharma-ceuticals AFM-Telethon and Myotonic Dystrophy Founda-tion serves as a consultant for Lupin pharmaceuticals andreceives research support from FP7 EU AFM-Telethon andMyotonic dystrophy registry B Fossati and J Gamez reportno disclosures C Heatwole serves on the scientific advisoryboards of Biogen has received funding for travel from Myo-tonic Dystrophy Foundation serves as a consultant for Ime-decs Maximus Johns Hopkins University Biogen Atyr IonisAcceleron Cytokinetics ExpansionRX AMO and the Mari-gold Foundation receives research support from Pfizer
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 347
Technology Development Fund (University of Rochester)Cure Spinal Muscular Atrophy Amyotrophic Lateral SclerosisAssociation Huntington Study GroupNJ Cure HD Founda-tion NIH (NIAMS NINDS) and United States Food andDrug Administration has royalties for use of the MyotonicDystrophy Health Index (MDHI) a disease-specific patient-reported outcomemeasure for use in clinical trials and royaltiesfrom licensing instruments for FSHD congenital DM1 CMTSMA and Huntington disease and has participated in medi-colegal cases J Hilbert receives research support from BiogenNIH Abrams Family Fund FSH Society and Friends of FSHResearch C Kornblum has received funding for travel orspeaker honoraria from Sanofi-Genzyme Santhera NovartisStealth BioTherapeutics Deutsche Gesellschaft fur Musk-elkranke eV andMarigold Foundation Canada has served asa consultant for Stealth BioTherapeutics and receives researchsupport from Stealth Biotherapeutics BMBF (German FederalMinistry of Education and Research) mitoNET MarigoldFoundation Canada Deutsche Gesellschaft fur MuskelkrankeeV grant number Me41 since 2014 A Kostera-Pruszczykserves on the scientific advisory boards of Biogen PTC Sar-epta and Shire has received honoraria from Kedrion BaxterShire CSL Behring and Sanofi Aventis and serves on theeditorial board of Neurology Neurosurgery and Psychiatry RKrahe serves as an academic editor for PLoS One A Lusa-kowska and G Meola report no disclosures R Moxley IIIserves on the scientific advisory boards of NIHNINDS andMyotonic Dystrophy Foundation and receives research sup-port from Ionis NIH (NCRR NCI) FDA Saunders FamilyFoundation and Abrams Family Fund C Thornton serves onthe scientific advisory boards of the Myotonic DystrophyFoundation and Dyne and on the NIH data safety monitoringboard has received funding for travel from University ofFlorida University of Michigan American Association ofNeurology Muscular Dystrophy Association Myotonic Dys-trophy Foundation World Muscle Society Fulcrum Thera-peutics Dyne Therapeutics Lion Therapeutics and NatureConferences is an author on patents regarding Modulation ofDystrophia Myotonica-Protein Kinase (DMPK) ExpressionCompositions and Methods Related to Protein DisplacementTherapy for Myotonic Dystrophy and Methods and Com-positions for Treatment of Diseases Associated with AberrantMicrosatellite Expansion serves as a consultant for Isis Phar-maceuticals andBiogen Inc receives research support from IsisPharmaceuticals Biogen Inc and NIH and has receivedlicense fee paymentsroyalties from Isis Pharmaceuticals formodel of myotonic dystrophy B Udd serves as an associateexecutive Editor for Neuromuscular Disorders and receives re-search support from Finnish Academy the Sigrid JuseliusFoundation and the Jane and Aatos Erkko Foundation PFormaker reports no disclosures Full disclosure form in-formation provided by the authors is available with the full textof this article at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 10 2018 Accepted infinal form February 18 2019
Appendix Authors
Name Location Role Contribution
BenediktSchoser MD
Ludwig-Maximilians-UniversitatMunich Germany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
FedericaMontagneseMD
Friedrich-Baur-Institut MunichGermany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
GuillaumeBassez MDPhD
Institut deMyologie ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
BarbaraFossati MD
UO NeurologiaIRCCS PoliclinicoSan Donato MilanItaly
Author Data acquisitiondrafting andrevision of themanuscript
Josep GamezMD PhD
Vall drsquoHebronUniversity HospitalBarcelona Spain
Author Data acquisitiondraft and revisemanuscript
ChadHeatwoleMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
JamesHilbert MS
University ofRochesterRochester NY
Author Drafting andrevision of themanuscript
CorneliaKornblumMD
University Hospitalof Bonn BonnGermany
Author Data acquisitiondrafting and revisionof the manuscript
AnneKostera-PruszczykMD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondrafting andrevision of themanuscript
Ralf KrahePhD
University of TexasMD Andersoncancer center
Author Data acquisitiondrafting andrevision of themanuscript
AnnaLusakowskaMD PhD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondraft and revisemanuscript
GiovanniMeola MD
Department ofBiomedical Sciencesfor health Universityof Milan Milan Italy
Author Data acquisitiondrafting andrevision of themanuscript
RichardMoxley IIIMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
CharlesThorntonMD
University ofRochesterRochester NY
Author Data acquisitiondraft and revisemanuscript
Bjarne UddMD PhD
TampereUniversityTampere Finland
Author Data acquisitiondraft and revisemanuscript
PaulFormaker
MyotonicDystrophyFoundation SanFrancisco
CorrespondingAuthor
Obtaining fundingdrafting and reviewof the manuscriptstudy concept anddesign
348 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
The CCTG-expansion is extremely unstable It increases withage and shows marked heterogeneity in length within differenttissues of the same subject2 Unlike DM1 there is no clearcorrelation between the length of the CCTG expansion andclinical severity Symptoms in DM2 patients usually begin inthe third to fifth decades of life No congenital or infantile caseshave been reported Muscular symptoms are usually the majorcomplaints that cause patients to see a physician Howeverextramuscular manifestations such as cataracts may precedethe muscular complaints Muscle weakness andor myalgia arethe most common symptoms at onset whereas about40ndash50 of patients initially complain of myotoniamusclestiffness34 As the duration of DM2 increases many organs andsystems may be affected hence the patientrsquos managementshould include screening for heart diseases (cardiomyopathyarrhythmias) diabetes mellitusinsulin resistance thyroiddysfunctions cataract gastrointestinal disturbances respiratoryinvolvement mild cognitive disorders and tumors5ndash8 Symp-tom severity widely varies among patients even within mem-bers of the same family Age-dependent worsening of muscularsymptoms and an increase of the multi-systemic complicationshas been observed4
Because of the low diagnosed prevalence of DM2 patientsworldwide and the relatively recent discoveryof this disease thereis a lack of rigorous evidence regarding the care andmanagementof patients For this reason evidence-based guidelines cannotcurrently be developed Consensus-based clinical care recom-mendations can serve as a support and guide for clinicians notfamiliar with the heterogeneous nature of DM2 enabling qualitystandardized patient care for those living with DM2
MethodologyThe Myotonic Dystrophy Foundation (MDF) recruitedclinicians from the United States and Europe who have ex-perience in the treatment of patients with DM2 to developconsensus-based care recommendations
The project included a total working group of 15 clinicalprofessionals MDF provided project design developmentand management support A complete list of working groupmembers and authors is provided below
The principles of the single text procedureweremainly adoptedto steer the consensus-building process9 The single text pro-cedure employs the use of a single document as a starting pointto incorporate the input and contributions of stakeholders In
this approach stakeholders add subtract and refine a draft textthat becomes the foundation for a final ratified document
This consensus-building model was selected because it could beeffectivewithin the contextof the limited clinical caredata availablefor DM2 the clinical content already available and the com-plexities of working across a large international group of experts
Having already developed consensus-based care recom-mendations for DM110 and given the similarity of system in-volvement and management between DM1 and DM2 MDFcreated a draft document for DM2 based on DM1-consensuscare recommendations (for further methodological detailsrefer to the Consensus-based Care Recommendations forAdults with Myotonic Dystrophy Type 1 2018 myotonicorgclinical-resources)
MDF circulated the draft document toworking groupmemberswho read the draft content and provided their recom-mendations MDF aggregated all the revisions and suggestionsinto a single updated document Recommendations in conflictwere circulated within the group for discussion and resolvedthrough serial conference calls
These efforts led to the final consensus-based care recom-mendations and Quick Reference Guide for DM2 which werecompleted inmid-2018 TheQuick Reference Guide content isprovided as an appendix and the full document is availableonline (appendix e-1 linkslwwcomCPJA88) Both featureflowcharts and other infographics for ease of use
ResultsSee full recommendations at Neurologyorgcp
Life-threatening symptomsmdashClinicalcare recommendations Cardiovascular management
DM2-related cardiac pathophysiology although affect-ing all myocardial tissues preferentially targets thecardiac conduction system Conduction system defectsare progressive and although initially asymptomaticincrease the risk for symptomatic arrhythmias
DM2 has a later onset usually milder
phenotype and lacks the severe
congenital form seen in DM1
Consensus-based clinical care
recommendations can serve as
a support and guide for clinicians not
familiarwith theheterogeneousnature
of DM2 enabling quality standardized
patient care for those living with DM2
344 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
Significant cardiac involvement that subsequentlyleads to adverse cardiac events is often asymptomatic
At diagnosis check for cardiac symptoms performa 12-lead ECG and consider a 24-hour Holter ECG
Conduction abnormalities on a standard 12-lead ECGincluding sinus rate lt 50 beats per minute PR intervalgt 200 ms QRS duration gt 100 ms left anterior orposterior fascicular block abnormal Q-waves atrialtachycardia fibrillation or flutter and ventriculararrhythmias are indicative of cardiac involvement
Refer patients with cardiac symptoms abnormalannual 12-lead ECG indicative of cardiac involvementand patients older than 40 years without previouscardiac evaluation to a cardiologist for furtherevaluation
See Flowchart figure 1 in Quick Reference Guide(appendix linkslwwcomCPJA87)
See full recommendations at myotonicorgclinical-resources
Respiratory management Some DM2 patients have significant breathing
problems that can result from muscle weakness ofthe diaphragm abdominal and intercostal musclesand myotonia of these muscles leading to poorventilatory force and resulting in low blood oxygenand elevated blood carbon dioxide levels
Clinicians must look for respiratory symptoms inDM2 patients
In asymptomatic patients a pulmonary functionassessment every 2 years is recommended
Refer DM2 patients with respiratory symptoms in-cluding ineffective cough (normal peak expiratorycough flow rate is gt270 Lmin) respiratory in-sufficiency recurrent pulmonary infections prominentsnoring and maximal inspiratory pressure lt60 cmH2Oor forced vital capacity values of 50 less thanpredicted normal values to a pulmonologist knowl-edgeable in neuromuscular disorders
Vaccinate for pneumonia and flu treat respiratoryinfections quickly and use cough assistance andmechanical ventilation as needed along with obtainingconsultations from respiratory therapy and pulmonarymedicine groups
Some patients will eventually require nighttimeventilator support Most patients with chronic re-spiratory insufficiency respond to noninvasive venti-latory support (NIV)
For chronic respiratory insufficiency use supplemen-tal oxygen with caution and in conjunction with NIV
If surgery is planned reassess clearance capacity ifneeded possible adaptation to NIV or cough assistance
See Flowchart figure 2 in Quick Reference Guide(appendix linkslwwcomCPJA87)
See full recommendations at myotonicorgclinical-resources
Severe symptomsmdashClinicalcare recommendations Pain control
Muscle pain can occur in the neck back shoulders hipflexors and lower limbs Statin-induced myopathy isoften accompanied by muscle pain
Treat with conventional pain medications which maybe useful in treating the painful aspects of myotonicdystrophy (eg Ibuprofen)
Opioids can be used but should be avoided if possible Ifimplemented low doses should be used with closemonitoring for side effects (see Anesthesia and surgery)
Other remedies such as massage nerve blocks heatice or chiropractic can be used Some patients havereported that cannabis cannabinoids or phytocanna-binoids ease pain however this needs to be proven incontrolled clinical trials
Refer to Physical Therapy or Occupational Therapy ifconventional treatment is not successful
See full recommendations at myotonicorgclinical-resources
Skeletal muscle weakness and rehabilitationSkeletal muscle weakness and myalgia are major featuresof DM2 Initial weakness is in proximal hip girdle and neck
(flexors gt extensors) muscles Axial muscle weakness isfrequent in DM2 and may result in lower back pain
The progression is relatively slow 1ndash3 percent peryear
Mild ptosis might be occasionally present Calfhypertrophy may occur
Myalgia can be the most prominent clinical feature in theearly stages and may severely affect occupationalperformance
Impacts to employment and activities of daily livingoccur because of the proximal and axial muscleweakness (eg climbing stairs and standing up fromthe floor)
Treat with moderate- or low-intensity aerobic andresistance exercise orthoses or braces It is advised toobtain a cardiac evaluation before starting a new exerciseroutine
See full recommendations at myotonicorgclinical-resources
Skeletal muscle myotonia Myotoniamdasha sustained muscle contraction and diffi-
culty in relaxing musclesmdashmay occur and be symp-tomatic in DM2 patients
Myotonia can contribute to muscle stiffness painprolonged hand grip speech and swallowing difficultiesand gastrointestinal issues
Mexiletine may be considered in select patients formyotonia treatment of the hands with appropriatecardiac monitoring
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 345
See full recommendations at myotonicorgclinical-resources
Ocular symptoms Major and clinically relevant eye manifestations in DM2
can include the following cataracts eyelid ptosis andincomplete eyelid closure retinal changes and changes inintraocular pressure
Bilateral eyelid ptosis is a rare feature of DM2 but canoccur in some patients
See full recommendations at myotonicorgclinical-resources
Gastrointestinal symptoms Limited information is available and manifestations are
less severe than in DM1 Ask about problems with chewing swallowing
drooling reflux bloating abdominal pain bowelmovement frequency and characteristics diarrheaand incontinence
Physical examination should include abdominal pal-pation including around gall bladder and rectalexamination for anal sphincter spasm and dyssynergicdefecation for symptomatic patients
DM2 patients are at risk for pseudo-obstruction andexperience other problems that may cause actualobstruction of small or large intestine includingendometriosis acute gallbladder inflammation rup-tured ovarian cysts and sigmoid volvulus Monitorpotential obstructions to determine whether they arepseudo or actual and treat accordingly
Nonmedical interventions High-fiber diet for diarrhea or constipation increasewater intake
Nutritional supplement for weight loss weight gainor dysphagia
Dysphagia therapy referral for oral pharyngealdysphagia
Possible medical interventions Loperamide for diarrhea control Laxatives for constipation
First-line therapy Miralax Senna Ducosate orLinaclotid
Second-line therapy Bisacodyl Lubiprostone orLinaclotide Metoclopramide for gastroparesis pseudo-obstruction reflux
Antibiotics for bacterial overgrowth-induced diar-rhea (based on breath testing)
Enteral feeding only for recurring pneumonia orsevere dysphagia causing weight loss or causinginability to swallow safely without recurrentaspiration
Mexiletine may be considered to treat diarrhea orconstipation in DM2 however its use for theseindications requires further study
See full recommendations at myotonicorgclinical-resources
Neuropsychiatric symptoms Advise patients that DM2 is also a ldquobrain disorderrdquo that
can involve cognitive deficits and changes in cognitionover time
Include psychiatric and behavioral examination atbaseline and during regularly scheduled follow-upappointments or when symptoms appear
Refer patients with psychiatric or behavioral disordersand patients with cognitive complaints to a mentalhealth care professional for testing and follow-uppatients may have limited insight into these issuesmdashconsider input from partners and family members asappropriate
Treat with psychostimulants if apathy is associated withan impairing level of fatigue or excessive daytimesleepiness (EDS) (see Excessive daytime sleepiness) orantidepressant medication (cardiac examination beforestarting treatment including a 12-lead ECG)
See full recommendations at myotonicorgclinical-resources
Excessive Daytime Sleepiness symptoms EDS is very rare in DM2 but can be a life-altering
symptom In contrast fatigue is relatively common inDM2 and may be seriously disabling
Assess for EDS with Epworth Sleepiness Scale orsimilar standardized questionnaire instrument pre-scribe sleep study if sleep disturbance is suspected
Monitor periodic limb movements (muscle activityduring sleep) as well as EEG and respiratory measuresduring sleep study to assess possible obstructive sleepapnea and CNS-mediated sleep apnea
Refer to pulmonologist andor sleep specialist if EDSscores are positive on scales
Question patients regarding alcohol or caffeineconsumption medications and sleep habits forcontribution to EDS
Evaluate effect of possible respiratory muscle weakness(forced vital capacity value sitting and supine) onpresence of EDS
If nocturnal or daytime hypoventilation is suspectedconsider noninvasive positive pressure ventilationand refer to a pulmonologist with experience inneuromuscular diseases regarding possible need forNIV
Consider modafinil for treatment if coexisting CNSalteration is suspected as the cause for EDS
Consider cognitive behavioral therapy or behavioraltherapy for apathy also help treat fatigue psychostimu-lant treatment can be considered if apathy is associatedwith an impairing level of fatigue or EDS
See full recommendations at myotonicorgclinical-resources
346 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
Endocrine and metabolic symptoms Follow criteria from American Diabetes Association
regarding the type of initial testing to obtain typicallyfasting blood glucose or HbA1c and if symptomaticdiabetes is suspected
Consider formal glucose tolerance testing to monitorglucose control in patients request serial measure-ment of HbA1c and fasting plasma glucose annuallyand coordinate care with diabetes specialist asnecessary
Consider treating insulin resistance with lifestylechanges in diet and exercise
Measure liver and bilirubin levels at baseline andannually chronic liver enzyme elevation is typical anddoes not necessarily indicate the need for obtaininga liver biopsy
Request thyroid-stimulating hormone (TSH) andcirculating thyroid hormone (TSH and Free T4) leveltests at baseline and at least every 3 years morefrequently if indicated
Test for hyperlipidemia using serum blood lipidlevels at baseline and every 3 years more frequentlyif indicated Treat hyperlipidemia per currentpractice
Gender-specific recommendations Women Inquire about painful or irregular mensesovarian cysts endometriosis reproductive history
Men Inquire about erectile dysfunction considerfurther workup and medications to treat erectiledysfunction Consider possible cardiovascularrisksmdashside effects associated with some erectiledysfunction medications (over the counter andprescribed)
Inquire about infertility and family planning See full recommendations at myotonicorgclinical-
resources
Tumors Follow general population cancer screening guidelines
particularly for breast testicular cervical and coloncancer
Evaluate suspicious new CNS abdominopelvic andthyroid symptoms for possible cancer consider cancersof the brain uterus and ovary
See full recommendations at myotonicorgclinical-resources
Pregnancy and obstetric management The effects of DM2 on both smooth and striated
muscle can complicate pregnancy labor and deliveryand increase myotonia
Prenatal and preimplantation genetic diagnosis canallow for termination of the pregnancy or selectiveimplantation of unaffected embryos if desired
See full recommendations at myotonicorgclinical-resources
Surgery anesthesia and pain Although a higher incidence of adverse reactions to
medications used for anesthesia and analgesia has beenreported for DM1 (about 8) it is yet not clearwhether similar risks occur also in DM2 patientsHowever given this uncertainty and the potentiallyserious complications reported in some DM2 patientsour advice is to adopt similar anesthesia guidelines assuggested for DM1
See MDFrsquos Practical Suggestions for the AnestheticManagement of a Myotonic Dystrophy Patient (myo-tonicorgclinical-resources) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia
See full recommendations at myotonicorgclinical-resources
ConclusionsThese consensus-based care recommendations for patientswith DM2 are the product of an international group of ex-perienced clinicians They are intended to lead to more in-formed and prepared clinical professionals and more readilyavailable and high-quality care for affected families
AcknowledgmentThis project would not have been possible without the majorcommitment made by the 15 international professionalsinvolved in its development MDF team leads included PaulFormaker Leah Hellerstein and Molly White
Study fundingMyotonic Dystrophy Foundation
DisclosureB Schoser serves on the scientific advisory boards of andreceived funding for travel from Sanofi-Genzyme BiomarinAmicus Therapeutics and Audentes Therapeutics serves onthe editorial boards of Neuromuscular Disorders and Journal ofNeuromuscular Disorders and as a Section Editor for CurrentOpinion in Neurology F Montagnese served on a scientificadvisory board organized by Lupin Europe GmbH for theapproval of mexiletin for the treatment of myotonia G Bassezserves on the scientific advisory boards of Lupin pharma-ceuticals AFM-Telethon and Myotonic Dystrophy Founda-tion serves as a consultant for Lupin pharmaceuticals andreceives research support from FP7 EU AFM-Telethon andMyotonic dystrophy registry B Fossati and J Gamez reportno disclosures C Heatwole serves on the scientific advisoryboards of Biogen has received funding for travel from Myo-tonic Dystrophy Foundation serves as a consultant for Ime-decs Maximus Johns Hopkins University Biogen Atyr IonisAcceleron Cytokinetics ExpansionRX AMO and the Mari-gold Foundation receives research support from Pfizer
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 347
Technology Development Fund (University of Rochester)Cure Spinal Muscular Atrophy Amyotrophic Lateral SclerosisAssociation Huntington Study GroupNJ Cure HD Founda-tion NIH (NIAMS NINDS) and United States Food andDrug Administration has royalties for use of the MyotonicDystrophy Health Index (MDHI) a disease-specific patient-reported outcomemeasure for use in clinical trials and royaltiesfrom licensing instruments for FSHD congenital DM1 CMTSMA and Huntington disease and has participated in medi-colegal cases J Hilbert receives research support from BiogenNIH Abrams Family Fund FSH Society and Friends of FSHResearch C Kornblum has received funding for travel orspeaker honoraria from Sanofi-Genzyme Santhera NovartisStealth BioTherapeutics Deutsche Gesellschaft fur Musk-elkranke eV andMarigold Foundation Canada has served asa consultant for Stealth BioTherapeutics and receives researchsupport from Stealth Biotherapeutics BMBF (German FederalMinistry of Education and Research) mitoNET MarigoldFoundation Canada Deutsche Gesellschaft fur MuskelkrankeeV grant number Me41 since 2014 A Kostera-Pruszczykserves on the scientific advisory boards of Biogen PTC Sar-epta and Shire has received honoraria from Kedrion BaxterShire CSL Behring and Sanofi Aventis and serves on theeditorial board of Neurology Neurosurgery and Psychiatry RKrahe serves as an academic editor for PLoS One A Lusa-kowska and G Meola report no disclosures R Moxley IIIserves on the scientific advisory boards of NIHNINDS andMyotonic Dystrophy Foundation and receives research sup-port from Ionis NIH (NCRR NCI) FDA Saunders FamilyFoundation and Abrams Family Fund C Thornton serves onthe scientific advisory boards of the Myotonic DystrophyFoundation and Dyne and on the NIH data safety monitoringboard has received funding for travel from University ofFlorida University of Michigan American Association ofNeurology Muscular Dystrophy Association Myotonic Dys-trophy Foundation World Muscle Society Fulcrum Thera-peutics Dyne Therapeutics Lion Therapeutics and NatureConferences is an author on patents regarding Modulation ofDystrophia Myotonica-Protein Kinase (DMPK) ExpressionCompositions and Methods Related to Protein DisplacementTherapy for Myotonic Dystrophy and Methods and Com-positions for Treatment of Diseases Associated with AberrantMicrosatellite Expansion serves as a consultant for Isis Phar-maceuticals andBiogen Inc receives research support from IsisPharmaceuticals Biogen Inc and NIH and has receivedlicense fee paymentsroyalties from Isis Pharmaceuticals formodel of myotonic dystrophy B Udd serves as an associateexecutive Editor for Neuromuscular Disorders and receives re-search support from Finnish Academy the Sigrid JuseliusFoundation and the Jane and Aatos Erkko Foundation PFormaker reports no disclosures Full disclosure form in-formation provided by the authors is available with the full textof this article at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 10 2018 Accepted infinal form February 18 2019
Appendix Authors
Name Location Role Contribution
BenediktSchoser MD
Ludwig-Maximilians-UniversitatMunich Germany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
FedericaMontagneseMD
Friedrich-Baur-Institut MunichGermany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
GuillaumeBassez MDPhD
Institut deMyologie ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
BarbaraFossati MD
UO NeurologiaIRCCS PoliclinicoSan Donato MilanItaly
Author Data acquisitiondrafting andrevision of themanuscript
Josep GamezMD PhD
Vall drsquoHebronUniversity HospitalBarcelona Spain
Author Data acquisitiondraft and revisemanuscript
ChadHeatwoleMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
JamesHilbert MS
University ofRochesterRochester NY
Author Drafting andrevision of themanuscript
CorneliaKornblumMD
University Hospitalof Bonn BonnGermany
Author Data acquisitiondrafting and revisionof the manuscript
AnneKostera-PruszczykMD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondrafting andrevision of themanuscript
Ralf KrahePhD
University of TexasMD Andersoncancer center
Author Data acquisitiondrafting andrevision of themanuscript
AnnaLusakowskaMD PhD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondraft and revisemanuscript
GiovanniMeola MD
Department ofBiomedical Sciencesfor health Universityof Milan Milan Italy
Author Data acquisitiondrafting andrevision of themanuscript
RichardMoxley IIIMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
CharlesThorntonMD
University ofRochesterRochester NY
Author Data acquisitiondraft and revisemanuscript
Bjarne UddMD PhD
TampereUniversityTampere Finland
Author Data acquisitiondraft and revisemanuscript
PaulFormaker
MyotonicDystrophyFoundation SanFrancisco
CorrespondingAuthor
Obtaining fundingdrafting and reviewof the manuscriptstudy concept anddesign
348 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
Significant cardiac involvement that subsequentlyleads to adverse cardiac events is often asymptomatic
At diagnosis check for cardiac symptoms performa 12-lead ECG and consider a 24-hour Holter ECG
Conduction abnormalities on a standard 12-lead ECGincluding sinus rate lt 50 beats per minute PR intervalgt 200 ms QRS duration gt 100 ms left anterior orposterior fascicular block abnormal Q-waves atrialtachycardia fibrillation or flutter and ventriculararrhythmias are indicative of cardiac involvement
Refer patients with cardiac symptoms abnormalannual 12-lead ECG indicative of cardiac involvementand patients older than 40 years without previouscardiac evaluation to a cardiologist for furtherevaluation
See Flowchart figure 1 in Quick Reference Guide(appendix linkslwwcomCPJA87)
See full recommendations at myotonicorgclinical-resources
Respiratory management Some DM2 patients have significant breathing
problems that can result from muscle weakness ofthe diaphragm abdominal and intercostal musclesand myotonia of these muscles leading to poorventilatory force and resulting in low blood oxygenand elevated blood carbon dioxide levels
Clinicians must look for respiratory symptoms inDM2 patients
In asymptomatic patients a pulmonary functionassessment every 2 years is recommended
Refer DM2 patients with respiratory symptoms in-cluding ineffective cough (normal peak expiratorycough flow rate is gt270 Lmin) respiratory in-sufficiency recurrent pulmonary infections prominentsnoring and maximal inspiratory pressure lt60 cmH2Oor forced vital capacity values of 50 less thanpredicted normal values to a pulmonologist knowl-edgeable in neuromuscular disorders
Vaccinate for pneumonia and flu treat respiratoryinfections quickly and use cough assistance andmechanical ventilation as needed along with obtainingconsultations from respiratory therapy and pulmonarymedicine groups
Some patients will eventually require nighttimeventilator support Most patients with chronic re-spiratory insufficiency respond to noninvasive venti-latory support (NIV)
For chronic respiratory insufficiency use supplemen-tal oxygen with caution and in conjunction with NIV
If surgery is planned reassess clearance capacity ifneeded possible adaptation to NIV or cough assistance
See Flowchart figure 2 in Quick Reference Guide(appendix linkslwwcomCPJA87)
See full recommendations at myotonicorgclinical-resources
Severe symptomsmdashClinicalcare recommendations Pain control
Muscle pain can occur in the neck back shoulders hipflexors and lower limbs Statin-induced myopathy isoften accompanied by muscle pain
Treat with conventional pain medications which maybe useful in treating the painful aspects of myotonicdystrophy (eg Ibuprofen)
Opioids can be used but should be avoided if possible Ifimplemented low doses should be used with closemonitoring for side effects (see Anesthesia and surgery)
Other remedies such as massage nerve blocks heatice or chiropractic can be used Some patients havereported that cannabis cannabinoids or phytocanna-binoids ease pain however this needs to be proven incontrolled clinical trials
Refer to Physical Therapy or Occupational Therapy ifconventional treatment is not successful
See full recommendations at myotonicorgclinical-resources
Skeletal muscle weakness and rehabilitationSkeletal muscle weakness and myalgia are major featuresof DM2 Initial weakness is in proximal hip girdle and neck
(flexors gt extensors) muscles Axial muscle weakness isfrequent in DM2 and may result in lower back pain
The progression is relatively slow 1ndash3 percent peryear
Mild ptosis might be occasionally present Calfhypertrophy may occur
Myalgia can be the most prominent clinical feature in theearly stages and may severely affect occupationalperformance
Impacts to employment and activities of daily livingoccur because of the proximal and axial muscleweakness (eg climbing stairs and standing up fromthe floor)
Treat with moderate- or low-intensity aerobic andresistance exercise orthoses or braces It is advised toobtain a cardiac evaluation before starting a new exerciseroutine
See full recommendations at myotonicorgclinical-resources
Skeletal muscle myotonia Myotoniamdasha sustained muscle contraction and diffi-
culty in relaxing musclesmdashmay occur and be symp-tomatic in DM2 patients
Myotonia can contribute to muscle stiffness painprolonged hand grip speech and swallowing difficultiesand gastrointestinal issues
Mexiletine may be considered in select patients formyotonia treatment of the hands with appropriatecardiac monitoring
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 345
See full recommendations at myotonicorgclinical-resources
Ocular symptoms Major and clinically relevant eye manifestations in DM2
can include the following cataracts eyelid ptosis andincomplete eyelid closure retinal changes and changes inintraocular pressure
Bilateral eyelid ptosis is a rare feature of DM2 but canoccur in some patients
See full recommendations at myotonicorgclinical-resources
Gastrointestinal symptoms Limited information is available and manifestations are
less severe than in DM1 Ask about problems with chewing swallowing
drooling reflux bloating abdominal pain bowelmovement frequency and characteristics diarrheaand incontinence
Physical examination should include abdominal pal-pation including around gall bladder and rectalexamination for anal sphincter spasm and dyssynergicdefecation for symptomatic patients
DM2 patients are at risk for pseudo-obstruction andexperience other problems that may cause actualobstruction of small or large intestine includingendometriosis acute gallbladder inflammation rup-tured ovarian cysts and sigmoid volvulus Monitorpotential obstructions to determine whether they arepseudo or actual and treat accordingly
Nonmedical interventions High-fiber diet for diarrhea or constipation increasewater intake
Nutritional supplement for weight loss weight gainor dysphagia
Dysphagia therapy referral for oral pharyngealdysphagia
Possible medical interventions Loperamide for diarrhea control Laxatives for constipation
First-line therapy Miralax Senna Ducosate orLinaclotid
Second-line therapy Bisacodyl Lubiprostone orLinaclotide Metoclopramide for gastroparesis pseudo-obstruction reflux
Antibiotics for bacterial overgrowth-induced diar-rhea (based on breath testing)
Enteral feeding only for recurring pneumonia orsevere dysphagia causing weight loss or causinginability to swallow safely without recurrentaspiration
Mexiletine may be considered to treat diarrhea orconstipation in DM2 however its use for theseindications requires further study
See full recommendations at myotonicorgclinical-resources
Neuropsychiatric symptoms Advise patients that DM2 is also a ldquobrain disorderrdquo that
can involve cognitive deficits and changes in cognitionover time
Include psychiatric and behavioral examination atbaseline and during regularly scheduled follow-upappointments or when symptoms appear
Refer patients with psychiatric or behavioral disordersand patients with cognitive complaints to a mentalhealth care professional for testing and follow-uppatients may have limited insight into these issuesmdashconsider input from partners and family members asappropriate
Treat with psychostimulants if apathy is associated withan impairing level of fatigue or excessive daytimesleepiness (EDS) (see Excessive daytime sleepiness) orantidepressant medication (cardiac examination beforestarting treatment including a 12-lead ECG)
See full recommendations at myotonicorgclinical-resources
Excessive Daytime Sleepiness symptoms EDS is very rare in DM2 but can be a life-altering
symptom In contrast fatigue is relatively common inDM2 and may be seriously disabling
Assess for EDS with Epworth Sleepiness Scale orsimilar standardized questionnaire instrument pre-scribe sleep study if sleep disturbance is suspected
Monitor periodic limb movements (muscle activityduring sleep) as well as EEG and respiratory measuresduring sleep study to assess possible obstructive sleepapnea and CNS-mediated sleep apnea
Refer to pulmonologist andor sleep specialist if EDSscores are positive on scales
Question patients regarding alcohol or caffeineconsumption medications and sleep habits forcontribution to EDS
Evaluate effect of possible respiratory muscle weakness(forced vital capacity value sitting and supine) onpresence of EDS
If nocturnal or daytime hypoventilation is suspectedconsider noninvasive positive pressure ventilationand refer to a pulmonologist with experience inneuromuscular diseases regarding possible need forNIV
Consider modafinil for treatment if coexisting CNSalteration is suspected as the cause for EDS
Consider cognitive behavioral therapy or behavioraltherapy for apathy also help treat fatigue psychostimu-lant treatment can be considered if apathy is associatedwith an impairing level of fatigue or EDS
See full recommendations at myotonicorgclinical-resources
346 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
Endocrine and metabolic symptoms Follow criteria from American Diabetes Association
regarding the type of initial testing to obtain typicallyfasting blood glucose or HbA1c and if symptomaticdiabetes is suspected
Consider formal glucose tolerance testing to monitorglucose control in patients request serial measure-ment of HbA1c and fasting plasma glucose annuallyand coordinate care with diabetes specialist asnecessary
Consider treating insulin resistance with lifestylechanges in diet and exercise
Measure liver and bilirubin levels at baseline andannually chronic liver enzyme elevation is typical anddoes not necessarily indicate the need for obtaininga liver biopsy
Request thyroid-stimulating hormone (TSH) andcirculating thyroid hormone (TSH and Free T4) leveltests at baseline and at least every 3 years morefrequently if indicated
Test for hyperlipidemia using serum blood lipidlevels at baseline and every 3 years more frequentlyif indicated Treat hyperlipidemia per currentpractice
Gender-specific recommendations Women Inquire about painful or irregular mensesovarian cysts endometriosis reproductive history
Men Inquire about erectile dysfunction considerfurther workup and medications to treat erectiledysfunction Consider possible cardiovascularrisksmdashside effects associated with some erectiledysfunction medications (over the counter andprescribed)
Inquire about infertility and family planning See full recommendations at myotonicorgclinical-
resources
Tumors Follow general population cancer screening guidelines
particularly for breast testicular cervical and coloncancer
Evaluate suspicious new CNS abdominopelvic andthyroid symptoms for possible cancer consider cancersof the brain uterus and ovary
See full recommendations at myotonicorgclinical-resources
Pregnancy and obstetric management The effects of DM2 on both smooth and striated
muscle can complicate pregnancy labor and deliveryand increase myotonia
Prenatal and preimplantation genetic diagnosis canallow for termination of the pregnancy or selectiveimplantation of unaffected embryos if desired
See full recommendations at myotonicorgclinical-resources
Surgery anesthesia and pain Although a higher incidence of adverse reactions to
medications used for anesthesia and analgesia has beenreported for DM1 (about 8) it is yet not clearwhether similar risks occur also in DM2 patientsHowever given this uncertainty and the potentiallyserious complications reported in some DM2 patientsour advice is to adopt similar anesthesia guidelines assuggested for DM1
See MDFrsquos Practical Suggestions for the AnestheticManagement of a Myotonic Dystrophy Patient (myo-tonicorgclinical-resources) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia
See full recommendations at myotonicorgclinical-resources
ConclusionsThese consensus-based care recommendations for patientswith DM2 are the product of an international group of ex-perienced clinicians They are intended to lead to more in-formed and prepared clinical professionals and more readilyavailable and high-quality care for affected families
AcknowledgmentThis project would not have been possible without the majorcommitment made by the 15 international professionalsinvolved in its development MDF team leads included PaulFormaker Leah Hellerstein and Molly White
Study fundingMyotonic Dystrophy Foundation
DisclosureB Schoser serves on the scientific advisory boards of andreceived funding for travel from Sanofi-Genzyme BiomarinAmicus Therapeutics and Audentes Therapeutics serves onthe editorial boards of Neuromuscular Disorders and Journal ofNeuromuscular Disorders and as a Section Editor for CurrentOpinion in Neurology F Montagnese served on a scientificadvisory board organized by Lupin Europe GmbH for theapproval of mexiletin for the treatment of myotonia G Bassezserves on the scientific advisory boards of Lupin pharma-ceuticals AFM-Telethon and Myotonic Dystrophy Founda-tion serves as a consultant for Lupin pharmaceuticals andreceives research support from FP7 EU AFM-Telethon andMyotonic dystrophy registry B Fossati and J Gamez reportno disclosures C Heatwole serves on the scientific advisoryboards of Biogen has received funding for travel from Myo-tonic Dystrophy Foundation serves as a consultant for Ime-decs Maximus Johns Hopkins University Biogen Atyr IonisAcceleron Cytokinetics ExpansionRX AMO and the Mari-gold Foundation receives research support from Pfizer
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 347
Technology Development Fund (University of Rochester)Cure Spinal Muscular Atrophy Amyotrophic Lateral SclerosisAssociation Huntington Study GroupNJ Cure HD Founda-tion NIH (NIAMS NINDS) and United States Food andDrug Administration has royalties for use of the MyotonicDystrophy Health Index (MDHI) a disease-specific patient-reported outcomemeasure for use in clinical trials and royaltiesfrom licensing instruments for FSHD congenital DM1 CMTSMA and Huntington disease and has participated in medi-colegal cases J Hilbert receives research support from BiogenNIH Abrams Family Fund FSH Society and Friends of FSHResearch C Kornblum has received funding for travel orspeaker honoraria from Sanofi-Genzyme Santhera NovartisStealth BioTherapeutics Deutsche Gesellschaft fur Musk-elkranke eV andMarigold Foundation Canada has served asa consultant for Stealth BioTherapeutics and receives researchsupport from Stealth Biotherapeutics BMBF (German FederalMinistry of Education and Research) mitoNET MarigoldFoundation Canada Deutsche Gesellschaft fur MuskelkrankeeV grant number Me41 since 2014 A Kostera-Pruszczykserves on the scientific advisory boards of Biogen PTC Sar-epta and Shire has received honoraria from Kedrion BaxterShire CSL Behring and Sanofi Aventis and serves on theeditorial board of Neurology Neurosurgery and Psychiatry RKrahe serves as an academic editor for PLoS One A Lusa-kowska and G Meola report no disclosures R Moxley IIIserves on the scientific advisory boards of NIHNINDS andMyotonic Dystrophy Foundation and receives research sup-port from Ionis NIH (NCRR NCI) FDA Saunders FamilyFoundation and Abrams Family Fund C Thornton serves onthe scientific advisory boards of the Myotonic DystrophyFoundation and Dyne and on the NIH data safety monitoringboard has received funding for travel from University ofFlorida University of Michigan American Association ofNeurology Muscular Dystrophy Association Myotonic Dys-trophy Foundation World Muscle Society Fulcrum Thera-peutics Dyne Therapeutics Lion Therapeutics and NatureConferences is an author on patents regarding Modulation ofDystrophia Myotonica-Protein Kinase (DMPK) ExpressionCompositions and Methods Related to Protein DisplacementTherapy for Myotonic Dystrophy and Methods and Com-positions for Treatment of Diseases Associated with AberrantMicrosatellite Expansion serves as a consultant for Isis Phar-maceuticals andBiogen Inc receives research support from IsisPharmaceuticals Biogen Inc and NIH and has receivedlicense fee paymentsroyalties from Isis Pharmaceuticals formodel of myotonic dystrophy B Udd serves as an associateexecutive Editor for Neuromuscular Disorders and receives re-search support from Finnish Academy the Sigrid JuseliusFoundation and the Jane and Aatos Erkko Foundation PFormaker reports no disclosures Full disclosure form in-formation provided by the authors is available with the full textof this article at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 10 2018 Accepted infinal form February 18 2019
Appendix Authors
Name Location Role Contribution
BenediktSchoser MD
Ludwig-Maximilians-UniversitatMunich Germany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
FedericaMontagneseMD
Friedrich-Baur-Institut MunichGermany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
GuillaumeBassez MDPhD
Institut deMyologie ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
BarbaraFossati MD
UO NeurologiaIRCCS PoliclinicoSan Donato MilanItaly
Author Data acquisitiondrafting andrevision of themanuscript
Josep GamezMD PhD
Vall drsquoHebronUniversity HospitalBarcelona Spain
Author Data acquisitiondraft and revisemanuscript
ChadHeatwoleMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
JamesHilbert MS
University ofRochesterRochester NY
Author Drafting andrevision of themanuscript
CorneliaKornblumMD
University Hospitalof Bonn BonnGermany
Author Data acquisitiondrafting and revisionof the manuscript
AnneKostera-PruszczykMD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondrafting andrevision of themanuscript
Ralf KrahePhD
University of TexasMD Andersoncancer center
Author Data acquisitiondrafting andrevision of themanuscript
AnnaLusakowskaMD PhD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondraft and revisemanuscript
GiovanniMeola MD
Department ofBiomedical Sciencesfor health Universityof Milan Milan Italy
Author Data acquisitiondrafting andrevision of themanuscript
RichardMoxley IIIMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
CharlesThorntonMD
University ofRochesterRochester NY
Author Data acquisitiondraft and revisemanuscript
Bjarne UddMD PhD
TampereUniversityTampere Finland
Author Data acquisitiondraft and revisemanuscript
PaulFormaker
MyotonicDystrophyFoundation SanFrancisco
CorrespondingAuthor
Obtaining fundingdrafting and reviewof the manuscriptstudy concept anddesign
348 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
See full recommendations at myotonicorgclinical-resources
Ocular symptoms Major and clinically relevant eye manifestations in DM2
can include the following cataracts eyelid ptosis andincomplete eyelid closure retinal changes and changes inintraocular pressure
Bilateral eyelid ptosis is a rare feature of DM2 but canoccur in some patients
See full recommendations at myotonicorgclinical-resources
Gastrointestinal symptoms Limited information is available and manifestations are
less severe than in DM1 Ask about problems with chewing swallowing
drooling reflux bloating abdominal pain bowelmovement frequency and characteristics diarrheaand incontinence
Physical examination should include abdominal pal-pation including around gall bladder and rectalexamination for anal sphincter spasm and dyssynergicdefecation for symptomatic patients
DM2 patients are at risk for pseudo-obstruction andexperience other problems that may cause actualobstruction of small or large intestine includingendometriosis acute gallbladder inflammation rup-tured ovarian cysts and sigmoid volvulus Monitorpotential obstructions to determine whether they arepseudo or actual and treat accordingly
Nonmedical interventions High-fiber diet for diarrhea or constipation increasewater intake
Nutritional supplement for weight loss weight gainor dysphagia
Dysphagia therapy referral for oral pharyngealdysphagia
Possible medical interventions Loperamide for diarrhea control Laxatives for constipation
First-line therapy Miralax Senna Ducosate orLinaclotid
Second-line therapy Bisacodyl Lubiprostone orLinaclotide Metoclopramide for gastroparesis pseudo-obstruction reflux
Antibiotics for bacterial overgrowth-induced diar-rhea (based on breath testing)
Enteral feeding only for recurring pneumonia orsevere dysphagia causing weight loss or causinginability to swallow safely without recurrentaspiration
Mexiletine may be considered to treat diarrhea orconstipation in DM2 however its use for theseindications requires further study
See full recommendations at myotonicorgclinical-resources
Neuropsychiatric symptoms Advise patients that DM2 is also a ldquobrain disorderrdquo that
can involve cognitive deficits and changes in cognitionover time
Include psychiatric and behavioral examination atbaseline and during regularly scheduled follow-upappointments or when symptoms appear
Refer patients with psychiatric or behavioral disordersand patients with cognitive complaints to a mentalhealth care professional for testing and follow-uppatients may have limited insight into these issuesmdashconsider input from partners and family members asappropriate
Treat with psychostimulants if apathy is associated withan impairing level of fatigue or excessive daytimesleepiness (EDS) (see Excessive daytime sleepiness) orantidepressant medication (cardiac examination beforestarting treatment including a 12-lead ECG)
See full recommendations at myotonicorgclinical-resources
Excessive Daytime Sleepiness symptoms EDS is very rare in DM2 but can be a life-altering
symptom In contrast fatigue is relatively common inDM2 and may be seriously disabling
Assess for EDS with Epworth Sleepiness Scale orsimilar standardized questionnaire instrument pre-scribe sleep study if sleep disturbance is suspected
Monitor periodic limb movements (muscle activityduring sleep) as well as EEG and respiratory measuresduring sleep study to assess possible obstructive sleepapnea and CNS-mediated sleep apnea
Refer to pulmonologist andor sleep specialist if EDSscores are positive on scales
Question patients regarding alcohol or caffeineconsumption medications and sleep habits forcontribution to EDS
Evaluate effect of possible respiratory muscle weakness(forced vital capacity value sitting and supine) onpresence of EDS
If nocturnal or daytime hypoventilation is suspectedconsider noninvasive positive pressure ventilationand refer to a pulmonologist with experience inneuromuscular diseases regarding possible need forNIV
Consider modafinil for treatment if coexisting CNSalteration is suspected as the cause for EDS
Consider cognitive behavioral therapy or behavioraltherapy for apathy also help treat fatigue psychostimu-lant treatment can be considered if apathy is associatedwith an impairing level of fatigue or EDS
See full recommendations at myotonicorgclinical-resources
346 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
Endocrine and metabolic symptoms Follow criteria from American Diabetes Association
regarding the type of initial testing to obtain typicallyfasting blood glucose or HbA1c and if symptomaticdiabetes is suspected
Consider formal glucose tolerance testing to monitorglucose control in patients request serial measure-ment of HbA1c and fasting plasma glucose annuallyand coordinate care with diabetes specialist asnecessary
Consider treating insulin resistance with lifestylechanges in diet and exercise
Measure liver and bilirubin levels at baseline andannually chronic liver enzyme elevation is typical anddoes not necessarily indicate the need for obtaininga liver biopsy
Request thyroid-stimulating hormone (TSH) andcirculating thyroid hormone (TSH and Free T4) leveltests at baseline and at least every 3 years morefrequently if indicated
Test for hyperlipidemia using serum blood lipidlevels at baseline and every 3 years more frequentlyif indicated Treat hyperlipidemia per currentpractice
Gender-specific recommendations Women Inquire about painful or irregular mensesovarian cysts endometriosis reproductive history
Men Inquire about erectile dysfunction considerfurther workup and medications to treat erectiledysfunction Consider possible cardiovascularrisksmdashside effects associated with some erectiledysfunction medications (over the counter andprescribed)
Inquire about infertility and family planning See full recommendations at myotonicorgclinical-
resources
Tumors Follow general population cancer screening guidelines
particularly for breast testicular cervical and coloncancer
Evaluate suspicious new CNS abdominopelvic andthyroid symptoms for possible cancer consider cancersof the brain uterus and ovary
See full recommendations at myotonicorgclinical-resources
Pregnancy and obstetric management The effects of DM2 on both smooth and striated
muscle can complicate pregnancy labor and deliveryand increase myotonia
Prenatal and preimplantation genetic diagnosis canallow for termination of the pregnancy or selectiveimplantation of unaffected embryos if desired
See full recommendations at myotonicorgclinical-resources
Surgery anesthesia and pain Although a higher incidence of adverse reactions to
medications used for anesthesia and analgesia has beenreported for DM1 (about 8) it is yet not clearwhether similar risks occur also in DM2 patientsHowever given this uncertainty and the potentiallyserious complications reported in some DM2 patientsour advice is to adopt similar anesthesia guidelines assuggested for DM1
See MDFrsquos Practical Suggestions for the AnestheticManagement of a Myotonic Dystrophy Patient (myo-tonicorgclinical-resources) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia
See full recommendations at myotonicorgclinical-resources
ConclusionsThese consensus-based care recommendations for patientswith DM2 are the product of an international group of ex-perienced clinicians They are intended to lead to more in-formed and prepared clinical professionals and more readilyavailable and high-quality care for affected families
AcknowledgmentThis project would not have been possible without the majorcommitment made by the 15 international professionalsinvolved in its development MDF team leads included PaulFormaker Leah Hellerstein and Molly White
Study fundingMyotonic Dystrophy Foundation
DisclosureB Schoser serves on the scientific advisory boards of andreceived funding for travel from Sanofi-Genzyme BiomarinAmicus Therapeutics and Audentes Therapeutics serves onthe editorial boards of Neuromuscular Disorders and Journal ofNeuromuscular Disorders and as a Section Editor for CurrentOpinion in Neurology F Montagnese served on a scientificadvisory board organized by Lupin Europe GmbH for theapproval of mexiletin for the treatment of myotonia G Bassezserves on the scientific advisory boards of Lupin pharma-ceuticals AFM-Telethon and Myotonic Dystrophy Founda-tion serves as a consultant for Lupin pharmaceuticals andreceives research support from FP7 EU AFM-Telethon andMyotonic dystrophy registry B Fossati and J Gamez reportno disclosures C Heatwole serves on the scientific advisoryboards of Biogen has received funding for travel from Myo-tonic Dystrophy Foundation serves as a consultant for Ime-decs Maximus Johns Hopkins University Biogen Atyr IonisAcceleron Cytokinetics ExpansionRX AMO and the Mari-gold Foundation receives research support from Pfizer
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 347
Technology Development Fund (University of Rochester)Cure Spinal Muscular Atrophy Amyotrophic Lateral SclerosisAssociation Huntington Study GroupNJ Cure HD Founda-tion NIH (NIAMS NINDS) and United States Food andDrug Administration has royalties for use of the MyotonicDystrophy Health Index (MDHI) a disease-specific patient-reported outcomemeasure for use in clinical trials and royaltiesfrom licensing instruments for FSHD congenital DM1 CMTSMA and Huntington disease and has participated in medi-colegal cases J Hilbert receives research support from BiogenNIH Abrams Family Fund FSH Society and Friends of FSHResearch C Kornblum has received funding for travel orspeaker honoraria from Sanofi-Genzyme Santhera NovartisStealth BioTherapeutics Deutsche Gesellschaft fur Musk-elkranke eV andMarigold Foundation Canada has served asa consultant for Stealth BioTherapeutics and receives researchsupport from Stealth Biotherapeutics BMBF (German FederalMinistry of Education and Research) mitoNET MarigoldFoundation Canada Deutsche Gesellschaft fur MuskelkrankeeV grant number Me41 since 2014 A Kostera-Pruszczykserves on the scientific advisory boards of Biogen PTC Sar-epta and Shire has received honoraria from Kedrion BaxterShire CSL Behring and Sanofi Aventis and serves on theeditorial board of Neurology Neurosurgery and Psychiatry RKrahe serves as an academic editor for PLoS One A Lusa-kowska and G Meola report no disclosures R Moxley IIIserves on the scientific advisory boards of NIHNINDS andMyotonic Dystrophy Foundation and receives research sup-port from Ionis NIH (NCRR NCI) FDA Saunders FamilyFoundation and Abrams Family Fund C Thornton serves onthe scientific advisory boards of the Myotonic DystrophyFoundation and Dyne and on the NIH data safety monitoringboard has received funding for travel from University ofFlorida University of Michigan American Association ofNeurology Muscular Dystrophy Association Myotonic Dys-trophy Foundation World Muscle Society Fulcrum Thera-peutics Dyne Therapeutics Lion Therapeutics and NatureConferences is an author on patents regarding Modulation ofDystrophia Myotonica-Protein Kinase (DMPK) ExpressionCompositions and Methods Related to Protein DisplacementTherapy for Myotonic Dystrophy and Methods and Com-positions for Treatment of Diseases Associated with AberrantMicrosatellite Expansion serves as a consultant for Isis Phar-maceuticals andBiogen Inc receives research support from IsisPharmaceuticals Biogen Inc and NIH and has receivedlicense fee paymentsroyalties from Isis Pharmaceuticals formodel of myotonic dystrophy B Udd serves as an associateexecutive Editor for Neuromuscular Disorders and receives re-search support from Finnish Academy the Sigrid JuseliusFoundation and the Jane and Aatos Erkko Foundation PFormaker reports no disclosures Full disclosure form in-formation provided by the authors is available with the full textof this article at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 10 2018 Accepted infinal form February 18 2019
Appendix Authors
Name Location Role Contribution
BenediktSchoser MD
Ludwig-Maximilians-UniversitatMunich Germany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
FedericaMontagneseMD
Friedrich-Baur-Institut MunichGermany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
GuillaumeBassez MDPhD
Institut deMyologie ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
BarbaraFossati MD
UO NeurologiaIRCCS PoliclinicoSan Donato MilanItaly
Author Data acquisitiondrafting andrevision of themanuscript
Josep GamezMD PhD
Vall drsquoHebronUniversity HospitalBarcelona Spain
Author Data acquisitiondraft and revisemanuscript
ChadHeatwoleMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
JamesHilbert MS
University ofRochesterRochester NY
Author Drafting andrevision of themanuscript
CorneliaKornblumMD
University Hospitalof Bonn BonnGermany
Author Data acquisitiondrafting and revisionof the manuscript
AnneKostera-PruszczykMD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondrafting andrevision of themanuscript
Ralf KrahePhD
University of TexasMD Andersoncancer center
Author Data acquisitiondrafting andrevision of themanuscript
AnnaLusakowskaMD PhD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondraft and revisemanuscript
GiovanniMeola MD
Department ofBiomedical Sciencesfor health Universityof Milan Milan Italy
Author Data acquisitiondrafting andrevision of themanuscript
RichardMoxley IIIMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
CharlesThorntonMD
University ofRochesterRochester NY
Author Data acquisitiondraft and revisemanuscript
Bjarne UddMD PhD
TampereUniversityTampere Finland
Author Data acquisitiondraft and revisemanuscript
PaulFormaker
MyotonicDystrophyFoundation SanFrancisco
CorrespondingAuthor
Obtaining fundingdrafting and reviewof the manuscriptstudy concept anddesign
348 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
Endocrine and metabolic symptoms Follow criteria from American Diabetes Association
regarding the type of initial testing to obtain typicallyfasting blood glucose or HbA1c and if symptomaticdiabetes is suspected
Consider formal glucose tolerance testing to monitorglucose control in patients request serial measure-ment of HbA1c and fasting plasma glucose annuallyand coordinate care with diabetes specialist asnecessary
Consider treating insulin resistance with lifestylechanges in diet and exercise
Measure liver and bilirubin levels at baseline andannually chronic liver enzyme elevation is typical anddoes not necessarily indicate the need for obtaininga liver biopsy
Request thyroid-stimulating hormone (TSH) andcirculating thyroid hormone (TSH and Free T4) leveltests at baseline and at least every 3 years morefrequently if indicated
Test for hyperlipidemia using serum blood lipidlevels at baseline and every 3 years more frequentlyif indicated Treat hyperlipidemia per currentpractice
Gender-specific recommendations Women Inquire about painful or irregular mensesovarian cysts endometriosis reproductive history
Men Inquire about erectile dysfunction considerfurther workup and medications to treat erectiledysfunction Consider possible cardiovascularrisksmdashside effects associated with some erectiledysfunction medications (over the counter andprescribed)
Inquire about infertility and family planning See full recommendations at myotonicorgclinical-
resources
Tumors Follow general population cancer screening guidelines
particularly for breast testicular cervical and coloncancer
Evaluate suspicious new CNS abdominopelvic andthyroid symptoms for possible cancer consider cancersof the brain uterus and ovary
See full recommendations at myotonicorgclinical-resources
Pregnancy and obstetric management The effects of DM2 on both smooth and striated
muscle can complicate pregnancy labor and deliveryand increase myotonia
Prenatal and preimplantation genetic diagnosis canallow for termination of the pregnancy or selectiveimplantation of unaffected embryos if desired
See full recommendations at myotonicorgclinical-resources
Surgery anesthesia and pain Although a higher incidence of adverse reactions to
medications used for anesthesia and analgesia has beenreported for DM1 (about 8) it is yet not clearwhether similar risks occur also in DM2 patientsHowever given this uncertainty and the potentiallyserious complications reported in some DM2 patientsour advice is to adopt similar anesthesia guidelines assuggested for DM1
See MDFrsquos Practical Suggestions for the AnestheticManagement of a Myotonic Dystrophy Patient (myo-tonicorgclinical-resources) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia
See full recommendations at myotonicorgclinical-resources
ConclusionsThese consensus-based care recommendations for patientswith DM2 are the product of an international group of ex-perienced clinicians They are intended to lead to more in-formed and prepared clinical professionals and more readilyavailable and high-quality care for affected families
AcknowledgmentThis project would not have been possible without the majorcommitment made by the 15 international professionalsinvolved in its development MDF team leads included PaulFormaker Leah Hellerstein and Molly White
Study fundingMyotonic Dystrophy Foundation
DisclosureB Schoser serves on the scientific advisory boards of andreceived funding for travel from Sanofi-Genzyme BiomarinAmicus Therapeutics and Audentes Therapeutics serves onthe editorial boards of Neuromuscular Disorders and Journal ofNeuromuscular Disorders and as a Section Editor for CurrentOpinion in Neurology F Montagnese served on a scientificadvisory board organized by Lupin Europe GmbH for theapproval of mexiletin for the treatment of myotonia G Bassezserves on the scientific advisory boards of Lupin pharma-ceuticals AFM-Telethon and Myotonic Dystrophy Founda-tion serves as a consultant for Lupin pharmaceuticals andreceives research support from FP7 EU AFM-Telethon andMyotonic dystrophy registry B Fossati and J Gamez reportno disclosures C Heatwole serves on the scientific advisoryboards of Biogen has received funding for travel from Myo-tonic Dystrophy Foundation serves as a consultant for Ime-decs Maximus Johns Hopkins University Biogen Atyr IonisAcceleron Cytokinetics ExpansionRX AMO and the Mari-gold Foundation receives research support from Pfizer
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 347
Technology Development Fund (University of Rochester)Cure Spinal Muscular Atrophy Amyotrophic Lateral SclerosisAssociation Huntington Study GroupNJ Cure HD Founda-tion NIH (NIAMS NINDS) and United States Food andDrug Administration has royalties for use of the MyotonicDystrophy Health Index (MDHI) a disease-specific patient-reported outcomemeasure for use in clinical trials and royaltiesfrom licensing instruments for FSHD congenital DM1 CMTSMA and Huntington disease and has participated in medi-colegal cases J Hilbert receives research support from BiogenNIH Abrams Family Fund FSH Society and Friends of FSHResearch C Kornblum has received funding for travel orspeaker honoraria from Sanofi-Genzyme Santhera NovartisStealth BioTherapeutics Deutsche Gesellschaft fur Musk-elkranke eV andMarigold Foundation Canada has served asa consultant for Stealth BioTherapeutics and receives researchsupport from Stealth Biotherapeutics BMBF (German FederalMinistry of Education and Research) mitoNET MarigoldFoundation Canada Deutsche Gesellschaft fur MuskelkrankeeV grant number Me41 since 2014 A Kostera-Pruszczykserves on the scientific advisory boards of Biogen PTC Sar-epta and Shire has received honoraria from Kedrion BaxterShire CSL Behring and Sanofi Aventis and serves on theeditorial board of Neurology Neurosurgery and Psychiatry RKrahe serves as an academic editor for PLoS One A Lusa-kowska and G Meola report no disclosures R Moxley IIIserves on the scientific advisory boards of NIHNINDS andMyotonic Dystrophy Foundation and receives research sup-port from Ionis NIH (NCRR NCI) FDA Saunders FamilyFoundation and Abrams Family Fund C Thornton serves onthe scientific advisory boards of the Myotonic DystrophyFoundation and Dyne and on the NIH data safety monitoringboard has received funding for travel from University ofFlorida University of Michigan American Association ofNeurology Muscular Dystrophy Association Myotonic Dys-trophy Foundation World Muscle Society Fulcrum Thera-peutics Dyne Therapeutics Lion Therapeutics and NatureConferences is an author on patents regarding Modulation ofDystrophia Myotonica-Protein Kinase (DMPK) ExpressionCompositions and Methods Related to Protein DisplacementTherapy for Myotonic Dystrophy and Methods and Com-positions for Treatment of Diseases Associated with AberrantMicrosatellite Expansion serves as a consultant for Isis Phar-maceuticals andBiogen Inc receives research support from IsisPharmaceuticals Biogen Inc and NIH and has receivedlicense fee paymentsroyalties from Isis Pharmaceuticals formodel of myotonic dystrophy B Udd serves as an associateexecutive Editor for Neuromuscular Disorders and receives re-search support from Finnish Academy the Sigrid JuseliusFoundation and the Jane and Aatos Erkko Foundation PFormaker reports no disclosures Full disclosure form in-formation provided by the authors is available with the full textof this article at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 10 2018 Accepted infinal form February 18 2019
Appendix Authors
Name Location Role Contribution
BenediktSchoser MD
Ludwig-Maximilians-UniversitatMunich Germany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
FedericaMontagneseMD
Friedrich-Baur-Institut MunichGermany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
GuillaumeBassez MDPhD
Institut deMyologie ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
BarbaraFossati MD
UO NeurologiaIRCCS PoliclinicoSan Donato MilanItaly
Author Data acquisitiondrafting andrevision of themanuscript
Josep GamezMD PhD
Vall drsquoHebronUniversity HospitalBarcelona Spain
Author Data acquisitiondraft and revisemanuscript
ChadHeatwoleMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
JamesHilbert MS
University ofRochesterRochester NY
Author Drafting andrevision of themanuscript
CorneliaKornblumMD
University Hospitalof Bonn BonnGermany
Author Data acquisitiondrafting and revisionof the manuscript
AnneKostera-PruszczykMD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondrafting andrevision of themanuscript
Ralf KrahePhD
University of TexasMD Andersoncancer center
Author Data acquisitiondrafting andrevision of themanuscript
AnnaLusakowskaMD PhD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondraft and revisemanuscript
GiovanniMeola MD
Department ofBiomedical Sciencesfor health Universityof Milan Milan Italy
Author Data acquisitiondrafting andrevision of themanuscript
RichardMoxley IIIMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
CharlesThorntonMD
University ofRochesterRochester NY
Author Data acquisitiondraft and revisemanuscript
Bjarne UddMD PhD
TampereUniversityTampere Finland
Author Data acquisitiondraft and revisemanuscript
PaulFormaker
MyotonicDystrophyFoundation SanFrancisco
CorrespondingAuthor
Obtaining fundingdrafting and reviewof the manuscriptstudy concept anddesign
348 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
Technology Development Fund (University of Rochester)Cure Spinal Muscular Atrophy Amyotrophic Lateral SclerosisAssociation Huntington Study GroupNJ Cure HD Founda-tion NIH (NIAMS NINDS) and United States Food andDrug Administration has royalties for use of the MyotonicDystrophy Health Index (MDHI) a disease-specific patient-reported outcomemeasure for use in clinical trials and royaltiesfrom licensing instruments for FSHD congenital DM1 CMTSMA and Huntington disease and has participated in medi-colegal cases J Hilbert receives research support from BiogenNIH Abrams Family Fund FSH Society and Friends of FSHResearch C Kornblum has received funding for travel orspeaker honoraria from Sanofi-Genzyme Santhera NovartisStealth BioTherapeutics Deutsche Gesellschaft fur Musk-elkranke eV andMarigold Foundation Canada has served asa consultant for Stealth BioTherapeutics and receives researchsupport from Stealth Biotherapeutics BMBF (German FederalMinistry of Education and Research) mitoNET MarigoldFoundation Canada Deutsche Gesellschaft fur MuskelkrankeeV grant number Me41 since 2014 A Kostera-Pruszczykserves on the scientific advisory boards of Biogen PTC Sar-epta and Shire has received honoraria from Kedrion BaxterShire CSL Behring and Sanofi Aventis and serves on theeditorial board of Neurology Neurosurgery and Psychiatry RKrahe serves as an academic editor for PLoS One A Lusa-kowska and G Meola report no disclosures R Moxley IIIserves on the scientific advisory boards of NIHNINDS andMyotonic Dystrophy Foundation and receives research sup-port from Ionis NIH (NCRR NCI) FDA Saunders FamilyFoundation and Abrams Family Fund C Thornton serves onthe scientific advisory boards of the Myotonic DystrophyFoundation and Dyne and on the NIH data safety monitoringboard has received funding for travel from University ofFlorida University of Michigan American Association ofNeurology Muscular Dystrophy Association Myotonic Dys-trophy Foundation World Muscle Society Fulcrum Thera-peutics Dyne Therapeutics Lion Therapeutics and NatureConferences is an author on patents regarding Modulation ofDystrophia Myotonica-Protein Kinase (DMPK) ExpressionCompositions and Methods Related to Protein DisplacementTherapy for Myotonic Dystrophy and Methods and Com-positions for Treatment of Diseases Associated with AberrantMicrosatellite Expansion serves as a consultant for Isis Phar-maceuticals andBiogen Inc receives research support from IsisPharmaceuticals Biogen Inc and NIH and has receivedlicense fee paymentsroyalties from Isis Pharmaceuticals formodel of myotonic dystrophy B Udd serves as an associateexecutive Editor for Neuromuscular Disorders and receives re-search support from Finnish Academy the Sigrid JuseliusFoundation and the Jane and Aatos Erkko Foundation PFormaker reports no disclosures Full disclosure form in-formation provided by the authors is available with the full textof this article at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 10 2018 Accepted infinal form February 18 2019
Appendix Authors
Name Location Role Contribution
BenediktSchoser MD
Ludwig-Maximilians-UniversitatMunich Germany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
FedericaMontagneseMD
Friedrich-Baur-Institut MunichGermany
Author Data acquisitiondrafting and revisionof the manuscriptpublication of draftand revision
GuillaumeBassez MDPhD
Institut deMyologie ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
BarbaraFossati MD
UO NeurologiaIRCCS PoliclinicoSan Donato MilanItaly
Author Data acquisitiondrafting andrevision of themanuscript
Josep GamezMD PhD
Vall drsquoHebronUniversity HospitalBarcelona Spain
Author Data acquisitiondraft and revisemanuscript
ChadHeatwoleMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
JamesHilbert MS
University ofRochesterRochester NY
Author Drafting andrevision of themanuscript
CorneliaKornblumMD
University Hospitalof Bonn BonnGermany
Author Data acquisitiondrafting and revisionof the manuscript
AnneKostera-PruszczykMD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondrafting andrevision of themanuscript
Ralf KrahePhD
University of TexasMD Andersoncancer center
Author Data acquisitiondrafting andrevision of themanuscript
AnnaLusakowskaMD PhD
Medical Universityof WarsawWarsaw Poland
Author Data acquisitiondraft and revisemanuscript
GiovanniMeola MD
Department ofBiomedical Sciencesfor health Universityof Milan Milan Italy
Author Data acquisitiondrafting andrevision of themanuscript
RichardMoxley IIIMD
University ofRochesterRochester NY
Author Data acquisitiondrafting andrevision of themanuscript
CharlesThorntonMD
University ofRochesterRochester NY
Author Data acquisitiondraft and revisemanuscript
Bjarne UddMD PhD
TampereUniversityTampere Finland
Author Data acquisitiondraft and revisemanuscript
PaulFormaker
MyotonicDystrophyFoundation SanFrancisco
CorrespondingAuthor
Obtaining fundingdrafting and reviewof the manuscriptstudy concept anddesign
348 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 349
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
350 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 351
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
352 Neurology Clinical Practice | Volume 9 Number 4 | August 2019 NeurologyorgCP
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
References1 Liquori CL Ricker K Moseley ML et al Myotonic dystrophy type 2 caused by
a CCTG expansion in intron 1 of ZNF9 Science 2001293864ndash8672 Udd B Meola G Krahe R et al Report of the 115th ENMC workshop DM2
PROMM and other myotonic dystrophies 3rd Workshop 14ndash16 February 2003Naarden The Netherlands Neuromuscul Disord 200313589ndash596
3 Day JW Ricker K Jacobsen JF et al Myotonic dystrophy type 2 molecular di-agnostic and clinical spectrum Neurology 200360657ndash664
4 Montagnese FMondello SWenninger S KressW Schoser B Assessing the influenceof age and gender on the phenotype of myotonic dystrophy type 2 J Neurol 20172642472ndash2480
5 Meola G Sansone V Perani D et al Executive dysfunction and avoidant personalitytrait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy(PROMMDM-2) Neuromuscul Disord 200313813ndash821
6 Sansone VA Brigonzi E Schoser B et al The frequency and severity of cardiacinvolvement in myotonic dystrophy type 2 (DM2) long-term outcomes Int J Cardiol20131681147ndash1153
7 Sansone V Gagnon C Participants of the 207th ENMC Workshop 207th ENMCWorkshop on chronic respiratory insufficiency in myotonic dystrophies managementand implications for research 27-29 June 2014 Naarden The Netherlands Neuro-muscul Disord 201525432ndash442
8 Hilbert JE Barohn RJ Clemens PR et al High frequency of gastrointestinal mani-festations in myotonic dystrophy type 1 and type 2 Neurology 2017891348ndash1354
9 Smith MS Single text negotiation In Beyond Intractability [Online] BoulderConflict Information Consortium University of Colorado Available atbeyondintractabilityorgessaysingle-text- negotiation Accessed October 21 2018
10 Ashizawa T Gagnon C Groh WJ et al Consensus-based care recommendations foradults with myotonic dystrophy type 1 Neurol Clin Pract 20188507ndash520
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 4 | August 2019 353
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
DOI 101212CPJ000000000000064520199343-353 Published Online before print April 24 2019Neurol Clin Pract
Benedikt Schoser Federica Montagnese Guillaume Bassez et al Consensus-based care recommendations for adults with myotonic dystrophy type 2
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent94343fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent94343fullhtmlref-list-1
This article cites 9 articles 2 of which you can access for free at
Subspecialty Collections
httpcpneurologyorgcgicollectiongenetic_linkageGenetic linkage
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract