Evidence-based Guideline - Neurology

Evidence-based Guideline: Diagnosis and Treatment of Limb-Girdle and
Distal Dystrophies
Report of the Guideline Development Subcommittee of the American Academy of
Neurology and the Practice Issues Review Panel of the American Association
of Neuromuscular & Electrodiagnostic Medicine Pushpa Narayanaswami, MBBS, DM, FAAN1; Michael Weiss, MD, FAAN2; Duygu
Selcen, MD3; William David, MD, PhD4; Elizabeth Raynor, MD1; Gregory
Carter, MD5; Matthew Wicklund, MD, FAAN6; Richard J. Barohn, MD, FAAN7;
Erik Ensrud, MD8,10; Robert C. Griggs, MD, FAAN9; Gary Gronseth, MD, FAAN7;
Anthony A. Amato, MD, FAAN10 (1) Department of Neurology, Beth Israel Deaconess Medical Center/Harvard
Medical School, Boston, MA
(2) Department of Neurology, University of Washington Medical Center,
Seattle, WA
(3) Department of Neurology, Mayo Clinic, Rochester, MN
(4) Department of Neurology, Massachusetts General Hospital, Boston,
MA/Harvard Medical School, Boston, MA
(5) St Luke's Rehabilitation Institute, Spokane, WA
(6) Department of Neurology, Penn State Hershey Medical Center, Hershey, PA
(7) Department of Neurology, University of Kansas Medical Center, Kansas
City, KS
(8) Neuromuscular Center, Boston VA Medical Center, Boston, MA
(9) Department of Neurology, University of Rochester Medical Center,
Rochester, NY
(10) Department of Neurology, Brigham and Women's Hospital, Boston,
MA/Harvard Medical School, Boston, MA Correspondence to
American Academy of Neurology:
guidelines@aan.com Approved by the AAN Guideline Development Subcommittee on July 13, 2013; by
the AAN Practice Committee on February 3, 2014; by the AANEM Board of
Directors on July 10, 2014; and by the AANI Board of Directors on July 7,
2014. STUDY FUNDING
Funding for this publication was made possible (in part) by grant DD10-1012
from the Centers for Disease Control and Prevention. The findings and
conclusions in this report are those of the authors and do not necessarily
represent the official position of the Centers for Disease Control and
Prevention. The remaining funding was provided by the American Academy of
Neurology. This guideline was endorsed by the American Academy of Physical Medicine
and Rehabilitation on April 17, 2014; by the Child Neurology Society on
July 11, 2014; by the Jain Foundation on March 14, 2013; and by the
Muscular Dystrophy Foundation on August 27, 2014. AUTHOR CONTRIBUTIONS
Pushpa Narayanaswami: study concept and design, acquisition of data,
analysis or interpretation of data, drafting/revising the manuscript,
critical revision of the manuscript for important intellectual content,
study supervision.
Michael Weiss: study concept and design, acquisition of data, analysis or
interpretation of data, drafting/revising the manuscript, critical revision
of the manuscript for important intellectual content.
Duygu Selcen: study concept and design, acquisition of data, analysis or
interpretation of data, drafting/revising the manuscript, critical revision
of the manuscript for important intellectual content.
William David: study concept and design, acquisition of data, analysis or
interpretation of data, drafting/revising the manuscript, critical revision
of the manuscript for important intellectual content.
Elizabeth Raynor: study concept and design, acquisition of data, analysis
or interpretation of data, drafting/revising the manuscript, critical
revision of the manuscript for important intellectual content.
Gregory Carter: study concept and design, acquisition of data, analysis or
interpretation of data, drafting/revising the manuscript, critical revision
of the manuscript for important intellectual content.
Matthew Wicklund: study concept and design, acquisition of data, analysis
or interpretation of data, drafting/revising the manuscript, critical
revision of the manuscript for important intellectual content.
Richard J. Barohn: study concept and design, acquisition of data, analysis
or interpretation of data, drafting/revising the manuscript, critical
revision of the manuscript for important intellectual content.
Erik Ensrud: study concept and design, acquisition of data, analysis or
interpretation of data, drafting/revising the manuscript, critical revision
of the manuscript for important intellectual content.
Robert C. Griggs: study concept and design.
Gary Gronseth: study concept and design, acquisition of data, analysis or
interpretation of data, drafting/revising the manuscript, critical revision
of the manuscript for important intellectual content.
Anthony A. Amato: study concept and design, acquisition of data, analysis
or interpretation of data, drafting/revising the manuscript, critical
revision of the manuscript for important intellectual content, study
supervision.
DISCLOSURE Dr. Narayanaswami has received honoraria from the American Academy of
Neurology (AAN) and the American Association of Neuromuscular &
Electrodiagnostic Medicine (AANEM). Dr. Weiss has served as a speaker for the AAN, AANEM, American Academy of
Physical Medicine & Rehabilitation (AAPM&R), Athena Diagnostics, Nufactor,
Walgreens, and Grifols Inc.; serves on speakers' bureaus for Athena
Diagnostics and Walgreens; has consulted for Genzyme Corporation, CSL
Behring, Questcor Pharmaceuticals, and Washington State Labor and
Industries; and has received research funding support from the ALS Therapy
Alliance and Northeast ALS Consortium. Dr. Selcen has served as an editorial board member for Neuromuscular
Disorders and has received funding for research from the National
Institutes of Health (NIH). Dr. David reports no relevant disclosures. Dr. Raynor reports no relevant disclosures. Dr. Carter has served as the senior associate editor for Muscle & Nerve,
has received honoraria from the AANEM and the Canadian Association of
Physical Medicine and Rehabilitation, has received funding for research
from the National Institutes on Aging and the National Institute on
Disability and Rehabilitation Research, and has testified on a case
regarding the use of marijuana in pain. Dr. Wicklund has served on a scientific advisory board for Sarepta
Therapeutics, has served on a speakers' bureau for Genzyme, has received
grant funding from Eli Lilly, and has collaborated on research without
compensation with Athena Diagnostics.. Dr. Barohn has served as a consultant or on a scientific advisory board for
Genzyme, Grifols, MedImmune, and Novartis; has received honoraria from
Alexion, Isis, Baxter, Sarepta, and CSL Behring; and has received funding
for research from the US Food and Drug Administration (FDA) and the NIH. Dr. Ensrud reports no relevant disclosures. Dr. Gronseth serves as an editorial advisory board member of Neurology Now,
is an associate editor of Neurology, and receives honoraria from the AAN. Dr. Griggs consults for PTC Therapeutics (Chair of DSMB), Novartis (DSMB),
Marathon Pharmaceuticals, Taro Pharmaceuticals, and Viromed (DSMB);
receives funding from the NIH, the Italian Telethon (DSMB Chair), the
Muscular Dystrophy Association, the Parent Project for Muscular Dystrophy,
and the AAN; and receives royalties from Elsevier (for Cecil Essentials and
Cecil Textbook of Medicine). Dr. Amato has served as a consultant or on scientific advisory boards for
MedImmune, Amgen, Biogen, DART, and Baxter; serves as an associate editor
for Neurology and Muscle & Nerve; has received royalties from publishing
from Neuromuscular Disorders; has received honoraria from the AAN and
AANEM; and has received funding for research from Amgen, MedImmune,
Novartis, the FDA, and the NIH.
ABBREVIATIONS
AAN = American Academy of Neurology
AD = autosomal dominant
AE = adverse event
ALS = amyotophic lateral sclerosis
AR = autosomal recessive
BMD = Becker muscular dystrophy
CDC = Centers for Disease Control and Prevention
CHF = congestive heart failure
CI = confidence interval
CK = creatine kinase
CMD = congenital muscular dystrophy
CMT = Charcot-Marie-Tooth syndrome
CyA = cyclosporine A
DMD = Duchenne muscular dystrophy
EDB = extensor digitorum brevis
EDMD = Emery-Dreifuss muscular dystrophy
EF = ejection fraction
EM = electron microscopy
fALS = familial amyotophic lateral sclerosis
FCMD = Fukuyama congenital muscular dystrophy
FVC = forced vital capacity
GH = growth hormone
hIBM = hereditary inclusion body myopathy
hIBMPFD = hereditary inclusion body myopathy with Paget disease and
frontotemporal dementia
HMERF = hereditary myopathy with early respiratory failure
LDM = Laing distal myopathy
LGMD = limb-girdle muscular dystrophyLVEF = left ventricular ejection
fraction
MEB = muscle-eye-brain disease
MFM = myofibrillar myopathy
MM3= Miyoshi myopathy type III
MR = mental retardation
PDB = Paget disease of bone
PIRCs = percussion-induced rapid contractions
RAE = right atrial enlargement
ULN = upper limit of normal
VO2 max = maximal oxygen uptake
Wmax = maximal workload
WWS = Walker-Warburg syndrome
ABSTRACT
Objective: To review the current evidence and make practice recommendations
regarding the diagnosis and treatment of limb-girdle muscular dystrophies
(LGMDs).
Methods: Systematic review and practice recommendation development using
the American Academy of Neurology guideline development process.
Results: Most LGMDs are rare, with estimated prevalences ranging from 0.07
per 100,000 to 0.43 per 100,000. The frequency of some muscular dystrophies
varies based on the ethnic background of the population studied. Some LGMD
subtypes have distinguishing features, including pattern of muscle
involvement, cardiac abnormalities, extramuscular involvement and muscle
biopsy findings. The few published therapeutic trials were not designed to
establish clinical efficacy of any treatment.
Principal Recommendations: For patients with suspected muscular dystrophy,
clinicians should use a clinical approach to guide genetic diagnosis based
on clinical phenotype, inheritance pattern, and associated manifestations
(Level B). Clinicians should refer newly