LAMA2-related Muscular Dystrophy Brain Study

Sponsor

Cure CMD (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01952028

Collaborator

Congenital Muscle Disease International Registr (Other)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Laminin alpha-2 (LAMA2)-related muscular dystrophy (LAMA2-MD, Merosin Deficient CMD) is a form of congenital muscular dystrophy (CMD). A person with LAMA2-MD will have changes on brain imaging (MRI), a decrease or absence of the protein merosin (laminin 211) on muscle or skin biopsy and changes in the LAMA2 gene that are inherited from both parents. Several studies have described the changes on brain MRI. Brain changes on MRI do not correlate with the partial reduction or absence of merosin on muscle or skin biopsy. 8-30% of people with LAMA2-MD develop seizures. The types of seizures, electroencephalogram changes and common treatment regimens have not been characterized. This study will review the magnetic resonance imaging (MRI) changes, determine whether certain brain MRI changes are linked to seizures and define the common seizure treatment regimens.

Condition or Disease	Intervention/Treatment	Phase
LAMA2-MD (Merosin Deficient Congenital Muscular Dystrophy, MDC1A)

Detailed Description

LAMA2-MD is a congenital muscular dystrophy (CMD) subtype caused by mutations in the laminin alpha 2 gene. LAMA2-MD may present clinically as an early onset, severe phenotype or a late onset limb girdle phenotype. The early onset form is most commonly associated with a complete absence of merosin on muscle biopsy with profound neonatal hypotonia, possible respiratory distress and feeding difficulties while the late onset form presents with proximal muscle weakness, contractures and is able to achieve walking. In both early and late onset forms, brain white matter abnormalities have been described on brain MRI and approximately 8-30% develop a seizure disorder. On magnetic resonance (MR) spectroscopy, white matter changes are shown to be due to increased water content rather than areas of demyelination. Both, non-ambulant and ambulant patients may develop respiratory insufficiency requiring non-invasive ventilation and scoliosis.

Although several studies have evaluated the correlation between brain MRI white matter changes and cognition, no studies to date have provided a systematic evaluation of brain imaging, electrophysiologic testing and seizures in patients identified by molecular or immunohistochemical testing to have LAMA2-MD.

Study Design

Study Type:

Observational

Actual Enrollment :

0 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

A LAMA2-related Muscular Dystrophy Study: Brain Magnetic Resonance Imaging (MRI)and Brain Electrophysiology Evaluation

Study Start Date :

Nov 1, 2013

Anticipated Primary Completion Date :

Nov 1, 2014

Anticipated Study Completion Date :

Dec 1, 2014

Outcome Measures

Primary Outcome Measures

Identify and grade the structural brain abnormalities observed on MRI [up to 5 months]
Both single and longitudinal brain MRIs will be retrieved with patient consent from hospitals within the United States. Two trained neuroradiologists will evaluate de-identified brain MRIs using a pre-determined scoring system to identify and classify structural abnormalities.

Secondary Outcome Measures

Seizure History [up to 8 months]
To obtain a seizure history on all individuals with LAMA2-MD who have had a seizure, including: type of seizures, age of seizure onset, seizure frequency, need for mechanical ventilation, seizure medications, and need for emergency room (ER) visit or hospitalization.
Evaluation of baseline and diagnostic electroencephalograms [up to 8 months]
Both baseline and diagnostic electroencephalograms (EEG) will be obtained with patient consent from hospitals within the United States. An epileptologist will review de-identified EEG recordings to identify and classify abnormalities using a predetermined scoring system.
Examine the association between brain MRI structural abnormalities and EEG findings [up to 11 months]
Compare the frequency of various grades of brain MRI abnormalities in individuals with LAMA2-MD with and without seizures. Identify any association between MRI abnormality and type of seizure.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Genetic confirmation of 2 variants in LAMA2 gene OR muscle biopsy with complete absence of merosin
Complete authorization to obtain medical records for Congenital Muscle Disease International Registry
Complete authorization to obtain medical records for National Institutes of Health (NIH)
Reside in United States or Canada
Complete registration and intake survey in the Congenital Muscle Disease International Registry