Abstract Details

Title Clinical findings in amyotrophic lateral sclerosis type 4

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S54 - Motor Neuron Disease (3:52 PM-4:03 PM)

Poster/Presentation
Number 003

Background

ALS4 is a slowly progressive degenerative disease of the nervous system caused by mutation in the senataxin gene (SETX). This autosomal-dominant form of ALS is characterized by early-onset, muscle atrophy, weakness, and hyperreflexia. We evaluated a cohort of ALS4 patients to identify features of disease that could be used to quantify severity and track progression.

Objective

To measure clinical features of disease in subjects with amyotrophic lateral sclerosis type 4 (ALS4).

Design/Methods

21 subjects with a 1166 T>C (p.Leu389Ser) mutation in SETXwere evaluated, with exclusion of other ALS4 SETXmutations. Neurological examination including manual muscle testing was done on all subjects, with follow-up examinations in 12 subjects. Laboratory testing of serum biochemical and hormonal profiles included creatine kinase, creatinine, testosterone, estradiol, phosphorylated neurofilament heavy chain, and insulin-like growth factor 1. Dual-energy X-ray absorptiometry (DXA) and thigh muscle MRI were performed on 10 subjects.

Results Both male and female subjects with ALS4 had increased levels of creatine kinase compared to age and sex-matched controls evaluated at the NIH (p <0.0001 and <0.001, respectively), and males had significantly lower levels of creatinine (p < 0.0001). No significant changes in phosphorylated neurofilament heavy chain were detected. Thigh muscle myofiber volume was found to correlate with disease duration (R²=0.54, p = 0.02). DXA analysis showed higher fat z-score values in the legs (mean 1.8, SD 1.5) compared to the arms (mean 0.6, SD 1.3), and a reduction in appendicular lean body mass adjusted by height (z-score mean -1.7, SD 1.5). Ankle dorsiflexion strength decreased over the mean time frame of 3.1 years of observation by -30%.

Conclusions This study has identified changes in clinical and imaging measurements in subjects with ALS4. Studies with longer duration would help to assess further the relationship between the change in the imaging markers and disease progression.

Authors/Disclosures
Christopher Grunseich, MD (National Institutes of Health) PRESENTER	Dr. Grunseich has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Kenneth H. Fischbeck, MD, FAAN (NINDS, NIH, Neurogenetics)	Dr. Fischbeck has received research support from NINDS/NIH. Dr. Fischbeck has received intellectual property interests from a discovery or technology relating to health care. Dr. Fischbeck has a non-compensated relationship as a Scientific Review Board member with Kennedy's Disease Association that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Scientific Council member with Association Francaise contre les Myopathies that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Independent Review Committee member with Target ALS that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Scientific Advisory Board member, Musculoskeletal Diseases with Novartis that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Senior Clinical Consultant with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Scientific Advisory Committee member with Stanford GNE myopathy program that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Scientific Advisory Board member with Hereditary Disease Foundation that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Scientific Advisory Board member with Packard Center for ALS Research that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a Scientific Advisory Board member with Huntington's Disease Society of America that is relevant to AAN interests or activities. Dr. Fischbeck has a non-compensated relationship as a TACT review panel member with TREAT-NMD that is relevant to AAN interests or activities.
	No disclosure on file

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