AANEM News Express

AANEM News Express

Science News: Muscle and Not Neuronal Biomarkers Correlate With Severity in Spinal and Bulbar Muscular Atrophy

Submitted by Bryan X. DeSouza, MD
Edited by Elliot Bodofsky, MD

Muscle and Not Neuronal Biomarkers Correlate With Severity in Spinal and Bulbar Muscular Atrophy. Vittoria Lombardi, PhD, Giorgia Querin, MD, Oliver J. Ziff, MD, MRCP et al. Neurology 2019; 92:e1205-e1211.doi:10.1212/WNL.000000000007097

This study prospectively collected blood from 2 cohorts of patients, 93 genetically confirmed SBMA patients, and ALS patients and healthy relatives without neurological symptoms. SBMA and ALS disease severity and progression were evaluated using functional rating scale scores. Progression rate in patients with ALS was calculated as progression rate to last visit (PRL).

AR 100 mice which express the human androgen receptor with an expanded CAG repeat were used. Biomarkers were obtained from male AR100 mice and controls. Patient NfL, CK, and creatinine concentrations were compared, as were mouse NfL levels. Correlations of CK and creatinine levels with SBMAFRS and AMAT scores were assessed.

NfL levels were unchanged and stable over 2 years in 2 independent SBMA cohorts of patients. NfL levels did not show a significant increase in well-established mouse model of the disease over 1.5 years. CK levels (muscle injury marker) were similar in both cohorts and significantly increased compared to ALS patients and healthy controls. CK levels did not differ between slow and fast ALS patients. Creatinine levels (muscle mass marker) were very similar in both cohorts and significantly decreased compared to controls and ALS patients. Creatinine levels significantly correlate with SBMA severity. There was no significant correlation between clinical measures and CK, but creatinine levels strongly inversely correlated with clinical measures both SBMAFRS and AMAT in both SBMA cohorts.

Comments: This is an elegant study with important information, but there are limitations in study design. The authors report that not all data was collected and included in the statistical analysis. The cohort was limited in size, which may affect generalizability of the study results. Thus, a larger prospective study would be needed.

This is an important article for neuromuscular and electrodiagnostic practitioners because biomarkers are commonplace and widely accepted in research as well as clinical practice. In electrodiagnosis, SBMA is characterized by muscle denervation and loss of lower motor neurons in the spinal cord and the brainstem mimicking motor neuron disease. Recent animal research shows a primary myopathic mechanism in this disorder. This study validates the use of serum biomarkers (NfL, CK, and creatinine) in distinguishing neuronal degeneration and muscular disease mechanisms. It also provides strong clinical evidence to support a primary myopathic mechanism in SBMA. 

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