Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies.

Abstract

OBJECTIVE:

To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialized electrophysiological exercise test parameters.

METHODS:

We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming.

RESULTS:

Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for paramyotonia congenita and myotonia congenita, respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fiber conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive "tornado-shaped" neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-compound muscle action potential (CMAP) in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls.

INTERPRETATION:

Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients with negative exercise tests, specific clinical features are helpful in differentiating sodium from chloride channel myotonia. A modified algorithm is suggested.

• Authors: S Veronica Tan, Emma Matthews, Melissa Barber, James A Burge, Sanjeev Rajakulendran, Doreen Fialho, Richa Sud, Andrea Haworth, Martin Koltzenburg, Michael G Hanna
• Journal: Annals of neurology (Ann Neurol) Vol. 69 Issue 2 Pg. 328-40 (Feb 2011) ISSN: 1531-8249 [Electronic] United States
• PMID: 21387378 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Neurological Association.

Topics

• Adolescent
• Adult
• Aged
• Channelopathies (diagnosis, genetics)
• Electromyography
• Exercise Test
• Female
• Humans
• Male
• Middle Aged
• Muscle Weakness (diagnosis, genetics)
• Muscle, Skeletal (pathology)
• Myotonic Disorders (diagnosis, genetics)