The long exercise test as a functional marker of periodic paralysis

Abstract

Aims:The aim of this study was to evaluate the sensitivity of the long exercise test (LET) in the diagnosis of periodic paralysis (PP) and assess correlations with clinical phenotypes and genotypes.Methods: From an unselected cohort of 335 patients who had an LET we analyzed 67 patients with genetic confirmation of PP and/or a positive LET.Results: 32/45 patients with genetically confirmed PP had a significant decrement after exercise (sensitivity of 71%). Performing the short exercise test before the LET in the same hand confounded results in four patients. Sensitivity was highest in patients with frequent (daily or weekly) attacks (8/8, 100%), intermediate with up to monthly attacks (15/21, 71%) and lowest in those with rare attacks (9/16, 56%) (p = .035, Mann-Whitney U-test). Patients with a positive LET without confirmed PP mutation comprised those with typical PP phenotype and a group with atypical features.Discussion: In our cohort, the LET is strongly correlated with the frequency of paralytic attacks suggesting a role as a functional marker. A negative test in the context of frequent attacks makes a diagnosis of PP unlikely but it does not rule out the condition in less severely affected patients.

Pathogenic SCN5A Mutation and Thyrotoxicosis-Related Neurological Syndrome: Casual or Causal Relationship?

“…Thyroid hormone (TH) directly and indirectly stimulates the Na/K ATPase pump and eventually contributes to hyperpolarization of the muscle cell membranes [14]. Myalgia and stiffness could be atypical phenotype of skeletal muscle channelopathies and lead to a positive LET results presenting as a post-exercise decrement of more than 40% from peak CMAP amplitude [15,16]. Thus, we infer that exercise-induced myalgia and muscle stiffness in this patient possibly associate with the function of ion channel which is sensitive to excess TH.…”

The long exercise test: New insights on an old technique

“…It is known that patients with genetically negative PP often have atypical features such as older age of onset, absence of dietary precipitants and absence of vacuolar myopathy on muscle biopsy 15 . And in this issue, Ribeiro et al 10 also advance this theme. Of their 67‐patient cohort, 22 patients (33%) had a positive LET and negative genetic testing for known mutations.…”

“…In this issue of the journal, Ribeiro et al 10 look at the LET from a different angle. Of 67 patients from their muscle channelopathy service with positive genetic testing for PP or a positive LET, 45 (67%) had genetically proven PP due to known CACNA1S , KCNJ2, SCN4A HypoPP, SCN4A HyperPP , and RYR1 mutations.…”

“…Beyond its diagnostic utility, Ribeiro et al 10 speculate that the LET could serve as a functional marker for potential benefit from treatment, specifically in identifying reversible weakness in patients with fixed weakness and superimposed attacks or with fluctuating strength. The authors offer no proof of this, but intuitively this also is an appealing hypothesis.…”

“…The four double-blind, randomized, placebocontrolled trials reporting benefit of DCP in PP in reducing attack frequency and severity, 12,13 enrolled only patients with frequent attacks of at least one per week. Although the LET was not a diagnostic requirement in any of these trials, one would predict, based on the work of Ribeiro et al 10 and Tengan et al 9 that essentially all would have had a positive LET at study entry before treatment, consistent with, if not proof of, a treatable component to their disease. If the LET decrement were a viable biomarker for disease activity or for reversible disease, then it should improve or normalize after successful treatment with disease-modifying therapy and reduction in attack frequency.…”