Science News: New EAN Guideline Streamlines Evaluation of Persistent HyperCKemia

Submitted by: Ben Becker, MD

Edited by: Rebecca O'Bryan, MD

Citation: Kyriakides T, Aleksovska K, Angelini C, Argov Z, Claeys KG, de Visser M, FIlosto M, Jovanovic I, Kostera-Pruszczyk A, Molnar MJ, Sacconi S, Schaefer J, Siciliano G, Vilchez JJ, Schoser B, Toscano A. EAN 2024 Guideline on the Diagnostic Approach to Oligo/Asymptomatic HyperCKemia. Eur J Neurol. 2026 Feb;33(2):e70493. doi: 10.1111/ene.70493. PMID: 41619221; PMCID: PMC12860458.

The 2024 European Academy of Neurology (EAN) guideline provides an updated, evidence‑based diagnostic framework for adults with persistent oligo‑ or asymptomatic hyperCKemia, a population representing roughly 1.3% of the general public according to epidemiologic data.

The Task Force recommends investigating individuals with CK >1.5× upper limit of normal (ULN), using age, ethnicity, and gender matched reference intervals. Elevated creatine kinase (CK) should be repeated after ≥72 hours of rest, ideally after a week, and confirmed with two repeat measurements at least one month apart. Before pursuing neuromuscular testing, clinicians should exclude non‑neuromuscular contributors such as exercise, medications, cardiac, endocrine and metabolic disorders. The guideline provides an extensive table of these conditions. The guideline emphasizes a structured, minimally invasive approach. Alfa-Glucosidase Assessment-dried blood spot (GAA-DBS) testing is strongly recommended as a first‑line screen for late‑onset Pompe disease, given similar detection rates in symptomatic and oligo/asymptomatic individuals. There was a weak recommendation to obtain nerve conduction study and electromyography (NCS/EMG) to identify a neuropathic or myopathic bases of hyperCKemia. Muscle MRI is strongly recommended as it may be helpful in interpreting genetic testing results and to determine presence of subclinical abnormalities. When metabolic myopathies are suspected it is reasonable to test lactate at rest and with activation, as well as fasting acyl carnitine test. Next generational sequencing (NGS) is strongly recommended instead of muscle biopsy once neuropathic and acquired myopathic causes are ruled out, and this is the preferred method of genetic testing over single gene testing unless there is a known family history of a mutation. Biopsy is reserved for cases where NGS is nondiagnostic and specific concerns remain - such as a genetic variant of unknown significance (VUS), suspected inflammatory or metabolic myopathy, abnormal MRI, CK ≥3× ULN, family history, or age <25.

The guideline reflects major advances since the 2010 European Federation of Neurological Societies (EFNS) recommendations, particularly the widespread availability of NGS‑based genetic testing and muscle MRI, both of which now play central roles in evaluating subclinical neuromuscular disease.

Given the vast improvements in muscle MRI techniques and ease of access to next generation sequencing, updates to prior consensus guidelines for oligosymptomatic/asymptomatic hyperCKemia were needed. Expert panel developed a reasonable set of recommendations including how to identify true hyperCKemia (after 72 hours to 7 days of rest with 2 repeat measurements). Authors highlight a reasonable diagnostic algorithm for hyerCKemia and a list of non-neuromuscular etiologies. Once myopathic etiology is suspected certain functional tests (GAA-DBS, lactic acid test, fasting acyl carnitine) are reasonable first evaluation followed by either next generation sequencing, nerve conduction studies/electromyography, or muscle MRI. 

This is a population that may have a non-neuromuscular etiology therefore discerning appropriate from unnecessary work up is essential.