Specific EEG markers in POLG1 Alpers’ syndrome

•EEG RHADS are specific for Alpers’ syndrome and can be reliably recognized.•Probability of detecting RHADS increases with number of EEGs.•RHADS might signify an epileptic phenomenon. To examine whether rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS) in EEG allow a reliable early diagnosis of Alpers-Huttenlocher syndrome (AHS) and contribute to recognition of this disease. EEGs of nine patients with DNA-proven AHS and fifty age-matched patients with status epilepticus were retrospectively examined by experts for the presence of RHADS and for accompanying clinical signs and high-frequency ripples. Reproducibility of RHADS identification was tested in a blinded panel. Expert defined RHADS were found in at least one EEG of all AHS patients and none of the control group. RHADS were present at first status epilepticus in six AHS patients (67%). Sometimes they appeared 5–10 weeks later and disappeared over time. RHADS were symptomatic in three AHS patients and five AHS patients showed distinct ripples on the (poly)spikes of RHADS. Independent RHADS identification by the blinded panel resulted in a sensitivity of 87.5% (95% CI 47–100) and a specificity of 87.5% (95% CI 77–94) as compared to the experts’ reporting. RHADS are a highly specific EEG phenomenon for diagnosis of AHS and can be reliably recognized. Clinical expression and EEG ripples suggest that they signify an epileptic phenomenon. RHADS provide a specific tool for AHS diagnosis.