Abstracts

Rationale: Recent recognition of the encephalopathy associated with CDKL5 (cyclin-dependent kinase-like 5) mutations has led to molecular diagnosis in affected girls. Onset is by 3 months of age with tonic seizures, evolving to an epileptic encephalopathy with spasms. Here, we report a distinctive complex seizure type which will facilitate diagnosis in patients with CDKL5 mutations. Methods: Video-EEG monitoring and clinical details of 6 girls with abnormalities in CDKL5 (3 missense mutations, 2 truncation mutations, 1 deletion) were reviewed. Results: Four of six patients with abnormalities of CDKL5 (2 missense mutations, 1 truncation mutation, 1 deletion) showed a characteristic unusual seizure type. Onset of the hypermotor-tonic-spasms sequence was between 3.5 and 13 months (median 7.5 months), between 1.5 and 11 months after seizures first began. This sequence continued at 4 years in 3 cases. Seizures were long (3.5-17 minutes) and started with an arousal from sleep followed by a quiet phase for 10-40 seconds in 3 patients. In all patients a hypermotor phase lasting 10-60 seconds followed and evolved to a tonic phase with bilateral upper limb abduction for 20-45 seconds. The seizure then evolved to a series of epileptic spasms with arms abducted and legs adducted in a cruciate posture, which lasted 2.5-15 minutes. Ictal EEG showed bilateral frontocentral beta activity evolving to bilateral delta activity with frontal or posterior maximum during the hypermotor phase, followed by diffuse attenuation during the tonic phase and high voltage transients at the vertex with diffuse attenuation during the spasms phase. These unusual seizures occurred during the epileptic encephalopathy. The clinical history and VEM in the second year of life did not suggest this sequence in the two remaining patients. Conclusions: We highlight a distinctive, complex hypermotor-tonic-spasms sequence as a feature of CDKL5 epileptic encephalopathy. We have found that this unusual seizure type can be suspected from history alone leading epileptologists to consider the diagnosis. Video-EEG monitoring can confirm this characteristic and unusual seizure type. Funding: NHMRC of Australia. KMK is supported by a research fellowship from the Deutsche Forschungsgemeinschaft (KL 2254/1-1) and a scholarship from The University of Melbourne.