Reflex Seizures in a Patient with CDKL5 Deficiency Disorder

• Published in: Canadian journal of neurological sciences 2019-07, Vol.46 (4), p.482-485
• Main Authors: Peikes, Tyler, Hartley, Jessica N., Mhanni, Aizeddin A., Greenberg, Cheryl R., Appendino, Juan Pablo
• Format: Article
• Language: English
• Subjects: Age; Convulsions & seizures; Electroencephalography; Epilepsy; Epileptic Syndromes - complications; Epileptic Syndromes - physiopathology; Female; Humans; Letter to the Editor; Mutation; Seizures - etiology; Seizures - physiopathology; Sleep; Spasms, Infantile - complications; Spasms, Infantile - physiopathology
• ISSN: 0317-1671; 2057-0155
• DOI: 10.1017/cjn.2019.29

CDKL5 deficiency disorder (CDD) has been increasingly recognized in the last decade as a distinct clinical entity (OMIM #300672), presenting in early infancy with seizures, severe developmental delay, loss of milestones, and postnatal microcephaly.1 This disorder was originally described in the mid-2000s motivated in part by the heterogeneity of the loose grouping of diseases referred to as atypical Rett syndrome (RTT), variant RTT, or Rett-like syndromes.2 Several seizure types have been associated with CDD, particularly “hypermotor-tonic-spasms” sequence; however, water-related reflex seizures have not been associated with CDD. [...]the appearance of reflex seizures later in RTT after the plateau period may be explained by the delayed appearance of dysregulated multigene transcription, as seen in hypothalamic neurons, leading to neuronal network dysmaturation, autonomic dysfunction, and cortical hyperecitability.8,9 Reflex seizures are described in other epileptic syndromes secondary to a known genetic disorder such as Down syndrome where nearly 20% of patients report reflex seizures.10 Its cortical hyperexcitability is thought to be secondary to similar findings to CDD (decreased density and size of synapses, dendritic spines of pyramidal neurons, lack of growth of dendritic trees, and reduction of neuronal density).10 Other syndromes with reported reflex seizures include, but do not limit to, Angelman syndrome, Juvenile Myoclonic Epilepsy, SCN1A, LGI1, FOXG1, and Synapsin 1 mutations.10,11 They could be focal or generalized and appear similar to unprovoked seizures with the exception that a consistent trigger can be identified. The most common trigger factor is visual stimuli in up to 75% of the cases.10 The different reflex seizure types are ultimate expressions of excitatory and inhibitory dysregulation mechanisms in specific corticosubcortical and thalamocortical pathways with a common outcome: the activation of a critical neuronal mass that eventually results in a seizure when the seizure suppression threshold is exceeded.12 Treatment of CDD is symptomatic, and anti-seizure medication, vagal nerve stimulator, and the ketogenic diet are mainstays with variable success. Despite the possibility of achieving some control of reflex seizures in CDD and RTT, the prognosis for spontaneous seizure control remains poor. [...]in all infants who present with reflex seizures, the prognosis should be guarded until an underlying syndromic cause is identified as t