Management of epilepsy in patients with Rett syndrome: perspectives and considerations

Abstract

Rett syndrome (RTT) is a common neurodevelopmental disorder that appears in infancy with regression of acquired motor skills, loss of purposeful activity, hand stereotypies, loss of acquired spoken language, and seizures. Epilepsy affects the majority of patients in a specific clinical stage of the disease and is drug resistant in approximately one-third of cases. The association of epilepsy and even drug-resistant epilepsy has been reported in certain genotypes of the methyl-CpG-binding protein 2 mutation, which is present in a majority of patients with classical RTT. The evolution of electroencephalographic abnormalities accompanying the clinical development of the syndrome is well described, but much less is known about the seizure semiology and the effectiveness of specific antiepileptic drugs. The aim of this review is to present the clinical and electrophysiological aspects of epilepsy in RTT and the current treatment approach.

Keywords:

• Rett syndrome
• epilepsy
• treatment

Supplementary material

This 32-year-old patient presented at the age of 3.5 years due to a 1-year history of screaming spells occurring 2–3 times daily.

The family history was normal; she had a healthy older brother. She was born after a normal pregnancy with a normal labor and postnatal course. Birth measurements were normal and proportional, including the occipito-frontal circumference. She acquired independent walking at the age of 13 months and used 5–10 meaningful words at the age of 2 years. She did not acquire a pincer-grasp but was able to use a spoon for feeding.

At 2.5 years, her parents noticed a quite sudden behavioral change; she became irritable, with screaming spells lasting up to 1 hour. This was followed by regression of verbal communication, hand stereotypies (clapping and washing movements, circular hand-to-mouth movements), and loss of interest in play and social interaction.

When she presented 1 year later, her neurologic examination revealed a broad-based dyspraxic gait, loss of verbal and nonverbal communication, loss of eye contact, and hand stereotypies. Muscle tone was generally low, and proprioceptive reflexes were normal, with a flexor plantar response. There was no deceleration of head growth.

EEG disclosed irregular background activity in the awake state and preserved sleep structure, but bursts of bilateral spike-wave complexes, more pronounced over the right hemisphere, were recorded.

Six months later she experienced her first epileptic seizure during sleep with eye and mouth-angle deviation to the left side, followed by generalized tonic-clonic convulsions, lasting for 5 minutes. The seizures were repeated over the next few months, so antiepileptic treatment with valproate was started. She has remained seizure-free since the age of 11 years. Total discontinuation of treatment was not possible due to behavioral deterioration on two successive attempts, with her autoaggressive behavior attributed to the mood-stabilizing effect of valproate.

Brain MRI was normal at the age of 7 years. The clinically established diagnosis of RTT was confirmed years later by MECP2 mutation analysis at the age of 20 years, when genetic testing became available.

She did not lose the ability to walk independently in the following years, but her gait was broad-based and dyspraxic. Currently, she has no functional hand use and hand stereotypies are still very prominent. She is not able to communicate verbally but her eye contact is very intense. Episodes of hyperventilation are obvious in the awake state. She has small, cold feet, slight scoliosis, and generally higher muscle tone with brisk reflexes and a flexor plantar response.

She is still on low-dose valproate treatment and oral calcium supplementation due to osteopenia.

Disclosure

The author reports no conflicts of interest in this work.