Rett Syndrome: Symptom-Based Treatment Approach Needed

Studies on Rett syndrome need to focus on a holistic approach encompassing each of the emotional, behavioral, and autonomic dysregulation symptoms within the disorder, according to a new report. Only then, can a successful treatment come about.

Rett syndrome can be life-threatening and often involves multiple physiological symptoms; one of the signature symptoms is autonomic dysregulation, or dysautonomia, which is the imbalance between the sympathetic and parasympathetic branches of the autonomic nervous system. The condition affects approximately 1 in 10,000 people and is predominantly found in females.

Investigators from King’s College London examined the issues related to Emotional, Behavioral, and Autonomic Dysregulation (EBAD) in Rett syndrome patients in order to target treatment breakthroughs and improve the quality of life for patients. The study authors wrote that it is important to consider EBAD in these patients when developing a treatment plan, as “complex neurodevelopmental disorders need multidisciplinary treatment approaches for optimal care.”

The investigators found 34 relevant, published articles, peer reviewed articles, and electronically available articles to include in their study. They searched the PubMed, Cochrane, and Scopus databases for papers related to Rett syndrome clinical trials.

Patients with Rett syndrome can have symptoms such as generalized anxiety, panic attacks, breathing dysfunction, temperature dysregulation, peripheral vascular changes, enteric changes, and cardiac abnormalities—all due to the autonomic dysregulation, the investigators said. Current treatment strategies, largely personalized for each patient, attempt to normalize symptoms. The best approach for a viable clinical outcome is to modify the deleterious cardio-respiratory phenotype.

The investigators explained that the emotional state of a patient with Rett syndrome can be worsened by physical difficulties observed. Their example: “Epileptic seizures can lead to a heightened emotional state and often leads to anxiety but can also include screaming, labile mood, and uncontrollable crying.”

A “holistic” view of the links between emotion, behavior, and autonomic function needs to be the focus of Rett syndrome treatment, the study authors write. Using sensor-based biometric tools, such as a wearable heart rate monitor, can be a useful tool in capturing data about autonomic states. Measuring emotional and behavioral states is largely done with assessments, scales, and questionnaires, though the authors said those proctors are often lacking without a general consensus on how they should be scored.

The investigators acknowledged the unlikelihood of a “one-size-fits-all” treatment approach for Rett syndrome patients. The lack of 1 specific drug being able to treat the various symptoms is another inhibiting factor.

The team did identify a handful of Rett syndrome clinical trials, however, that had “limited success.” Despite that fact that none of them specifically used EBAD as a clinical trial intervention, some of them offered promising conclusions about improving the indices of EBAD leading to improved emotional, behavioral, and autonomic dysregulation in the patients.

“Given the state of dysregulation of multiple overlapping physiological systems in EBAD, it is probable that there is a need for a symptom-based approach where different medications will be needed to manage different symptoms that impair subjects with Rett syndrome, thus requiring a truly personalized approach to treatment,” the study authors write.

The investigators called this “an exciting time for the Rett syndrome field.” They also said this is the first study of its kind to describe EBAD in Rett syndrome patients and provide context and insights to influence the development of EBAD as a target for future clinical trials.

“The implementation of new outcome measures such as those focusing on EBAD will provide researchers with the opportunity to target a number of systems and aid in the development of better clinical trial designs,” the study authors conclude.