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06/10/2020

Organic Features of Autonomic Dysregulation in Paediatric Brain Injury – Clinical and Research Implications for the Management of Patients with Rett Syndrome

In August, a paper entitled, Organic Features of Autonomic Dysregulation in Paediatric Brain Injury – Clinical and Research Implications for the Management of Patients with Rett Syndrome was published in the journal, Neuroscience and Biobehavioural Reviews (Singh et al. 2020) at the Centre for Personalised Medicine in Rett Syndrome (CPMRS) in London headed by Professor Santosh.

This paper, with its complicated title, may seem confusing and irrelevant to many Rett families, but we think it is critical for the health and well-being of people with Rett that we clarify the take-home learnings from this paper, for you to share with Healthcare Professionals and carers helping to manage their health.

Key recommendations from the paper may help keep people with Rett Syndrome of any age as safe as possible from complications, or at least healthier than they would be otherwise, without having this information to hand.

Here, Reverse Rett CEO, Rachael Stevenson, attempts to better understand the paper in Q and A format with the first author and Reverse Rett Advisor, Dr Singh.

1. What does Paediatric Brain Injury (PBI) have to do with Rett Syndrome anyway?

We know that the symptoms of Rett Syndrome have a significant impact on the quality of life for individuals affected. There is, however, a huge lack of recommendations for investigations and treatments concerning the autonomic nervous system (ANS) in Rett. As the ANS is difficult to investigate, we thought it would be a good idea to learn from other conditions if possible.

To address this, we searched the literature on autonomic dysregulation (AD) following brain injury in children to provide an enriched picture of the AD in Rett Syndrome.

2. Please give us a simple, layman’s explanation of the Autonomic Nervous System and Autonomic Dysregulation (AD)

The autonomic nervous system (ANS) is the system in the body which manages both voluntary and involuntary actions. For example, we can consciously breathe or forget about our breathing completely and let the ANS take over. When the ANS does not function properly, it leads to dysregulation.

In patients with Rett Syndrome, this autonomic dysregulation (AD) can lead to a variety of problems ranging from breathing difficulties, cardiac problems to gastrointestinal issues and sleep disturbances.

3. It was interesting to read how you narrowed down the papers to review for this work. Over 500 papers were initially considered. What questions were you seeking to answer, and why?

AD is a serious complication following childhood brain injury and the purpose of the study was to see whether the information from studies in children with AD following brain injuries can be used to further our understanding of the AD seen in children with RTT. We were trying to address the following questions in Rett Syndrome:

I)  If we find symptoms early enough, will this help us to better manage AD in Rett Syndrome over the longer term?

II) How do we objectively measure the problem and any improvements we are able to bring about?

III) What can we do to treat AD, better manage EBAD symptoms and ultimately improve the person’s quality of life?

4. Briefly, can you tell us what was the overall finding from the study?

The overall finding is that studies of AD following childhood brain injury do provide valuable information on the recognition, treatment and clinical management of AD in patients with Rett.

Whilst management of AD is complex in patients with Rett due to so many different symptoms, occurring at different times, in different patients during the course of the condition, early recognition of the clinical signs and symptoms which predict AD would be of benefit to these patients.

Some of the symptoms which can be monitored alone or in combination are:

·      Heart rate variability (HRV-the variation of time between each heartbeat)

·      Preventing bedsores in bed-bound patients

·      Avoiding tight clothing

·      Ensuring room temperature is not too low

·      Recognising the signs of diaphoresis (sweating, especially to an unusual degree) and dystonia

5. How can monitoring Heart Rate Variability (HRV) and Electrodermal Activity (EDA) help detect initial signs of infection, and why is this helpful in patients with Rett Syndrome?

We suggested that infections could be triggers for EBAD and assessment of HRV and EDA might be useful indicators of a pending infection. In particular, because the EDA is usually dependent on a specific aspect of the ANS, monitoring of EDA using non-invasive wearable sensors can provide valuable information on the early physical decline of patients. Clinical studies in this area are much needed, however, and more evidence is required to assess what impact AD has on infections in Rett patients.

6. Can you give us three key clinical recommendations for families and carers to take to their Healthcare Professional?

I) AD in Rett Syndrome involves multiple overlapping systems. It would be useful, following a clinical diagnosis of Rett, to adopt the use of non-invasive wearable sensor technology for the assessment of HRV and EDA to provide information on functional outcomes and serious physical deterioration.

II) Sensory issues as well as diaphoresis and dystonia, should be closely monitored.

III) Medication-induced side effects – especially centrally acting medications such as benzodiazepines and morphine that have multi-system side effects and may worsen autonomic function, ought to be used with caution.

Thank you Dr Singh, for taking the time to help us better understand this work and congratulations on this publication. We look forward to reading more emerging publications from CPMRS in the coming months.

Singh J, Lanzarini E, Santosh P. Organic Features of Autonomic Dysregulation in Paediatric Brain Injury – Clinical and Research Implications for the Management of Patients with Rett Syndrome. Neurosci Biobehav Rev. 2020 Aug 27:S0149-7634(20)30550-9. doi: 10.1016/j.neubiorev.2020.08.012. Epub ahead of print. PMID: 32861739.

The Centre for Personalised Medicine in Rett Syndrome (CPMRS), funded by Reverse Rett, is a U.K. based service that provides highly specialist assessment and psychopharmacological treatment for neuropsychiatric difficulties/disorders in people with Rett Syndrome, as well as conducting clinical trials and research into the condition.