Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report

Santosh, Paramala; Bell, L. G. E.; Lievesley, Kate; Singh, Jatinder; Fiori, Federico

doi:10.1186/s12887-016-0734-3

Cited by 9 publications

(6 citation statements)

References 31 publications

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“…Heart rate variability (HRV) is an indirect measure of autonomic arousal [ 89 , 90 ] and can be measured using wearable sensor technology. Wearable sensor technology has been used as a biometric proxy measure to monitor treatment outcomes of EBAD in RTT [ 40 , 91 ] and in those with other complex neurodevelopmental disorders [ 92 ]. In these cases, sensor-based biometrics can assist in the individualisation of patient care allowing the management of patients with EBAD.…”

Section: Emotional Behavioural and Autonomic Dysregulation In Rttmentioning

confidence: 99%

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Singh

Santosh

2018

Orphanet J Rare Dis

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Complex neurodevelopmental disorders need multi-disciplinary treatment approaches for optimal care. The clinical effectiveness of treatments is limited in patients with rare genetic syndromes with multisystem morbidity. Emotional and behavioural dysregulation is common across many neurodevelopmental disorders. It can manifest in children across multiple diagnostic groups, including those on the autism spectrum and in rare genetic syndromes such as Rett Syndrome (RTT). There is, however a remarkable scarcity in the literature on the impact of the autonomic component on emotional and behavioural regulation in these disorders, and on the longer-term outcomes on disorder burden.RTT is a debilitating and often life-threatening disorder involving multiple overlapping physiological systems. Autonomic dysregulation otherwise known as dysautonomia is a cardinal feature of RTT characterised by an imbalance between the sympathetic and parasympathetic arms of the autonomic nervous system. Unlocking the autonomic component of emotional and behavioural dysregulation would be central in reducing the impairment seen in patients with RTT. In this vein, Emotional, Behavioural and Autonomic Dysregulation (EBAD) would be a useful construct to target for treatment which could mitigate burden and improve the quality of life of patients.RTT can be considered as a congenital dysautonomia and because EBAD can give rise to impairments occurring in multiple overlapping physiological systems, understanding these physiological responses arising out of EBAD would be a critical part to consider when planning treatment strategies and improving clinical outcomes in these patients. Biometric guided pharmacological and bio-feedback therapy for the behavioural and emotional aspects of the disorder offers an attracting perspective to manage EBAD in these patients. This can also allow for the stratification of patients into clinical trials and could ultimately help streamline the patient care pathway for optimal outcomes.The objectives of this review are to emphasise the key issues relating to the management of EBAD in patients with RTT, appraise clinical trials done in RTT from the perspective of autonomic physiology and to discuss the potential of EBAD as a target for clinical trials.

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Section: Emotional Behavioural and Autonomic Dysregulation In Rttmentioning

confidence: 99%

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Singh

Santosh

2018

Orphanet J Rare Dis

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“…Autonomic dysregulation is likely to be a critical driver for the diverse symptoms exhibited by patients with RTT. The autonomic component can be exploited and targeted therapeutically using biometricguided therapy to manage EBAD in patients with RTT 15,16 and in those with multi-comorbid neurodevelopmental disorders. 17 This is important given that the autonomic component of EBAD is pervasive and has widespread effects on multiple overlapping systems.…”

Section: Introductionmentioning

confidence: 99%

Autonomic dysfunction and sudden death in patients with Rett syndrome: a systematic review

Singh

Lanzarini

Santosh

2020

jpn

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Background: Rett syndrome (RTT), a debilitating neuropsychiatric disorder that begins in early childhood, is characterized by impairments in the autonomic nervous system that can lead to sudden unexpected death. This study explores the mechanisms of autonomic dysfunction to identify potential risk factors for sudden death in patients with RTT. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, we undertook comprehensive systematic reviews using the PubMed, Scopus, Cochrane, PsycINFO, Embase and Web of Science databases. Results: We identified and critically appraised 39 articles for autonomic dysfunction and 5 for sudden death that satisfied the eligibility criteria. Following thematic analysis, we identified 7 themes: breathing irregularities, abnormal spontaneous brainstem activations, heart rate variability metrics, QTc changes, vagal imbalance, fluctuation in peptides and serotonergic neurotransmission. We grouped these 7 themes into 3 final themes: (A) brainstem modulation of breathing, (B) electrical instability of the cardiovascular system and (C) neurochemical changes contributing to autonomic decline. We described key evidence relating to each theme and identified important areas that could improve the clinical management of patients with RTT. Limitations: The heterogeneity of the methods used to assess autonomic function increased the difficulty of making inferences from the different studies. Conclusion: This study identified the important mediators of autonomic dysfunction and sudden death in patients with RTT. We proposed brainstem mechanisms and emphasized risk factors that increase brainstem vulnerability. We discussed clinical management to reduce sudden death and future directions for this vulnerable population.We performed 2 separate systematic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. 29 The first review examined autonomic dysfunction, and the second focused on the causes of sudden death in patients with RTT. Article selectionThe selection of articles for each systematic review was performed by the first (J.S.) and the second author (E.L.) independently. Database searches were done in a blinded manner using the same search terms. Once the eligible articles had been identified independently by J.S. and E.L., any doubts were resolved during a meeting to review the queried article(s) against the inclusion and exclusion criteria. The final selection of eligible articles included in the critical appraisals was made based on agreement between J.S. and E.L.

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“…Changes in EDA could also provide useful information on seizures since when compared to adults, children with epilepsy were found to have a higher EDA response (36). We have previously shown that the EDA is disordered in RTT patients (61,62). In our recent evidence synthesis (59), we proposed that EDA could also be useful in monitoring the physical health of the patient, and we can now extend its use to provide valuable information on the sympathetic response in RTT patients who are more prone to frequent seizures.…”

Section: Discussionmentioning

confidence: 99%

Autonomic Characteristics of Sudden Unexpected Death in Epilepsy in Children—A Systematic Review of Studies and Their Relevance to the Management of Epilepsy in Rett Syndrome

2021

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Aim: To systematically identify and critically appraise studies that investigate the autonomic characteristics of Sudden Unexpected Death in Epilepsy (SUDEP) in the pediatric population. We also wanted to explore how this information would be relevant to the management of epilepsy in patients with Rett Syndrome.Method: Using PRISMA guidelines, a systematic review of PubMed, Scopus, Cochrane, PsycINFO, Embase, and Web of Science databases was performed to identify eligible studies. After extracting data from the included studies, a thematic analysis was undertaken to identify emerging themes. A quality appraisal was also done to assess the quality of the included studies.Results: The systematic search revealed 41 records, and 15 full-text articles on the autonomic characteristics of SUDEP in children were included in the final analysis. Following thematic analysis, three themes were identified (I) modulation in sympathovagal tone, (II) pre- and post-ictal autonomic changes, and (III) other markers of autonomic dysregulation in children with epilepsy. Modulation in sympathovagal tone emerged as the theme with the highest frequency followed by pre- and post-ictal autonomic changes. While the themes provide additional insight into the management of epilepsy in the Rett Syndrome population, the quality of evidence concerning the autonomic characteristics of SUDEP in the pediatric population was low and underscores the importance of much needed research in this area.Conclusion: The mechanism of SUDEP in the pediatric population is complex and involves an interplay between several components of the autonomic nervous system. While direct clinical inferences regarding pediatric SUDEP could not be made, the thematic analysis does suggest that in vulnerable populations such as Rett Syndrome, where there is already a pervasive autonomic dysregulation, pro-active surveillance of the autonomic profile in this patient group would be useful to better manage epilepsy and reduce the SUDEP risk.

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Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report

Cited by 9 publications

References 31 publications

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Autonomic dysfunction and sudden death in patients with Rett syndrome: a systematic review

Autonomic Characteristics of Sudden Unexpected Death in Epilepsy in Children—A Systematic Review of Studies and Their Relevance to the Management of Epilepsy in Rett Syndrome

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