23 Giugno 2023
Elisa Maria Zamperioli
Dottor Alberto Cossu
SONNO E RITMO CIRCADIANO NELLA SINDROME DI DRAVET: RISULTATI DI UNO STUDIO OSSERVAZIONALE SU 27 PAZIENTI IN UN SINGOLO CENTRO
Dravet Syndrome (DS) is a Developmental and Epileptic Encephalopathy characterised by a refractory epilepsy, developmental delay and motor impairment. The many comorbidities comprises autistic traits, behavioural dysregulation, and sleep disorders. Studies reported a complaint in the child's sleep quality in 72.4% of cases, and as much as 82%. The Parisian group (Losito et al., 2017) described Interictal Epileptiform Discharges (IEDs) activated by sleep and tonic seizures during sleep from 11-12 years old. We aim to investigate the effect of sleep on modulating epileptic phenomena in DS, and their effect on sleep architecture and circadian rhythm alterations.
We enrolled all patients with a diagnosis of DS with a whole night polygraphic recording (PSG). We analysed all traces and calculated PSG parameters for all recordings. We defined the recurring of EEG arousal events preceded by IEDs as IED-Related-Arousal (IRAs). We recorded a sub-group of patients with actigraphic recordings of 5 days to investigate sleep circadian rhythm in DS patients.
We identified two substages of N1: N1A, with abundant theta over the central-parietal regions, and N1B, dominated by sigma activity. Patients with tonic seizure had shorter REM. Those with convulsive seizures, and those with a higher IRA-index, had shorter N3. Patients treated with Fenfluramine had a lower IRA-index. Older patients had shorter REM and longer N3, and lower Sleep Efficiency and longer sleep latency. The mean Sleep Regularity Index was 56%.
Our findings show a peculiar age-dependent sleep microstructure of NREM sleep in DS. Sleep architecture had a developmental aspect, less efficient sleep an higher sleep latency in older patients. Regarding the effect of epilepsy on sleep stage dynamics macrostructure, we report an effect of morpheic motor seizures on NREM and REM sleep duration. The recurrence of IRAs was associated with a shorter N3 and a response to fenfluramine, which lowered their frequency. These are novel findings in DS, and they underlie the importance of EEG when assessing sleep in DS. We found a generally disrupted sleep regularity. This, interpreted with the previously reported age dependent higher sleep latency and lower SE, seems to suggest a progressive tendency to circadian sleep disruption, not related to the epileptic phenotype but to the developmental phenotype of DS. This is also supported by recent studies on mice with SCN1A loss-of-function (Han et al., 2012; Papale et al., 2013; Sanchez et al., 2019), that found a disruption of the GABAergic effect on the dorsal portion of the SCN that produced a phase shift in the circadian rhythm.
Our multimodal approach to the study of sleep in DS allowed us to investigate different properties expressed in different time resolutions, showing the effect of morpheic ictal phenomena on sleep architecture, underlying the importance of EEG in sleep studies, and a progressive sleep impairment, possibly linked to circadian rhythm disruptions.
Dottoressa Elisa Maria Zamperioli
VALUTAZIONE NEUROPSICOLOGICA IN UN CAMPIONE DI 40 SOGGETTI CON SINDROME DI DRAVET E PROPOSTA DI UN NUOVO STRUMENTO DI VALUTAZIONE MULTIDIMENSIONALE (D.A.N.D)
Background and aim: Dravet syndrome (DS), also known as severe myoclonic epilepsy in childhood (SMEI), is a rare, drug-resistant epileptic and developmental encephalopathy associated with neurological and cognitive-behavioral impairment. Individuals with Dravet syndrome exhibit a unique set of clinical characteristics, making some of the commonly used cognitive and adaptive functioning rating scales inapplicable.; these scales frequently demonstrate "floor effects" or "ceiling effects", rendering them ineffective in assessing the overall functioning of the patient. Thus, there is a need for a specific, multidimensional, population-built scale to investigate disabilities and comorbidities in individuals with Dravet syndrome, in order to plan appropriate treatment strategies.
Methods: In this study, we conducted a longitudinal retrospective analysis of the epileptic phenotype, neurological and cognitive features of 40 patients with Dravet syndrome, aged 3 to 38 years old, who were followed at the Department of Childhood Neuropsychiatry, Verona, Italy. Additionally, we performed a prospective study of neuropsychological data obtained from the application of the D.A.N.D scale and other standardized scales.
Results: Our analysis revealed a progressive cognitive decline in the patient poolover time, which correlated with an arrest or regression in adaptive functioning. We found significant clinical variables in the population ( SCN1A gene truncating mutation, episodes of status epilepticus, absence, myoclonia in early life) correlate with increased motor impairment, worsening of personal autonomy, academic and learning abilities, associated with socialization impairment and worsening of executive functions.
Conclusions: Our study highlights the need for a sensitive and effective instrument to assess characteristic disabilities in individuals with Dravet syndrome accurately. From our results, the D.A.N.D. scale appears to be a practical and accurate tool capable of analyzing all multidisciplinary issues. This allows appropriate formulation of therapeutic and rehabilitation plans (psycho-educational programs, specialized assessments and treatments) in order to ensure the best possible quality of life for these patients.
Riconosciuta come personalità giuridica con provvedimento della Giunta Regionale del Veneto del 09.12.2015 n° 815.
Convenzionata con l’AOUI di Verona Prot. 1306 del 12/01/2021. Approvata con Delibera nr. 1392 del 30/12/2020
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