Prader-Willi Syndrome-Improvement of Cognitive Function through Noninvasive Ventilation in Children Syndrome-Improvement of Cognitive Function through Ventilation

Background: PWS is a rare genetic disease characterized by a variety of physical, psychological and physiological changes. The prevalence of PWS is estimated to be between 1:12000 - 1:25000 live births, no matter the gender or race. The pathology occurs in a percentage <1% of congenital diseases associated with mental retardation. The disease is diagnosed during the neonatal period and in infants with the help of the known association of facial dysmorphism with marked muscle hypotonia and eating disorders. In evolution, patients with PWS have sleep-related respiratory disorders with severity changes over time, depending on the clinical stage of the disease. Case report: Patient diagnosed in the neonatal period with PWS (intrauterine growth retardation, craniofacial dysmorphism, hypotonia, eating difficulties) and confirmed by molecular genetics tests; evaluated in our clinic at the age of 4 years. The polysomnography showed severe obstructive sleep apnea syndrome associated with severe intermittent hypoxemia. The patient suffers from mental retard with QD=45, attention and concentration disorders and aggression traits. It is decided to initiate nocturnal noninvasive ventilation, CPAP therapy throughout sleep period. The growth hormone substitution therapy is continued, and the patient is included in a cognitive-behavioral therapy program. Conclusions: The evaluation done at 12 months after the initiation of the noninvasive ventilation at home highlights the increase in both the concentration ability and the memory capacity, the improvement of the relationship abilities, the increase of the school performances, the reduction of the impulsivity traits associated with the improvement of QI/QD. The authors try to establish a correlation between reducing the hypoxemia through noninvasive nocturnal ventilation and the improvement in the cognitive-behavioral function.

Recent data suggest that there is an increase in the number of patients diagnosed with Prader-Willi Syndrome due to maternal disomy possibly secondary to the increased in maternal age at the time of conception [6][7][8][9][10]. Genotypic changes result in polymorphic phenotypic changes that associate various degrees of physical, physiological and psychological damage [10]. Physical factors include the association of infantile hypotonia with onset during the intrauterine life (reduced fetal movements), hypogonadism, craniofacial dysmorphism, scoliosis, obesity and short stature [11][12][13]. Patients have characteristic physiological traits (muscular hypotonia, metabolic imbalance, sleep related respiratory problems, excessive daytime sleepiness), associated with psychological traits with various degrees of impairment (tantrums, hyperphagia, obsessive-compulsive behavior, irritability, low frustration threshold, intellectual impairment) [11][12][13][14][15]. Phenotypic changes are the consequence of genetic damage in PWS.
Moreover, these patients frequently associate sleep related respiratory syndrome [11]. The authors aim to draw attention to the evolution of a patient diagnosed with Prader-Willi Syndrome who shows a dramatic improvement of both the cognitive function and the psychological component as a result of the correction of nocturnal hypoxemia.

Case Report
A male patient diagnosed with PWS during the neonatal period was referred to the cardiology department of our hospital, Bucharest, Romania, in September 2019, at the age of 4 years ols, for the investigation of an atrial septal defect. We know that he is a second-degree child of young parents (mother: 24 years, father: 26 years), healthy, not consanguineous, without congenital abnomalies, metabolic diseases or reproductive disorders. Pregnancy is monitored (the mother reports reduced fetal movements compared to the first pregnancy), it has intrauterine growth retardation in the third trimester of pregnancy. He is extracted by cesarean section at 39 weeks of gestation, birth weight: 2400 grams, length: 49cm, Apgar score 4 -shows marked muscular hypotonia at birth. In dynamics, the impossibility of natural feeding or bottle feeding is ascertained and feeding by gavage for 2 weeks is necessary.      Due to manual titration, the pressure established managed to treat episodes of sleep apnea and hipopnea and to improve the quality of sleep. Patient compliance is good for using CPAP at home.
He uses the CPAP every night with an appropriate number of hours/ night (average 7-8 hours/ night) and good tolerance. Figure 4 shows patient compliance and hours of CPAP use at home between 29 th february 2020 -11th september 2020, data obtined from reading compliance CPAP card According to the monitoring protocol of the patient with noninvasive ventilation, the child is evaluated periodically, at intervals of one month, 3 months, 6 months. As a result of reading the compliance card, it is decided to maintain the noninvasive ventilation parameters at the same values. The child is periodically monitored multidisciplinary: endocrinology, psychology, speech therapy and benefits from cognitive-behavioral therapy. He receives nutrition according to the recommendations of a nutritionist specialized in the nutrition of the patient with PWS.

Conclusion
The authors note the improvement in cognitive performance supported by increased QD in a patient diagnosed with PWS. The idea that reducing hypoxia and improving sleep quality (confirmed by polysomnographic findings and supported by anamnestic and psychological examination) increase the quality of life and academic performance in the PWS patient noninvasively ventilated at home, is credited. The monitoring of a patient with PWS will be performed in a multidisciplinary center, with the permanent intervention of the endocrinologist in order to adjust the dose of growth hormone, with regular polysomnography assessments. The patient will be assisted by a specialized nutritionist and will benefit from the competence of behavioral therapists. The authors work in a highly addressable clinic for patients with Prader-Willi Syndrome and benefit from a high-performance laboratory and specialized staff in the sleep study. The authors aim to expand the group of patients with PWS who require nocturnal noninvasive ventilation to confirm a correlation between hypoxia secondary to respiratory sleep disorders and improved academic and behavioral performance after 12months post initiation of noninvasive ventilation with continuous positive airway pressure.