**4. Pathophysiology**

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

respiratory events (hypopneas and apneas).

**2. Epidemiology**

adenotonsillar hypertrophy [4].

environmental factors [6].

**3. Risk factors**

adults and in children.

primary snoring and of 1.8% for OSAS [5].

related breathing disorders in pediatric age.

lower incidence of daytime excessive somnolence.

number of tandem repeat (INS VNTR) sequence regulation [9].

obstruction of the upper airways. The nocturnal episodes of total or incomplete breathing interruption are identified and recorded in the apnea/hypopnea index per hour (AHI), and the nocturnal oxygen desaturation is expressed as oxygen desaturation index per hour (ODI). In children, in contrast to the adult, definition of OSAS, which requires an AHI ≥ 5 episodes per hour of sleep lasting more than 10 seconds,

In 1976, OSAS syndrome was identified and described in pediatric age by Guilleminault et al. [3], and from that time on, studies on this pediatric pathology have multiplied, considering its important impact on all aspects of life often linked to the intermittent nocturnal hypoxia not ever associated with the nocturnal

In the developmental age, prevalence in preschool and school age for primary snoring ranges from 3.2 to 12.1%, while for OSAS, it varies from 1.1 to 2.9%. The peak incidence is observed between 3 and 6 years and coincides with the age of maximum development of lymphatic tissue. In all the studies found in the literature, it can in fact be noted that the incidence of OSAS is greater in children with

The prevalence of OSAS in Italy shows a prevalence in children of 4.9% for

On the other hand, African American children were reported four to six times more likely to have OSAS than children of Caucasian origin [6], while the predisposition to OSAS in African Americans has been attributed to different upper airway anatomy and pharyngeal neuromotor control in addition to other genetic and

In clinical practice, there are many screening tests for the identification of sleep-

Furthermore, in children, sleep is less fragmented than adults because the behavioral awakenings seem to be less frequent in children than in adults with a

OSAS is a complex and multifactorial syndrome, and it is believed that some specific genes may play a crucial role in its pathogenesis, particularly involved in the expression of the CLOCK gene [7], IL-10 polymorphisms [8], and insulin variable

In general, there are some conditions that may predispose to OSAS, such as alterations of craniofacial structures, obesity with fat deposition on side walls of the pharynx, endocrine changes, alcohol intake, and cigarette smoking [10] both in

In pediatric population, the main risk factor is adenotonsillar hypertrophy [11, 12], but others are rhinitis [13], nasal structure alteration [14, 15], cleft palate, velopharyngeal flap surgery, pharyngeal masses, craniofacial malformations [16], genetic syndrome (i.e. Down syndrome, Crouzon syndrome, and Apert syndrome), genetic hypoplasia mandibular (Pierre Robin syndrome, Treacher Collins syndrome, Shy-Drager syndrome, and Cornelia De Lange syndrome) [17, 18], craniofacial traumas [19, 20], chronic or seasonal rhinitis [13],

with persistent thoracoabdominal movements [1], does not require so.

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In OSAS, due to a reduction in the size of the upper airways and a reduction in the activity of the pharynx dilator muscles, there are an increase in critical pressure (transmural pressure value at which the area of the pharyngeal section is equal to zero) and an enormous reduction in the pharyngeal lumen [29].

The obstructive events will therefore lead to the appearance of hypoxemia and hypercapnia, which will first cause an increase in respiratory effort, and then a wake-up, of a few seconds, which will serve to restore the patency of the upper airways; all these will repeat cyclically during sleep, causing an alteration of the structure.

In the adult, there is a reduction in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep, and consequently, the major symptom is daytime sleepiness; in children, on the other hand, intermittent hypoxia has a role in the appearance of neocognitive deficits, which are the most common signs and symptoms in the case of OSAS in the developmental age [29].

Behavioral awakenings in the child with OSAS are less frequent than in adults, and this on the one hand allows the child to retain the benefits of sleep, and on the other hand, it can cause long periods of hypoventilation. Moreover, in children, the desaturation of O2 can also be achieved during short apnea due to the reduced functional lung capacity and the most frequent respiratory rate in pediatric age [29].

In OSAS, there is also a state of chronic systemic inflammation, mainly linked to intermittent hypoxia, which promotes the activation of some factors responsible for inflammation such as C-reactive protein (PCR) and IL-6 and is therefore responsible for a state of oxidative stress [30].

Oxidative stress and increased production of oxygen-free radicals represent the pathophysiological substrate of the onset of cardiovascular, cerebrovascular, and metabolic complications [31, 32].

### **5. Clinical signs**

Clinical signs of OSAS appear to be different in pediatric age with respect to adulthood, and therefore, the diagnostic and therapeutic management overlapping may be considered a severe clinical mistake.

In adults with OSAS, the most common presentation is excessive daytime sleepiness (EDS) that results from sleep fragmentation and from the frequent nocturnal intermittent hypoxic episodes [33], while in nonobese children, EDS is a rare complain. Conversely, children with OSAS tend to be not drowsy but rather hyperkinetic during the day, and often, these children are misdiagnosed with attentiondeficit/hyperactivity disorder (ADHD) and treated with methylphenidate.

This common diagnostic mistake is derived from the lack of evaluation of sleep habits in children presenting with suspected hyperactivity behavior that may highlight the presence of ADHD-like symptoms and not of ADHD syndrome [34, 35].

In pediatric age, the symptoms and major signs of suspected nocturnal respiratory problems are mainly oral breathing [36], nocturnal hyperkinesia, snoring or breathing pauses [37], nocturnal positional abnormalities [38], behavioral problems [39, 40], poor academic performance [41], failure to thrive and growth delay, recurrent airway infections [37], recent enuresis onset [42, 43], and night sweating and drooling [44].

### **6. Polysomnography (PSG)**

Pediatric respiratory disorders during sleep find their diagnostic gold standard in the overnight polysomnography. This term commonly means the simultaneous and continuous recording during the night of functional parameters suitable for defining the cardiorespiratory events in relation to the various phases of sleep. Normally, during the test, two or more electroencephalogram (EEG) channels, two or more electromyographic channels, chest and abdomen movements, oronasal flow, oxygen saturation in the blood, and CO2 measurement are recorded. The polysomnographic result must always be contextualized with the symptoms and signs and referred to the general clinical picture since there is not always a correspondence between the severity of the polysomnographic instrumental data (in terms of number of events and levels of O2 desaturation) and the gravity of symptoms [45].

The severity identification of SRBD is identified by apnea/hypopnea index (AHI) and oxygen desaturation index (ODI). In pediatric age, AHI cut-off has been established between 1.2 and 1.3 nocturnal events per hour, while for ODI are conflicting and nonconclusive results.

#### **7. Diagnosis and classification**

For the diagnosis of OSAS, the anamnesis, the physical examination, and the polysomnographic examination that allows an early diagnosis and therefore an early therapy to prevent the development of complications are fundamental.

During the visit, a careful history assessment must be made, considering if there is the presence of familiarity for OSAS and if there are symptoms such as snoring, attention deficit, predominantly oral breathing, nocturnal hyperkinesia, behavioral problems and academic performance, recurrent airway infections, recently onset enuresis, night sweats, and nocturnal sialorrhea [43].

On physical examination, the signs and findings most closely linked to a high risk of respiratory disorders in sleep are adenotonsillar hypertrophy, rhinitis, macroglossia, and obesity [43].

Analyzing the oronasal flow is used to assess ventilation and to identify and differentiate central apnea from obstructive apnea, whereas hypopneas are more difficult to identify as they are not greater than 50% of respiratory flow. Analyzing thoracoabdominal movements and respiratory effort, on one hand, and quantitative and qualitative information on breathing, on the other hand, can be obtained.

The respiratory parameters are useful for the diagnosis of OSAS, and the American Academy of Sleep Medicine distinguishes respiratory events in central, obstructive, and hypopneic episodes [46].

Central apnea is caused by the damage to the nerve centers that regulate ventilation and is characterized by a complete cessation of ventilation with no thoracoabdominal movements. In the child, it can be an occasional event that becomes

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*Neuropsychological Alterations in Children Affected by Obstructive Sleep Apnea Syndrome*

pathological if there are more than three episodes per hour of sleep with a desatura-

The obstructive apnea is instead caused by a complete or partial obstruction of the upper airways associated with inspiratory effort evidenced by the variation of thoracoabdominal movements in an attempt to overcome the obstruction. In children, even only one obstructive event per hour of sleep has a pathological character

Obstructive hypopnea consists of a reduction in oronasal flow >50%, with a desaturation of >3% for at least two respiratory cycles, and accompanied by thora-

Children may present four grades of OSAS severity classified by the Italian

**minimum OSAS:** AHI between one and three episodes per hour and/or the presence of continuous snoring for at least 50% of sleep associated with O2

Adenotonsillectomy is the main treatment in children, but if this failed or in the case of obese patients, continuous positive airway pressure (CPAP) or other positive

**8. The link between the severity of respiratory disturbance in sleep** 

According to many reports [47–49], neurocognitive alterations seem to be the direct effect of nocturnal intermittent hypoxia, sleep fragmentation, hormonal imbalance, systemic subclinical inflammation [50, 51], and endothelial dysfunction [52]. Nocturnal intermittent hypoxia causes a chronic state of neuroinflammation due to the production of proinflammatory cytokines such as interleukin (IL)- 10, IL-6, IL-1, and TNF-α [53], although also serum C-reactive protein (CRP), pentraxin-3 (PTX-3), procalcitonin (ProCT), IL-33, and its soluble receptor ST2 (sST2) may be identified as putative biomarkers for OSAS severity almost in adults [54]. Interestingly, in children affected by OSAS and cognitive alteration, there is an increase in PCR and proinflammatory cytokines that are reduced following the

Oxidative stress also directly and indirectly causes endothelial and vascular alterations that provoke an alteration in cerebral perfusion and play an important

Although IGF1, the insulin-like growth factor, is mainly produced by the liver under the stimulation of growth hormone (GH), its mechanism of action is mediated by its specific receptor, IGF1R, which is present on many cell types in many tissues, where it promotes cell proliferation and differentiation, especially at cartilage and muscle levels, so it is essential for growth processes in children. IGF1 can also be produced from other tissues as well as from the liver, including the brain, where it is synthesized without control by circulating GH. IGF1 promotes neuron survival and differentiation. It is involved in brain plasticity processes and regulates synapse formation, neurotransmitter release, and neuronal excitability. In children with OSAS, it was seen that high systemic levels of IGF1 appear to have a neuroprotective role because they reduce the risk of cognitive impairment [55, 56].

role in the onset of neurocognitive alteration in OSAS children [53].

*DOI: http://dx.doi.org/10.5772/intechopen.91818*

tion of >3% [46].

(AHI ≥ 1/h) [46].

coabdominal movements [46].

Society of Sleep Medicine [46] as follows:

pressure devices need to be considered [43].

**and neurocognitive disorders**

adenotonsillectomy [51, 52].

desaturations above 4% and average SaO2 > 97%; **mild OSAS:** 3 < AHI < 5 and average SaO2 > 97%;

**severe OSAS:** AHI > 10 or with average SaO2 < 95%.

**moderate OSAS:** 5 < AHI < 10 and average SaO2 > 95%; and

*Neuropsychological Alterations in Children Affected by Obstructive Sleep Apnea Syndrome DOI: http://dx.doi.org/10.5772/intechopen.91818*

pathological if there are more than three episodes per hour of sleep with a desaturation of >3% [46].

The obstructive apnea is instead caused by a complete or partial obstruction of the upper airways associated with inspiratory effort evidenced by the variation of thoracoabdominal movements in an attempt to overcome the obstruction. In children, even only one obstructive event per hour of sleep has a pathological character (AHI ≥ 1/h) [46].

Obstructive hypopnea consists of a reduction in oronasal flow >50%, with a desaturation of >3% for at least two respiratory cycles, and accompanied by thoracoabdominal movements [46].

Children may present four grades of OSAS severity classified by the Italian Society of Sleep Medicine [46] as follows:

**minimum OSAS:** AHI between one and three episodes per hour and/or the presence of continuous snoring for at least 50% of sleep associated with O2 desaturations above 4% and average SaO2 > 97%; **mild OSAS:** 3 < AHI < 5 and average SaO2 > 97%; **moderate OSAS:** 5 < AHI < 10 and average SaO2 > 95%; and **severe OSAS:** AHI > 10 or with average SaO2 < 95%.

Adenotonsillectomy is the main treatment in children, but if this failed or in the case of obese patients, continuous positive airway pressure (CPAP) or other positive pressure devices need to be considered [43].
