**4.2 Excessive Daytime Sleepiness (EDS) and narcolepsy in ADHD**

As previously reported in this chapter, the "hypoarousal state" theory regarding ADHD claims that there may be decreased sleep oscillations (CAP) in ADHD children without major co-occurring sleep disorders, and this might explain their daytime drowsiness as confirmed by MSLT data and, indirectly, by the Epworth Sleepiness Scale (ESS) results in ADHD adults (Oosterloo et al., 2006).

On a modified version of MSLT, ADHD children were found to be objectively more sleepy than controls, albeit a higher rate of OSAS in probands with respect to controls (50% vs. 22%) could represent a strong bias in this study (Golan et al., 2004).

Also, Lecendreux et al. (2000) found a shorter mean sleep latency in ADHD children compared to controls, with a significant correlation to hyperactivity impulsivity and inattentive-passivity indexes, as measured by Conners Parent and Teacher rating scales (CPRS & CTRS respectively).

Differences in nocturnal sleep could not account for any of these results. None of these authors, however, sought for the instrumental hallmark of narcolepsy (2 Sleep onset REMs) in their studies, nor reported on the clinical secondary features of narcolepsy (cataplexy, hypnagogic hallucinations and paralysis) in ADHD children.

The fact that reaction time values in these studies (Lecendreux et al., 2000) hold a negative correlation with the hyperactivity-impulsivity index of the CPRS indicates that a major distinction must be drawn between IADHD and HADHD. Generally, only a subgroup of ADHD children are found to be sleepier than most average ADHD subjects, thus suggesting an impaired control of their arousal system, which may induce them to switch rapidly from wakefulness to sleep when insufficiently externally stimulated during daytime (Ramos Platon et al., 1990).

A consequent implication of this theory would be an improved therapeutic option through the employment of noradrenergic -1 agonists (Biederman & Spencer, 1999) such as modafinil, rather than the commonly used dopaminergic stimulants.

In a more recent study (Prihodova et al., 2010), SL on MSLT in unmedicated ADHD children exhibited significant time-related changes compared to the control group, but no intergroup differences were found regarding MSLT mean sleep latency when comparing the whole ADHD group with controls.

Sleep Disorders Diagnosis and Management in

**4.4 Sleep related movement disorders** 

ADHD and RLS/PLMD.

et al., 2005).

**4.4.1 Periodic Leg Movements (PLMD) and RLS** 

depending on their age-related verbal abilities.

ADHD-related symptoms and scores.

**4.4.2 Rhythmic Movement Disorder (RMD)** 

proved reduced iron stores in the brain of RLS subjects.

Children with Attention Deficit/Hyperactivity Disorder (ADHD) 37

Symptoms of ADHD have been found in 44% of children with PSG evidence of PLMs (Crabtree et al., 2003). Conversely, between 26% and 64% of ADHD children have a PLMs index >5/h of sleep (Picchietti et al., 1998; 1999). Furthermore, between 44% and 67% of the positive probands have a parental history of RLS, suggesting a possible genetic link between

When an additional co-morbidity with SDB was reported, the link between PLMs and ADHD appeared to be stronger, mediating the secondary SDB-ADHD association (Gaultney

The reported prevalence of RLS in ADHD children ranges from 44% (Cortese et al., 2005) to no association at all (Gamaldo et al., 2007). Silvestri et al. (2009) reported that an RLS prevalence of 12% by interview and clinical criteria was increased to 25.4% after PSG evaluation, reflecting the frequent difficulties to elicit an appropriate history from children

PLM during wakefulness (PLMW) but not RLS itself were associated to lower ferritin values, unlike previous reports (Konofal et al., 2007, 2008; Oner et al., 2008). In particular, lower ferritin values in ADHD children, whether or not RLS+, were reported by Konofal et al. (2004), compatible with the ADHD dopaminergic dysfunction hypothesis. Iron, in fact, is a co-factor

Cerebrospinal fluid (CSF), Magnetic Resonance Imaging (MRI) and autoptic studies also

Iron deficiency could therefore represent a link and an interpretation key to the dual pathology of RLS and ADHD related disorders (Cortese et al., 2008), D1 and D2 receptor density being also altered by an iron-deficient state (Walters et al., 2000; Konofal et al., 2008). RLS was found to be significantly associated with H- and CADHD, rather than IADHD, with a strong impact on CPRS, CTRS and SNAP IV Teacher and Parent Rating Scale

Preliminary data on dopaminergic treatment of ADHD-associated RLS suggested a dual improvement of RLS and ADHD symptoms (Walters et al., 2000). However, these results were not further replicated (England et al., 2011) since dopaminergic treatment of a larger number of ADHD-RLS+ children led to RLS improvement without any change in the

Iron supplementation (Konofal et al., 2008), or most recently levetiracetam (Gagliano et al.,

Even if it is not yet clear whether RLS and ADHD share a common genetic basis or have a distinct pathogenesis with one disorder (RLS) mimicking or leading to the other (ADHD), it is certainly important to look for RLS-related aggravation of ADHD symptoms to address

RMD consists of head banging or body rocking behaviors primarily occurring in young

The disorder often disappears with age over 18 months, but it is estimated to last sometimes in adolescents or adults with psychiatric problems or epilepsy (Simonds & Parraga, 1984; Mayer et al., 2007). Other PSG studies in pediatric populations disclosed RMD in 6/10

of the rate-limiting enzyme, tyrosine-hydroxylase, regulating dopamine synthesis.

(Swanson, 1992) hyperactive and oppositional scores (Silvestri et al., 2009).

2011) seem to hold promising results for the management of RLS in ADHD.

separate or additional treatment of sleep related symptoms.

children prior to sleep onset or during subsequent sleep.

ADHD children, mostly with CADHD (Stepanova et al., 2005).

Likewise, no such differences were found when comparing different subgroups of ADHD with or without SDB/PLMs.

Again, a dysregulated arousal mechanism could be postulated in the absence of an overall objectively proven daytime sleepiness in ADHD.

Conversely, as for signs of ADHD in narcoleptic patients, memory, attention and executive functions were found to be affected in most, but not all, studies (Naumann & Daum, 2003). In particular, divided attention and complex cognitive tasks prove selectively sensitive to arousal fluctuations in narcolepsy (Hood & Bruck, 1996). However, automatic but not hyperactive behaviors have been reported or searched for in narcolepsy research in an attempt to allow a better clinical comparison between the two disorders.

#### **4.3 Sleep apnea (OSAS)**

Most of the recent attention to the ADHD co-morbidity with OSAS came from a paper reporting the impact of adenotonsillectomy on adverse events and behavioral problems in SDB children (Li et al., 2006). The authors described an overall improvement of all measures [AHI, tests of variable attention (TOVA), and child behavior check list (CBCL) scores] with no correlation, however, between AHI and TOVA values.

The correlation between OSAS and ADHD is difficult to explore, due to several confounding factors such as age, gender, recruitment sources and methodological approaches including the definition and the measurement of respiratory events in children (Sadeh et al., 2006).

Cortese et al. (2006) found and AHI 1/hour greater than controls in children with ADHD.

Race plays also an important role in the association between ADHD and OSAS. Hispanic children show a greater co-morbidity than Caucasian probands as far as learning problems, snoring and witnessed apneas (Goodwin et al., 2003).

Also, Huang et al. (2004), reported worse attention deficit and higher hyperactivity on the CBCL of ADHD with SDB compared to ADHD without SDB children, with an overall 57% of elevated AHI (>1) in their total group of ADHD subjects, against an AHI (>1) in only 4% of their control group. Both the cranio-facial predisposition to OSAS and the high prevalence of ADHD in Taiwan could, however, impede a generalization of these results. Adenotonsillectomy more than pharmacological treatment with stimulants lead to a favorable outcome in the same group (Huang et al., 2007).

Interestingly, most researchers agree on the association of only mildly severe OSAS to ADHD (O'Brien et al., 2003b; Sangal et al., 2005; Silvestri et al., 2009) suggesting that SDB leads to a mild mimic of ADHD, rather than a true form of it.

Possible mechanisms accounting for the association between ADHD and OSAS are intermittent hypoxia and sleep fragmentation which could both be responsible for neurochemical alterations of the pre-frontal cortex and their related effects including executive dysfunction with emotional liability and impulse control disorders (ICD).

Severe OSAS in the pediatric community is rare and usually linked to EDS rather than to hyperactivity, with a phenotypical change of behavior from mild to severe ADHD. It is unclear so far whether SDB may contribute only to mild ADHD mimics or really impact ADHD clinical expression and therapeutic management. While it is known that surgical treatment of OSAS may improve ADHD symptoms, no classic non-stimulant drugs (atomoxitin, clonidine, modafinil) used for the management of ADHD (Walters et al., 2008) induce a parallel improvement of OSAS.
