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

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 ADHD and RLS/PLMD.

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 et al., 2005).

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 depending on their age-related verbal abilities.

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

Cerebrospinal fluid (CSF), Magnetic Resonance Imaging (MRI) and autoptic studies also proved reduced iron stores in the brain of RLS subjects.

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

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 ADHD-related symptoms and scores.

Iron supplementation (Konofal et al., 2008), or most recently levetiracetam (Gagliano et al., 2011) seem to hold promising results for the management of RLS in ADHD.

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 separate or additional treatment of sleep related symptoms.
