Background: Play is the child’s natural world. According to psychoanalytical studies, play has an important role in children’s development, and the absence of play during a child’s life could lead to severe pathological implications. Based on this theory and being aware that physiotherapy treatment programs could be long lasting, tiresome and lacking motivation for children, this literature review presents a perspective regarding the integration of play within physiotherapy programs and examines the physical and emotional outcomes during this integration. Aim: To investigate the outcomes of integrating play in physiotherapy for children with chronic health conditions. Method: The research strategy for this review was a thorough search of peer-reviewed articles in the databases CINAHL and AMED which include articles from the fields of allied and complementary medicine, as well as the database Scope Med. Participants were children with chronic health conditions, ranging from 2-18 years old. In the term ‘play’ virtual reality and video game activities were included due to the lack of research. In addition, articles from a previous literature review conducted by the author were also included in the present paper. Results: The focus of researchers on children with CP and the lack of evidence for children with other health conditions, the persistence of physiotherapists to assess mainly physical outcomes and not emotional needs of children, and the measurement tools used for this purpose are presented. Conclusions: For children with chronic health conditions who attend physiotherapy sessions, play could serve as a mediate and an appropriate developmental approach in order to achieve physical and emotional changes. There is a need for physiotherapists to balance physical and emotional needs, and have a more ‘human’ relationship, rather than a ‘bodily’ - strict professional relationship with children. Although the information presented in this review is not considered as sufficient to draw conclusions, it could serve as a first step for researchers to study this integration in greater depth, and to focus on children with conditions other than CP.

Neurodegeneration with Brain Iron Accumulation (NBIA) disorders, such as Phospholipase A2G6-Associated Neurodegeneration (PLAN) and Pantothenate Kinase-Associated Neurodegeneration (PKAN), are a group of rare early-onset, genetic disorders characterized by neurodegeneration and iron accumulation inside of the basal ganglia (BG), which is accompanied by progressive motor symptoms. In order to address the limitations in available models of NBIA, a B6.C3-Pla2g6m1J/CxRwb mouse model of PLAN was characterized. This model demonstrated key hallmarks of the disease presentation in NBIA, including a severe and early-onset motor deficit, neurodegeneration inside of the substantia nigra (SN) including a loss of dopaminergic function and the formation of abnormal spheroid inclusions as well as iron accumulation. The capture of these hallmarks of NBIA makes this an ideal animal research model for NBIA. Additionally, exploration of candidate systemic biomarkers of NBIA was performed in a case study of a patient with PLAN and in a cohort of 30 patients with PKAN. These investigations demonstrated reductions in transfer and slight, but not significant elevations in soluble transferrin receptor. No significant difference was seen in serum iron parameters. A systemic disease burden including chronic oxidative stress; elevated malondialdehyde, and inflammation; elevated C-reactive protein (CRP), IL-6 and TNFα was noted in both investigations. A number of candidate protein biomarkers including: fibrinogen, transthyretin, zinc alpha-2 glycoprotein and retinol binding protein were also identified. These markers correlated with measures of the severity of iron loading in the globus pallidus (GP); based on R2* magnetic resonance imaging (MRI) and the severity of motor symptoms (Barry-Albright Dystonia Rating Scale) making them potential candidates markers of dysfunction in NBIA. In the patient with PLAN, 37 weeks of therapy with the iron chelator deferiprone (DFP) as well as 20 months of therapy with the antioxidants alpha lipoic acid (ALA) and n-acetylcysteine (NAC) were efficacious in reducing the systemic oxidative and inflammatory disease burden, but it did not significantly alter the progression of the disease. In the antioxidant therapy, this efficacy was primarily due to ALA. When the cohort of patients with PKAN were treated with DFP for 18 months it was highly efficacious in lowering brain iron accumulation in the GP. No significant reduction in the speed of disease progression was seen in DFP treated patients compared to placebo based on initial analysis. Similar to the PLAN patient, DFP also mitigated the systemic disease burden in PKAN patients. In both cases DFP was well tolerated and had minimal impact on serum iron levels, TIBC and transferrin saturation. Collectively these investigations provide valuable insights into disease progression in NBIA. They also provide tools to aid further investigations in NBIA. These are provided in the form of a well-characterized B6.C3-Pla2g6m1J/CxRwb model of PLAN, which robustly captures the disease presentation seen in patients, as well as a panel of systemic blood-based markers of disease burden in NBIA and candidate markers of dysfunction in NBIA. These markers were used to assess two novel therapies in NBIA chelation with DFP and antioxidant therapy with ALA and NAC. / Graduate / 2019-04-19