**2. Inflammation early in life**

*Advancement and New Understanding in Brain Injury*

and infections like meningitis [5–7].

makes a voluntary movement [8].

characteristic [3]:

ophthalmic (strabismus, visual deficit), otorhinolaryngological, (hearing deficit, mouth breathing), pneumological (recurrent pneumonias), gastroenterological (oropharyngeal dysphagia, gastroesophageal reflux), nutritional (diet, deglutition), neurological (epilepsy, hydrocephalus), orthopedic (limbs, spine deformity, osteoporosis), behavioral disturbances and proprioception (disturbances in sensorial integration) and impact on the secondary musculoskeletal, constipation and epilepsy **Figure 1** [1]. Although the structural damage to the immature brain is static and permanent, the consequences vary and can of change during the child's growth and development

The estimated prevalence of CP varies from 2.3 to 2.9 per 1000 live births in the United States. (National Infant Health Research 2011–2013) **Figure 1** [4]. About 80% of the causes of CP are attributed to intrauterine events such as inflammations, congenital infections, reduced oxygen delivery, and encephalic strokes [5]. The remaining 20% are due to occurrences at birth, such as peripartum suffocation, low birth weight, acute maternal viral infections during pregnancy and postnatal and early childhood factors caused by accidental and non accidental traumas, hypoxia,

Individuals with CP can be classified according to the most dominant clinical

• Dyskinetic: the lesions are located in groups of neurons at the base of the brain and present atypical movements, which are more evident when the individual

• Ataxic: caused by a dysfunction in the cerebellum, presents generalized hypotonia with a loss of muscular coordination, characterized by abnormal

*Characteristics that accompany the subject's life with Cerebral Palsy. (Figures Source: Adobe stock).*

force, rhythm and control or precision of movement [8].

through physical rehabilitation and assisted individualized therapy [1].

**42**

**Figure 1.**

Intrauterine inflammation is observed in approximately 20% of all pregnancies and a surprising 85% of premature child-birth and is associated with a series of neurodevelopment disturbances [10]. Maternal respiratory and genitourinary infections which occur during prenatal hospitalizations and at the moment of birth, emphasize the role of the maternal inflammatory medium in CP's pathogenesis, even though one should not discard an additional causal path involving hypoxemia in the scenario of respiratory infections. Intrauterine infections, extra-uterine infections, and maternal extra-amniotics diagnosed in the hospital during a pregnancy are also associated with a moderately increased risk of pathology in the child [11].

Epidemiological studies of premature births correlate the presence of high levels of inflammatories in the umbilical cord, amniotic liquid and fetal blood with white matter injury, CP and damaged development. In truth, premature babies are born in a serious state of inflammation [12–14].

When there is an association between inflammation and infection, premature delivery may be initiated with ramification of the corona amniotic membranes to the amniotic liquid, resulting in systemic fetal inflammation, which can affect several organs, including the brain. Mothers in premature labor display elevated concentrations of Interleukin (IL)-6 and IL-8 in the amniotic liquid [12]. The most commonly found cytokines were: Tumor necrosis factor alpha (TNF-α), Interferon (IFN)-gamma, IL-1, IL-6 and IL-18 and the imbalance in these cytokines in the beginning of development can have deep and long-term impact on several illnesses, such as CP. These alterations can occur starting in the intrauterine life to early infancy. The cytokines probably exert their effects, and may include modulation of other immunological mechanisms [15]. These cytokines coordinate the host's immune response and mediate normal signalling between immune and non immune cells, including in the CNS [16]. Pro-inflammatory cytokine induction in the maternal infectious process or in the beginning of life demonstrated an adverse effect on neurodevelopment [17]. While certain cytokines are considered pro or anti-inflammatory, certain types may exhibit both properties in different situations [17]. Strategies must be elaborated to inhibit the imbalance effect of cytokines as a therapeutic way of preventing or treating neurological diseases [15]. Recently, attributed to deregulated production of cytokines, CP inflammation is mainly

modulated through dietary restrictions, intestinal dysfunction, and medication intake. Convulsions alone stimulate the pro-inflammatory and pro-convulsive cytokine synthesis in epileptic individuals [18].
