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Advanced Neurology Neonatal encephalopathy and cerebral palsy

1. Introduction perinatal vascular accidents (e.g., arterial ischemic stroke
and intracranial hemorrhage) [12,13] , metabolic disturbances
Cerebral palsy (CP) stands as the most prevalent movement (e.g., hypoglycemia and electrolyte abnormalities) [14,15] ,
disorder emerging in early childhood attributed to brain seizures or epilepsies , genetic or congenital factors [17,18] ,
[16]
damage during development [1,2] . Globally, CP impacts and exposure to prenatal medications that cause
[3]
approximately 2 in every 1000 live births . Despite medical toxicity [19,20] . Hypoxic-ischemic encephalopathy (HIE),
advancements, the prevalence of CP has not exhibited a which is the direct result of a perinatal hypoxic, ischemic,
decline in recent decades, potentially attributable to the and/or asphyxial event, is the most common cause of NE.
increased survival rate of pre-term infants who face a HIE affects up to 8/1000 infants in developed countries
heightened risk of CP [4,5] . The manifestations of CP vary and 26/1000 infants in underdeveloped countries ,
[21]
among individuals and may develop over time . The responsible for up to 1 million neonatal deaths each year
[6]
common symptoms include impaired motor function, globally .
[22]
such as challenges in maintaining balance and posture
[6]
and deficient muscle coordination . In certain cases, the Significantly, NE may result in brain damage, which in
[7]
patients develop seizures and/or cognitive comorbidities . the context of HIE is due to inadequate levels of oxygen
Classification of CP hinges on the distributional and blood to the brain [23,24] . As a result of brain injury,
pattern of affected limbs and the prevailing neuromotor patients may suffer from periods of apnea, seizures,
[8]
abnormality . Pertinent subtypes for the present analysis cardiorespiratory failure, and even death [24,25] . Currently,
include (i) Spasticity affecting all four limbs (quadriplegia), hypothermia therapy stands as the sole acute treatment
(ii) spasticity affecting both lower extremities without upper for neonates following HIE, offering some degree of
limb involvement (diplegia), (iii) spasticity manifesting on neuroprotection [26,27] . However, its efficacy is limited by
one side of the body (hemiplegia), and (iv) dyskinetic. the short time window of delivery. Recent studies have
It is evident that CP results from a series of events reported that TRPM7 channel blockers [28,29] or ryanodine
[30]
that combine to cause injury to the brain during the receptor inhibitor can effectively mitigate brain damage
[9]
developmental period of the fetus or infant . While risk and improve neurobehavior outcomes in mouse models of
factors for the development of CP may occur at any stage HIE. Nevertheless, as of now, there is no pharmacological
of development – from prenatal to postnatal – (Figure 1), it solution available for clinical NE patients that would
is reported that perinatal events contribute to 30.5% of CP permit early prevention of the development of severe
[25]
cases . A number of risk factors may cause damage to the complications . Following the current standard of care,
[10]
central nervous system at the early stage of its development. survivors living with NE can develop long-term behavioral
Neonatal encephalopathy (NE) results from various impairments, including motor disability [21,24,31] .
conditions, including infections (e.g., neonatal sepsis) , Previous studies have identified NE as a significant risk
[11]
factor for CP. One study has reported a significant increase
in the incidence of CP in neonates experiencing asphyxia
[5]
or hypoxic conditions at birth . Children with birth defect,
such as NE, were found to be three times more likely to
develop CP . Among those children with CP following
[32]
NE, 1 in every 5 succumbed to death before the age of 5 .
[33]
For those who survived, NE was linked to a poor clinical
prognosis in individuals with CP due to irreversible
HIE brain damage, contributing to more debilitating CP
features compared to non-NE patients [4,32-34] . Furthermore,
approximately one-quarter of CP cases in term-born
infants had preceding moderate or severe NE, and CP
following NE was more likely to manifest as the spastic
quadriplegic and spastic dyskinetic subtypes .
[33]
While studies have found that standard physical
therapy, treadmill training, and functional gait training are
safe, feasible, and effective interventions to improve walking
Figure 1. Predominant events and risk factors leading to cerebral ability in patients with CP [35,36] , CP remains a permanent
palsy [9,48] . Examples of risk factors are listed under each category, with a
specific emphasis on the perinatal NE event. The image was created using disability in children. Additionally, beyond motor disability,
BioRender.com. children with CP also suffer from other complications that

Volume 2 Issue 4 (2023) 2 https://doi.org/10.36922/an.1719