CEREBRAL PALSY: GENERAL MOTOR DISABILITY IN CHILDHOOD

CEREBRAL PALSY: GENERAL MOTOR DISABILITY IN CHILDHOOD

Ashwani Arya ^* and Anuradha Punia

Department of Pharmaceutical Education and Research, BPS Women University, South Campus, Bhainswal Kalan, Sonipat - 131305, Haryana, India.

ABSTRACT: Cerebral palsy is main general motor disability in the infancy and 2 to 2.5 per 1000 live births affected by the cerebral palsy. The movement restrictions in the cerebral palsy are credited to non-progressive interruption that occurs in developing brain of the infants. It is characterized by means of spasticity, weakness of muscle, primitive reflexes loss, interfering of growth of normal motor control. The motor disorders of the cerebral palsy are frequently accompanied as a result of disturbances of the cognition, sensation, perception, communication and behaviour. The frequent threat factors are, multiple pregnancy, prematurity, small-for-gestational age and infections of the maternal genitourinary.  The causal pathways, classification of cerebral palsy and prognostication can play a role in development to prevent the cerebral palsy and arrangement of health services to assemble the desires of the affected infants with disease. This paper covers the causes, clinical features, types, risk factors, pathophysiology and complications of cerebral palsy.

Cerebral palsy, Motorimpairment, Spastic, Dyskinetic

INTRODUCTION: Cerebral palsy describes a cluster of the permanent illness of the development of movement and posture, causing the activity restriction, which is attributed to disturbances of non-progressive that occurred inside developing brain of the child or infant. The motor disorders of the cerebral palsy are frequently accompanied as a result of disturbances of the cognition, sensation, perception, communication and behaviour ¹.  Cerebral palsy are neurodevelopmental disorder which are the commonest “physical” disabilities in early days and influence on development of the child ^{2, 3}. Cerebral palsy is frequent in the infants born preterm by means of small birth weights ⁴.

The 2 to 3 of every 1000 live births affected by cerebral palsy. Cerebral palsy is “an umbrella name covering a cluster of the non-progressive, but often altering, motor impairment syndromes secondary to lesions or anomalies of the brain arising in the early stages of development” ⁵. The incidence is higher in premature infants and in twin births ⁶. The incidence is superior in the males as compared to the females (ratio of 1.33:1). The lower socioeconomic category might be a threat issue intended for the disease ⁷.

As the mechanisms of damage to the developing CNS are better understood, the neuroprotective agents are probable to take part in a rising function in ongoing efforts at key prevention of the illness ^{8, 9, 10}. Cerebral palsy is a chronic motor disorder consequential as of a non-progressive (static) insult to developing brain. Kids suffering from cerebral palsy have multiple problems and potential disabilities for example epilepsy, mental retardation, difficulties of feeding and ophthalmologic and hearing impairments. Cerebral palsy is a clinical appearance of an extensive range of the cerebral cortical or sub-cortical insults taking place throughout the first year of life.  The preterm infants are at the maximum risk for rising cerebral palsy. The vulnerable brain is injured for the duration of a serious stage of the expansion mainly by recognized central nervous system complications of prematurity such as the intraventricular hemorrhage and   periventricular leukomalacia ¹¹.

Low birth weight, prematurity, twins or increased multiple births and perinatal infection are the risk factors for enlargement of the cerebral palsy ¹². Brain growth continues for the period of first two years of the life, and any brain insult throughout the prenatal, postnatal or perinatal period can later outcome in cerebral palsy ¹³. It is a heterogeneous form with multiple clinical types; multiple causes;  multiple patterns of neuropathology on the imaging of brain; multiple related developmental pathologies, such as, autism, epilepsy, intellectual disability and visual impairment; and more recently multiple rare pathogenic genetic variations (mutations). Thus, the various pathways and etiologies has each resulted in a nonspecific nonprogressive disease of posture and movement control ¹².

The advances in investigatation are growing the considerate of the causal pathways and the opportunities for key avoidance of the illness. The cerebral palsy cannot be cured, other than a host of interventions be able to get better the functional abilities, participation, and excellence of life.  The community of the cerebral palsy are significantly more probable to have functional difficulties not linked to the movement but associated to their sensory, epileptic, learning, behavioural and related developmental impairments of the central nervous system ^{14, 15}.

These impairments may commence early in life as difficulties in feeding, irritability, and various disease of sleep patterns. These troubles, when present, which influence the day to day living conditions and can cause considerable distress to kids and their parents. These harms are not inevitable or intractable, but it is essential to ask about, identify, and intervene before problems become entrenched. Cerebral palsy can be present with the global physical and mental dysfunction. Thus, CP is an incurable illness, has caused significant burdens to both affected families and societies, not to mention the quality of life of the patients themselves ^{16, 17}.

Clinical Features of Cerebral Palsy: Kids suffering from Cerebral Palsy (CP) generally nearby means of developmental postponement and the motor deficits. The positive phenomena like clonus, rigidity, spasticity and the spasms and the negative phenomena like fatigue, weakness, in coordination occur in the deficits of cerebral palsy. The spasticity is a velocity dependent enlarged the tone of muscle with the hyper reflexia consequential of the hyperexcitability of stretch reflex, stiffness of muscle, atrophy and the functional destruction.

The condition is not managed, it be able to development to contractures, muscle fibrosis and consequent deformities of the musculoskeletal. Disease can be classified according to severity of the motor deficits because mild, moderate, or severe. The number of other classification of cerebral palsy based on the etiology, path physiology, and allocation of the motor deficits as describes belows ¹⁸.  The various clinical features of the neurological illness depend on the site of the harm to nervous system. The site of harm can be subdivided into the UMN or LMN ^{18, 19}.

Upper Motor Neuron (UMN): In which the neurons in central nervous system (spinal cord and brain) that organize the movement of the muscles.  The UMN travel via the pyramidal tracts (i.e., corticospinal tracts). The UMN lesions be able to cause negative (like weakness or loss of dexterity, generally due to reduced descending excitatory signals from the brain) or and positive signs (like muscle overactivity and spasticity, generally due to reduced descending inhibitory signals from the brain).

In the tonic stretch reflex (normally, passively stretching a muscle group (e.g., stretching the biceps by passively extending the elbow) causes contraction of the same muscle set to prevent overstretching and injury. This tonic stretch reflex is a spinal reflex (which does not needed the input from brain). The spasticity (which injury to the descending UMNs that frequently give inhibitory signals to spinal reflexes causes net disinhibition, which contraction the muscle tone (increases muscle tone) as the muscle is inactively stretched. The more rapidly the velocity of the stretching, the reflexes is stronger ²⁰.

Lower Motor Neuron (LMN): In which the neurons from ventral horn of spinal cord grey matter that exit the spinal cord and connect to the skeletal muscles. The lower motor neuron send signals from the UMNs to the skeletal muscles for start the excitation-contraction coupling, which allowing entity units of a muscle to contract in a coordinated way. Their purpose is in the direction of give muscle tone to skeletal muscles. In LMN lesions, there is no neural input to the muscles, which leads to flaccid paralysis due to be short of resting muscle tone and subsequent atrophy from disuse. The lack of excitation-contraction coupling leads to fasciculations in muscles, where individual sacromeres (contractile units in muscles) fire and contract at random.

Cerebral palsy is characterized by abnormalities of the posture and movement. The abnormal sensation and perception, destruction of the speaking, swallowing, eating, hearing, eyesight and the coordination of eye movements, be deficient in of coordination and mental underdevelopment, difficulties in walking, balance, and the motor control, learning disabilities, bladder and bowel control present in the cerebral palsy ^{21, 18}. The some of the symptoms of the cerebral palsy are summarized in the Fig. 1.

FIG. 1: CLINICAL FEATURES OF CEREBRAL PALSY

Causes of Cerebral Palsy: The statistics of kids with further severe forms of the illness are rising, chiefly within the crowd born prematurely as a consequence of larger continued existence of these kids  to an age while cerebral palsy be capable of examined. The low birth weight prematurity, perinatal infection and twins or higher multiple births are threat factors for expansion of cerebral palsy. The causes of illness are multifactional, including restriction of intrauterine growth, prenatal and perinatal asphyxia, unusual expansion at pre-natal, perinatal, and post-natal stages, post-term at forty two weeks pregnancy or later, low birth weight, prematurity, fetal infections, several pregnancies, intraventricular hemorrhage, periven-tricular leukomalacia, vascular insufficiency, underlying genetic abnormalities, various toxins, chorioamnionitis and  maternal factors ^{22, 23, 24}. The various causes of the cerebral palsy are described in the Table 1.

TABLE 1: THE CAUSES OF CEREBRAL PALSY ^{23, 24}

The periventricular leukomalacia (injure to the white matter of the brain), the unusual progress of the brain which is cerebral dysgenesis, intracranial hemorrhage and the brain damage caused by means of a be short of the oxygen in brain (hypoxicischemic encephalopathy or intrapartum asphyxia). The warning signs of cerebral palsy are shown in Table 2 and risk factors of cerebral palsy are summarized in Table 3.

TABLE 2 : WARNING SIGNS OF CEREBRAL PALSY ^{21, 23}

TABLE 3: RISK FACTORS OF CEREBRAL PALSY ^{12, 25, 27}

Types of Cerebral Palsy: Cerebral Palsy (CP) is categorized into the spastic cerebral palsy, dyskinetic cerebral palsy, ataxic cerebral palsy and mixed cerebral palsy on the basis of the predominant motor disorder ^{1, 25, 26, 27}. The spastic cerebral palsy is the majority type, taking place in 80% cases. The spastic cerebral palsy is subdivides into diplegic (21%), hemiplegic (31%), quadriplegic (35%), and monoplegic with other forms of CP, including dyskinetic, hypotonic, mixed, and ataxic cerebral palsy contributing to the remainder which 13% cases ²⁸. Dyskinetic cerebral palsy is occasionally referred to as dystonic, athetoid, extrapyramidal, choreoathetotic, or choreoathetoid cerebral palsy ²⁹. Cerebral Palsy (CP) is the mainly general neuromotor disability in the world. Dyskinetic CP is the second most common subtype, affecting 15%- 20% of children with CP ^{30, 31}. The damage to the developing brain in cerebral palsy is heterogeneous in nature. The grey and white matter is at risk to the different mechanisms of damage. The diffuse injury of the white matter and periventricular leukomalacia are usually linked by means of prolonged hypoxic-ischemic events, preterm delivery or moderate-intensity events.

This damage outline is linked among the expansion of spastic cerebral palsy ³². The dyskinetic cerebral palsy has been linked among the basal ganglia and thalamic injury following brief, profound the hypoxic insults and is more usually seen in term infants ^{33, 34}.  The various types of cerebral palsy are summarized in the Table 4.

TABLE 4: VARIOUS TYPES OF CEREBRAL PALSY ^{28, 34 - 43}

Pathophysiology of Cerebral  Palsy: Insults consequential in the loss of the neurons be able to:

• Cortical(pyramidal), resulting in the spasticity
• Basal ganglia(extrapyramidal), resulting in irregular movements like choreoathetosis
• Cerebellar, resulting in hypotonia
• Mixed spastic cerebral palsy is the mainly general type, which accounting for up to seventy five percentage of cases.

A minor percentage of kids with cerebral palsy show the extrapyramidal (dyskinetic) features, which including the combinations of chorea, athetosis and dystonia. The irregular movements generally build up in the second year of life and develop into the majority apparent through volitional motor activities with related to impairments of speech. Many children with extrapyramidal cerebral palsy have usual intelligence, but their abilities be able to under estimated due to the severity of their deficits of the motor and communication. Kernicterus (bilirubinencephalo-pathy) is a most important reason of the extrapyramidal cerebral palsy. The affected neonate appears weak, listless and hypotonic, with poor feeding. The choreoathetosis, opisthotonus and sensorineural hearing loss develops subsequent to the episode of months ⁴⁴.

The pathophysiological mechanisms that outcome in cerebral palsy can be classified as  hypoxia and ischemia that triggers a cascade of excito-oxidative actions in the intrauterine infections/inflammation that reason of neuroinflammation and fetal inflammatory response syndrome, prematurity, PVL  and genetic or other congenital causes  ^{45 - 49}. The pathogenesis of cerebral palsy may be explained by every or a blend of these mechanisms ^{50, 25}.

Preterm infantst the premature neonatal brain is susceptible to two main pathologies: intraven-tricular hemorrhage (IVH) and periventricular leukomalacia (PVL). Although equally the pathophysiology which increases the threat of the disease and periventricular leukomalacia is more intimately lonked to cerebral palsy and is the most important reason in preterm infants. The term periventricular leukomalacia describes white matter in  periventricular region that is damaged or  underdeveloped (“leukomalacia”). Both periven-tricular leukomalacia and intraventricular hemorrhage causes the cerebral palsy ⁵⁰.

Intraventricular Hemorrhage (IVH): Bleeding from the subependymal matrix (the origin of fetal brain cells) into the ventricles of the brain. The blood vessels around the ventricles develop late in the third trimester, thus preterm infants have underdeveloped periventricular blood vessels, predisposing them to increased risk of IVH. The risk of CP increases with the severity of IVH Prematurity is the main risk factors for CP.

Preterm infants are at risk of both intraventricular hemorrahage (IVH) and periventricular leukomalacia (PVL). Anatomical factors, including distal arterial perfusion of watershed zones and in mature vessel autoregulation, the premature brain (periventricular area) to ischemia. Cellular factors such as cytokines, reactive oxygen, and excitotoxicity, target the premyelinating oligodendrocytes, interfering with myelination of white matter. Together, these factors gives rise to under development of the white, matter in the periventricular area, known as periventricular leukomalacia ⁵¹.

Ischemia/Hypoxia: The periventricular white matter of the neonatal brain is supplied by the distal segments of adjacent cerebral arteries. Although collateral blood flow from two arterial sources protects the area when one artery is blocked (e.g., thromboembolic stroke), this watershed zone is susceptible to damage from cerebral hypoperfusion (i.e., decreased cerebral blood flow in the brain overall). Since preterm and even term neonates have low cerebral blood flow, the periventricular white matter is susceptible to ischemic damage. Autoregulation of cerebral blood flow usually protects the fetal brain from hypoperfusion, however, it is limited in preterm infants due to immature vasoregulatory mechanisms and under development of arteriolar smooth muscles ^{50, 51}.

Infection and Inflammation: In this microglial (brain macrophage) cell commencement and release of the cytokine, which causes injured to a particular type of cell in the during developing brain called as oligodendrocyte. The oligo-dendrocytes are a kind of supportive cell of brain that wraps around the neurons to appearance the myelin sheath, which is necessary for the white matter expansion. The infections of the intrauterine stimulate the fetal immune system, which produces the cytokines (and TNF-α, interferon γ) so as to are toxic to oligodendrocytes, premyelinating.

Microglial cells activated by the infection, which discharge the free radicals. Premyelinating oligodendrocytes have immature defences against the reactive oxygen species (example, low production of the glutathione, a significant antioxidant). IVH is hypothesized to grounds of PVL because iron-rich blood causes iron-mediated conversion of hydrogen peroxide to hydroxyl radical, contributing to oxidative damage ^{46, 50}.

Excitotoxicity is a course where enlarged the extracellular glutamate levels stimulate the oligodendrocytes to raise the calcium influx, which stimulates the reactive oxidative species release. Glutamate is raised because hypoxia causes the white matter cells to reduce reuptake of glutamate due to be deficient in of energy to function of the glutamate pumps. Glutamate is as well released from microglial cells for the duration of inflammatory response ^{30, 50}.

The risk factors for the cerebral palsy are prematurity, preterm infants (intraventricular hemorrhage and periventricular leukomalacia. The anatomical factors comprised of distal arterial perfusion of watershed zones and immature vessel autoregulation, periventricualr area to ischemia, cellular factors comprised of reactive oxygen species, cytokines and excitotoxicity which targerts the premyelinating oligodendrocytes, interfering among myelination of white matter. All these factors give augment to under developement of the white matter in the periventricular area ⁵⁰. The pathophysiological mechanism of PVL described in the Fig. 2.

FIG. 2:  PATHOGENESIS OF PVL ⁵⁰

Brain Regions Involved in Cerebral Palsy: Cerebral palsy is a heterogenous cluster of the neurological disorders which are mostly observed in the infants. It consequences due to a static brain lesion at the instance of pregnancy or the early life. Cerebral palsy is limited to lesions of brain. Therefore, diseases particular to peripheral nerves of spinal cord such as the traumatic peripheral nerve lesions myelomeningocele, spinal muscular atrophy, vascular malformations, or tumors of the spinal cord, or inherited metabolic disorders, metabolic myopathies, metabolic neuropathy, or movement disorders, although causing early motor abnormalities, are not considered CP ^{52, 53}.

TABLE 5: THE AFFECTED AREA OF BRAIN IN CEREBRAL PALSY ^{51, 55 - 59}

CP involves injure to numerous types of cells in the brain with multifaceted manifestations. A sequence of interventions of useful remedial strategies are essential to give the comprehensive curative plan for the person’s suffering from the cerebral palsy by the various physiatrists, orthopedic surgeons, neurologists ^{54, 17}. Cerebral palsy has caused significant burdens to affected families and societies ^{55, 41}. In simple conditions, it implies that usual and fewer injured areas of the brain have the capability to enlarge and maturate with time to result in developmental sequence and motor improvements ^{56 - 58}. The affected area of brain in cerebral palsy are summarized in Table 5.

Complications of Cerebral Palsy: The spasticity and contractures; difficulties of feeding; drooling; communication difficulties; osteopenia; osteoporosis; fractures; pain; and functional gastrointestinal abnormalities contributing to the bowel obstruction, vomiting and constipation comprise of complications of the cerebral palsy ⁶⁰.  The mainly frequent related conditions in patients suffering from the cerebral palsy are learning disability or mental impairment (40%); visual impairment (16%); seizures (30%); complex movement disorders (20%); malnutrition and related conditions, such as gastroesophageal reflux, obesity, and undernutrition (15%); and hydrocephalus (14%). Mental impairment and learning disability be able to variety from extremely mild deficits to severe destruction and incapability to live separately. The osteopenia with greater risk of the fracture as well is widespread in the severely affected individuals suffering from the illness such as cerebral palsy ^{61, 62}. The complications of the cerebral palsy are summarized in the Table 6.

Prevention of the premature delivery, ensuring sufficient nutrition, advanced thoughtful of the placental function and detecting placental pathology, diagnosis of illness and management of maternal genitourinary infection in pregnancy are the key areas to preventing cerebral palsy ⁶².

TABLE 6: COMPLICATIONS OF CEREBRAL PALSY ^{62 - 75}

CONCLUSION: Cerebral palsy are the commonest “physical” disabilities in childhood which severely influence on the growth of the child. Understanding of the contributory pathways, opportunities for key prevention, value of precise intervention strategies are the various key factors which are rising for the advancement of research. The quality of life for the child’s relatives is also affected with implications for parents being able to work, housing and care of a disabled young person through childhood into adult life. The state also has a main impact on the health, community and education services with increasing survival of more severely affected children with cerebral palsy.

Kids among cerebral palsy experience from the multiple troubles and the potential disabilities like mental retardation of the child, epilepsy, feeding difficulties, vision problem and impairments of the hearing. Thus, cerebral palsy is motor impairment and be able to present with global physical and mental dysfunction and cerebral palsy has caused significant burdens to affected families and societies.

ACKNOWLEDGEMENT: The author was conveys deep sense of gratitude to the DPER, Bhagat Phool Singh Women University for their continuous support and inspiration.

CONFLICT OF INTEREST: Nil

REFERENCES:

1. Rosenbaum P, Paneth N and Leviton A: A report: the definition and classification of cerebral palsy. Dev Med Child Neurol 2007; 49: 8-14.
2. Bax M, Goldstein M and Rosenbaum P: Proposed definition and classification of cerebral palsy. Dev Med Child Neurol 2005; 47: 571-6.
3. Sankar C and Mundkur N: Cerebral palsy-definition, classification, etiology and early diagnosis. Indian J Pediatr 2005; 72(10): 865-8.
4. Johnson A: Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol 2002; 44(09): 633-40.
5. Stanley F, Blair E and Alberman E: Cerebral Palsies: Epidemiology and causal pathways. London, United Kingdom: MacKeith Press 2000.
6. Escobar GJ, Littenberg B and Petitti DB: Outcome among surviving very low birth weight infants: a meta-analysis. Arch Dis Child 1991; 66: 204-11.
7. Plessis DAJ and Volpe JJ: Perinatal brain injury in the preterm and term new born. Curr Opin Neurol 2002; 15(7): 151.
8. Berker AN and Yalcin MS: Cerebral palsy orthopedic aspects and rehabilitation. Pediatr Clin North Am 2008; 55: 1209-1225.
9. Tilton AH: Management of spasticity in children with cerebral palsy. Seminpe Diatorneurol 2004; 11: 58-5.
10. Graham HK, Rosenbaum P and Paneth N: Cerebral palsy. Nat Rev Dis Prim 2016; 2: 15082.
11. King S, Teplicky R, King G and Rosenbaum P: Family-centered service for children with cerebral palsy and the families: a review of the literature. Semin Pediatr Neurol 2004; 11 (1): 78-86.
12. Odding E, Roebroeck ME and Stam HJ: The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil 2006; 28: 183-191.
13. Bass N: Cerebral palsy and neurodegenerative disease. Curr Opin Pediatr 1999; 11: 504-507.
14. Kennes J, Rosenbaum P, Hanna SE, Walter S, Russell D and Raina P: Health status of school-aged children with cerebral palsy: information from a population-based sample. Dev Med Child Neurol 2002; 44: 240.
15. Harvey S, Singer, Jonathan W, Mink, Donald L, Gilbert and Jankovic J: Chapter 20 - Cerebral Palsy, Movement Disorders in Childhood 2016; 453-475.
16. Colver A, Fairhurst C and Pharoah PO: Cerebral palsy. Lancet 2014; 383(9924): 1240-1249.
17. Kulak W, Sobaniec W, Kuzia JS and Bockowski L: Neurophysiologic and neuroimaging studies of brain plasticity in children with spastic cerebral palsy. Exp. Neurol 2006; 198(1): 4-11.
18. Jan MMS: Approach to children with suspected neuro-degenerative disorders. Neurosciences 2002; 7(1): 2-6.
19. Girard S, Kadhim H, Roy M, Lavoie K, Brochu ME, Larouche A and Sébire G: Role of perinatal inflammation in cerebral palsy. Pediatr Neurol 2009; 40(3): 168-74.
20. Ashwal S, Russman BS, Blasco PA, Miller G, Sandler A, Shevell M and Stevenson R: Practice parameter: Diagnostic assessment of the child with cerebral palsy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2004; 62 (6): 851-863.
21. Rosenbaum P: Cerebral palsy: What parents and doctors want to know. BMJ 2003; 326(7396): 970-974.
22. Frisch, Dana, Msall and Michael E: Health, functioning, and participation of adolescents and adults with cerebral palsy: A review of outcomes research. Developmental Disabilities Research Reviews 2013; 18(1): 84-94.
23. Smith M and Kurian MA: The medical management of cerebral palsy. Paediatrics and Child Health 2012; 22: 9.
24. Pruitt DW and Tsai T: "Common medical comorbidities associated with cerebral palsy. Physical Medicine and Rehabilitation Clinics of North America 2008; 20(3): 453-67.
25. Bhattacharya B, Mangilal TR and Nagakishore R: Cerebral Palsy - A curse: Etiology, pathophysiology and current approach of treatment. Central European Journal of Experimental Biology 2014; 3(4): 52-58.
26. Monbaliu E, Cock DP, Ortibus E, Heyrman L, Klingels K and Feys H: Clinical patterns of dystonia and choreo-athetosis in participants with dyskinetic cerebral palsy. Dev Med Child Neurol 2016; 58: 138-44.
27. Kate EM, Lin HJP, Bonouvrié EOL, Dan HFB: Clinical presentation and management of dyskinetic cerebral palsy. Th e Lancet Neurology 2017; 16(9): 741-749.
28. Shevell MI, Dagenais L and Hall N: The relationship of cerebral palsy subtype and functional motor impairment: A population-based study. Dev. Med. Child Neurol 2009; 51 (11): 872-877.
29. Himmelmann K, McManus V, Hagberg G, Uvebrant P, Krägeloh-Mann I and Cans C: Dyskinetic cerebral palsy in Europe: trends in prevalence and severity. Arch Dis Child (2009); 94: 921-26.
30. Hou M, Zhao J and Yu R. Recent advances in dyskinetic cerebral palsy. World J Pediatr 2006; 2(1): 23-28.
31. Jones MW, Morgan E and Shelton JE. Cerebral palsy: introduction and diagnosis (part I). Journal of Pediatric Health Care 2007; 21(3): 146-152.
32. Tilton AH: Approach to the rehabilitation of spasticity and neuromuscular disorders in children. Neurol Clin 2003; 21(4): 853-81.
33. Graham HK, Rosenbaum P and Paneth N: Cerebral palsy. Nat Rev Dis Prim 2016; 2: 15082.
34. Monbaliu E, Cock DP, Ortibus E, Heyrman L, Klingels K and Feys H: Clinical patterns of dystonia and choreo-athetosis in participants with dyskinetic cerebral palsy. Dev Med Child Neurol 2016; 58: 138-44.
35. Bottcher L: Children with spastic cerebral palsy, their cognitive functioning and social participation: A review. Child Neuropsychology 2010; 16(3): 209-228.
36. Pakula AT, Van Naarden BK and Yeargin-Allsopp M: Cerebral palsy: Classification and epidemiology. Phys. Med. Rehabil. Clin. N. Am 2003; 20(3): 425-452.
37. Wiklund LM and Uvebrant P: Hemiplegic cerebral palsy: correlation between CT morphology and clinical findings. Dev Med Child Neurol 1991; 33: 512.
38. Uvebrant P: Hemiplegic cerebral palsy. Aetiology and outcome. Acta Paediatr Scand Suppl 1988; 345: 1.
39. Martinez-Biarge M, Diez-Sebastian J and Kapellou O: Predicting motor outcome and death in term hypoxic-ischemic encephalopathy. Neurology 2011; 76: 2055-2061.
40. Aravamuthan BR and Waugh JL: Localization of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Pediatr Neurol 2016; 54: 11-21.
41. Himmelmann K and Uvebrant P: Function and neuro-imaging in cerebral palsy: a population-based study. Dev. Med. Child Neurol 2016; 53: 516-521.
42. McHale DP, Jackson AP, Campbell DA, Levene MI, Corry P, Woods CG, Lench NJ, Mueller RF and Markham AF: A gene for ataxic cerebral palsy maps to chromosome 9p12-q12. European Journal of Human Genetics 2000; 8 (4): 267-272.
43. Strauss D, Brooks J, Rosenbloom R and Shavelle R: Life expectancy in cerebral palsy: an update. Developmental Medicine and Child Neurology 2008; 50(7): 487-493.
44. Matthews D, Wilson P, In Molnar G and Alexander M: (eds). Pediatric Rehabilitation Philadelphia: Hanley and Belfus, Inc Edition 3^rd, 1999; 193: 218.
45. Rosenbaum P, Paneth N and Leviton A: A report: the definition and classification of cerebral palsy collabora-tion. Pediatrics 2008; 121: 547-54.
46. Romero R, Espinoza J,  Goncalves  LF, Kusanovic JP, Frie  L and Hassan  S: The role of inflammation and infection in preterm birth. Semin. Reprod. Med 2007; 25 (1): 21-39.
47. Tommiska V, Heinonen K, Lehtonen L, Renlund M, Saarela T, Tammela O, Virtanen M and Fellman V: No improvement in outcome of nationwide extremely low birth weight infant populations between 1996-1997 and 1999-2000. Pediatrics 2007; 119(1): 29-36.
48. Isaac JT: Postsynaptic silent synapses, Evidence and mechanisms. Neuropharmacology 2003; 45(4): 450-460.
49. Schaefer GB: Genetics considerations in cerebral palsy. Semin. Pediatr Neurol 2008; 15(1): 21-26.
50. Khwaja O and Volpe JJ: Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed. 2003; 93(2): F153-F161.
51. Marret S, Vanhulle C and Laquerriere A: Pathophysiology of cerebral palsy. Handbook of Clinical Neurology 2013; 11: 169-176.
52. Paneth N: Establishing the diagnosis of cerebral palsy. Clin. Obstet. Gynecol 2008; 51(4): 742-748.
53. Dennis M, Spiegler BJ, Juranek JJ, Bigler ED, Snead OC and Fletcher JM: Age, plasticity, and homeostasis in childhood brain disorders. Neurosci Biobehav Rev 2013; 37(10): 2760-73.
54. Susan A, Rethlefsen PT, Deirdre D, Ryan MD and Kay RM: Classification Systems in Cerebral Palsy. Orthop Clin N Am 2010; 41: 457-467.
55. Hoon AH: Jr. Neuroimaging in cerebral palsy: Patterns of brain dysgenesis and injury. J. Child. Neurol 2005; 20 (12): 936-939.
56. Johnston MV: Clinical disorders of brain plasticity. Brain Dev 2004; 26(2): 73-80.
57. Lonneke WR, Vermeulen J and Boyd RN: Brain structure and executive functions in children with cerebral palsy: A systematic review. Research in Developmental Disabilities 2013; 1678-1688.
58. Aisen NL, Kerkovich D, Mast J, Mulroy S and Rethlefsen SA: Cerebral Palsy: clinical care and neurological rehabilitation. The Lancet Neurology 2011; 10(9): 844-852.
59. Bhooma R, Aravamuthan MD, Jeff L and Waugh MD: Localization of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Pediatric Neurology 2016; 11-21.
60. Eunson P: Aetiology and epidemiology of cerebral palsy. Paediatrics and Child Health 2016; 26(9): 367-372.
61. Sankar C and Mundkur N: Cerebral Palsy-Definition, classification, etiology and early diagnosis. Indian Journal of Pediatrics 2005; 72: 865-868.
62. Gajdosik CG, Cicirello N: Secondary conditions of the musculoskeletal system in adolescents and adults with cerebral palsy. Phys Occup Ther Pediatr 2001; 21: 49-68.
63. Rapp CE Jr and Torres MM: The adult with cerebral palsy. Arch Fam Med 2000; 9: 466-72.
64. Reid SM, Johnson HM and Reddihough DS: The Drooling Impact Scale: A measure of the impact of drooling in children with developmental disabilities. Dev. Med. Child Neurol 2010; 52(2): 23-28.
65. Jan MMS: Assessment of the utility of pediatric electroencephalography. Seizure 2002; 11(2): 99-103.
66. Fennell EB and Dikel TN: Cognitive and neuro-psychological functioning in children with cerebral palsy. J Child Neurol 2001; 16: 58-63.
67. Tsirikos AI and Spielman P: Spinal deformity in paediatric patients with cerebral palsy. Current Orthopaedics 2007; 21(2): 122-134.
68. Practice parameters: American Academy of Neurology and Child Neurology Society practice committee. Neurology 2003; 60: 367-380.
69. Menaker S and Batshaw M: In: Batshaw M. Our window to the world. Baltimore: Brooks 1997; 211-240.
70. Siegel L and Klingbeil M: Control of drooling with transdermal scopolamine in a child with cerebral palsy. Dev Med Child Neurol 1991; 33: 1010-1014.
71. Eltumi M and Sullivan PB: Nutritional management of the disabled child: the role of percutaneous endoscopic gastrostomy. Dev Med Child Neurol 1997; 39: 66-68.
72. Stevenson R, Roberts C and Vogtle L: The effects of non nutritional factors on growth in cerebral palsy. Dev Med Child Neurol 1995; 37: 124-130.
73. Dormans J and Pellegrino L: In caring for children with cerebral palsy, Paul H. Brookes Publishing Co, Baltimore, Md 1998; 533.
74. Roijen LEG, Postema K, Limbeek J and Kuppevelt HJM: Development of bladder control in children and adole-scents with cerebral palsy. Dev Med Child Neurol 2001; 43: 103-107.
75. Jan MMS: Melatonin for the treatment of handicapped children with severe sleep disorder. Ped Neurol 2000; 23(3): 229-232.
    

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    How to cite this article:

    Arya A and Punia A: Cerebral Palsy: general motor disability in childhood. Int J Pharm Sci & Res 2018; 9(9): 3579-88. doi: 10.13040/ IJPSR.0975-8232.9(9).3579-88.

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