Table 1.

Summary of multi-organ involvement, management and potential future directions for research in Cerebral Palsy (CP).

	Possible considerations for care	Treatment and potential future directions
Neurological	• MRI brain for all (12) • Cognitive impairment • Epilepsy • Behavioral issues, including inattention and hyperactivity • Spasticit	• Consider genetic and metabolic investigations if brain malformation, unclear etiology, or findings atypical (12) • Seizure management does not significantly differ from children without CP (13) • Medical options for spasticity management include diazepam, baclofen (oral or intrathecal) and botulinum toxin (14)
Hearing and vision	• Hearing impairment • Cortical Visual Impairment (CVI), refractive errors and accommodative dysfunction are common in CP (15, 16)	• Consider thorough audiological assessment if concerned • Screening questionnaires are available to help with recognition of CVI (15) • Early and periodic screening of vision recommended
Respiratory	• Significant cause of morbidity and mortality • Largest cause of premature death in children and young people with CP (17) • Dysphagia • Aspiration • LRTI more common and severe (18) • Bronchiectasis (19) SNI and GOR most significant risk factors	• Benefit of treating GOR for respiratory reasons unclear. Large prospective trials required • Mucolytics and physical therapies may help with tenacious secretions (20) • Prophylactic antibiotics – randomized controlled trials required
Sleep	• Sleep disorders • Association with seizures (21) • DIMS most common subtype (22) • Sleep disordered breathing more common in CP (21, 23)	• Screen for sleep disorders using validated tools • First-line therapy – sleep hygiene (24, 25) • Trial of melatonin where no identifiable cause of sleep disturbance found (13) • Adenotonsillectomy first-line treatment for OSA (26) • Consider non-invasive ventilation but high failure rate (27)
Cardiac	• Adults with CP have 3-fold increase in CVS disorders (28) • Altered inflammation and reduced activity are risk factors for endothelial dysfunction and later atherosclerosis (29–31).	• Long-term follow up studies required to demonstrate predictive value of CIMT and HRV on adult morbidity and mortality • Potential for use of serum biomarkers, such as Troponin, and advanced echocardiography to evaluate cardiac dysfunction in CP
Renal and urinary tract	• Lower urinary tract dysfunction (32) • Urinary incontinence most common • Bladder dysfunction may be linked with upper urinary tract deterioration • UTI more common in CP (33) • Higher risk of CKD (34)	• Blood pressure and urinary protein currently useful for monitoring renal function • Potential for novel biomarkers such as Cystatin-C, NGAL and IL-6 in the future but further research required in this population • Minimize nephrotoxic drugs • Low Creatinine may not be a reliable method of monitoring for renal dysfunction in CP
Gastrointestinal	• Dysphagia • Drooling • Diagnosis of GOR may be challenging due to communication difficulties • Nutritional optimisation associated with better functional status (35) • Constipation • Increased risk of acute and chronic abdominal pain which may be difficult to diagnose particularly if non-verbal (36, 37)	• Multi-disciplinary approach to management of drooling • Anticholinergic agents and intraglandular botulinum toxin are mainstay of medical treatment of drooling (38) • Use PPI as first line treatment of GORD with H2RAs as alternative. Consider surgical alternatives if medical treatment fails (39) • Annual monitoring of micronutrients (35) • Thorough assessment for any nociceptive sources of abdominal pain. If no source evident consider trial of gabapentin (40) • Further research required on gut failure in CP
Hematological	• Thrombophilias have been associated with neonatal stroke and hemiplegic CP (41) • Increased blood loss seen during spinal surgery (42) • Iron deficiency has a negative effect on functional ability and muscle strength (43)	• Consider prophylactic tranexamic acid and early use of blood products for surgical interventions (44) • Monitor for iron deficiency and anemia and treat accordingly
Inflammation and Infection	• Children post-neonatal encephalopathy have altered inflammatory responses which persist until school age (31). • Children with CP are at increased risk of all infections, including respiratory infections, post-operative infective complications and invasive pneumococcal disease (45–48)	• Further research is required to show whether children with CP have persistent inflammatory and immune dysfunction • Follow national immunization schedule, recommend influenza vaccination and consider extended-coverage polyvalent pneumococcal vaccine
Metabolic	• Metabolic disorders may mimic CP	• Consider metabolic testing if progression, developmental regression, atypical history or neuroimaging, positive family history (49)
Genetics	• Single gene disorders may produce a CP phenotype (50) • Genetic polymorphisms may increase susceptibility to developing CP (51)	• Further research will likely expand the number of genetic disorders and polymorphisms known to cause or increase susceptibility to CP • The epigenome provides promise as a therapeutic target to improve neurodevelopmental outcome in CP
Endocrine	• Increased risk of growth anomalies secondary to GH deficiency and nutritional deficiency (52) • Most common childhood condition associated with osteoporosis (53) • Early adrenarche is seen in CP but often not indicative of true central precocious puberty (54)	• Formal measurement of body proportions at least twice per year • If concerned re osteoporosis, perform DXA at 6 years and then biennially (53) • Evidence for treatment with bisphosphonates, vitamin D and calcium in CP but further work required on benefit of weight-bearing (55, 56) • Regularly assess puberty with Tanner staging (57)
Orthopedic	• Scoliosis – associated with poorer gross motor function (58) • Hip dislocation - associated with poorer gross motor function (59) • Upper limb contractures	• Hip surveillance -dependent on GMFCS • Further research on effectiveness of interventions to prevent hip dislocation essential • Level of evidence for interventions relating to the upper limb is lower and requires further study

MRI, Magnetic Resonance Imaging; LRTI, Lower Respiratory Tract Infection; SNI, Severe Neurological Impairment; GOR, Gastro-esophageal Reflux; QoL, Quality of Life; DIMS, Disorders of Initiation and Maintenance of Sleep; OSA, Obstructive Sleep Apnoea; CVS, Cardiovascular; CIMT, Carotid Intima Media Thickness; HRV, Heart Rate Variability; UTI, Urinary Tract Infection; CKD, Chronic Kidney Disease; CVI, Cortical Visual Impairment; GH, Growth Hormone; DXA, Dual-energy X-ray absorptiometry; PPI, Proton Pump Inhibitors; H2RA, Histamine 2 Receptor Antagonists; GORD, Gastro-esophageal Reflux Disease.