The Need to Standardize the Diagnosis of Cerebral Palsy

“A group of permanent disorders of the development of movement and posture causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain.”—The 2006 consensus definition of cerebral palsy (CP)1“Cerebral palsy is a bad term”—An anonymous physician caring for children with CP2CP is the most common childhood-onset physical disability3 and the most common lifelong neurologic disability.4 Primary care pediatricians are called to create medical homes for people with CP, including initiating discussions of CP diagnosis as early as possible.5 This is complicated by physicians across specialties (including pediatricians) variably interpreting the 2006 CP definition, leading some to conceptualize CP as a “bad term.”2,6 Growing data on CP genetics,7 lifelong CP manifestations,8 CP phenotypes,9 and prediction of future motor disability10 should facilitate early, accurate, and consistent CP diagnoses. However, these data have yet to be codified in a way that can be readily operationalized in a general pediatrics clinic visit. Therefore, CP is not a “bad term,” but it is badly in need of a standardized diagnostic framework to facilitate practical clinical diagnosis and reduce diagnostic variability.Genetic testing advances have revealed that up to 30% of people with CP phenotypes can have contributing genetic etiologies.7 Up to 8% of people with a known predisposition to brain injury (eg, prematurity) have a contributing genetic etiology.11 Expert consensus12 and the 2006 consensus definition1 say that identifying a CP etiology, although valuable, is NOT necessary to make a CP diagnosis, which is contingent only on the CP phenotype being caused by a nonprogressive disturbance in the developing brain. However, the practical application of this view is fraught, particularly in the setting of genetic etiologies.2,6 A child with spastic diplegia without loss of motor milestones can have CP even if they have a genetic etiology. But what if that genetic etiology eventually causes “progressive” spasticity in some but not all people? What if there is not enough information about that genetic condition to know whether it is typically “progressive” or not? Physicians caring for people with CP struggle to consider these variable genotype-phenotype correlations when making a CP diagnosis.6Moreover, what does it mean to be “nonprogressive?” The previous emphasis on CP being a pediatric condition has meant adult voices about progressive decline have not received sufficient attention. People with CP reach peak mobility in late adolescence, after which they often experience mobility decline likely owing to many contributing factors, including a potential early aging phenomenon, decreased access to therapies, and musculoskeletal complications like contractures.8 Furthermore, people with CP have a 9-fold higher risk of Alzheimer disease, perhaps one of the quintessential neurodegenerative conditions.13 Adults with CP may thus experience symptoms that “progress” despite a brain disturbance that is initially thought to be static. Therefore, can CP truly be defined by whether the brain disturbance is nonprogressive/nondegenerative?Could imaging help? Magnetic resonance imaging (MRI) findings, taken together with a standardized neurologic examination and birth history, can facilitate CP diagnosis within the first several months of life.10 However, imaging findings depend highly on access, timing, image quality, and neuroradiological interpretation quality. To create a globally standardized CP definition it is impossible to rely on a globally variable technique. To assess the face validity of using imaging to establish whether a CP-related brain disturbance was progressive, child neurologists were presented with the case of a teenager who had spastic diplegia without loss of motor milestones but had changes on a repeat brain MRI scan obtained for clinically spurious reasons. These child neurologists did not wring their hands regarding whether the child’s diagnosis of CP still applied. Instead, they bemoaned that the repeat MRI scan was done when the child was otherwise doing well.6Although the scenarios discussed thus far have involved spasticity, there are myriad other potential motor manifestations of CP to consider. Growing data confirm something many clinicians have always known: most people with CP have a mix of different movement patterns, including spasticity, dystonia, chorea, ataxia, and hypotonia, many of which can be challenging to differentiate from each other accurately.9,14 Globally, the views on hypotonia are remarkably variable. Half of global CP registries include people with a predominant hypotonic movement pattern, whereas the other half do not.15 Paralleling this variability across registries, the interpretation of hypotonia as a CP phenotype is a source of considerable diagnostic variability for physicians.2 Given how common mixed movement manifestations of CP are,9 it is clinically impractical and inaccurate to exclude a CP diagnosis based on a single “pure” phenotype alone. CP diagnostic guidance for clinicians should reflect this.Is CP a valuable diagnosis at all? People with CP and caregivers say yes. In one survey, the majority would hold on to their CP diagnosis because it gave them access to, among other things, community, a way to explain their symptoms to others, and an understanding of the evolution of their condition.16 The CP label is also valuable for guiding clinical care. Just like evidence-based care pathways exist for other heterogenous neurodevelopmental conditions like epilepsy17 and autism,18 evidence-based care pathways also exist for CP.19,20 The CP label cues clinicians to apply CP-specific care pathways, just like the epilepsy label cues clinicians to think about treatment guidelines and surgical candidacy in a way that an isolated etiologic diagnosis (eg, a specific genetic variant or brain injury pattern) might not.17,21 Both epilepsy22 and autism18,23 benefit from standardized evidence-based definitions. Epilepsy’s definition additionally incorporates prediction of future symptoms.22 The data now exist to do the same for CP.The aggregate data are powerful, but they must be comprehensively synthesized in a meaningful and clinically relevant way. Wordsmithing the definition is insufficient to consider these myriad scientific advances and the complexity of clinical evaluation. Instead, an evidence-based approach to defining CP should ensure an inclusive, standardized, and easily operationalized diagnostic framework that any primary care physician can use in any clinic visit, anywhere, including in low-resource settings, with clarity and confidence.Simple guidelines have recently been suggested to address CP diagnostic uncertainties and facilitate practical diagnosis6: Motor symptoms because of a brain disturbance should begin before age 2 years.Previously acquired motor milestones should not be lost by age 5 years.A CP diagnosis should be provided as early as possible as long as motor disability without loss of motor milestones can be predicted or reported to be present at age 5 years.These guidelines aim to operationalize the 2006 consensus definition in a concrete and evidence-based way, but it is unknown whether their clinical application will reduce diagnostic variability. This should be transparently assessed by consulting with clinicians across specialties, as has been done previously with the 2006 consensus definition.2,6 Although clinician expertise is valuable, the largest community of experts on CP are the people directly affected. Noting that people with CP and caregivers have stated the value of a CP diagnosis,16 their perceptions of any CP diagnostic frameworks should be explicitly ascertained. Finally, a complete evidence-based CP diagnostic framework should allow for documentation of CP as a phenotypic diagnostic label separate from listing its potential etiologic contributors.16 Therefore, although the above operationalization is a start, the work is not done. CP is not a bad term, but we must do better. Together, we will.