Clinical Review & Education

JAMA Pediatrics | Review

Early, Accurate Diagnosis and Early Intervention

in Cerebral Palsy
Advances in Diagnosis and Treatment
Iona Novak, PhD; Cathy Morgan, PhD; Lars Adde, PhD; James Blackman, PhD; Roslyn N. Boyd, PhD; Janice Brunstrom-Hernandez, MD;
Giovanni Cioni, MD; Diane Damiano, PhD; Johanna Darrah, PhD; Ann-Christin Eliasson, PhD; Linda S. de Vries, PhD; Christa Einspieler, PhD;
Michael Fahey, PhD; Darcy Fehlings, PhD; Donna M. Ferriero, MD; Linda Fetters, PhD; Simona Fiori, PhD; Hans Forssberg, PhD; Andrew M. Gordon, PhD;
Susan Greaves, PhD; Andrea Guzzetta, PhD; Mijna Hadders-Algra, PhD; Regina Harbourne, PhD; Angelina Kakooza-Mwesige, PhD; Petra Karlsson, PhD;
Lena Krumlinde-Sundholm, PhD; Beatrice Latal, MD; Alison Loughran-Fowlds, PhD; Nathalie Maitre, PhD; Sarah McIntyre, PhD; Garey Noritz, MD;
Lindsay Pennington, PhD; Domenico M. Romeo, PhD; Roberta Shepherd, PhD; Alicia J. Spittle, PhD; Marelle Thornton, DipEd; Jane Valentine, MRCP;
Karen Walker, PhD; Robert White, MBA; Nadia Badawi, PhD

Supplemental content
IMPORTANCE Cerebral palsy describes the most common physical disability in childhood and
occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24
months but now can be made before 6 months’ corrected age.

OBJECTIVES To systematically review best available evidence for early, accurate diagnosis of
cerebral palsy and to summarize best available evidence about cerebral palsy–specific early
intervention that should follow early diagnosis to optimize neuroplasticity and function.

EVIDENCE REVIEW This study systematically searched the literature about early diagnosis of
cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the
Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy,
diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and
specificity. The study included systematic reviews with or without meta-analyses, criteria of
diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according
to the PRISMA statement, and recommendations are reported according to the Appraisal of
Guidelines, Research and Evaluation (AGREE) II instrument.

FINDINGS Six systematic reviews and 2 evidence-based clinical guidelines met inclusion
criteria. All included articles had high methodological Quality Assessment of Diagnostic
Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy
emerge and evolve before age 2 years; therefore, a combination of standardized tools should
be used to predict risk in conjunction with clinical history. Before 5 months’ corrected age, the
most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89%
sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and
the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months’
corrected age, the most predictive tools for detecting risk are magnetic resonance imaging
(86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological
Examination (90% sensitivity), and the Developmental Assessment of Young Children (83%
C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy,
and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may
be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with
cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence.

CONCLUSIONS AND RELEVANCE Early diagnosis begins with a medical history and involves
using neuroimaging, standardized neurological, and standardized motor assessments that
Author Affiliations: Author
indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should affiliations are listed at the end of this
understand the importance of prompt referral to diagnostic-specific early intervention to article.
optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance Corresponding Author: Iona Novak,
caregiver well-being. PhD, Cerebral Palsy Alliance, The
University of Sydney, PO Box 187,
Frenchs Forest, New South Wales,
JAMA Pediatr. 2017;171(9):897-907. doi:10.1001/jamapediatrics.2017.1689 Australia 2086 (inovak
Published online July 17, 2017. Corrected on September 5, 2017. @cerebralpalsy.org.au).

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 Clinical Review & Education Review Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy

A
ccording to a 2007 report, “Cerebral palsy is a group of per-
manent disorders of the development of movement and Key Points
posture, causing activity limitation, that are attributed to Question What are the most accurate evaluations for diagnosing
non-progressive disturbances that occurred in the developing fe- cerebral palsy early?
tal or infant brain.”1(p9) Cerebral palsy is a clinical diagnosis based on
Findings In this systematic review of the literature, we found
a combination of clinical and neurological signs. Diagnosis typically
diagnosis can be accurately made before 6 months’ corrected age.
occurs between age 12 and 24 months.2-4 The following 4 motor Before 5 months’ corrected age, magnetic resonance imaging plus
types exist but may emerge and change during the first 2 years of the General Movements Assessment or the Hammersmith Infant
life: (1) spasticity (85%-91%); (2) dyskinesia (4%-7%), including dys- Neurological Examination are recommended; after 5 months’
tonia and athetosis; (3) ataxia (4%-6%); and (4) hypotonia (2%), corrected age, magnetic resonance imaging (where safe and
which is not classified in all countries.2 Dyskinesia, ataxia, and hy- feasible), the Hammersmith Infant Neurological Examination, and
the Developmental Assessment of Young Children are
potonia usually affect all 4 limbs, whereas spasticity is categorized
recommended.
topographically as (1) unilateral (hemiplegia) (38%) and (2) bilat-
eral, including diplegia (lower limbs affected more than upper limbs) Meaning Early diagnosis should be the standard of care because
(37%) and quadriplegia (all 4 limbs and trunk affected) (24%).2 Co- contemporary early interventions optimize neuroplasticity and
functional outcomes.
morbidities and functional limitations are common and disabling, in-
cluding chronic pain (75%), epilepsy (35%), intellectual disability
(49%), musculoskeletal problems (eg, hip displacement) (28%), be- nostic accuracy, and evidence-based clinical guidelines. Quality was
havioral disorders (26%), sleep disorders (23%), functional blind- appraised using the Quality Assessment of Diagnostic Accuracy Stud-
ness (11%), and hearing impairment (4%).5 ies (QUADAS) methodological rating checklist for systematic re-
Cerebral palsy is the most common physical disability in child- views of diagnostic accuracy.19
hood, with a prevalence of 2.1 cases per 1000 in high-income The Grading of Recommendations Assessment, Develop-
countries.6 The prevalence is declining in Australia and Europe.7,8 ment, and Evaluation (GRADE) framework was used to assess qual-
Exact rates in countries of low to middle income are less certain9 but ity and formulate recommendations along a 4-part continuum, in-
appear to be higher, with worse physical disability, because of greater cluding strong for, conditional for, conditional against, and strong
infectious disease burden and prenatal and perinatal care against.20 As per the GRADE method, we weighed (1) the balance
differences.10 The complete causal path to cerebral palsy is unclear between desirable and undesirable consequences of different man-
in approximately 80% of cases, but risk factors are often identifi- agement strategies or not acting; (2) family preferences, including
able from history taking about conception, pregnancy, birth, and the benefits vs risks and inconvenience; and (3) cost. Recommenda-
postneonatal period.11 The full causal path is a complex interplay be- tions were discussed face-to-face among all authors, and the manu-
tween several risk factors across multiple epochs,11 including new script was reviewed, edited, and agreed on by all coauthors. Au-
evidence suggesting that 14% of cases have a genetic thors were clinicians involved in the diagnosis of cerebral palsy,
component.12-14 Early diagnosis does not preclude further specific including neurologists, pediatricians, neonatologists, rehabilita-
etiological investigation, and identifying a specific etiology does not tion specialists, general practitioners, neuroradiologists, psychia-
then preclude individuals from also having cerebral palsy. Genetic trists, physical therapists, psychologists, occupational therapists,
advances are likely to soon amend the diagnostic process. speech pathologists, nurses, and early educators. Individuals with
Our primary objective was to systematically review best avail- cerebral palsy and parents also contributed as equal authors, en-
able evidence for early, accurate diagnosis of cerebral palsy. Our sec- suring that recommendations addressed their views and prefer-
ondary objective was to summarize best available evidence about ences.
cerebral palsy–specific early intervention that should follow early di-
agnosis to optimize neuroplasticity and function.
Results
Six systematic reviews 21-26 and 2 evidence-based clinical
Methods guidelines27,28 met inclusion criteria. The methodological quality of
We conducted a systematic review to develop an international clini- the evidence was very high (eTable in the Supplement), enabling
cal practice guideline in accord with the World Health Organiza- strong GRADE recommendations.20 Many standardized tools exist
tion’s Handbook for Guideline Development15 and the Institute of that predict risk of cerebral palsy early. Best available evidence was
Medicine’s standards.16 We followed the Equator Network report- summarized (eTable in the Supplement), and a PRISMA diagram sum-
ing recommendations outlined in the Appraisal of Guidelines, Re- marized study flow (eFigure in the Supplement).
search and Evaluation (AGREE) II instrument17 and the Preferred Re-
porting Items for Systematic Reviews and Meta-analyses (PRISMA)
statement.18 We systematically searched MEDLINE (1956-2016),
Advances in Diagnosis: Early Clinical Diagnosis
EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Li-
Is Now Possible
brary (1988-2016) and hand searched using the following terms: ce-
rebral palsy, diagnosis, detection, prediction, identification, predic- Before age 12 to 24 months was historically regarded as the latent
tive validity, accuracy, sensitivity, and specificity. We included or silent period where cerebral palsy could not be identified accu-
systematic reviews with or without meta-analyses, criteria of diag- rately. Experts now consider the silent period as outdated because

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 Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy Review Clinical Review & Education

cerebral palsy or “high risk of cerebral palsy” can be accurately pre- that assessments be carried out by a professional skilled at deter-
dicted before age 6 months’ corrected age. mining atypical movement from variation in typical movement.
The 3 tools with best predictive validity for detecting cerebral
palsy before 5 months’ corrected age are (1) neonatal magnetic reso- Additional Criteria (at Least One Required)
nance imaging (MRI) (86%-89% sensitivity),21,27 (2) the Prechtl Abnormal Neuroimaging
Qualitative Assessment of General Movements (GMs) (98% Abnormal MRI21,27 with or without serial cranial ultrasound in pre-
sensitivity),21 and (3) the Hammersmith Infant Neurological Exami- term infants21,28 may identify neuroanatomical abnormalities pre-
nation (HINE) (90% sensitivity)25 (eTable in the Supplement). Af- dictive of cerebral palsy. The most predictive patterns are (1) white
ter 5 months’ corrected age, the most predictive tools for detect- matter injury (cystic periventricular leukomalacia or periventricu-
ing risk are MRI (86%-89% sensitivity) (where safe and feasible), lar hemorrhagic infarctions) (56%), (2) cortical and deep gray mat-
the HINE (90% sensitivity), and the Developmental Assessment of ter lesions (basal ganglia or thalamus lesions, watershed injury [para-
Young Children (83% C index). High-quality evidence also indi- sagittal injury], multicystic encephalomalacia, or stroke) (18%), and
cates that a trajectory of abnormal GMs or HINE scores, in combi- (3) brain maldevelopments (lissencephaly, pachygyria, cortical dys-
nation with abnormal MRI, producing congruent findings, is even plasia, polymicrogyria, or schizencephaly) (9%).
more accurate than individual clinical assessments in isolation.21,25
To make an early clinical diagnosis before 6 months’ corrected Clinical History Indicating Risk for Cerebral Palsy
age, a combination of assessments with strong predictive validity Preconception risks include history of stillbirths, miscarriages, low
coupled with clinical reasoning is recommended. We have made 12 socioeconomic status, assisted reproduction, and abnormal ge-
recommendations from best available evidence (Table 1). A highly netic copy number variations.
experienced clinical team should ideally conduct and interpret the Pregnancy risks include genetics, birth defects, multiples, males,
standardized assessments and then communicate the news com- maternal thyroid disease or preeclampsia, infection, intrauterine
passionately. growth restriction, prematurity, and substance abuse.
Perinatal birth risks include acute intrapartum hypoxia-
Interim High Risk of Cerebral Palsy Clinical Diagnosis ischemia, seizures, hypoglycemia, jaundice, and infection.
When the clinical diagnosis is suspected but cannot be made with Postneonatal risks include stroke, infection, surgical complica-
certainty, we recommend using the interim clinical diagnosis of tions, and accidental and nonaccidental brain injury31 occurring be-
high risk of cerebral palsy until a diagnosis is confirmed. We rec- fore age 24 months, as per the Surveillance of Cerebral Palsy Eu-
ommend specifying cerebral palsy because infants with cerebral rope and Australian Cerebral Palsy Register inclusion criteria.
palsy require and benefit from different early interventions than
infants “at risk of developmental delay,” “at risk of autism,” “at risk Two Early Detection Pathways Based on Different Risks
of harm,” or with “social risk.” When the infant is perceived to be at Half of all infants with cerebral palsy have high-risk indicators iden-
risk of cerebral palsy, he or she should be referred for cerebral tifiable in the newborn period, enabling early screening31 (eg, pre-
palsy–specific early intervention (see the Advances in Treatment maturity, atypical intrauterine growth, encephalopathy, genetic ab-
section), with regular medical, neurological, and developmental normalities, and seizures). We have described this population as
monitoring from the infant’s pediatrician or neurologist to assist having “newborn-detectable risks for cerebral palsy,” and this path-
with forming a diagnostic picture. To assign the interim clinical way occurs before 5 months’ corrected age. For the other half of all
diagnosis of high risk of cerebral palsy, the infant must have motor infants with cerebral palsy, the pregnancy and labor may have ap-
dysfunction (essential criterion) and at least one of the other 2 peared to be uneventful,31 and parents, caregivers, or community-
additional criteria. based professionals first notice delayed motor milestones (eg, not
sitting at 9 months or hand asymmetry). This finding may be espe-
Essential Criterion (Required) cially true for infants with unilateral cerebral palsy, who often mas-
Motor Dysfunction ter early rudimentary motor skills, such as smiling, swallowing, and
In motor dysfunction, the infant’s quality of movement is reduced head control, and it is not until they attempt more complex motor
(eg, absent fidgety GMs)29 or neurologically abnormal (eg, early ob- skills, such as grasp, that asymmetries become observable. We have
servable hand asymmetry or suboptimal HINE scores).30 In addi- described this population as having “infant detectable risks for ce-
tion, the infant’s motor activities may be substantially below those rebral palsy,” and this pathway occurs after 5 months’ corrected age.
expected for chronological age (eg, abnormal score on a standard- We developed a conceptual framework for early diagnosis based on
ized motor assessment or parent and caregiver or clinical observa- these 2 pathways to ensure that the most sensitive and specific tools
tions of head lag, not sitting, inability to grasp, or not reaching for a are used to reduce false-positive and false-negative results. The clini-
toy when appropriate). cal diagnostic pathway algorithm for these 2 groups varies because
As a caveat, in milder presentations, especially unilateral cere- the tools have different psychometric properties depending on the
bral palsy, it is possible for an infant to score within the normal range infant’s age (Figure).
on a standardized motor assessment, while still displaying abnor-
mal movements. For example, an infant with hemiplegia might ob- Determining Severity
tain a normal fine-motor score but complete the assessment one- Parents or caregivers will want to learn about the severity of their
handed. Similarly, an infant with diplegia may achieve normal upper infant’s physical disability to understand his or her capabilities to plan
limb scores and abnormal lower limb scores, producing a combined their future. In infants younger than 2 years, motor severity is diffi-
total motor score within the normal range. Therefore, it is essential cult to accurately predict for the following reasons: (1) almost half

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 Clinical Review & Education Review Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy

Table 1. Early Detection and Diagnosis Recommendations From Best Available Evidence

Recommendations Strength of Recommendations and Quality of Evidence

1.0 The clinical diagnosis of CP can and should be made as early as possible so that: Strong recommendation based on moderate-quality
• The infant can receive diagnostic-specific early intervention and surveillance to optimize evidence for infant and parent outcomes
neuroplasticity and prevent complications
• The parents can receive psychological and financial support (when available)
1.1 When the clinical diagnosis is suspected but cannot be made with certainty, the interim clinical Strong recommendation based on moderate-quality
diagnosis of high risk of CP should be given so that: evidence for infant and parent outcomes
• The infant can receive diagnostic-specific early intervention and surveillance to optimize
neuroplasticity and prevent complications
• The parents can receive psychological and financial support (when available)
• Ongoing diagnostic monitoring can be provided until a diagnosis is reached
2.0 Early standardized assessments and investigations for early detection of CP should always be Strong recommendation based on high-quality evidence
conducted in populations with newborn-detectable risks (ie, infants born preterm, infants with of test psychometrics
neonatal encephalopathy, infants with birth defects, and infants admitted to the NICU)
Early Detection of CP Before 5 mo CA
3.0 Option A: The most accurate method for early detection of CP in infants with newborn-detectable Strong recommendation based on high-quality evidence
risks and younger than 5 mo (CA) is to use a combination of a standardized motor assessment and of test psychometrics in newborn-detectable risk
neuroimaging and history taking about risk factors populations
Standardized motor assessment Strong recommendation based on high-quality evidence
3.1 Test: GMs to identify motor dysfunction (95%-98% predictive of CP), combined with neuroimaging of test psychometrics in newborn-detectable risk
populations
Neuroimaging Strong recommendation based on high-quality evidence
3.2 Test: MRI (before sedation is required for neuroimaging) to detect abnormal neuroanatomy in of test psychometrics in newborn-detectable risk
the motor areas of the brain (80%-90% predictive of CP). Note that normal neuroimaging does not populations
automatically preclude the diagnosis of risk of CP
4.0 Option B: In contexts where the GMs assessment is not available or MRI is not safe or affordable Strong recommendation based on moderate-quality
(eg, in countries of low to middle income), early detection of CP in infants with newborn-detectable evidence of test psychometrics in newborn-detectable
risks and younger than 5 mo (CA) is still possible and should be carried out to enable access to early risk populations
intervention
Standardized neurological assessment Strong recommendation based on moderate-quality
4.1 Test: HINE (scores <57 at 3 mo are 96% predictive of CP) evidence of test psychometrics in newborn-detectable
risk populations
Standardized motor assessment Conditional recommendation based on low-quality
4.2 Test: TIMP evidence of test psychometrics in at-risk populations
Early Detection of CP After 5 mo CA
Accurate early detection of CP in those with infant-discernible risks and age 5-24 mo can and should still occur as soon as possible, but different diagnostic tools
are required
5.0 Any infant with: Strong recommendation based on high-quality evidence
(a) Inability to sit independently by age 9 mo, or of motor norms
(b) Hand function asymmetry, or
(c) Inability to take weight through the plantar surface (heel and forefoot) of the feet should receive
standardized investigations for CP
6.0 Option A: The most accurate method for early detection of CP in those with infant detectable Conditional recommendation based on moderate-quality
risks older than 5 mo (corrected for prematurity) but younger than 2 y is to use a combination of a evidence of test psychometrics in newborn-detectable
standardized neurological assessment, neuroimaging, and a standardized motor assessment with a risk populations
history taking about risk factors
Standardized neurological assessment Conditional recommendation based on moderate-quality
6.1 Test: HINE (90% predictive of CP). Those with HINE scores <73 (at 6, 9, or 12 mo) should be evidence of test psychometrics in newborn-detectable
considered at high risk of CP. HINE scores <40 (at 6, 9, or 12 mo) almost always indicate CP, risk populations
combined with neuroimaging and standardized motor assessments
Neuroimaging Conditional recommendation based on moderate-quality
6.2 Test: MRI to detect abnormal neuroanatomy in the motor areas of the brain (sedation may be evidence of test psychometrics in newborn-detectable
required from >6 wk up to age 2 y). Well-defined lesions can be seen early, but subtle white matter risk populations
lesions may be difficult to detect owing to rapid growth, myelination, and activity-dependent
plasticity. Repeated MRI scans are recommended at age 2 y for infants with initially normal findings on
MRI (at 12-18 mo) but persistent motor or neurological abnormality, combined with standardized
motor assessments
Standardized motor assessment Conditional recommendation based on low- to
6.3 Test: DAYC for parents to self-report and quantify motor delay (89% predictive of CP) moderate-quality evidence of test psychometrics in
Additional assessments can improve triangulation of findings newborn-detectable risk populations
6.4 Tests: AIMS (86% predictive of an abnormal motor outcome) and NSMDA (82% predictive of an
abnormal motor outcome)
7.0 Option B: In contexts where MRI is not safe or affordable, early detection of CP is still possible in Strong recommendation based on moderate-quality
those with infant detectable risks between 5 and 24 mo CA and should be carried out to enable evidence of test psychometrics in newborn-detectable
access to early intervention risk populations
Standardized neurological assessment Strong recommendation based on moderate-quality
7.1 Test: HINE (90% predictive of CP at age 2-24 mo) evidence of test psychometrics in newborn-detectable
HINE scores at 6, 9, or 12 mo: risk populations
<73 Indicates high risk of CP
<40 Indicates abnormal outcome, usually CP
Standardized motor assessment Conditional recommendation based on low- to
7.2 Test: DAYC to quantify motor delay (89% predictive of CP) moderate-quality evidence of test psychometrics in
7.3 Test: MAI to quantify motor delay (73% predictive of CP) newborn-detectable risk populations

(continued)

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Table 1. Early Detection and Diagnosis Recommendations From Best Available Evidence (continued)

Recommendations Strength of Recommendations and Quality of Evidence

Early Detection of Motor Severity of CP
Prognosis of long-term motor severity is most accurate in children older than 2 y using the GMFCS
8.0 In infants younger than 2 y, prognosis of motor severity predictions should be made cautiously Conditional recommendation based on low-quality
and always involve the use of standardized tools because incomplete development of voluntary motor evidence
skills or abnormal tone might confound clinical observations. Motor severity of CP in those younger
than 2 y is most accurately predicted using the following:
Standardized neurological assessment Conditional recommendation based on moderate-quality
8.1 Test: HINE. Cutoff scores predict the probable severity evidence in newborn-detectable risk populations
HINE scores at 3, 6, 9, or 12 mo:
• 50-73 Indicates likely unilateral CP (ie, 95%-99% will walk)
• <50 Indicates likely bilateral CP
HINE scores at 3-6 mo:
• 40-60 Indicates likely GMFCS I-II
• <40 Indicates likely GMFCS III-V
Neuroimaging Conditional recommendation based on moderate-quality
8.2 Test: MRI evidence in newborn-detectable risk populations
Nonambulant CP is more likely after:
• Bilateral parenchymal hemorrhages (grade IV)
• Bilateral cystic periventricular leukomalacia (grade III)
• Brain maldevelopment
• Basal ganglia injury
Ambulant CP is more likely after:
• Unilateral lesions (grade IV hemorrhage or perinatal arterial ischemic stroke)
• Periventricular leukomalacia (noncystic)
• Moderate to severe white matter injury
Normal imaging does not preclude CP, and abnormal findings on MRI imaging does not automatically
precede CP
Early Detection of Motor Subtype and Topography of CP
9.0 Early detection of motor subtype and topography can be difficult in those younger than 2 y, Conditional recommendation based on low- to
but wherever possible it is important to identify unilateral vs bilateral CP early because the early high-quality evidence
interventions (eg, constraint-induced movement therapy) and long-term musculoskeletal outcomes
and surveillance needs differ (eg, hip surveillance)
Early Intervention
10.0 The clinical diagnosis of CP or the interim diagnosis of high risk of CP should always be followed Strong recommendation based on low- to high-quality
by a referral to CP-specific early intervention (eg, constraint-induced movement therapy and hip evidence
surveillance). Parent concern is a valid reason to trigger formal diagnostic investigations and referral
to early intervention
Early Detection of Associated Impairments
11.0 The clinical diagnosis of CP or the interim diagnosis of high risk of CP should always include Strong recommendation based on high-quality
standard medical investigations for associated impairments and functional limitations (eg, vision population register evidence of rates of associated
impairment, hearing impairment, and epilepsy) impairments
Communicating the Diagnosis Well to Parents
12.0 Parents experience grief and loss at the time of diagnosis or high-risk notification; therefore, Strong recommendation based on high-quality
communication with a family should be a series of well-planned and compassionate conversations. qualitative parent interviews
Communication should be face-to-face, with both parents or caregivers present (where appropriate),
private, honest, jargon free, and with empathic communication tailored to the family, followed by
written information, identification of strengths, invitation to ask questions, discussion of feelings,
recommendations to use parent-to-parent support, and arrangement of early intervention
Abbreviations: AIMS, Alberta Infant Motor Scale; CA, corrected age; CP, cerebral MAI, Motor Assessment of Infants; MRI, magnetic resonance imaging;
palsy; DAYC, Developmental Assessment of Young Children; GMFCS, Gross NICU, neonatal intensive care unit; NSMDA, Neuro Sensory Motor Development
Motor Function Classification System; GMs, Prechtl Qualitative Assessment of Assessment; TIMP, Test of Infant Motor Performance.
General Movements; HINE, Hammersmith Infant Neurological Examination;

of all infants younger than 2 years have their Gross Motor Function indicate that 2 in 3 individuals with cerebral palsy will walk, 3 in 4
Classification System (GMFCS) reclassified, (2) little natural history will talk, and 1 in 2 will have normal intelligence.5
data exist about infants with cerebral palsy (eg, the onset of spas-
ticity, dyskinesia, or contractures), (3) motor skills are developing, Determining Motor Type and Topography
(4) the presence or absence of hypertonia changes and evolves, and The motor types and topography of cerebral palsy may emerge and
(5) there is rapid brain growth and use-dependent reorganization change during the first 2 years of life. Cerebral palsy can be difficult
in response to caregiving and therapy. In children 2 years or older, to accurately classify early, but clinical signs exist33-37 (Table 2). For
severity is reliably classified using the 5-level GMFCS Extended & example, the onset of spasticity may occur after age 1 year; there-
Revised.32 In infants younger than 2 years, prediction of motor se- fore, the absence of early detectable spasticity does not mean that
verity should be made cautiously using standardized tools, includ- the infant does not have spastic cerebral palsy. In addition, infants
ing the cutoff scores on the HINE, combined with neuroimaging may have more than one motor disorder because spasticity and dys-
data.25 Parents or caregivers may mistakenly assume that the diag- tonia often coexist. As the infant’s voluntary activity levels in-
nosis means their child will need a wheelchair and have an intellec- crease, some symptoms may resolve (eg, nonuse of a limb), while
tual disability. However, in high-income countries, population data other symptoms may worsen (eg, increased involuntary dystonic

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 Clinical Review & Education Review Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy

Figure. Algorithm for Early Diagnosis of Cerebral Palsy or High Risk of Cerebral Palsy

Newborn detectable risks Infant detectable risks

Preterm Encephalopathy History or neurological risk Parent identified concern Unable to sit at 9 mo or hand
factors (eg, birth defect, IUGR) asymmetry

Risks or concerns warrant an investigation for CP

Conduct a medical history and clinical examination

with or without investigations for etiology and
differential diagnoses (as indicated)

<5 mo CA >5 mo CA

A B A B

Clinical neurological examination 4.1 HINE 6.1 HINE 7.1 HINE

+ + +

Neurological imaging 3.2 MRI 6.2 MRI

+ +

Motor tests 3.1 GMs 4.2 TIMP 6.3 DAYC 6.3 AIMS 6.3 NSM DA 7.2 DAYC 7.3 MAI

Combined assessment data indicates

1.1 High risk of CP 1.1 Definitely CP 1.1 Unclear 1.1 Definitely NOT CP

8.0 Determine preliminary severity of CP

8.1 HINE ≥40 8.1 MRI WMI 8.1 HINE <40 8.1 MRI GMI

Likely ambulant Likely nonambulant As indicated, continue testing

for differential diagnoses and
relevant associated impairments

9.0 Determine preliminary topography

11.0 Assess for associated impairments

12.0 Communicate findings to parents compassionately

10.0 Arrange early intervention and parent support Monitor Confirm diagnosis

A indicates the best available evidence pathway. B indicates the next best Movements; HINE, Hammersmith Infant Neurological Examination;
available evidence pathway when some pathway A tools are not available. The IUGR, interuterine growth restriction; MAI, Motor Assessment of Infants;
numerals correspond to the numbering in Table 1. AIMS indicates Alberta Infant MRI, magnetic resonance imaging; NSMDA, Neuro Sensory Motor Development
Motor Scale; CA, corrected age; CP, cerebral palsy; DAYC, Developmental Assessment; TIMP, Test of Infant Motor Performance; and WMI, white matter
Assessment of Young Children; GMs, Prechtl Qualitative Assessment of General injury.

posturing in response to voluntary movement). Wherever pos- False Positives and False Negatives
sible, differentiate between unilateral vs bilateral cerebral palsy early Without a laboratory biomarker, an early diagnosis is not always clini-
because treatments differ.5,38 cally clear-cut because of the possibility of false positives and false

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 Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy Review Clinical Review & Education

Table 2. Clinical Signs Indicating Motor Type and Topography in Infants

Unilateral Spastic Hemiplegia Bilateral Spastic Diplegia Bilateral Spastic Quadriplegia Dyskinesia Ataxia
GMs34
• Poor repertoire or cramped • Cramped synchronized • Early onset and long duration • Poor repertoire GMs, • Unknown
synchronized GMs, followed by GMs, followed by absent of cramped synchronized GMs, followed by absent fidgety
absent fidgety movements plus an fidgety movements followed by absent fidgety movements with circular
asymmetry in segmental movements arm movements and
movements (eg, wrist or hand). finger spreading
Note that some cases of hemiplegic
CP may be missed by GMs
MRI35,36
• Focal vascular insults (24%) • Bilateral white matter • Gray matter injury (34%) • Gray matter injury • Malformations (18%)
• Malformations (13%) injury (31%-60%) • Malformations (16%) (21%) with thalamic and • Normal imaging (24%-57%)
• Unilateral hemorrhage (grade IV) • Cystic PVL (grade II-III) • Cystic PVL (grade III) with lentiform nuclear injury • Cerebellar injury
with porencephaly with sparse or absent absent myelination of the PLIC
• Lesions in the parietal white myelination of the PLIC • Severe white matter injury
matter involving the trigone • Moderate to severe white with or without deep nuclear
• Middle cerebral artery stroke with matter injury (also known gray matter
asymmetry of myelination of the as PVE)
PLIC
HINE Scores37
50-73 <50 <50 <50 Unknown
<40 GMFCS level IV-V
Motor Tests
• Asymmetrical hand preference • Good hand function • Head lag • Twisting arm or neck • Nonspecific
• Stuck in floor sitting (ie, unable to compared with lower limb • Persistent rounded back in postures on voluntary
transition out of sitting) function supported sitting movement (may be
• Cruises or steps consistently in • Dislike or avoidance of • Bilateral fisted hands painful)
one direction or with the same leg floor sitting • Slow to reach and grasp with • Finds midline play
always leading • Weight bears on toes either hand difficult, prefers toys
• Reduced variation in motor • Reduced variation in • Reduced variation in motor positioned at shoulder
behavior motor behavior behavior width
• Switches hands during
reaching task
• Requires a lot of extra
time to initiate movement
• Voluntary movement
and emotion worsens
postures
• Reduced variation in
motor behavior
Abbreviations: CP, cerebral palsy; GMFCS, Gross Motor Function Classification imaging; PLIC, posterior limb internal capsule; PVE, periventricular
System; GMs, Prechtl Qualitative Assessment of General Movements; HINE, echogenicity; PVL, periventricular leukomalacia.
Hammersmith Infant Neurological Examination; MRI, magnetic resonance

negatives.22 Experienced clinicians acknowledge that, because all caregivers dissatisfied with a prolonged diagnostic process are more
infants have an expanding and changing voluntary motor reper- likely to experience depression39 and lasting anger.40 Parents and
toire, determining whether their current motor dysfunction is per- caregivers acknowledge that, while receiving the diagnosis is al-
manent and causing long-term activity limitations, as per the inter- ways difficult, they prefer to know earlier rather than later so that
national definition,1 is difficult. False negatives can occur for the they can assist in their infant’s development.39 Early detection is im-
following reasons: (1) there is a latency between the initial brain le- portant for the whole family unit because it helps foster acceptance41
sion and the later onset of clinical neurological signs (eg, exagger- and leads to increased confidence in the infant’s medical team.39
ated spasticity or dystonia from voluntary movement25), (2) ap- Early detection allows improved access to early intervention and ef-
proximately 10% have normal neuroimaging,27 (3) half have a ficient use of resources.
seemingly uneventful pregnancy and birth,31 and (4) one-third have
the mildest form (GMFCS I)2,32 and may initially achieve all of their
motor milestones on time, offering false reassurance about their mo-
Advances in Treatment: Cerebral Palsy–Specific
tor development. False positives can also occur because prematu-
rity, stroke, and encephalopathy do not always result in long-term Early Intervention Improves Outcomes
motor disabilities.25,31 Australian cerebral palsy population register Neuroscience evidence indicates that brain development and refine-
data indicate that less than 5% of registrations are false-positive ment of the motor system continue postnatally, driven by motor cor-
diagnoses.2 In almost all of these instances, the infant was rediag- tex activity.42,43 Early active movement and intervention are essential
nosed as having another neurological disability (eg, intellectual dis- because infants who do not actively use their motor cortex risk los-
ability or autism), not a normal developmental outcome.11 ing cortical connections and dedicated function.42,43 Furthermore,
Eighty-six percent of parents of a child with cerebral palsy sus- there is increasing evidence that the infant’s motor behavior, via dis-
pect it before the clinical diagnosis is made.39 Population data indi- covery and interaction with the environment, controls and gener-
cate that seeking to avoid false-positive results by delaying diagno- ates the growth and development of muscle, ligament, and bone, as
sis is harmful to parent and caregiver well-being.39 Parents and well as driving ongoing development of the neuromotor system.44-48

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 Clinical Review & Education Review Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy

Therefore, the clinical diagnosis of cerebral palsy or high risk of tice, and environmental adaptations that stimulate independent
cerebral palsy should always be followed by a referral for the infant to task performance.52 These include Learning Games Curriculum
receivecerebralpalsy–specificinterventionandfortheparentsorcare- (diplegia), 57 CIMT or bimanual (hemiplegia), 45 and GAME (all
givers to receive emotional support. Family concern is a valid reason subtypes).49
to trigger formal diagnostic investigations and intervention referrals. For communication, speech language pathology interven-
Cerebral palsy–specific early intervention maximizes neuro- tions should foster parent-infant transactions and provide
plasticity42,43 and minimizes deleterious modifications to muscle and compensation when speech is not possible or is inadequate.
bone growth and development.44 Before commencing interven- Examples include the Hanen It Takes Two to Talk and More Than
tion, unilateral vs bilateral cerebral palsy should be identified be- Words programs, as well as alternative and augmentative
causetreatmentsandlong-termmusculoskeletaloutcomesdiffer.46-48 communication.58
Randomized clinical trial data are beginning to indicate the follow-
ing: (1) that infants with hemiplegic cerebral palsy who receive early Interventions to Prevent Secondary Impairments
constraint-induced movement therapy (CIMT) have better hand func- and Minimize Complications
tion than controls in the short term and probably substantially bet- Regarding pain, procedural pain should be avoided where possible
ter hand function in the long term45; (2) that infants with bilateral ce- because untreated pain elevates the risk for long-term neuro-
rebral palsy who receive regular surveillance and intervention have pathic pain.59 Recommendations include pharmacological therapy
lower rates of hip displacement, contracture, and scoliosis46-48 (based and environmental interventions for ongoing pain and preemptive
on population register data); (3) that infants with any type and to- analgesia for procedural pain.59
pography of cerebral palsy who receive Goals–Activity–Motor Enrich-
ment (GAME), which is an early, intense, enriched, task-specific, Orthopedics
training-based intervention at home, have better motor and cognitive For hips, anteroposterior pelvic radiographs every 6 to 12 months
skills at 1 year than those who receive usual care49; and (4) that im- are recommended commencing at age 12 months. This recommen-
provements are even better when intervention occurs at home50,51 dation is in accord with hip surveillance guidelines.60
because children learn best in supported natural settings where train-
ing is personalized to their enjoyment. Task-specific, motor training– Neurologic
based early intervention (eg, GAME49 and CIMT45) are recommended For epilepsy, standard antiepileptic pharmacological management
as the new paradigm of care for cerebral palsy because they induce is recommended.5
neuroplasticity and produce functional gains.52 Larger replication ran-
domized clinical trials are under way, including the following: (1) Ran- Urinary Tract
domised Trial of Rehabilitation Very Early in Congenital Hemiplegia For the bladder, medical investigations should be conducted be-
(REACH) (ACTRN12615000180516) (n = 150) CIMT vs bimanual53 and cause abnormal anatomical findings are common.5 Standard toilet
(2) GAME (ACTRN12617000006347) (n = 300) GAME vs usual training should be provided over a longer duration because control
care.54 In addition, regenerative agents to induce brain repair are may take longer.5
being studied, including (1) Preventing Adverse Outcomes of Neonatal
Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Sleep
Randomised Controlled Multicentre Australian Trial (PAEAN) For sleep, specialist assessments and early treatment are recom-
(ACTRN12614000669695) (n = 300) erythropoietin plus mendedbeforesecondaryacademicandbehavioralproblemsemerge.
hypothermia vs hypothermia alone55 and (2) NCT02612155 (n = 160) Examples include sleep hygiene, parental education, spasticity man-
umbilical cord blood plus hypothermia vs hypothermia alone.56 agement, melatonin (2.5-10 mg), and gabapentin (5 mg/kg).5
The aim of early intervention for children with cerebral palsy
should be to (1) optimize motor, cognition, and communication out- Oral Care
comes using interventions that promote learning and neuroplastic- For sialorrhea, botulinum toxin A, benztropine mesylate, or glyco-
ity (all have motor impairments, 1 in 2 have intellectual disability, and pyrrolate should be considered.61
1 in 4 are nonverbal5); (2) prevent secondary impairments and mini-
mize the influence of complications that worsen function or inter- Ophthalmologic Issues
fere with learning (3 in 4 have chronic pain, 1 in 3 have hip displace- Vision can be assessed in the first 48 hours of life using the early as-
ment, 1 in 4 have epilepsy, 1 in 4 have bladder control problems, 1 in sessment of visual function in full-term newborns by Ricci et al.62
5 have a sleep disorder, 1 in 5 have sialorrhea, 1 in 10 are blind, 1 in 15 Any infant with abnormal vision at term-equivalent age should re-
require tube feeding, and 1 in 25 are deaf5); and (3) promote parent ceive vision intervention and be reassessed at 3 months.63 Vision
or caregiver coping and mental health to reduce stress, anxiety, and intervention is recommended.
depression, which are compounded when a behavior disorder is pres-
ent (1 in 4 have behavior disorders). Recommendations from best Feedings
available evidence are listed below. For nonoral feeding, swallowing safety should be comprehensively
assessed if concerns or clinical history of pneumonia exists be-
Early Interventions to Optimize Motor, Cognition, cause it is the leading cause of death in individuals with cerebral
and Communication Skills palsy64 and is mitigated by tube feeding.65 Weight should be mea-
For motor and cognition, physical and occupational therapy inter- sured regularly because severe physical disability elevates the risk
ventions should use child-initiated movement, task-specific prac- for malnutrition.5

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 Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy Review Clinical Review & Education

Aural in infants with newborn discernible risks (eg, prematurity and en-
For hearing, standard early hearing accommodations are cephalopathy) because these infants are more often in newborn fol-
recommended.5 low-up. Little has been published about early diagnosis in the 50%
of all cerebral palsy cases that are discernible later in infancy after a
Interventions to Promote Parent or Caregiver Coping seemingly uneventful pregnancy and birth because these samples
and Mental Health are difficult to assemble. Advances in genetics and understanding
Parental education in behavior management is recommended. An of congenital anomalies may provide more clues about how to iden-
example is the Positive Parenting Program (Triple P).66 tify these children earlier. Second, no study to date has investi-
Parent-child attachment interventions are also helpful. Kanga- gated the combined predictive power of 3 or more of the individual
roo Mother Care67 and music therapy68 are examples. tools identified in this review article and represents a gap in the lit-
Finally, parent or caregiver mental health interventions69,70 are erature. Third, we have not reviewed or discussed the literature about
suggested. One such intervention is Acceptance and Commitment evidence-based testing for other childhood disabilities on the dif-
Therapy (ACT).66 ferential diagnosis list. Fourth, we have not provided a systematic
description of the early intervention evidence. More information on
assessment tools and early intervention is contained in a related but
Discussion separate clinical guideline that is being developed from systematic
review data.
Clinical Bottom Line
• Infants with cerebral palsy require an early diagnosis because mo-
tor and cognitive gains are greater from diagnostic-specific early
Conclusions
intervention.
• An interim diagnosis of high risk of cerebral palsy should be used Cerebral palsy or high risk of cerebral palsy can be diagnosed
if a diagnosis of cerebral palsy cannot yet be used with certainty. accurately and early using clinical reasoning and a combination of
• Clinical signs emerge and evolve before age 2 years. Therefore, a standardized tools. High-quality evidence indicates that, for
combination of standardized tools should be used to predict risk. infants with newborn-detectable risks before 5 months’ corrected
• Before 5 months’ corrected age, MRI, GMs, or the HINE are most age, the GMs assessment plus neonatal MRI is more than 95%
predictive of risk for cerebral palsy. accurate and is thus recommended. For infants with infant
• After 5 months’ corrected age, MRI and the HINE are most predic- detectable risks after 5 months’ corrected age, the HINE plus neo-
tive of risk for cerebral palsy. natal MRI is more than 90% accurate and is therefore recom-
• In countries of low to middle income where MRI is not available, mended. The accuracy of these diagnostic methods in infants
the HINE is recommended. with later infancy discernible risks for cerebral palsy is not yet
• Topography and severity of cerebral palsy are important to estab- known, but they are conditionally recommended. Accurate early
lish for clinical purposes. Magnetic resonance imaging and the HINE diagnosis is possible even when assessments of GMs are not avail-
provide guidance. able or MRI is not safe or affordable (eg, in countries of low to
• Falsepositivesoccurlessthan5%ofthetimewithstandardizedtools. middle income) by using the HINE, which detects cerebral palsy
• False negatives resulting in late diagnoses and late intervention are with more than 90% accuracy and provides objective informa-
detrimental to parents, caregivers, and infants. tion about severity. Early detection of high risk of cerebral palsy,
followed by cerebral palsy–specific early intervention, is recom-
Limitations mended and should be the standard of care to optimize infant
This review article has some limitations. First, our literature search neuroplasticity, prevent complications, and enhance parent and
revealed that almost all studies focus on identifying cerebral palsy caregiver well-being.

ARTICLE INFORMATION Health, Bethesda, Maryland (Damiano); Faculty of Pittsburgh, Pennsylvania (Harbourne); Makerere
Accepted for Publication: April 19, 2017. Rehabilitation Medicine, University of Alberta, University, Kampala, Uganda (Kakooza-Mwesige);
Edmonton, Canada (Darrah); Karolinska Institutet, University Children’s Hospital Zurich, Zurich,
Correction: This article was corrected on Stockholm, Sweden (Eliasson, Forssberg, Switzerland (Latal); Children’s Hospital Westmead,
September 5, 2017, to fix an error in Table 1. Krumlinde-Sundholm); University Medical Centre The University of Sydney, Sydney, Australia
Published Online: July 17, 2017. Utrecht, Utrecht, the Netherlands (de Vries); (Loughran-Fowlds, Walker, Badawi); Nationwide
doi:10.1001/jamapediatrics.2017.1689 Medical University of Graz, Graz, Austria Children’s Hospital, The Ohio State University,
Author Affiliations: Cerebral Palsy Alliance, The (Einspieler); Monash University, Melbourne, Columbus (Maitre, Noritz); Newcastle University,
University of Sydney, Sydney, Australia (Novak, Australia (Fahey); Holland Bloorview Kids Newcastle Upon Tyne, England (Pennington);
Morgan, Karlsson, McIntyre, Thornton, Walker, Rehabilitation Hospital, University of Toronto, Pediatric Neurology Unit, Fondazione Policlinico
White, Badawi); Norwegian University of Science Toronto, Ontario, Canada (Fehlings); University of Universitario A. Gemelli, Università Cattolica del
and Technology, St Olavs University Hospital, California, San Francisco (Ferriero); University of Sacro Cuore, Rome, Italy (Romeo); The University of
Trondheim (Adde); Cerebral Palsy Alliance Research Southern California, Los Angeles (Fetters); Teachers Sydney, Sydney, Australia (Shepherd); Murdoch
Foundation, New York, New York (Blackman); The College, Columbia University, New York, New York Childrens Research Institute, University of
University of Queensland, Brisbane, Australia (Gordon); The Royal Children’s Hospital, Melbourne, Melbourne, Australia (Spittle); Princess
(Boyd); Children’s Medical Center Dallas, Plano, Melbourne, Australia (Greaves); Department of Margaret Hospital, University of Western Australia,
Texas (Brunstrom-Hernandez); Stella Maris Pediatrics, University Medical Center Groningen, Perth (Valentine).
Scientific Institute, University of Pisa, Pisa, Italy University of Groningen, Groningen, the Author Contributions: Drs Novak and Morgan had
(Cioni, Fiori, Guzzetta); National Institutes of Netherlands (Hadders-Algra); Duquesne University, full access to all of the data in the study and take

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 Clinical Review & Education Review Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy

responsibility for the integrity of the data and the cerebral palsy and rehabilitation: current practices. presentation of recommendations. J Clin Epidemiol.
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Darrah, Eliasson, Ferriero, Forssberg, Gordon, cerebral palsy. Pediatrics. 2012;130(5):e1285-e1312. in young children. Dev Med Child Neurol. 2013;55
Greaves, Guzzetta, Krumlinde-Sundholm, (5):418-426.
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Shepherd, Spittle, Valentine, Walker, Badawi. Pringsheim T. An update on the prevalence of 22. Burger M, Louw QA. The predictive validity of
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