PHOTO

Professor (Neonatology)

PGIMER, Chandigarh

MD,DM

RESEARCH AND AREA OF

INTEREST

Neurodevelopment

RIGHT TOOLS FOR EARLY DIAGNOSIS OF CEREBRAL PALSY FOR AT RISK NEWBORN

DIAGNOSIS OF CEREBRAL PALSY

Clinical HISTORY + Neurological

Supported by neuroimaging

Most common physical disability in childhood

Physical disability worse in LMIC due to sepsis

PREVALENCE OF CEREBRAL PALSY

• 14.6% in extreme preterm (22-27 weeks )

• 6.2% in very preterm (28-31 weeks )

• 0.7% in late preterm ( 32-36 weeks)

• 0.11% in term

(Oskoui M et al. A systematic review and meta-analysis, DMCN 2013)

OUR CP RATES IN VLBW AND ELBW COHORTS

• Neurodevelopmental and Behavioral Outcome of

Very Low Birth Weight Babies at Corrected Age of

2 Years ( Mukhopadhyay et al, IJP,2010) - 3% had CP

• Neurodevelopmental Outcome of Extremely Low

Birth Weight Children at Corrected Age of Two

Years (Mukhopadhyay et al, IP, 2016) – 10% had CP

IN EARLY LATE 80’S AND EARLY 1990’S…….

Diagnosis was based on

• RISK FACTORS

• CLINICAL and NEURO EXAMINATION

• ULTRASOUND/CT SCAN

WAIT TILL 1 YEAR BEFORE FINAL LABELING OF CP IS DONE !!!

It could be transient

Preterm often have transient dystonia

which may improve

TYPICAL RISK FACTORS

• h/o SB, abortion,low SES

• ART, abn genetics, PEAntenatal

• Hypoxia, seizures, hypoglycemia

• IUGR, infections,NNJ, prematurity

• IVH,PVL, STEROIDSPerinatal

• trauma

• infections

Post-neonatal

SUMMARY OF RISK FACTORS FROM SYSTEMATIC REVIEWS

Risk fators Risk

Lower GA (<37 WKS) 8.3% in <28 wks

4.3% in 28-31 wks

0.7% in 32-36 wks

Low birth weight (<2500 g) 5.6% in <1000g

5.9% in 1000-1499 g

0.1% in 1500-2499 g

SGA OR 2.34 , 95% CI 1.4-3.8

Chorioamnionitis (<37 wks) RR 1.9 , 95%CI 1.4-2.5

Postnatal steroids <32 wks) ,

EARLY USE (<7 days)

RR 1.45 , 95% CI 1.06 – 1.98

TYPICAL NEURO EXAMINATION

Warning signs

• Lack of alertness

• Decreased spontactivity

• Abnormal movements

• Fisting after 2-3 mo

Abnormal signs

• Low HC

• Delayed social smile

• Persistent NNR/ATNR

• EXCESS EXTENSOR TONE

• ASYMMETRY

Associated signs

• Ocular –roving eye movements

• Squint

• Poor fixation and following

• Auditory –poor response

NEUROIMAGING

• USG

• CT scan ( not preferred any more, helpful to see

calcification in IU infections)

• MRI

CRANIAL ULTRASOUND

• Excellent bedside tool

• Being used since 70’s

• Can detect major brain injuries

- IVH, PVH (Periventricular haemorrhagic infarcts)

- CEREBELAR HAEMORRHAGE (58% children with

CP have cerebellar injury after IVH)

- PVL - cystic

Grade IV IVH, risk of CP 47%Cystic PVL, PPV 77%

CAN WE DIAGNOSE CP EARLY ?

WHY EARLY DIAGNOSIS IMPORTANT

• Delayed intervention if diagnosis is delayed

• Plasticity of brain period is missed

• To maximize functional outcomes

• To reduce parents anxiety

• TO AVAIL SOCIAL BENEFITS

EARLY DIAGNOSIS < 5 MONTHS

• History of high risk factors

+

• Standardized motor assessment (if available)

+

• Standardized neurological examination

+

• Neuroimaging (MRI)

EARLY DIAGNOSIS-BEST PREDICTIVE VALIDITY

• Prechtl general movement assessment (GMA)

(98% sensitivity)

+

• Hammersmith Infant Neuro Exam ( 90% sensitivity)

Best combination of sensitivity and specificity

(Novak 2017,Bosanquet 2013,Spittle AJ 2008)

• MRI (86-89% sensitivity)

STANDARIZED NEUROLOGICAL EXAMINATIONS

• HAMMERSMITH NEONATAL/INFANT

NEUROLOGICAL EXAMINATION ( HNNE/HINE)

( Dubowitz et al, 1998)

• Amiel-Tison scale for neurological

examination – no scoring

HNNE ( RICCI D ET AL, 2008)

HNNE

• Tone and posture – UL, LL, Neck ,trunk

• Reflexes

• Movements

• Abnormal signs

• Behavioral signs

• Vision

• Hearing

HINE

• Standarized 26 item neuro exam for 2-24 months

• Part I (SCORED) – 5 components

• Part II – motor milestones

• Part III - behavior

Dubowitz L et al, J Pediatrics1998;133:406-416

Haataja L et al, J Peds 1999;135: 153-61

PART –I. HINE (SCORING )

1.Cranial nerve function - Max 15

2.Posture - max 18

3.Movements – max 6

4.Tone – max 24

5.Reflexes and reactions –max 15

INTERPRETATION OF HINE SCORES

• Global score 0 - 78

• Score of < 40 always predicted CP

• Score of > 73 never associated with CP

• At 3 months , score of < 56 was highly predictive of

CP at 2 years ( Romeo DM, 2008 , Eur J Ped Neuro)

PREDICTIVE VALIDITY OF CP BY GENERAL MOVEMENTS ASSESSMENT

• SENSITIVITY - 98% ( 95% CI 73-100%)

• SPECIFICITY – 91% ( 95% CI 83-95%)

(Bosanquet M, DMCN 2013)

GENERAL MOVEMENTS

• Definition

• Typical normal pattern

• What is abnormal GM

• Role in predicting Cerebral Palsy

CAN’T SHOW VIDEO DUE TO COPYRIGHT AND CONSENTISSUES

NORMAL GM (DEFINITION)

• 1st used by Dr Prechtl in 1990 – A variety of spontaneous motor

movements starting in fetal life

- Variable sequence of arm, leg, neck and trunk

- Variable amplitude and speed and variable intensity

- Gradual beginning and end

- Fluent and elegant rotations

• These are generated by central pattern generators (CPG) located

in brain stem and modulated by supra spinal pathways

( Prechtl 1990 , Einspieler 2005 )

6-9 wks post term - writhing3-5 months post term - fidgety

NORMAL GM - DEFINITION

Preterm

Large amplitude

Faster spped

Sometimes jerky

Term

Moderate amp

Writhing

Mod speed

Fidgety

• Small amplitude

• All directions

• Variable acceleration

• Moderate speed

• Throughout body

Writhing

WHAT IS ABNORMAL GM?

• During writhing period (upto 6 weeks) post-term

Poor repertoire (PR)

Cramped synchronized (CS)- simultaneous stiff limb and

trunk movements

Chaotic

• During Fidgety period ( 6-20 weeks post-term)

absent

Abnormal/exaggerated

INTERPRETATION

Absent fidgety movements at 12-16 weeks

• Sensitivity of 95-100%

• Specificity of 85% for prediction of CP in high risk population

(Spittle AJ 2009, Noble Y 2012)

Cramped –synchronized (CS) GMs – good

predictor of CP ( Prechtl1997,Einspieler 2012b)

GENERAL MOVEMENT ASSESSMENT +

HINE

BEST COMBINATION OF SENSITIVITY

and SPECIFICITY to predict CP

GM TO PREDICT COGNITION- SYSTEMATIC REVIEW

( EINSPIELER ,2016) • Preterm with consistently abnormal GMs upto 8 weeks post term

had lower IQ at school as compared to those in whom GM

normalized

• From 3-5 months, various postural patterns predicted intelligence

at 7-10 years

• Association weak if CP excluded

• Normal GMs and normal repertoire are markers of

normal cognitive development at least till 10 years of age

CAUTION FOR GM ASSESSMENTS

• Needs expertise – basic and advanced course

• Assessment time is important (writhing to fidgety )

• Low specificity ( high false positive), may cause more anxiety in parents

• False negatives ( milder cases, assessor bias)

• Topography and type of CP not well predicted as of now

• May be use “GM optimality score” alongwith (Einspieler- 2016)

MRI – STRUCTURAL AND FUNCTIONAL

• Sensitivity - 86-89%

• Abnormal signal in white matter

• Ventriculomegaly

• Small brain size

• Presence of cysts

• Decreased myelination

• Corpus callosum thickening

• Mod to severe white matter injury – odds for CP

9.55 ( 3.2-28.3)

CLASSICAL AGE OLD SIGNS

• History – poor sleep pattern, excessive irritability, lack of interest

in surroundings, poor interaction, choking during feeding, excessive

drooling

• Tends to stand up while pull to sit

• Examination – poor head growth/small head, excess head lag,

tight fisting after 3 months, crossed legs, back arching, persistent

MORO/ATNR after 3-4 months, brisk DTR

KEEP IN MIND DIFFERENTIALS

• Global developmental delay

• Neuroregression – slowly progressive

• Spinal/Muscular/neuromuscular disorders

• Metabolic

• Transient dystonia

TAKE HOME MESSAGES

Regular follow up of high risk

neonates

Early diagnosis based on risk factors,

examination and neuroimaging

Early referral and intervention