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