JC125 (Paediatrics) - Paediatric neurological diseases

Question 1

Differentiate neurological disorder and neurodisability

Answer 1

Neurological disorders = diseases of the:
 Central nervous system (brain, spine)
 Peripheral nervous system (nerves)
 Muscles

Neurodisability = limitation of activity due to impairment of the central (e.g. brain) and peripheral nervous system

Question 2

Examples of neurodisability

Answer 2

Cerebral palsy, neuromuscular diseases&raquo_space; predominant physical difficulties

Intellectual disorder&raquo_space; learning difficulties

Autism&raquo_space; social communication difficulties

Question 3

Define neurodevelopmental disorders

Common characteristics of neurodevelopmental disorders

Answer 3

Group of disorders with disabilities in brain functions that:
 Are noticed at birth/ during early childhood
 Predominantly affect the individual behaviour, memory, concentration and/or ability to learn

Common characteristics:
 Defined to behavior
 Tend to run in families
 No single biological cause
 Male preponderance

Question 4

2 major clinical etiology of childhood intellectual disability

Answer 4

1) Developmental delay = when a child does not reach their milestones at the expected times

2) Global developmental delay = significant delay (>2 SDs below the mean on age-appropriate standardized tests) in >2 developmental domains

Question 5

Define developmental delay

Answer 5

when a child does not reach their milestones at the expected times

Can occur in >1 areas:

a) Language – comprehension & expression
b) Motor – gross and fine motor skills
c) Social communication skills
d) Cognition skills

Question 6

Define global developmental delay

Answer 6

significant delay (>2 SDs below the mean on age-appropriate standardized tests) in >2 developmental domains:
 Gross/ fine motor;
 Speech/ language;
 Cognition;
 Social/ personal;
 Activities of daily living (the only additional domain from developmental delay)

Reserved for younger children under 5

Question 7

Severity score of global developmental delay

Answer 7

Severity calculated by developmental quotient (DQ) = developmental age/ chronological age × 100

DQ = 100 = age-appropriate performance

Lower DQ = more severe delay = closer screening and support
 DQ > 85 = routine developmental screening
 DQ 75-85 = close developmental follow-up and some support
 DQ <75 = comprehensive evaluation for early intervention

Question 8

Causes of global developmental delay

Answer 8

Question 9

Outline history taking questions for global developmental delay

Answer 9

Family history: 3-generation review for Pre-natal causes
- Previous birth complications: miscarriages, birth defects, infant deaths
- Intellectual disabilities/ GDD/ Neurological conditions
- Genetic conditions, syndrome
- Inborn Errors of Metabolism
- Ethnicity and consanguinity

Prenatal history: infection and drugs
- Full screening for fetal and maternal diseases, infections
- Exposure to teratogenic drugs/ toxins

Birth history: size and complications
- Size at birth, Apgar score
- Length of hospital stay, birth complications (e.g. asphyxiation, IVH, kernicterus)

Psychosocial history: screen for child abuse, psychological deprivation
- Parents background, education, employment
- Parental substance abuse
- Child care arrangements, neglect, abuse

Development: young childhood causes
- Reaching developmental milestones, timing of first visit for neurodisability, diseases during childhood

Question 10

Symptoms/ complaints from history that indicate specialist referral for global developmental delay

Answer 10

Consider referral to a specialist in metabolic, genetic, neurology if:

 Regressive cognitive decline and/or significant change in behavior
 Possible/definite seizures
 Movement disorder, e.g. dystonia
 Recurrent episodes of vomiting, ataxia, seizures, lethargy, coma
 Significant sensory decline/ deficit in visual acuity (e.g. cataracts, retinopathy)/ hearing
 Family history of IEM, unexplained neonatal/ sudden infant death

Question 11

Outline the scope of P/E for global developmental delay

Answer 11

Physical exam: Head to toe exam
 Growth parameters
 Head shape, Fontanelle
 Cutaneous stigmata
 Spine
 Heart abnormalities
 Abdomen check for organomegaly
 Limb abnormalities
 Genital abnormalities

Neurodevelopmental exam:
 Neurological exam
 Congenital abnormalities
 Dysmorphic features
 Grade current developmental level

Question 12

Signs/ physical abnormalities that indicate specialist referral for global developmental delay /

Answer 12

Consider referral to a specialist in metabolic, genetic, neurology if:
 Neurocutaneous features
 Cardiomegaly
 Organomegaly
 Musculoskeletal signs: arthrogryposis (joint contractures)
 Neurological signs: dystonia, ataxia, chorea, cranial nerve signs, muscle weakness
 Cerebral palsy-like picture without a clear cause from history
 Multiple congenital anomalies
 Coarse/dysmorphic facial features

Vision and hearing exam:
 Ocular signs: nystagmus, eye movement disorder, abnormal fundi, cataract
 sensorineural deafness

Question 13

Outline approach to global developmental delay

Answer 13

1. History
2. Examination
3. Formal vision and hearing assessment (must do)

• if exogenous cause suspected: monitor and investigate
• If underlying etiology suspected: Tailor/ selective investigations
• if no clue: 1st line investigations and follow-upA

Question 14

First-line investigations for global developmental delay

Answer 14

Genetic tests:

• Chromosomal microarray (e.g. Fragile X test for triple expansion of FMR1 gene, Phelan-Dermid syndrome test for SHANK3 deletion)
• Whole exome sequencing

Blood test: normal + TFT, CK, Lead level, Homocysteine, Acycarnitine
- CBC
- Ferritin (IDA,Thal.)
- Renal function test: Urea and electrolytes
- CK (for seizures)
- TFT
- Lead level
- Homocysteine, Acylcarnitine profile

Urine: for metabolites
- Organic acids, Glycosaminoglycans, Oligosaccharides
- Purine, pyramidines
- Creatine/GAA

MRI brain

Question 15

Indications for MRI brain for global developmental delay

Answer 15

microcephaly, macrocephaly, abnormal head shape
seizures,
abnormal neurological signs

Question 16

10 most common causes of progressive intellectual and neurological deterioration in children /

Answer 16

NCL late infantile
Mucopolysaccharidosis IIA
Rett syndrome
Metachromatic leukodystrophy
Adrenoleukodystrophy
NCL juvenile
Niemann-Pick type C
Krabbe
GM2 gangliosidosis type 1
GM2 gangliosidosis type 2

(covered in lectures: Fragile X syndrome, Phelan-Dermid syndrome, Angelman syndrome, Tuberous Sclerosis)

Question 17

Management for global developmental delay

Answer 17

• Ongoing monitoring and support: to Early Intervention Programs and multidisciplinary team training
• Confirm Dx at older age with standardised intellectual assessment
• Monitor for development of IDD (Intellectual Disability Disorder)

Question 18

Definition of IDD (Intellectual Disability Disorder)

Answer 18

Intellectual disabilities (ID) = learning disorder: significant limitation in both intellectual functioning and in adaptive skills, and fulfil 3 criteria:

1. Deficits in intellectual functions:
 E.g. reasoning, problem-solving, planning, abstract thinking, judgment, academic learning and learning from experience
 Confirmed by both:
 Clinical assessment; and
 Individualized, standardized intelligence testing

2. Deficits in adaptive functioning:
 Result in failure to meet developmental and socio-cultural standards for personal independence and social responsibility
 Without ongoing support
 limits >1 activities of daily life (e.g. communication, social participation, independent living) across multiple environments (e.g. home, school, work, community)

3. Onset of intellectual and adaptive deficits during developmental period

Question 19

Autism spectrum disorder

• Age of manifestation
• Core symptoms

Answer 19

Manifests in early childhood

Core symptoms:

1. Deficit in social communication and social interactions
   - deficit in social and emotion reciprocity
   - deficit in non-verbal communication
   - deficit in developing and maintaining social relationships
2. Restricted repetitive behaviours (RBB)/ interests/ activities
   - Fixed on certain routines/ excessive resistance to change
   - Restricted thinking, fixed interest of abnormal intensity/focus
   - Stereotyped/repetitive speech/ motor movements/ use of objects
   - Hyper-/ hyposensitivity to sensory input
   - Unusual interest in sensory aspect of environment

Question 20

Presentations of social communication deficits in autism spectrum disorder

Answer 20

Deficit in social and emotional reciprocity
 Does not respond to name
 Does not share interest in object/activity with others
 Weak in the initiation of joint attentions

Deficit in non-verbal communication
 Little/no eye contact
 Weak in the use and interpretation of non-verbal communications (facial expression, gestural cues)

Deficit in developing and maintaining social relationships
 Prefers to be alone

Question 21

Presentations of Restricted repetitive behaviours (RRBs) in Autism spectrum disorder

Answer 21

Fixed on certain routines
 Displays rigidity (e.g. same school route, wear same shoes everyday)
 Insistence on sameness (same habit)

Restricted thinking, fixed interest of abnormal intensity/focus
 Narrow specific interest (e.g. names of all planet, dinosaurs, MTR stations)

Stereotyped/repetitive speech/ motor movements:
 Uses repetitive words/ phrases (echolalia: repeat without understanding)
 Lines up toys/ objects in obsessive manner
 Weak symbolic play/ inappropriate play with toys

Hyper-/ hyposensitivity to sensory input
 Displays self-injurious behaviors
 Absence of typical response to pain and physical injury
 Motor mannerism: Displays hand flapping (when excited) and/or toe walking; Rocks/ bangs head …etc

Unusual interest in sensory aspect of environment

Question 22

Associated symptoms/ commodities of Autism spectrum disorder

Answer 22

Cognitive comorbidities:
 Intellectual disability
 Language impairment

Behavioral comorbidities: Impulsiuve, aggressive, anxious

Medical comorbidities: Constipation and seizure

Question 23

Biomarkers of Autism spectrum disorder

Answer 23

Ix:
 Abnormal EEG
 Developmental macrocephaly
 Neuroimaging: altered brain region size
 Altered immune/ mitochondrial indices
 Hyperserotonemia

Question 24

Genetic disorders/ mutations associated with Autism spectrum disorder

Answer 24

 Simple genetic disorders: **fragile X (commonest), TS (tuberous sclerosis), Rett syndrome (girls), Angelman syndrome etc.

 Copy number variants (16p11- p12, 15q11-q13, 22q13, etc.)

 Rare variants: NRXN1, NLGN4, **SHANK3 (Phelman-Dermid) **, SERT, etc.

Question 25

Clinical diagnosis of autism spectrum disorder

Answer 25

 History of Observed behaviour (most important): best known by parents/ teachers
 Give severity scores for core symptoms: Social and communication deficit + repetitive/ restrictive behavior

Mild:
- Social communication: Able to speak in full sentences, but conversation is still difficult
- RRB: Difficult to switch activities
- Need support

Severe:
- Social communication: Speak a few words, rarely interact
- RBB: Extremely resistant to change
- Interferes with daily life, needs substantial support

Question 26

Causes of increasing prevalence of autism spectrum disorders

Answer 26

 Broadening of diagnostic concepts

 Dx of those in the milder spectrum (important contributing factor)

 Increasing awareness including milder cases with normal intelligence

Question 27

Risk factors of autism spectrum disorder

Answer 27

Sibling or twins with ASD

Birth history:
 Advanced maternal age (>40 yrs) and paternal age (>50 yrs)
 Preterm birth (<32 weeks)
 Low birth weight (<1500 g)
 SGA/LGA

Childhood vaccinations do not cause autism

Question 28

Cerebral palsy

Definition
Cause
Associated neurological deficits

Answer 28

Non-progressive developmental disorders of movement and posture (motor disorders), causing activity limitations

From pre-natal to 3 years old

Often accompanied by:
 Disturbance of sensation (vision, hearing)
 Disturbance of cognition (learning problems)
 Disturbance of communication, perception/ social behavior
 Seizure disorder

Question 29

Types of cerebral palsy

Answer 29

Spastic CP - 70-80% (most common)

Dyskinetic CP - 6%

Ataxic CP - 6%

Mixed CP - 8-18%

Question 30

Compare the areas of brain damage and movement characteristics in types of cerebral palsy

Answer 30

Spastic CP
- Motor cortex, pyramidal
- Muscles appear stiff and tight
- involvement varies from hemiplegia, diplegia or quadriplegia

Dyskinetic CP
- **Basal ganglia, extrapyramidal involvement **
- Global involvement: involuntary movement, athetoid or dystonic

Ataxic CP
- **Cerebellum, extrapyramidal **
- Global involvement: ataxic, shaky movement with poor balance and proprioception

Mixed CP: mix all types

Question 31

Presentation:
 Stands with crouching, flexed knee
 Jump knee gait, frequent tiptoe, cannot extend knee, gait instability
 Shoulder swaying suggests proximal weakness

Which type of cerebral palsy?

Answer 31

spastic diplegic CP

Question 32

Presentation:
 Couldn’t sit by herself – needs to be supported by mother
 Moves whole body instead of selectively move one arm or just the hand

Which type of cerebral palsy

Answer 32

spastic dystonic quadriplegic cerebral palsy

Question 33

Presentation:
 Right arm flexed
 Arm swinging decreased on right compared to left

Which type of Cerebral palsy

Answer 33

right hemiplegic spastic CP

Question 34

Risk factors of cerebral palsy (same as RF for GDD)

Answer 34

Prenatal
 Congenital infection
 Stroke
 Congenital malformation

Perinatal
 Birth process-related, e.g. asphyxia, brain injury from traumatic delivery
 Prematurity-related, e.g. intraventricular haemorrhage (spastic CP, esp diplegic)
 Severe neonatal jaundice (kernicterus - dyskinetic CP)

Postnatal- Acquired conditions, e.g.:
 Brain infection (meningitis/ encephalitis)
 Head injury
 Progressive hydrocephalus
 Hypoxic ischaemic injury in near drowning

Question 35

Neurological signs of cerebral palsy in babies

Answer 35

Neurobehavioral signs

 Excessive irritability, difficult to handle and cuddle
 Lethargy, sleeps poorly
 Vomits frequently
 Poor visual attention

Question 36

Reflex abnormalities in cerebral palsy

Answer 36

persistence of primitive reflex (should disappear within 6-12 months)

Delayed/ absent protective reflex (should be present in all children >12 months of age):
 Sideward parachute reflex (protective extension reaction sideward)
 Forward parachute reflex (protective extension reaction forward)
 Backward parachute reflex (protective extension reaction backward)

ULN signs: Brisk deep tendon reflex, clonus, up-going Babinski

Question 37

Motor deficits in cerebral palsy

Answer 37

 Initial Hypotonia&raquo_space; Later hypertonia

 Poor head control (Increase neck extensor and axial tone to compensate)

 Abnormal oromotor patterns (tongue thrusting/ grimacing)

 Persistent hand fisting

Delay in:
 Motor development
 +/- other developmental domains

Question 38

Types and age of disappearance for primal reflexes

Answer 38

Question 39

Staging system of motor deficit due to cerebral palsy

Answer 39

Gross Motor Function Classification System (GMFCS) – 5 different levels/ severity of physical disability

Question 40

Imaging for cerebral palsy

• Types of imaging
• Function for each imaging modality

Answer 40

CT scan
 Congenital malformation
 Intracranial bleeding
 Periventricular leukomalacia
 Hydrocephalus (gross ventricular dilatation)

MRI scan
 Congenital brain malformation
 Grey and white matter disease
 Cortical dysplasia

Regular X-ray: evaluating health and developmental problems
A. Hip surveillance
B. Spine X-ray for scoliosis
C. Chest X-ray for suspected chronic lung disease

Question 41

Management of feeding problem in cerebral palsy

Answer 41

oromotor training
Anti-reflux medication, gastrostomy, fundoplication for reflux
Failure to thrive> Nutritional support

Question 42

Management of respiratory problems in cerebral palsy

Answer 42

Medical treatment
Non-invasive ventilation

Question 43

Management of musculoskeletal problems in cerebral palsy

Answer 43

Use orthosis
Orthopedic and spinal surgery
Calcium and Vit D supplements

Question 44

Management of motor deficit in cerebral palsy

Answer 44

Motor training by physiotherapist
Use rehab equipment
Neuromotor: Botox injection/ casting/ muscle relaxants for hypertonia

Question 45

Management of hearing and vision problems in cerebral palsy

Answer 45

Hearing aid, cochlear implants
Glasses
Visual aids and training

Question 46

Management of developmental and mental health problems due to cerebral palsy

Answer 46

Early intervention at special schools
Early intervention by psychiatrist

Question 47

Management of family issues due to cerebral palsy

Answer 47

Family support centers
Government financial support schemes
Child care support

Question 48

Ddx of deteriorating motor function (e.g. motor impairment, abnormal tone, seizures) in a child with cerebral palsy

Answer 48

Neurodegenerative disorder, e.g.:
 Hereditary progressive spastic paraplegia
 Rett syndrome

CNS Tumour, e.g.:
 Brain tumour (e.g. basal ganglia germinoma)
 Spinal cord tumour

nborn error of metabolism/ neurometabolic disorder, e.g.:
 Urea cycle disorder
 Glutaric acidemia type 1
 Aminoacidopathies

Confirm with imaging and genetic studies

Question 49

Red flag signs of Cerebral palsy-like conditions

Answer 49

Cerebral palsy like conditions&raquo_space; Regressive motor development

 Loss of motor skills
 Loss of tone
 Unusual accompanying symptoms (e.g. unexplained hypoglycaemia, recurrent emesis, progressively worsening seizures)
 Family history of unexplained neurological symptoms/ infant deaths

Question 50

Floppy infant

Definition

Answer 50

generalized hypotonia, evidenced by:
 Low resistance to passive movement
 Unusual posture (e.g. frog-like posture)
 High ROM

Question 51

General causes of floppy infant (non - CNS/ PNS causes)

Answer 51

 Prematurity
 Intercurrent illness
 Benign hypotonia (well otherwise; diagnosis by exclusion)

Question 52

Peripheral nervous system causes of floppy infant

Answer 52

Anterior horn cell disease
 Spinal muscular atrophy
 Poliomyelitis

Peripheral neuropathies:
 Hereditary: Charcot Marie Tooth Disease
 Acquired: GBS, toxin, nutritional, metabolic cause

Neuromuscular junction disorder:
 Myasthenia gravis
 Congenital myasthenic syndrome

Muscle disease:
 Congenital myopathies
 Muscular dystrophies
 Mitochondrial myopathies
 Inflammatory myopathies

Question 53

Central nervous system cause of floppy infant

Answer 53

Same causes as GDD, CP:
Infection(congenital, e.g. TORCH, acquired), sepsis
 Cerebral malformation
 Neonatal asphyxia
 Intracranial haemorrhage

Others:
 Metabolic diseases
 Hypothyroidism
 Spinal cord lesions
 Chromosomal disorders
 Connective tissue diseases
 Drugs (e.g. benzodiazepines)

Question 54

Outline history taking questions for floppy infant

Answer 54

Hypotonia symptoms:
 How and when was it first noticed?
 Onset: Acute (infective, trauma cause) vs. subacute vs. chronic (genetic, metabolic cause)
 Progression
 Body parts involved

(the rest is the same as GDD and CP, screen from antenatal > pre-natal > birth > development)
Antenatal history: poor fetal movement, breech, maternal drug use

Birth history: trauma, birth anoxia (suggests central cause), poor Apgar score

Developmental history

Systemic review: feeding difficulties, respiratory problems, seizures

Detailed family history: weakness, parents consanguinity, previous early death or recurrent miscarriages

Question 55

Signs of floppy infant

Answer 55

Observation:
1. Need for nasogastric tube, O2 supplementation, ventilation support
2. **Frog-like posture **: hip externally rotated, flexed knee; scissoring posture
CNS cause:
- **Dysmorphic features, abnormal head size and shape, abnormal OFC ** (occipital frontal circumference)

PNS cause:
- Spinal muscular atrophy: **alert face + tongue fasciculation + Bell-shaped chest **
- Congenital myopathy: **ptosis, ophthalmoplegia **

**Paucity of limb movement **: subgravity, antigravity, vs against resistance

Question 56

Outline the 180 degree maneuver for floppy infant signs

Answer 56

1. **Supine (frog-like posture **, antigravity movement: If floppy but strong = more likely due to central cause
2. → **Pull to sit (head lag) **
3. → **Sitting (poor head /trunk control **, able to sit unsupported as expected age 6-7mo)
4. → **Vertical suspension, attempt weight bearing ** (slipping through the hand, lower
   limb scissoring)
5. → **Ventral suspension (inverted U shape ** – excessive floppiness, LMN signs)
6. → **Prone **

Question 57

Outline P/E for floppy infant

Answer 57

Observation for signs
- **Head size and shape, OFC
- Dysmorphic features
- Syndromal facial features **
- Respiratory pattern
- **Posture and hypotonia
- Paucity of limb movement **

**180o maneuver **

**Neurological exam to localize lesion **: UMN vs LMN lesion

Look for presence of **hepatosplenomegaly/ cardiac failure: **
- Metabolic causes, e.g. Pompe disease (cardiomegaly + hepatomegaly + generalized muscle weakness)
- Zellweger’s disease

Question 58

Typical motor deficit patterns for floppy infant

Answer 58

Spinal muscular atrophy: weak proximal muscles, hyporeflexia, tongue fasciculation, alert face

Peripheral neuropathy: Distal muscle weakness, hyporeflexia

MG: Facial weakness mostly, variable ptosis, ophthalmoplegia

Congenital muscular dystrophies: Facial and proximal muscle weakness, hyporeflexia, ptosis

Question 59

Investigations for central nervous system causes of floppy infant

Answer 59

 **Karyotype and genetic review (dysmorphism)
 CT/ MRI brain imaging
 TORCH screen **, infective screen
 **Metabolic screen **
– newborn screening, serum amino acid, lactate, ammonia, urine organic acid
 **Thyroid function test **

Question 60

Investigations for peripheral nervous system causes of floppy infant

Answer 60

For muscles:
 **Creatine kinase level
 Nerve conduction study (localize the pathology)
 Electromyography
 Muscle biopsy (more invasive) **

**Genetic study ** (getting more popular, can be targeted or panel): e.g.
 SMN1 (spinal muscular atrophy)
 CTG repeats (myotonic dystrophy)
 **Neuromuscular disorder gene panel **