JC125 (Paediatrics) - Paediatric neurological diseases Flashcards
Differentiate neurological disorder and neurodisability
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
Examples of neurodisability
Cerebral palsy, neuromuscular diseases»_space; predominant physical difficulties
Intellectual disorder»_space; learning difficulties
Autism»_space; social communication difficulties
Define neurodevelopmental disorders
Common characteristics of neurodevelopmental disorders
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
2 major clinical etiology of childhood intellectual disability
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
Define developmental delay
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
Define global developmental delay
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
Severity score of global developmental delay
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
Causes of global developmental delay
Outline history taking questions for global developmental delay
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
Symptoms/ complaints from history that indicate specialist referral for global developmental delay
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
Outline the scope of P/E for global developmental delay
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
Signs/ physical abnormalities that indicate specialist referral for global developmental delay /
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
Outline approach to global developmental delay
- History
- Examination
- 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
First-line investigations for global developmental delay
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
Indications for MRI brain for global developmental delay
microcephaly, macrocephaly, abnormal head shape
seizures,
abnormal neurological signs
10 most common causes of progressive intellectual and neurological deterioration in children /
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)
Management for global developmental delay
- 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)
Definition of IDD (Intellectual Disability Disorder)
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
Autism spectrum disorder
- Age of manifestation
- Core symptoms
Manifests in early childhood
Core symptoms:
-
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 -
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
Presentations of social communication deficits in autism spectrum disorder
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
Presentations of Restricted repetitive behaviours (RRBs) in Autism spectrum disorder
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
Associated symptoms/ commodities of Autism spectrum disorder
Cognitive comorbidities:
Intellectual disability
Language impairment
Behavioral comorbidities: Impulsiuve, aggressive, anxious
Medical comorbidities: Constipation and seizure
Biomarkers of Autism spectrum disorder
Ix:
Abnormal EEG
Developmental macrocephaly
Neuroimaging: altered brain region size
Altered immune/ mitochondrial indices
Hyperserotonemia
Genetic disorders/ mutations associated with Autism spectrum disorder
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.
Clinical diagnosis of autism spectrum disorder
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
Causes of increasing prevalence of autism spectrum disorders
Broadening of diagnostic concepts
Dx of those in the milder spectrum (important contributing factor)
Increasing awareness including milder cases with normal intelligence
Risk factors of autism spectrum disorder
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
Cerebral palsy
Definition
Cause
Associated neurological deficits
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
Types of cerebral palsy
Spastic CP - 70-80% (most common)
Dyskinetic CP - 6%
Ataxic CP - 6%
Mixed CP - 8-18%
Compare the areas of brain damage and movement characteristics in types of cerebral palsy
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
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?
spastic diplegic CP
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
spastic dystonic quadriplegic cerebral palsy
Presentation:
Right arm flexed
Arm swinging decreased on right compared to left
Which type of Cerebral palsy
right hemiplegic spastic CP
Risk factors of cerebral palsy (same as RF for GDD)
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
Neurological signs of cerebral palsy in babies
Neurobehavioral signs
Excessive irritability, difficult to handle and cuddle
Lethargy, sleeps poorly
Vomits frequently
Poor visual attention
Reflex abnormalities in cerebral palsy
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
Motor deficits in cerebral palsy
Initial Hypotonia»_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
Types and age of disappearance for primal reflexes
Staging system of motor deficit due to cerebral palsy
Gross Motor Function Classification System (GMFCS) – 5 different levels/ severity of physical disability
Imaging for cerebral palsy
- Types of imaging
- Function for each imaging modality
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
Management of feeding problem in cerebral palsy
oromotor training
Anti-reflux medication, gastrostomy, fundoplication for reflux
Failure to thrive> Nutritional support
Management of respiratory problems in cerebral palsy
Medical treatment
Non-invasive ventilation
Management of musculoskeletal problems in cerebral palsy
Use orthosis
Orthopedic and spinal surgery
Calcium and Vit D supplements
Management of motor deficit in cerebral palsy
Motor training by physiotherapist
Use rehab equipment
Neuromotor: Botox injection/ casting/ muscle relaxants for hypertonia
Management of hearing and vision problems in cerebral palsy
Hearing aid, cochlear implants
Glasses
Visual aids and training
Management of developmental and mental health problems due to cerebral palsy
Early intervention at special schools
Early intervention by psychiatrist
Management of family issues due to cerebral palsy
Family support centers
Government financial support schemes
Child care support
Ddx of deteriorating motor function (e.g. motor impairment, abnormal tone, seizures) in a child with cerebral palsy
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
Red flag signs of Cerebral palsy-like conditions
Cerebral palsy like conditions»_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
Floppy infant
Definition
generalized hypotonia, evidenced by:
Low resistance to passive movement
Unusual posture (e.g. frog-like posture)
High ROM
General causes of floppy infant (non - CNS/ PNS causes)
Prematurity
Intercurrent illness
Benign hypotonia (well otherwise; diagnosis by exclusion)
Peripheral nervous system causes of floppy infant
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
Central nervous system cause of floppy infant
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)
Outline history taking questions for floppy infant
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
Signs of floppy infant
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
Outline the 180 degree maneuver for floppy infant signs
- **Supine (frog-like posture **, antigravity movement: If floppy but strong = more likely due to central cause
- → **Pull to sit (head lag) **
- → **Sitting (poor head /trunk control **, able to sit unsupported as expected age 6-7mo)
- → **Vertical suspension, attempt weight bearing ** (slipping through the hand, lower
limb scissoring) - → **Ventral suspension (inverted U shape ** – excessive floppiness, LMN signs)
- → **Prone **
Outline P/E for floppy infant
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
Typical motor deficit patterns for floppy infant
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
Investigations for central nervous system causes of floppy infant
**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 **
Investigations for peripheral nervous system causes of floppy infant
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 **
