Global developmental delay (GDD)

2014年4月11日 13:43

• significant delay (≥ 2 SD below mean) in ≥ 2 developmental categories of 5 (gross motor, fine motor, language, cognition, social)
• occurs in 1-3% children younger than age 5

Physio

Ex
Antenatal Perinatal Postnatal
• syndromal: Down, Fragile X, Prader-Willi, • prematurity & ICH / PVL • infection: meningitis, encephalitis
Angelman • intrapartum asphyxia • anoxia: seizures, hypoxia
• cerebral dysgenesis & neural tube defect • birth trauma • trauma: head injury
• toxin & teratogens exposure • metabolic: hypoglycemia, hyperbilirubinemia, IBM
• congenital infection: eg. TORCH • vascular: stroke
• metabolic: hypothyroidism • psychosocial: child abuse, parental separation

Hx
• developmental history
○ current milestone (ask milestone on current age, going backwards if failed to do so)
○ developmental regression (previously achieved but lost later)
○ autism sx: lack of communication skills, repetitive behavior
○ co-existing sx: feeding, sleeping, emotional problem
• history
○ antenatal: obs disease, toxin exposure (smoking, alcohol, substance), IUGR
○ perinatal: term, mode, birth weight, birth asphyxia, trauma
○ postnatal: jaundice, infection, complication
○ MH: previous major illness, hospitalization, surgery
○ FH: genetic disease, similar problems in siblings, parents, consanguinity
○ DH: current medication
○ SH: school, family

PE
• general & observation
○ greet the parents & child
○ general inspection by observing height, head circumference, facial dysmorphism
○ quick assessment by observing child gait, playing with hands, speech and interaction
• gross motor
supine
○ observe: posture, limb movement
pull to sit

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 ○ pull to sit
put child's hands together and grab with one hand, another hand on the back of his head for caution
pull child to sit in SLOW motion, stop in 20-30° and observe for head control (3m)
sitting
○ hands behind child's back: sit with support (6m)
○ hands released: sit without support (9m)
standing
○ supported standing
grab child under armpit and hold him up vertically
observe for stepping, weight supporting (12m)
○ observe child play & gait: cruising (12m), walk independently (15m), squad (18m), jump on 2 feet (2y)
○ demonstrate test: walk upstairs / downstairs
• fine motor
Bricks
○ attract child with colorful toys: visual follow 90° (6 wks), 180° (3m)
○ approach child with one brick: reach out (3m), palmar grasp (6m)
○ give more bricks: one cube in each hand (6m), bang cubes (12m)
○ observe child play: mouthing (4m), hands transfer (6m), casting (12m), hand dominance (abnormal if <12m)
○ play with child on table, demonstrate building: tower of 3 (18m), train (2y) with chimney (2.5y), bridge (3y), stairs (4y)
Pen & paper
○ draw with child on table: scribbles (18m), vertical line (2y)
○ demonstrate drawing: circle (3y), cross (4y), triangle (5y)
• speech & language
○ observe child speech: babbling (6y), papa/mama (9m), 1 word (1y), 2 words phrase (2y), 3 words sentence (SVO) (3y)
○ what is your name? (2y)
○ how old are you? (2.5y)
○ are you a boy or girl? (beware of echolalia) (3y)
○ point out body parts (eye, ear, mouth, nose, arm, leg) (2 yrs)

Dx
• genetic tests: cytogenetics, FISH
• neuroimaging: MRI
• hearing & vision screening:
• autism screening

Tx
• referral
○ early education training centre (EETC): family training for pre-nursery school training
○ integrated child care centre (ICCC): integrated care in normal kindergarten
○ special child care centre (SCCC): individual care in special kindergarten
○ special school for physical handicapped or for mental handicapped
• early intervention program (EIP)
○ motor: physiotherapy, occupational therapy
○ cognition: speech therapy
○ education: special school enrollment
○ family training
• for parents
○ genetic counselling
○ psychologists support

Griffiths Mental Development Scale

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Motor delay
2014年4月11日 11:35

• failure to develop

Ex
• central (UMN lesion)
cortex • static (cerebral palsy): antenatal toxin exposure, • ctl. hemiplegia with pyramidal distribution (UL
hypoxic ischemic encephalopathy, metabolic extensors, LL flexors)
insult • ctl. hemianesthesia
• non-static: stroke, hematoma, abscess, tumor, • ctl. homonymous hemianopia
head trauma • ↓ consciousness, epilepsy
brainstem • vertebrobasilar stroke • ips. CN deficits + ctl. hemiplegia (crossed sign)
• cerebropontine angle tumor • ips. facial anesthesia + ctl. hemianesthesia
spinal cord • spina bifida • paraplegia (thoracolumbar)
• transverse myelitis • tetraplegia (cervical)
• primary bone tumor • sensory level
• LMN signs at lvl, UMN signs below lvl
• bladder & bowel dysfunction
• peripheral (LMN lesion - floppy baby syndrome)
ant horn cells • spinal muscular atrophy (SMA) • tongue fasciculation
• poliomyelitis (extinct)
peripheral • Charcot Marie Tooth (CMT) • distal weakness (proximal in GBS)
neuropathy • Guillain Barre Syndrome (GBS) • distal sensory loss (gloves & stocking) OR along
• Bell's palsy dermatome (mononeuropathy)
• ↓ reflex
NMJ disorder • Myasthenia Gravis (MG) • fatiguability
• normal reflex & sensory
• ophthalmoplegia & ptosis, bulbar palsy
myopathy • Duchenne / Becker's muscular dystrophies (DMD) • proximal weakness
• myotonic disorder • normal reflex & sensory
• metabolic myopathies
• myositis
• periodic paralysis

Hx
• motor delay
○ poor head control & trunk posture
○ abnormal limb tone & posture
○ poor feeding (∵ poor oromotor incoordination)
○ early acquisition of hand dominance (before age 1)
○ late walking (>18m), abnormal gait
• limb weakness
○ S: monoplegia, paraplegia, hemiplegia, tetraplegia
lvl: upper / lower limb / both
proximal: cannot comb hair, cannot squat & up / walk upstairs
distal: cannot hold chopsticks / write
○ O: gradual / acute onset?
○ C: spastic / flaccid?
○ T: duration? progressive / episodic?
○ E: ↑ by repeated movement (fatiguability)
○ S: functional impairment: ambulation, wheel-chair bound
• symptoms
○ sensory loss
○ bladder & bowel dysfunction
○ SOB, recurrent chest infection (resp failure)
↓ consciousness, seizure, headache (cortical signs)

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 ○ ↓ consciousness, seizure, headache (cortical signs)
○ diplopia, facial palsy, hearing loss, vertigo, dysarthria, hoarseness (CN deficit - brainstem)
○ fever, chills & rigors
○ weight loss, anorexia, malaise
○ systemic enquiry (for metabolic causes)
• history
○ recent back & head injury
○ recent infection (GBS, transverse myelitis)
○ perinatal: antenatal toxin / maternal disease, birth trauma, neonatal cx
○ immunization
○ developmental: esp. gross & fine motor
○ MH:
○ DH:
○ FH: early onset mus weakness ± resp failure, clarifying family tree (can distinguish AR / X-linked diseases)
○ SH:

Signs
• general
• neuro exam
○ inspection: posture, movement, gait
○ mus tone & strength: posture, head control, limb tone
○ reflex: tendon reflex, plantar reflex, clonus
○ coordination: finger nose test, heel-shin test, Romberg test, gait
○ sensory: pain, temp, vibration, touch
○ primitive reflex
• developmental assessment

Dx
• blood
○ CBC: ↑ WBC (infection)
○ inflam markers: ↑ ESR, CRP (inflam)
○ mus enzymes: ↑ CK, LDH (mus breakdown)
○ immune markers: anti-AChR Ab (MG)
○ karyotyping: DNA analysis
• imaging
○ CT / MRI brain
○ MRI spine: spinal pathology
• electrophysiology
○ NCS: peripheral n. pathology
○ EMG: repetitive n. stimulation test
• invasive
○ nerve biopsy
○ mus biopsy

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Cerebral palsy (CP)
2015年12月12日 21:41

• chronic disorder of motor domain due to static injury to developing brain before age 5
• causing UMN lesion ± global developmental delay
• most common childhood disability (2 in 1000), usu. in pre-term infants

Ex
• antenatal (70%)
○ vascular occlusion
○ neural tube defect
○ cortical migration disorder
○ syndromal disorder
○ congenital infection: toxoplasmosis, rubella, CMV, HSV (TORCH)
• perinatal (10%)
○ birth asphyxia: hypoxic-ischemic encephalopathy
○ birth trauma
• postnatal (10%)
○ infection: meningitis, encephalitis
○ anoxia: seizures, hypoxia
○ trauma: head injury
○ metabolic: hypoglycemia, hyperbilirubinemia, IBM
○ vascular: stroke

Types
spastic (90%) dyskinetic (6%) ataxic / hypotonic (4%)
corticospinal & pyramidal tract basal ganglia & extrapyramidal tract cerebellar & pathway
• stroke, IVH (hemiplegia) • term asphyxia
• preterm PVL (diplegia) • hyperbilirubinemia
• CNS malformation (tetraplegia)
• present in early neonatal • present in early first yr • hypotonia
○ hypertonia • hypotonia • incoordination of movement
• spastic paralysis of limb • involuntary movement, ↑ with active movement ○ ataxic gait
○ hemiplegia: asymmetrical movement ○ chorea: irregular, rapid, dance-like motion ○ intention tremor
○ diplegia: scissoring of legs ○ athetosis: slower, twisting motion ○ incoordinate movement
○ tetraplegia: microcephaly, seizures ○ dystonia: sustained contraction causing
abnormal posture

Sx
• gross & fine motor delay (global)
• abnormal gait
• poor feeding

Signs
• inspection
○ asymmetrical limb movement (spastic)
○ involuntary irregular movement (dyskinetic)
○ incoordination of movement (ataxic)
• posture
○ UL flexed: shoulder adducted, elbow flexed, wrist flexed & pronated, fingers flexed across adducted thumb (fisting)
LL extended: hip int rotated (scissoring of legs), knee extended, ankle plantar flexed (tip toeing)

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 ○ LL extended: hip int rotated (scissoring of legs), knee extended, ankle plantar flexed (tip toeing)
○ opisthotonus: neck hyperextension, arched back, UL flexed, LL extended
• tone
○ hypertonia
○ clasp-knife spasticity (sudden release of tone under pressure)
○ ankle clonus
• power
○ hemiplegia (or diplegia, quadriplegia)
• reflex
○ hyperreflexia
○ plantar reflex upgoing (Babinski sign)
• coordination
○ past-pointing, intention tremor
• gait
○ tip toeing walk (∵ spasticity of feet, UMN signs)
○ hemiplegia gait
○ diplegia gait
○ dyskinetic gait
○ ataxic gait

Cx
• developmental delay ± global
○ motor: impaired mobility, spinal deformities
○ speech & language (>50%): impaired communication
○ intellectual (40%)
• nutrition problem
○ dysphagia, dribbling
○ failure to thrive & malnutrition
• epilepsy
○ recurrent seizure

Dx
• blood
○ CBC: infection
○ RFT: uremia, electrolytes
○ LFT: liver failure
○ BG: hypoglycemia
○ ABG: resp failure
○ ammonia: protein metabolism defect
○ genetic tests: karyotyping, FISH analysis
• micbio
○ blood culture: sepsis
○ serology: TORCH titre
○ urine amino acids, reducing substances
○ LP: CNS infection
• imaging
○ CT/MRI brain: structural malformation & lesions
○ EEG: seizure

Tx
• supportive
○ motor: physiotherapy, mus relaxant (prevent joint contracture), walking aids, wheelchair (advance mobility)
○ sensory: skin care (prevent skin damage & ulcers)
○ bladder: catheterization, drugs (eg. oxybutynin), prophylactic Abio
○ bowel: regular toilet, laxatives, suppositories
○ scoliosis: bracing, surgical correction
○ resp: chest physiotherapy, mechanical ventilation

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Spinal dysraphism / bifida
2015年2月4日 18:05

Neural tube defect

• failure of normal fusion of neural plate to form neural tube during first 28 days pregnancy
• causing congenital disorder of the brain & spine
• declining incidence, due to regular folic acid supplement in antenatal period

Types
• anencephaly: failed development of most cranium and brain
• encephalocele: protrusion of brain & meninges through midline skull defect
• spinal dysraphism: protrusion of spinal cord & meninges through vertebral arch defect

Spinal dysraphism
• congenital malformations causing under-developed vertebral arch resulting protrusion of segment of spinal cord
• presented as overlying skin lesion containing skin appendages / neural tissues
• usu. in lumbar & sacral areas

Types
• closed
spina bifida occulta
○ no herniation of neural tissue
○ ax/ cord tethering (diastematomyelia)
○ often with overlying cutaneous signs: eg. lipoma, hemangioma
• open
spina bifida cystica with meningocele
○ herniation of meninges & spinal fluid only with skin covering
○ requires surgical closure, excellent prognosis
spina bifida cystica with myelomeningocele
○ herniation of spinal neural tissue, opened or covered by meninges
○ ax/ Arnold-Chiari malformation, spinal deformities

RF
• folate deficiency
• teratogen exposure

Signs
• cutaneous lesion along spine
○ occult: hemangioma, lipoma, hair patch (hypertrichosis), skin appendages
○ meningocele: fluid filled cystic mass
○ myelomeningocele:
Cx
• tethered cord syndrome (distal end of spinal cord is fixed in position, ie. motion may cause tearing / compression)
○ weakness in lower limb: spastic gait, mus imbalance may cause dislocation of hip
○ sensory loss
○ urinary & bowel dysfunction
• spinal deformities
○ low back pain
○ deformity: scoliosis, kyphosis
• associated: Arnold Chiari malformation (ax/ myelomeningocele)
○ herniation of cerebellar tonsils & brainstem tissue through foramen magnum
○ causing compression of resulting obstructive hydrocephalus
○ check fundi for papilloedema

Dx
• maternal AFP
○ ↑ in neural tube defect
• antenatal USG
○ hypoechoic mass protruding from end of spinal cord
• antenatal MRI
○ hyperintense mass protruding from sacral back of fetus
○ tethered spinal cord
• CT/MRI brain
○ enlargement of ventricles (hydrocephalus)

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 ○ hyperintense mass protruding from sacral back of fetus
○ tethered spinal cord
• CT/MRI brain
○ enlargement of ventricles (hydrocephalus)
○ tonsillar herniation below foramen magnum (Arnold-Chiari malformation)

Tx
• supportive
• surgery
○ relief of tethered cord
○ shunt for progressive hydrocephalus
○ orthopedic correction

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Ataxia in children
2016年2月27日 21:39

Ex
• acquired
○ drugs & toxin
○ infection: varicella
○ brain tumors: cerebellar astrocytoma, medulloblastoma
○ ataxic cerebral palsy
• congenital
○ Friedreich ataxia
○ ataxia telangiectasia
○ malformation: eg. Arnold-Chiari, Dandy Walker

Signs
• head
○ horizontal nystagmus (when looking to ips, fast phase to ips side)
○ dysarthria (scanning / Donald duck speech)
• upper limb
○ dysmetria: past-pointing, intention tremor
○ dysdiadochokinesia
• lower limb
○ failed heel-toe walking: ataxic, broad based gait
○ Romberg test: fall on open eye

Friedreich's ataxia
• most common inherited ataxia
• triad of cerebellar ataxia, sensory deficit and weakness (ddx: MS)
Ex
• FRDA gene
DDx - mixture of upgoing plantar & absent knee jerks
○ triplet repeat expansions in first intron
• motor neuron disease
○ on chromo 9
• subacute combined degeneration of cord
○ encodes frataxin, mitochondrial protein
• cauda equina syndrome
○ AR inheritance
• Friedreich ataxia
Sx
• peripheral neuropathy in stroke patient
• onset: age 8-16
• tabes dorsalis (demyelination by tertiary syphilis)
• coordination: ataxia & cerebellar dysarthria
• sensory: impairment in joint & vibration sense
• motor: pyramidal weakness in LL
Cx
• deformity: pes cavus, kyphoscoliosis
• sensory: optic atrophy, sensorineural deafness
• cardiomyopathy (HOCM), death at 40-50 yrs

Ataxia telangiectasia
Ex
• AR inheritance
Sx
• ataxia
• oculomotor problem
• ↑ infection & malignancy

Arnold Chiari syndrome

• downward displacement of cerebellar tonsils through foramen magnum
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Floppy infant (LMN disorders)
2014年4月11日 16:28

• state of low mus tone (hypotonia) in infants

Ex
central lesion peripheral lesion
non-paralytic: no / mild weakness paralytic: significant weakness
hyperreflexia, facial dysmorphism hyporeflexia, resp weakness
Antenatal Ant horn cells
• chromosomal disorder: Down, Prader-Willi • spinal muscular atrophy (SMA)
• CNS malformation NMJ disease
Perinatal • myasthenia gravis (MG)
• prematurity Peripheral neuropathy
• hypoxic-ischemic encephalopathy (HIE) • Charcot-Marie tooth disease
Postnatal • Guillain Barre syndrome
• metabolic: hypoglycemia, hypothyroidism Myopathy
• sepsis • Duchenne Muscular Dystrophy
• congenital myotonic dystrophy
• metabolic myopathies

Signs
• inspection
○ myopathic facies: little facial expression
• posture
○ frog-leg position: hip abducted, knee flexed when seated
• tone
○ hypotonia
○ scarf sign: arm easily pulled across chest to other side
○ heel to ear test:
○ head lag in pull to sit
○ slipped through shoulder in vertical suspension
○ inverted U shape in ventral suspension
• reflex
○ areflexia
○ tongue fasciculation
• power
○ no / mild weakness (non-paralytic - central causes)
○ severe weakness (paralytic - peripheral causes)
• gait
○ Gower sign: when child attempt to stand up, turn prone and uses his hand to climb up on his knees
○ waddling gait: bilateral circumduction of trunk

Cx
• motor developmental delay
○ limb weakness
○ joint deformities, hip dislocation
• resp failure

Dx
• blood
○ CBC
○ RFT: electrolytes disturbances
○ LFT
TFT: congenital hypothyroidism

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 ○ TFT: congenital hypothyroidism
○ BG: hypoglycemia
○ karyotyping
○ CK: inflam myopathy
• micbio
○ blood culture: sepsis
○ serology: TORCH titre
○ LP: CNS infection
• imaging
○ CT/MRI brain
○ MRI spine
• neuromuscular tests
○ EMG: distinguish neuropathy & myopathy
○ NCS: neuropathy
○ mus / sural n. biopsy: histological sx
○ Tensilon test: clinical test for MG

Tx
• supportive
○ motor: physiotherapy, mus relaxant (prevent joint contracture), walking aids, wheelchair (advance mobility)
○ sensory: skin care (prevent skin damage & ulcers)
○ bladder: catheterization, drugs (eg. oxybutynin), prophylactic Abio
○ bowel: regular toilet, laxatives, suppositories
○ scoliosis: bracing, surgical correction
○ resp: chest physiotherapy, mechanical ventilation

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Spinal muscular atrophy (SMA)
2014年4月11日 16:34

• AR inherited disease of motor neurons causing widespread progressive mus wasting

• variable onset ranges from neonatal to adulthood

Types

Ex
• SMN (survival of motor neuron) gene
○ AR inheritance
○ locates in chromo 5q13
○ 95% caused by homozygous deletion of exons 7 & 8 of SMN1 (telomeric) gene
○ phenotype modified by no. of copies of SMN2 (centromeric) gene
○ its protein involves in assembling cellular machinery needed for processing mRNA for
maintenance of motor neurons
○ defect causes death of motor neurons in ant spinal cord

Sx
• symmetrical proximal mus weakness
• gross & fine motor delay
• feeding problem
• resp failure: recurrent pneumonia, sepsis

Signs
• inspection
○ resp distress: tachypnea, intercostal insucking, abdominal paradoxical movement
○ on nasal CPAP
○ chest deformities: bell-shaped chest with prominent sternum, Harrison sulcus
• neurology
○ hypotonia: frog-leg position
○ tongue fasciculation
○ reduced mus power: more on proximal
○ hyporeflexia

Dx
• NCV: axonopathy
• EMG: large amplitude, polyphasic
• mus biopsy: group atrophy of type 1 & 2 mus fiber
• SMA carrier test*
gene dosage assay that measures the no. of exon-7 containing SMN1 copies

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 ○ gene dosage assay that measures the no. of exon-7 containing SMN1 copies
○ homozygous deletion of exons 7 & 8 of SMN1 gene, in 90% SMA patients regardless of severity

Tx
• supportive

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Charcot-Marie-Tooth (CMT) disease
2013年11月18日 21:13

• slowly progressive hereditary motor-sensory neuropathy (HMSN)

•

Ex
• duplication of large region on chromo 17p
○ AD inherited
○ encoding for neuronal protein, leading to defective myelin sheath / axon
○ type 1: primary demyelinating neuropathies
○ type 2: primary axonal neuropathies

Sx
• early onset, slowly progressive
Signs
• inspection
UL
○ small hand mus wasting
○ claw hands
LL
○ distal leg mus wasting (inverted champagne bottle sign)
○ pes cavus (high foot arch)
○ clawing of toes
○ foot drop, high stepping gait
• neurology
○ gloves & stocking sensory loss
○ distal mus weakness
○ hyporeflexia

Dx
• NCS
• genetic study

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Muscular dystrophies (DMD)
2013年11月18日 22:11

Duchenne muscular dystrophies (DMD)

• recessive X-linked form of muscular dystrophy
• results in progressive mus degeneration and eventually death

Types
• Becker type Muscular Dystrophy (BMD)
○ less severe form, slowly progressive
○ onset > age7
○ failure to walk 16 - 20 yrs
○ death in middle aged
• Outliers
○ intermediate between DMD & BMD
○ failure to walk 12 - 16 yrs

Ex
• mutation in dystrophin gene
○ X-linked recessive inheritence
○ located in chromo Xp21
○ dystrophin protein: maintain shape & structure of mus fiber
structural component of DGC (dystrophin-glycoprotein complex)
connects F-actin in cytoskeleton to laminin in ECM

Sx
• gross motor delay
• gait disturbances & wheelchair dependent (by 10)
Cx - mortality
• type 2 resp failure & aspiration pneumonia
• cardiomyopathy

Clinical course
age 0-1 asymptomatic, rare for any developmental delay to be noticed
age 1.5-4.5 symptomatic
age 8-9 weakness progress rapidly
age 10 wheel-chair bounded
age 20 death (resp failure)

Signs
• inspection
○ proximal mus wasting: first shoulder and pelvis, then upper trunk & arms
○ pseudohypertrophy: esp. calves
○ Gower's sign: the need to turn prone and arm support to get up
○ waddling lordotic gait
• neurology
○ hypotonia
○ hyporeflexia

Dx
• serum CK: ↑10-100x
• EMG: myopathy pattern
• muscle biopsy:
○ mus fibers become smaller and large interfiber space
○ reduced (BMD) / absent (DMD) dystrophin staining
• DNA blood test to analysis the X-chromo

Tx
• supportive
• drugs

Ped NEURO 第 91 頁
• drugs
○ mus relaxant: baclofen (reduce contracture)
○ steroid: prednisolone for 10 days each month (prevent scoliosis, preserve mobility)

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Myotonic disorder
2013年11月19日 0:24

• failure of muscle to relax causing tonic muscle spasm

• ion channelopathy causing failure to maintain muscle membrane in refractory state

Patho
• influx of ions through defective channels into mus cells
• causing spontaneous abnormal depolarization (ie. mus in refractory state, not excitable)
• when leakage is mild, normal channels can restore resting memb potential
○ repetitive activation & restoration → myotonia (spasm)
• when leakage is severe, cannot restore
○ continuous in excitable state → flaccid periodic paralysis
Ex
• inherited (AD)

Types
• myotonic dystrophy (unknown channel)
• myotonia congenita (Cl channel)
• paramyotonia congenita (Na channel)
• proximal myotonic myopathy

Sx
• delayed mus relaxation after contraction
• improves with repetitive contraction (warm up phenomenon)
• worsen in cold / prolonged rest

Myotonic dystrophy
• an inherited multisystemic disorder that is chronic and progressive
• causing systemic hypotonia in all skeletal muscle & smooth muscle
• age of onset 15-40, slowly progressive

Type
• DM1: DMPK gene (myotonic dystrophy protein kinase)
○ AD inheritance
○ gene on chromo 19q, encodes for skeletal mus
○ unstable expansion of CTG trinucleotide repeat
○ anticipation phenomenon: age of onset & clinical severity correlates with size of expansion
• DM2: ZNF9 gene
○ on chromo 3
○ defect: repeat of CCTF Tetranucleotide
○ milder signs & symptoms

Signs
• dystrophy (mus wasting & weakness)
○ apathic face (myotonic facies)
○ bil ptosis
○ facial mus wasting (temporalis, masseter, SCM → thin /swan neck)
○ distal limb mus wasting

Ped NEURO 第 93 頁
Signs
• dystrophy (mus wasting & weakness)
○ apathic face (myotonic facies)
○ bil ptosis
○ facial mus wasting (temporalis, masseter, SCM → thin /swan neck)
○ distal limb mus wasting
○ hypotonia, areflexia
○ foot drop, high steppage gait
• myotonia (impaired relaxation of mus after voluntary contraction)
○ difficulty in releasing hand grip
○ muscular stiffness

Cx
heart cardiomyopathy, conduction problem
resp OSA, resp hypoventilation
GI sm dysfunction
endo DM, gonadal atrophy, low metabolic rate
eyes cataract, retinal degeneration

Dx
• CK: ↑
• MRI muscle: hyperintense area
• biopsy: degeneration of mus fiber with cellular infiltrates

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Microcephaly & Macrocephaly
2015年12月12日 0:04

• abnormally low or high occipito-frontal circumference (OFC)

• microcephaly: OFC 2 SD below (<2nd) mean for age & sex
• macrocephaly: OFC 2 SD above (>98th) mean for age & sex

Patho
• head circumference
○ most head growth occurs in first 2 yrs
○ 80% of adult size is achieved before age 5
○ largely reflects brain growth during toddler period
• suture
○ metopic
○ coronal
○ sagittal
○ lambdoid
• fontanelle
○ anterior: close by 12-18 months
○ posterior: close by 8 wks

Macrocephaly

Ex
• idiopathic: familial
• syndrome: Sotos, achondroplasia, Fragile X
• skull: thalassemia, rickets
• CSF: hydrocephalus, hydrencephaly
• brain: chronic subdural effusion
• ct: mucopolysaccharidoses, maple syrup urine disease

PE
• general
○ hydrocephalus (sun setting eyes, dilated scalp vein, VP shunt / scar - behind ears!)
○ thalassemic facies (prominent maxilla)
○ Fragile X (prominent everted ear, long face)
○ Sotos (gigantism)
○ achondroplasia (short legs, prominent skin creases)
• skull exam
○ measure: head circumference
○ inspection: size, shape
○ palpation: fontanelle (closed / open), sutures
○ percussion: Crack pot sign (hydrocephalus)
○ auscultate: bruit over temporal & eyebrow (AV malformation)
○ transillumination: light up (hydrocephalus)
• neuro exam
○ inspection: lower back surgical scars
○ reflex: hyperreflexia (spina bifida, ax/ Arnold-Chiari malformation)

Microcephaly

Ex
• idiopathic: familial
• antenatal: IUGR - syndromal (eg. Down, Edward), brain malformation, congenital infection, maternal drug
• perinatal: birth asphyxia, birth trauma
• neonatal: brain insult - infection, trauma
• skull: craniosynostosis - isolated OR
generalized
○ Apert (acrocephaly, hypertelorism, down slanting, syndactyly)

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 • neonatal: brain insult - infection, trauma
• skull: craniosynostosis - isolated OR
generalized
○ Apert (acrocephaly, hypertelorism, down slanting, syndactyly)
○ Crouzon (proptosis, hearing loss
○ Carpenter
○ Pfeiffer

PE
• general
○ facial dysmorphism
○ short stature
○ rash (congenital infection)
○ head-to-toe exam
○ hand: syndactyly (Apert, Pfeiffer), polysyndactyly (Carpenter)
• skull
○ measure: head circumference
○ inspection: abnormal head shape
brachycephaly (↓ AP diameter) (Downs, hypotonic, coronal fusion)
plagiocephaly (oblique shape) (hypotonia, asymmetrical coronal fusion)
scaphocephaly / dolichocephaly (↑ AP diameter) (sagittal fusion, Marfan, Hurler)
acrocephaly (↑ height) (generalized craniosynostosis)
○ palpation: fontanelle (closed / open), sutures

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Seizure
2013年12月3日 19:45

• seizure: transient disturbance of motor, sensory or perception due to abnormal excessive cortical neuronal discharge
• epilepsy: chronic neurological disease with a tendency of recurrent (≥2) unprovoked seizures
• important to differentiate secondary provoked seizure from primary epilepsy (∵ dx may make patient lose his job, tx has sig SE)
• recurrence is common (60-80%) within 6 months after first idiopathic seizure
• occurs in 6 in 1000, higher among infants & elderly, 70% with new-onset epilepsy has focal seizures

Patho
• excessive cortical neuronal discharge ∵
○ neuronal synapse transmission
○ excitatory & inhibitory neurons
○ changes in intrinsic neuronal properties (eg. ion channelopathy by genetics)

Classification (New, 2011)

Generalized Partial / Focal

generalized onset, origins from widespread focal onset, origins limited to one hemisphere
cortical neural network structural brain insult
more genetic origin
Tonic-clonic (GTCS) / Grand mal simple: no LOC
Absence complex: impaired consciousness
Myoclonic secondary generalized: evolve into
Atonic: sx: sudden loss of postural mus tone generalized seizure
(eg. head nodding, collapse)

Ex
• epileptic seizures
• non-epileptic seizures
- structural (high recurrence, poor response to AED)
○ stroke (9%): infarction / hematoma
○ infection: esp. bacterial/TB meningitis, HSV/EV encephalitis, rotavirus/adenovirus URTI
○ trauma: esp. depressed skull fracture, ICH
○ tumors
○ necrosis: eg. radiation-induced (esp. temporal lobe after RT for NPC)
○ neurodegenerative diseases: eg. Alzheimer's
○ autoimmune (eg. NMDA receptors autoAb associated encephalitis)
- metabolic (correct underlying insult, no need AED) DDx
○ febrile seizures (children age <5) • syncope
○ metabolic: hypoglycemia • transient ischemic attack (TIA)
○ electrolytes: ↓/↑ Na, ↓ Ca, ↓ Mg
• migraine
• panic attack
○ encephalopathy: uremia, liver failure, IBM
• conversion disorder (psychogenic)
○ drugs: alcohol withdrawal, substance abuse
○ medications: eg. clozapine

Hx
• pre-ictal
○ background: onset, time, place, duration, witness
○ trigger: flash light, sleep deprivation, menstruation, alcohol
○ ddx from syncope: prolonged standing, n&v, dizziness, sweating
○ prodrome (rare, precede seizure by hours to days):
• inter-ictal (ask the witness!)
○ loss of consciousness (LOC)
○ motor
up-rolling of eyeball

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 up-rolling of eyeball
head turning (lateralization sign, lesion in occiput side)
tongue biting
limb twitching (symmetrical? asymmetrical - means ctl. focal lesions)
stiffened posture
complex motion: eg. dressing / un-buttoning,
○ sensory (aura)
○ autonomic:
irregular/stopped breathing
cyanosis
urinary & bowel incontinence
○ psychic
• post-ictal
○ confusion, amnesia
○ malaise, myalgia, headache
○ hemiparesis (Todd's paralysis), dysphasia
○ injury & head trauma
• previous symptoms
○ fever, chills & rigors
○ neck stiffness, photophobia (meningitis)
○ headache, projectile vomiting, visual disturbances (↑ ICP)
○ vomiting & diarrhea (electrolytes)
○ hunger feeling, hand tremor (hypoglycemia)
○ recent head injury
○ systemic enquiry
• history
○ previous episodes
○ obs: antenatal exposure, birth asphyxia / trauma, neonatal cx
○ ped: developmental delay
○ MH: known epilepsy (diagnosis, frequency of attack, control)
○ DH: AED, emergency rectal Valium, compliance, side effects
○ FH: epilepsy
○ SH: alcohol, substance abuse, high risk occupation (eg. driver)

Cx
• status epilepticus
○ lasting ≥ 5 mins
○ ≥ 2 epileptic seizures with no full recovery of consciousness
• acute
○ asphyxia
○ arrhythmia & cardiac asystole (∵ affecting autonomic neurons)
○ fall, trauma & head injury
○ rhabdomyolysis & lactic acidosis
• chronic
○ cognitive & developmental delay
○ psychiatric diseases

Signs
• vitals: BP, P, SaO2, temp
• general: jaundice, cyanosis, stigmata of CLD, ankle edema
• neurocutaneous signs: hypopigmented spots (TS), café au lait spots (NF)
• neuro exam: pupils, limb tone/power/reflex, CN deficit
• H'stix

Dx
• blood tests
○ CBC: ↑ WBC (infection)
○ RFT: electrolytes (esp. ↑/↓ Na, ↓ Ca, ↓ Mg)
○ LFT: liver diseases
○ RG: hypoglycemia
○ ABG:
○ toxicology screen: substance, drugs, ethanol
○ ammonia: hepatic encephalopathy
○ AED lvl: low level of maintenance medication
• micbio
○ blood culture
○ NPA: viral
○ throat & stool culture: EV
• imaging
○ CT/MRI brain: structural brain lesion
○ EEG: establish true dx, differentiate subtypes
• invasive
○ LP: glucose, protein, smear & culture, PCR (HSV, VZV, EV, TB, Cryptococcal Ag)

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 ○ EEG: establish true dx, differentiate subtypes
• invasive
○ LP: glucose, protein, smear & culture, PCR (HSV, VZV, EV, TB, Cryptococcal Ag)

Tx
• resuscitation
○ monitor vitals (BP, P, SaO2), EEG
○ general: ensure safe surroundings, do NOT put anything in seizing child's mouth
○ A: turn lateral/semiprone position (prevent aspiration & tongue falling back), intubation
○ B: oxygen + ventilation
○ C: set up IV access
• drugs
○ resume usual AED (if known epilepsy)
○ thiamine: IV Vit B1 (Pabrinex®) (if chronic alcoholism suspected)
○ glucose: IV D50 50 ml
○ empirical antibiotics: cefotaxime (if meningitis suspected)
○ empirical antiviral: acyclovir (if encephalitis suspected)
Stage 1 - early status benzodiazepines (short acting)
(0-10 mins) • IV lorazepam
• rectal diazepam, buccal midazolam (if NO IV access)
• rectal paraldehyde (if still no IV access)
Stage 2 - established status anti-epileptic drugs (long acting)
(10-60 mins) • IV phenytoin (preferred)
• IV phenobarbital (already in phenytoin)
• IV valproate, levetiracetam
• IV pyridoxine (children age <3 with unknown etiology)
Stage 3 - refractory status general anesthesia maintain 12- 24 hrs
(60 mins) • IV thiopentone
failure to response to 2-3 AED • midazolam, propofol, sodium valproate

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Generalized seizure
2016年2月16日 13:43

Generalized tonic clonic seizure

Sx
• tonic phase (sustained contraction & stiffness of mus): lasting few s
○ rapid postural change: extension / flexion of limbs, head turning (lateralization,
lesion usu. opp to side of involvement)
○ vocalization: loud moan / scream (∵ air forcefully expelled from lungs)
• clonic phase (rhythmic contraction of mus)
○ twitching of limbs, tongue biting
○ central cyanosis
○ incontinence
• post-ictal
○ confusion & amnesia
○ sleep with stertorous breathing (∵ physical & mental exhaustion)

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Febrile Seizure
2015年12月13日 15:00

• brief (<15 mins) generalized seizure that occur once in 24 hr in a febrile child (temp >38°C) with no CNS infection
• restricted to neurological normal child between age 6 month to 5 year
• occurs in 2-5% of all children, recurrence after 1st episode 30%

Types
simple complex
• primary generalized convulsion • focal convulsion
• lasting <15 mins • lasting >15 mins
• once within 24 hr • recurring ≥1 within 24 hr
higher risk of epilepsy → EEG & other investigation

RF (recurrence)
• previous febrile seizure: 30% after 1st attack, 50% after 2nd attack
• young age (<1.5 y)
• positive family hx: genetic predisposition

Sx
• generalized seizure
○ last for minutes or seconds
○ occurs at first day of fever (but maybe already down when seizure occurs)
• absence of red flag signs
○ no focal neuro signs, neck stiffness, bulging ant fontanelle
○ no severe projectile vomiting, infection
○ no
○ no past history of afebrile seizure

Dx DDx - seizure (life-threatening)

• blood • meningitis, encephalitis
○ CBC: infection • head injury (intracranial hemorrhage)
○ CRP: inflam • hypoglycemia / DKA
• metabolic encephalopathy
○ RFT: electrolytes
• poison / drugs
○ BG: hypoglycemia
• brain tumor
○ ABG: metabolic disturbances
• micbio
○ blood culture: sepsis
○ urine smear & culture: UTI
○ NPA: viral serology
• imaging
○ CXR: chest infection
○ CTB (NOT needed) unless 1) focal neuro signs 2) ↓ consciousness 3) CN palsy 4) papilloedema
○ EEG (NOT needed)
• invasive
○ LP (NOT needed) unless cannot exclude CNS infection

Tx - Acute
• resuscitation
○ monitor vitals (BP, P, SaO2), EEG, convulsion chart
○ general: ensure safe surroundings, remove dangerous objects, do NOT put anything in seizing child's mouth
○ A: turn lateral/semiprone position (prevent aspiration & tongue falling back), intubation
○ B: oxygen + ventilation
○ C: set up IV access
D: DAT when conscious

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 ○ D: DAT when conscious
• drugs
○ resume usual AED (if known epilepsy)
Stage 1 - early status benzodiazepines (short acting)
(≥ 5 mins) • IV lorazepam
• rectal diazepam, buccal midazolam (if NO IV access)
Stage 2 - established status anti-epileptic drugs (long acting)
(≥ 25 mins) • IV phenytoin (preferred)
• IV phenobarbital (already in phenytoin)
• IV valproate, levetiracetam
• rectal paraldehyde (if still no IV access)
• IV pyridoxine (children age <3 with unknown etiology)
Px
• counselling
○ minimal risk of epilepsy (2%, compared to 1% in general popu)
RF: recurrent febrile seizure, present at age <1 year, family hx of epilepsy → 2.4% risk
no study to prove tx of febrile seizure can prevent epilepsy
○ no structural brain damage & no cognitive decline
○ risk of recurrence: 30% after 1st attack, 50% after 2nd attack
○ educate parents acute management of seizure (eg. turn left lateral, remove dangerous obj)
• symptomatic drugs
○ anti-pyretic: paracetamol (only to improve comfort, no prophylactic action)
○ short acting AED: rectal diazepam (Valium®) (abortion of attack)
• prophylactic drugs
daily admin prevent recurrence in 90% cases, usu. not recommended ∵ sig SE
○ phenobarbital
○ sodium valproate
○ diazepam (given at onset of fever)

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Partial seizure
2016年2月16日 13:46

Temporal lobe epilepsy

• auditory & sensory phenomenon
Sx
• hallucination (olfactory/ gustatory/ auditory)
• epigastric rising sensation
• psychiatric sx: déjà vu (strangely familiar), jamais vu (unfamiliar), depersonalization
• automatism (complex semi-purposeful motor action): eg. speaking unintelligibly, screaming /
crying

Frontal lobe
• motor phenomenon
Sx
• Jacksonian march (spreading, start from face & thumb)

Parietal lobe
• sensory phenomenon (dysaesthesia) in contralateral side

Occipital lobe
• visual phenomenon
Sx
• visual hallucinations: eg. scotoma, strange lights, zig-zag lines

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Epilepsy
2015年12月13日 15:12

• occurrence of at least 2 unprovoked seizures, at least 24 hr apart

• brain disorder causing enduring predisposition to generate epileptic seizures

Classification

• classified based on age of onset, seizure types, EEG pattern, imaging features, co-morbidities (eg. MR)
• one syndrome can have multiple etiology
• has treatment & prognosis indication

Ex - epileptic seizure DDx - non-epileptic seizure

• idiopathic (70-80%): genetic predisposition • febrile seizure
• secondary • metabolic: ↓ G, ↓ Ca, ↓/↑ Na
○ cerebral dysgenesis / malformation • head trauma
○ cerebral vascular: stroke, AVM • CNS infection
○ cerebral damage: HIE, PVL, trauma, TORCH infection • toxin
○ brain tumor: low grade supratentorial tumors (NOT infratentorial)
○ neurocutaneous: tuberous sclerosis, NF1, Sturge Weber DDx - paroxysmal disorder
○ neurodegenerative: metabolic disorders • breath holding attacks
○ syndromal: Angelman, Rett, (cries & hold breaths → cyanosis; rapid recovery)
• reflux anoxic seizures
RF • syncope
• environ • migraine
○ flickering light: TV, video games, disco • benign paroxysmal vertigo
• fabrication
○ loud noises
• personal
○ sleep deprivation
○ emotional disturbances
• disease
○ concurrent infection
○ head trauma
○ alcohol withdrawal, drug abuse, medications

Dx
• EEG

use
○ diagnosis of seizure (but only 50% +ve)
classify focal / generalized types

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 ○ classify focal / generalized types
○ identify syndrome with distinct electrical features
type
○ sleep EEG
○ sleep deprived EEG
○ 24-hr ambulatory EEG
○ video-telemetry (video recording of clinical manifestations
result
○ interictal spikes
○ site: discrete area (focal), widespread involvement (generalized)
○ frequency: normally 9-13 Hz
• CT/MRI brain
○ hemorrhage
○ gross structural malformation
○ large tumors
○ calcified lesion

Tx
• general
○ lifestyle: ensure adequate sleeping, no full bath
○ activities: do not engage in high risk sports (eg. swimming, ice skating)
○ driving: prohibited, until license review by Transport Department
○ work relocation: esp. drivers, high risk machine operators, work at height
• anti-epileptic drugs (AED)
Ind
○ recurrent seizures (≥2)
○ underlying structural diseases
○ prophylaxis after head injury
○ intracranial surgery
Withdrawal
○ clinical remission = 2 years free of seizure
○ risk of recurrent seizure after AED withdrawal
Use
○ monotherapy for ≥ 2 years from last seizures
build up dose if not well controlled
add-on therapy with newer AED if severely not well controlled
Types
Narrow spectrum AED Broad spectrum AED
• restricted to focal seizure • more useful for generalized seizures
• may worsen some types of generalized
seizures
eg. carbamazepine (Tegretol®), phenytoin eg. valproate (Epilim), lamotrigine, topiramate,
tiagabine, pregabalin levetiracetam, zonisamide
• surgery
○ resection surgery (take out single epileptogenic focus for curative aim)
○ disconnection surgery (palliative)
○ vagal nerve stimulation VNS (extracranial stimulation of vagus nerve, ↓ 50% symptoms in intractable epilepsy)
○ responsive neurostimulation device (implanted device that gives continuous stimulation to epileptic foci, ↓ 50% symptoms in intractable
epilepsy)

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Specific epileptic syndromes
2016年2月15日 21:08

Infantile spasm / West's syndrome

• usu. in infants (4-6 months)
• poor px, most will have developmental delay and develop epilepsy
Sx
• episodic, jerky, bilateral & symmetrical
• flexion of head (head nodding), trunk, limbs
Cx
• developmental delay & recurrent epilepsy
Dx
• EEG: hypsarrhythmia (chaotic pattern of high voltage slow waves & multi-focal sharp waves)

Benign Rolandic Epilepsy / Benign epilepsy with centro-temporal spikes (BECTS)

• most common epilepsy syndrome in childhood
• started around age 3-13, but most children outgrow it in adolescence
Sx
• transient 1-3 mins, happens before sleep or just before awakening
• unilateral twitching of mouth corner ± strange sounds (eg. rattling, grunting)
• unilateral numbness of mouth corner & oral mucosa
• speech arrest: unable to speak
• drooling of saliva
Dx
• EEG: high voltage spikes followed by slow waves seen, in centro-temporal region
Tx
• no treatment needed
• anti-epileptic drugs: carbamazepine, valproate… (all effective)

Childhood absence epilepsy

• usu. in young children (age 4-12), female (2/3)
• good px, 95% remission in adolescence, 10% develop GTC in adult life
RF
• hyperventilation: blow on piece of paper / windmill
Sx
• typical: more genetical origin
○ sudden onset & rapid recovery
○ transient loss of LOC (like day-dreaming, staring momentarily)
○ subtle motor signs (eg. eyelid flickering, chewing)
• atypical: multiple structural lesion
○ longer duration of LOC, less abrupt onset, obvious motor sign
Dx
• EEG: three per second spikes

Juvenile myoclonic epilepsy (JVE)

• usu. in adolescents and adulthood
• good px, good response to tx but lifelong
Sx
• myoclonic seizures, usu. after drinking or in the morning
• brief & repetitive jerking movement of limbs, necks or trunk

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• brief & repetitive jerking movement of limbs, necks or trunk

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Tuberous sclerosis
2015年11月5日 15:59

• AD inherited disorder causing multiple hamartomatous lesions in brain, skin, heart, kidney and other organs
• about 1/3 cases are inherited, others are de novo mutations

Ex
• mutation in TSC1, TSC2 (tuberous sclerosis complex) gene
○ 30% AD inheritance, 70% de novo mutation
○ TSC1 on chromo 9q34, produces hamartin
○ TSC2 on chromo 16p13, produces tuberin that act as a tumor suppressor
○ mutation in TSC2 causes a more severe disease

Signs
• adenoma sebaceum (late childhood): flat reddish macular lesions in bil. cheeks
• hypo-melanotic nodules (Ash leaf): depigmented white area, examined under Wood's light
• fibrous plaque (Shagreen patch): raised, usu. in lumbosacral region
• dental pitting of enamel, gingival fibromas
• subungual fibroma: nodules beneath nails

Cx
NEURO • recurrent seizures (infantile spasm)
○ subependymal nodules (SEN) / giant cell astrocytoma (SEGA): nodules protruding from lining of ventricles, SEGA ≥ 5 mm
○ cortical tubers: hyperintense lesions (↑ in number with age, main cause of seizures)
• mental retardation (50% only)
CVS • rhabdomyomas (60%): present maximal at birth, tend to regress with age
RENAL • angiomyolipoma (AML) (bilateral): renal mass with hypodense fat attenuation, causing hematuria & retroperitoneal bleed
• polycystic kidney disease
• renal cell carcinoma
• isolated renal cysts
EYE • retinal astrocytomas (50-80%): calcified over time
GI • hamartoma & polyposis
HEPAT • liver cysts & AML
MSS • sclerotic & hypertrophic lesion
RESP • pulmonary lymphangioleiomyomatosis (LAM)
○ systemic neoplastic sm-like cells invasion into lung causing cystic destruction
○ usu. in girls age >25 ∵ estrogen dependent
○ recurrent pneumothorax, chylothorax, hemoptysis

Dx
• genetic dx
• complications mx
○ MRI brain: SEN, SEGA, cortical tuber
○ EEG: seizures
○ renal USG: AML, cysts
○ ECHO: cardiac rhabdomyoma

Tx
• drugs
○ targeted therapy: everolimus
trial: ↓ size of AML
SE: aphthous ulcer, fever, hyperlipidemia
○ anti-epileptic drugs:
• surgery
○ focal cortical resection: prevent further recurrent seizures
○ partial nephrectomy: removing renal mass

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Neurofibromatosis (NF)
2015年8月3日 18:23

NF type 1
• AD inherited disorder of malignant tumor from nerve tissues

Ex
DDx - café au lait spots
• mutation in NF1 (neurofibromatosis) gene
• neurofibromatosis
○ AD inherited, 50% new mutation
• Russel Silver syndrome
○ high penetrance
• McCune-Albright syndrome
○ NF1 gene on chromo 17q11.2
• ataxia telangiectasia
• Fanconi anemia
Signs
SKIN • café-au-lait spots: flat, coffee-ground patches
○ ≥ 6, size > 0.5 cm before puberty, > 1.5 cm after
○ usu. in trunk
• neurofibroma: small, violaceous nodules
○ dermal ≥2
○ plexiform ≥1 (spinal root compression)
• axillary freckles
○ in neck base, groin, submammary area
EYE • Lisch nodules (≥2): benign iris hamartomas (tiny brown / tranlucent lesion ≤ 2mm)
• optic glioma: may cause visual impairment

Cx
TUMOR • astrocytoma: seizures
• pheochromocytoma: hypertension
• soft tissue sarcoma
• leukemia
MSS • osteoporosis
• kyphoscoliosis
• chest wall deformities

Criteria

NF Type 2

Cx
• bilateral vestibular Schwannoma (acoustic neuroma): sensorineural hearing loss, tinnitus, vertigo
• juvenile posterior subcapsular lenticular opacity: a form of cataract
• meningioma: multiple
• fewer cutaneous neurofibroma

Criteria

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Criteria

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