Neurology Flashcards
Most common complication from perinatal asphyxia
Renal failure (40-70%)
When to initiate therapeutic hypothermia
Within 6 hours- reperfusion injury stage
NNT to prevent neuro disability for TH
<10
What stage of encephalopathy do you cool for?
MODERATE
SEVERE
MILD IS NOT PROVEN!!
Gold standard for seizure detection
Continuous EEG- at least 24 hours
aEEG useful adjunct or alternative
Monitoring for seizures is recommended by AAP, ACNS
25-40% of babies cooled for HIE have seizures in first 72 hrs of birth
HIE typical patterns of injury on MRI
Basal ganglia and thalami (relay station)
Posterior limb of the internal capsule (dense motor pathway through BGT)
Brain stem (preterm or severe)
Watershed- cortex and white matter
Most predictive of severity of motor in patient with HIE
Severity of basal ganglia and thalamus injury
Most predictive of walking at age 2 in HIE MRI
PLIC
Most common type of stroke
Arterial ischemic stroke (80%)
Seizures are most common presenting sign (>75%) - DO NOT PRESENT WITH HEMIPLEGIA but can have hemiplegia on contralateral side as sequelae
Vein of Galen
High output heart failure
Subgaleal bleed at risk for brain injury- how?
Size of bleed leads to ischemic brain injury
Major cause of neuro developmental impairment in preterm infants
IVH
Classification of IVH
Severity of outcome of IVH related to
Grade of hemorrhage
Unilateral/bilateral, midline shift
Extent of parenchyma involvement
Most common outcome from IVH/PVL
Spastic diplegia- hypertonia with spasticity
LE>UE
PVL outcomes
Increasing rates of disability with severity of white matter abnormalities
Pupillary response
CN 2,3
28 weeks
Extra-ocular movements
CN 2, 3, 4, 6
Fix/follow at 34 weeks
Disconjugate if not fixing
Dolls eyes
Facial grimace
CN 5 & 7
Strength, symmetry
Suck
Cranial nerves 5, 7, 12
Swallow
CN 9, 10
MORO
3 components:
1. ABDUCTION - arms/hands spread open (25-28 wks)
2. ADDUCTION- arms/shoulders “hugging/embracing” (33/34 wks)
3. Audible cry- may not always be elicited
Absent/incomplete- upper motor neuron
Asymmetric- consider brachial plexus injury
True or false?
Neonatal seizures are not reliably diagnosed by clinical observation alone
TRUE
True/false
Most neonatal seizures are symptomatic of acute brain illness (~80%)
TRUE!!
Most common:
- HIE (~50% in US)
- stroke/hemorrhage
- infection
- malformations
- electrolytes/hypoglycemia
Highest yield test for neonatal seizure
BRAIN MRI- ASAP
~90% will have diagnosis apparent on MRI
Prognosis following neonatal seizures
Etiology is the single most important prognostic factor
Higher seizure burden is associated with increased risk of poor outcome
Burst suppression
POOR prognosis
Persistent burst suppression at 72 hours in HIE carries a very poor prognosis
Neonatal onset epilepsies with burst suppression are typically ominous
MC localization of neonatal hypotonia
BRAIN
ANTERIOR HORN CELL- SMA
peripheral nerve- Riley-day
Peripheral=rare
MC cause of hydrocephalus in neonates
IVH
post hemorrhagic hydrocephalus - MC cause of obstructive and communicating hydrocephalus
Leads to significant increase in cerebral blood flow
Hypoglycemia
Hypercapnia
Anemia
Leads to decrease in cerebral blood flow
Polycythemia
Hypotension
Hypocarbia
When fetus becomes responsive to auditory information
26 weeks
Immature auditory system functional 25-29, complete by 30 weeks
Compared to UA, UV blood gas
Higher pH, lower pCO2, higher pO2
V (high, low, high)
Therapeutic hypothermia alters first or second energy failure most?
SECOND
When do you initiate cooling?
Latent phase- 1-6 hrs
Most common cause of CP in term neonate
HIE
HUS findings in HIE
Serial HUS over first 4 days most helpful
Edema peak=24 hrs
Single HUS in first week is normal in 50% HIE
Doppler US for resistive index (or pulsatility index) increases sensitivity and specificity
Deficits from stroke
Motor- depends on location
Learning/behavior
Epilepsy
IVH epidemiology
Highest risk <29 weeks, <1500g
Grade 3/4 highest among youngest and smallest
Risk factors for IVH
Gestational age- younger= higher risk
Lack of antenatal steroids
Lack of exposure to mag sulfate
Birth outside an experienced center/need for transport
CV and respiratory compromise at birth-1st week
Hypercapnia —> cerebral vasodilation
Hypernatremia (>150)
CP from PVL
SPASTIC DIPLEGIA
Neonate with PVL
oligodendrocytes affected
HIE leads to decreased…
phosphocreatinine
HIE type of CP
spastic quadriplegia
Learning and behavior issues in HIE after TH are indicative of injuries in what area?
Watershed
Why are preemies at risk for IVH?
Germinal matrix has a rich vascular supply because it produces oligodendrocytes (glial cell) which makes myelin sheaths between 23-32 was
Vascular supply of GMH does not have the same structural integrity of vessels that are built to last many years = prone to bleeding
Blood flow to GMH is variable because of the limited ability of preterm infants to auto regulate cerebral blood flow
Why does grade IV happen?
Known as parenchymal hemorrhagic infarction
Veins of the periventricular white matter drain into the terminal vein which runs through the germinal matrix
Hematoma in the GM can occlude venous drainage of the terminal vein leading to infarction and secondary bleeding
Most common area of the brain affected by PVL
Periventricular white matter dorsolateral to the external angles of the lateral ventricles
How does PVL occur?
Poor vascular supply to the periventricular white matter -> Ischemia in “watershed” areas of the periventricular white matter -> alters development of vulnerable oligodendrocyte progenitor cells
Describe cystic PVL
Focal cystic necrotic lesions deep in the periventricular white matter
Easily seen by US
Usually seen around 2-4 wis and beyond
Less common than diffuse PVL
Describe diffuse PVL
High signal intensity in the white matter on T2 weighted MRI images
MORE COMMON than cystic PVL
Describe Arnold Chianti malformation
Structural abnormality caused by primary neurulation defect
Hallmark: caudal displacement of the cerebellum before the foramen magnum
Symptom severity corresponds to the extent of the lesion
Describe Dandy Walker
Congenital abnormality of the cerebellum
Enlargement of the 4th ventricle
Complete or partial absence of the cerebellar vermis
Cyst formation at the skull base
Typical EEG pattern in HIE
Depression or burst suppression
May have seizures that are refractory to medical therapy
Most common cranial nerve to be injured during birth
Facial nerve- VII
While exiting the skull and before entering the parotid gland, this nerve becomes very superficial which makes it prone to external pressure injuries
Weakness in lower and upper facial muscles
Unilateral L>R
Asymmetric cry
Recover in 1-3 weeks
Protect involved eye with drops
What is Lissencephaly?
Developmental disorder of neuronal migration during 12-24th week, dx by US 26-28 wks
Smooth cerebral cortex without gyri or sulci
Associated findings: microcephaly, ventriculomegaly, widened Sylvian fissures, complete/partial agenesis of the corpus callosum
2 types:
1. Facial dysmorphism
2. Hydrocephaly, dysgenesis of the cerebellum
Associated with Walker-Warburg and Miller-Dierker syndromes
Highest risk for hearing loss
asphyxia
craniofacial anomalies
syndrome with hearing loss
RDS
bacterial meningitis
meconium aspiration syndrome
chromosomal abnormalities
maternal diabetes
multiple births
NOT ASSOCIATED WITH INCREASED RISK OF HEARING LOSS:
hydrocephalus
gentamicin use
birth weight < 1500g
Neurodevelopmental sequelae most likelly associated with IUGR and not prematurity
Decreased full scale and verbal IQ
Cerebral perfusion pressure
CPP = MAP - ICP
MAP = (2/3)DPB + (1/3) SBP
MAP = (CO x SVR) + CVP
Impairment
structural or functional abnormality at the organ level
Can occur without a disability
Disability
restriction at the personal level that results from an impairment
Can occur without a handicap
Handicap
occurs at the societal level and is a disadvantage as a result of a disability that prevents fulfillment of that individual’s usual role
How can you clinically diagnose an encephalocele?
Transillumination demonstrates lack of bony tissue
Mass will enlarge with straining or crying
Meckel syndrome is due to a defect in what?
Cilia!
secondary to the ciliary abnormality,
TRIAD: occipital encephalocele, multicystic dysplastic kidneys and polydactyly
Diagnosis of prenatal fetal ventriculomegaly
width of at least one ventricle > 10 mm
often associated with hydrocephalus but can also be related to a decrease in amount of normal brain tissue
Neurodevelopmental outcomes may correlate with severity of ventricle enlargement with wide variation based on cause and presence of other associated malformations
primary/secondary neurulation
dorsal induction
Primary: 3-4 weeks
Secondary: 4-7 weeks
Issues during primary:
anencephaly
myeloschisis
encephalocele
myelomeningocele
Arnold-Chiari
prosencephalic development
ventral induction
2-3 months
Issues:
Formation: aprosencephaly
Cleavage: holoprosencephaly
Midline development: agenesis of the corpus callosum, agnesis/absence of septum pellucidum, septo-optic dysplasia
neural and glial proliferation
3-4 months
Micrencephaly
Macrencephaly
neuronal migration
3-5 months
Schizencephaly- abnormal clefts of the brain
Lissencephaly- underdevelopemnet of gyri, smooth brain
Pachygyria- broad abnormally large gyri, leads to less sulci
Polymicrogyria- numerous small convolutions
schizencephaly
segmental developmental failure of cell migration to form cerebral cortex
can be due to vascular ischemia of portion of germinal matrix
abnormal clefting- most commonly involves posterior frontal or parietal lobes
sporadic
cleft filled with GREY MATTER
complete failure of midline division
FUSED thalami, ABSENT falx cerebri
holoprosencephaly
Neuronal organization
axonal outgrowth and proliferation- 3 months to birth
dendritic and synapse- 6 mo-1 yr
synaptic rearrangements- birth to years
Issues:
mental deficiency
Trisomy 21
Fragile Xx
Autism
Angelman
Prematurity
Myelination
birth to years
corticospinal tract- 38wks to 2yrs
last pathway to myelinate is the association bundle- connects prefrontal cortex with the temporal and parietal lobes (complete ~ 32 yrs)
Issues:
Cerebral white matter hypoplasia
Prematurity
Malnutrition
Type of Arnold-Chiari that presents in childhood/adulthood
caudal displacement of cerebellar tonsils below foramen magnum
4th ventricle and brainstem in NORMAL position
associated with syringomyelia (cyst in the spinal cord) or hydromelia (dilation with CSF of canal)
Type I
can be associated with skeletal anomalies (scoliosis)
Type of Arnold-Chiari that presents in infants
more extensive abnormality
elongation and caudal displacement into cervical spinal canal of cerebellar tonsils, 4th ventricle, choroid plexus, brainstem
Type II
often associated with hydrocephalus and myelomeningocele
Pattern of injury in hypoglycemia
Bilateral posterior occipital cortex
Can also include middle cerebral infarction and basal ganglia/thalamic abnormalities
Risk of injury related to duration of hypoglycemia rather than degree
Most common cranial nerve to be injured during birth
Facial nerve (VII)
Caused by nerve compression with hemorrhage and edema of the nerve sheath
Weakness of upper and lower facial muscles, assymetric cry
Unilateral L>R
Usually recover in 1-3 weeks
upper motor neuron vs lower motor neuron
Disorders of anterior horn cell
Hypoxic-ischemic myelopathy
SMA Type I- Werdnig-Hoffman Disease
Neurogenic arthogryposis
Disorders of the neuromuscular junction
Acquired transient neonatal myasthenia gravis
congenital myasthenia gravis
Diseases involving a defect in acetylcholine release:
- Clostridium tetani
- Clostridium botulinum
- hypermagnesemia
- aminoglycoside toxicity
Disorders of the muscle
congenital myopathy- myotubular myopathy
muscular dystrophy
- congenital myotonic dystrophy
- duchenne dystrophy
- congenital muscular dystrophy
SMA Type 1
Werdnig-Hoffmann disease
AR, chromosome 5
degeneration of anterior horn cell
presentation:
- severe generalized hypotonia
- “frog-leg” position, “jug-handle” UE abducted, rotated
- marked head lag
- facial sparing
- AREFLEXIA
- bell-shaped chest with abdominal breathing
- bulbar weakness: poor suck/swallow, weak cry, tongue fasciculations
Diagnosis:
- CPK normal
- EMG: nonspecific denervation, fasciculations, fibrillations
- muscle biopsy = atrophy of motor units
- nerve conduction velocity normal
Acquired transient neonatal myasthenia gravis
10-20% of infants born to mothers with myasthenia gravis
- NO correlation to severity or duration of maternal disease
IMMUNE process involving NEUROMUSCULAR JUNCTION
decreased fetal movements, arthrogryposis, polyhydramnios, pulmonary hypoplasia
Mean duration of illness = 18 days
Require anticholinesterase therapy - neostigmine
Dx:
-CPK normal
- EMG: progressive decline in amplitude with repetitive nerve stimulation
- muscle biopsy: normal
- Nerve conduction: normal
Congenital neonatal myasthenia gravis
Genetic defect of the NEUROMUSCULAR JUNCTION
Congenital myasthenia:
- AR, deficiency of endplate acetylcholine receptor
- less severe
- sxs in first few weeks
- dx features similar to acquired transient neonatal myasthenia gravis
Familial infantile myasthenia:
- AR, presynaptic def in acetylcholine synthesis or packaging into vessicles
- can be severe
- hypotonia, respiratory failure, apnea, severe feeding difficulties, facial weakness, ptosis
- occulomotor fx less affected than congenital type
- typically improvement with age
- Dx: EMG shows fatigue with prolonged stimuatlion of faster rates
Congenital myotonic dystrophy
AR, chromosome 19
- caused by expanded CTG repeat
- inherited almost entirely from mother
- caused by altered protein–> dysfunctional Na/K channels
- polyhydramnios, prolonged labor (uterine dysfunction- may be only sign in mother)
- DELAYED RELEASE OF HAND GRIP
Infant symptoms:
- “tent-shaped” mouth, respiratory failure, hypotonia, weakness, arthrogryposis
- AREFLEXIA, HYPOREFLEXIA
- muscle atrophy
DX:
- CPK normal
- EMG: “dive-bomber” sound
- Muscle biopsy: small/round muscle fibers, large nuclei, sparse myofibrils
- Nerve conduction: velocities normal
the more severe/earlier onset of maternal disease, > risk to baby
Riley-Day syndrome
familial dysautonomia
AR, Ashkenazi Jews
9p31-33 locus
Disorder of peripheral nervous sytem- reduced # of small unmyelinated nerves (pain, temp, taste, autonomic functions), reduced large myelinated afferent nerve fibers
symptoms evident in first year of life
CONFIRM: pupil constriction in response to METACHOLINE eye drops
fixed joints with limitation of movement
Arthrogryposis multiplex congenita
management: stretching, serial casting, tendon/ligament release
MC etiologies of seizures
HIE
ischemic stroke
intracranial hemorrhage
Others:
metabolic, infection, developmental cerebral anomalies, drug withdrawal (heroin, methadone, barbiturates)
Types of seizures most commonly found in full term infants
Multifocal clonic
focal clonic
Most frequent neonatal seizure type
subtle
type of seizure more commonly found in preterm infants
tonic
type of seizure found in preterm and full term infants
myoclonic
first line choice of seizure medications
phenobarbital
phenobarbital pharmacokinetics
barbiturate
increase time that chlorid channels are open by acting on a GABA-A receptor subunits–> depresses CNS
therapeutic level: 20-40 mg/L
metabolism in the cytochrome P450 system in liver
decreased cerebral metabolic rate
oral or IV
most common types of congenital intracranial tumors
Teratomas > neuroepithelial tumors
SUPRATENTORIAL- cerebrum region
MC presentation: increas HC with bulging fontanel
older children = INFRATENTORIAL - cerebellum/brainstem
Infant with hypopigmemted macules, cardiac rhabdomyoma, CNS tumors, seizures, enamel pits in teeth
Tuberous sclerosis
AD, chr 9, 16
Ash leaf spots- use Wood’s lamp, trunk and buttocks
Infant with cafe-au-lait spots, freckling in axilla, inguinal folds, perineum, macrocephaly, seizures
Neurofibromatosis syndrome
AD, chr 17
cafe-au-lait spots:
- dont cross midline
- sharp borders
- multiple, > 1.5cm
- rarely present at birth, 80% by 1yr, 100% by 4yr
Associated tumors:
- cutaneous neurofibroma
- schwannoma
- pheochromocytoma
Bilirubin encephalopathy
athetoid CP
hemiplegia
unilateral
involvement of one side
diplegia
involvement of legs only or legs > arms
quadriplegia
involvement of all four limbs
spastic CP
MOST COMMON
85-90%, 1/3 unilateral, 2/3 bilateral
Increased tone
increased DTRs
gross motor affected
fine motor/cognitive function usually not affected
dyskinetic/athetoid CP
extrapyramidal
repetitive, uncontrolled, involuntary movements
mixed tone in same muscle
dystonic- reduced activity with increased tone manifesting as stiff movements
choreoathetotic- increased activity and reduced tone manifesting as uncoordinated writing/jerky movements
gross AND fine motor affected
cognitive function usually not affected
hearing deficits
speech abnormalities
ataxic
least common
decrease tone, poor coordination
decreased reflexes
severe cognitive delay
GMFCS
gross motor functional classification system
5 levels corresponding to motor abilities in children 6-12 years
etiologies of mental deficiency
prenatal 60-80%
perinatal ~8-12%
postnatal ~10%
IQ for mental deficiency
fifth day fits
issue with potassium channel
AD
benign familial neonatal epilepsy
infant with intact skull that is macrocephalic or microcephalic, illuminates with bright light, no cortical tissue, +falx cerebri, UNFUSED thalami
brain stem, cerebellum, thalamus, striatum are preserved
due to early in utero vascular accident
no other dysmorphic features
hydrancephaly
x-linked hydrocephalus
due to acqueductal stenosis- acqueduct of sylvius
L1CAM gene
hydrocephalus with macrocephaly
thin semetric rim of cortical tissue, +falx cerebri, unfused thalami
porencephalic cysts
fluid filled cavities (cysts filled with CSF, lined by white matter) in the brain that typically communicate with the ventricular system
due to in utero vascular injury or infection leading to encephalomalacia
COLA4A1- familial form
most common teratogen that increases the risk for holoprosencephaly
maternal diabetes
presence of thalamic hemorrhage suggests..
cerebral sinovenous thrombosus]
MRI immediately
