Neurology/Ophtho Flashcards
How long does it take for facial nerve palsy to recover?
1-3 weeks
Glaucoma (measure intraocular pressure)
abnormalities in drainage of aqueous humor. Tearing, photophobia, enlarged globe - buphophthalmos, corneal edema, clouding (irregular corneal light reflex and dull red reflex), visual loss, conjunctival infection
What syndrome does congenital glaucoma affect 30-70% of individuals?
Sturge weber
Bilateral leukocoria = ____?
bilateral cataracts. rubella is most common infectious cause (CMV and toxo cause chorioretinitis)
Cochlear implants are indicated for hearing loss > _____ dB
- Use amplification device for hearing loss less than that
When does EEG activity become continuous?
31-33 weeks
Characteristics of Prader-Willi syndrome?
profound hypotonia, excessive sleepiness, poor suck, feeding difficulty. Dolichocephaly (elongation of skull), bitemporal narrowing, “almond-shaped” palpebral fissures, narrow nasal bridge
When does optic nerve myelination complete?
2 years
ROP and prematurity correlate to this eye abnormality
strabismus
What is the most common brain injury in preterm infants?
diffuse periventriculomalacia
Most common cause of congenital hearing loss?
Genetic (50%), most causes are autosomal recessive. Connexin 26 gene is most common genetic etiology
Palmar grasp appears at ____ weeks, established at ___ weeks, disappears at ____
28-32 weeks appears, established at 37 weeks, disappears at 6 mo
Crossed extensor (sole rubbed during leg extension), opposite leg first flexes and fans toes - appearance and dsiappears
absent at 26 weeks, complete at 34 weeks, disappears at 2 months
Tonic-neck reflex?
appears at 35 weeks, established at 1-2 months, disappears at 6 mo
Prader willi inheritance?
MATERNAL uniparental disomy (15q11-q13 gene)
If both copies of 15q11-q13 gene are from FATHER then it is _______
Angelman syndrome
Kernicterus sequelae? Do they get cognitive impairment?
Cognitive impairment is rare - usually have abnormal movements, gait, auditory dysfunction, dental-enamel dysplasia
What is ROP threshold disease?
Severe disease in which abnormal neovascuarization is observed in Zones I or II in at least 5 contiguous or 8 total clock hours with plus dz –> needs laser in 2-3 days
Plus dz - ROP of any stage in which retinal vessels appear thickened and tortuous
Trisomy 21 features
BOTH large epicanthal folds and upslanting palpebral fissures
Hyper or hypercapnia leads to higher risk of IVH?
hyper only
Why do we screen CUS < 32 weeks
Germinal matrix has rich vascular supply –> produces oligodendrocyte (glial cell) –> makes myelin sheaths b/w 23-32 weeks gestation. Blood flow to germinal matrix is variable due to limited cerebral auto regulation.
How do G4 IVH occur?
Veins of periventricular white matter drain into terminal vein –> germinal matrix. A hematoma in germinal matrix –> venous drainage of terminal vein leading to infarction and secondary bleeding
Why does periventricularmalacia occur?
PVL occurs due to ischemia in watershed areas of periventricular white matter. Hypoxia and ischemia in area laters development of vulnerable oligodendrocyte progenitor cells
Cystic PVL is _____ common, easily visualized on _____. Diffuse PVL is _____ common, more easily visualized on ______.
Cystic is LESS common, seen on CUS.
Diffuse is MORE common, seen on MRI
Brachycephaly? Which syndrome
premature closure of bilateral coronal sutures (Carpenter syndrome)
What is Arnold Chiari syndrome?
Structural abnormality in cerebellum caused by primary NEURULATION defect. Caudal displacement of cerebellum allow foramen magnum
Sx: neck pain, weakness, numbness, vision problems.
Surgical correction - decompression of posterior fossa and shunt
What is dandy-walker syndrome
Congenital abnormality of cerebellum. Enlarged 4th ventricle. complete or partial absence of cerebellar vermis, cyst formation at skull base
Tx. surgical with decompression of posterior fossa and /or shunt
Clonus is a normal or abnormal finding?
Normal up to 3 mo of age. Reflexes SHOULD be symmetric
Is Werdnigg Hoffman an upper or lower motor neuron disease
lower motor neuron
mobius syndrome
congenital facial diplegia syndrome - problems in cranial nerve nuclei, roots, nerves, or muscles
What is static encephalopathy (CP)
spasticity associated with cerebral white matter injury
What is the abnormal hearing threshold for ABR and OE? What GA can you use them?
35 dB. >34 weeks
What is lissencephaly? Associated syndromes?
rare d/o neuronal migration during 12-24th week GA -> smooth cerebral cortex without gyro or salvation. Microcephaly, ventriculomegaly, widened Sylvia fissures, complete/partial genesis of CC. Dx after 26-28 weeks
Type I: facial dysmorphism
Type II hydrocephaly, dysgenesis of cerebellum
Walker Warburg (crebro-ocular dysplasia syndrome) and Miller-dierker syndromes
Describe congenital myotonic dystrophy inheritance and biopsy appearance
Autosomal dominant inheritance - muscle biopsy shows abnormal small and round muscle fibers with large nuclei and sparse myofibrils
What is Riley Day syndrome?
Familial dysautonomia (AR) - peripheral nervous system that can be dx by pupil constriction in response to methacholine eye drops
Difference b/w sensorineural and conductive hearing loss (bone, air)
Sensorineural: decreased bone AND air conduction; damage to cochlear hair cells or auditory nerve
Conductive: bone good, air is poor. fluid in middle ear, microtia, canal stenosis, stapes fixation
HIE stages? When to start TH
Repercussion - 30-60 min period of recovery after acute insult
Latent phase is 6-15 hours
Must start TH before latent phase as apoptotic cascades are triggered during latent phase that stimulates inflammatory sequence –> secondary phase of cell death
ABR is less affected by outer and middle ear obstruction. ABR and OE are better at detecting which frequency of sounds?
Better at detecting mid to high frequency of sounds
Which type of oligodendrocyte are most vulnerable to inflammatory and ischemic injury?
Pre-oligodendrocyte and immature oligodendrocyte
What is % of kids with neurodevelopment problems with neonatal seizures?
40-60%
When does scarf sign progress?
at 28 weeks, elbow can be adducted to opposite shoulder
At 40 weeks, can only go to midline
Moro, ATNR, Grasp, stepping reflex
Moro: starts at 37 weeks, present until 3-6 months
ATNR: established bby 1 mo, disappears by 3-4 mo
Grasp: present at 32 weeks, present until 3 mo
Stepping reflex: 32 weeks, persist until 1-2 months
Ischemic infarcts lead to _____
spastic hemiplegia
Spastic diplegia involves both legs and is caused by
PVL in preterm patients
Spastic quadriplegia is caused by
global hypoxic event
IUGR + preterm affects full scale and verbal iq scores?
lower on both
Hearing loss occurs in some infants with isolated accessory tragus and pre auricular pits and also can have ______
urinary tract anomalies, esp if associated with branch-ot-renal syndrome or oculo-auriculo-vertebral syndrome (Goldenhar)
Occipital encephalocele is associated with ______
Meckel syndrome - ciliary dysfunction –> multi-cystic kidneys and polydactyly
Is achondroplasia associated with microcephaly
No
Most causes of retinoblastoma are hereditary or non-hereditary?
NON hereditary. Initiated by inactivation of both alleles of RB1 gene
MR Spec can detect increases in brain lactate as early as _____
2-8 hrs after injury
Which ethnicity has highest incidence of neural tube defecdts
hispanic
Transient neonatal myasthesnia gravis - clinical presentation, how many are affected to mothers with MG
3-72 hrs after birth with poor suck + hypotonia. 10-20% of newborns of mothers with MG are affected
If hyperthermia after HIE, experience neuronal cell death in ______
hippocampus
In HIE, the influx of intracellular calcium causes multiple downstream effects
- endonuclease activation that results in nuclear injury
- protease activation leading to cytoskeleton disruption
- protease and phospholipase activation that results in free radical production and activation of the apoptotic pathway
- nitric oxide synthase activation
- increase in glutamate (NT) release
What is highest risk for brachial plexus injury
shoulder dystocia
Beals syndrome
AD connective tissue disorder, fibrillin 2 gene on chromosome 5. similar to Marfan long arms, hands, feet, chest wall deformities, joint contractures, scoliosis, MVP
Genesis of corpus callosum can occur in isolation or with other brain malformations, or as part of syndrome like
Aicardi syndrome
Maternal SSRI use can lead to ______
neonatal adaptation syndrome - hypertonia, tremors, jitteriness, feeding issues, difficulty sleeping, respiratory distress
Myotonic dystrophy type 1
AD, expansion of CTG in myotonic dystrophy protein kinase (DMPK) gene on chromosome 19. hypotonia, respiratory distress, poor feeding, talipes equinovarus, eyelid ptosis. Increased risk of complications from sedation and anesthesia
Newborns in prenatal surgery group in MOMs trial had
increased urological complications compared with postnatal intervention group
Therapeutic hypothermia mechanisms that are beneficial
Decrease in tissue metabolic demand (cerebral metabolic rate)
Decrease in ionic perturbation with decreased intracellular Ca influx and mitochondrial dysfunction (less neurotoxicity)
Decreased free radicals
Attenuation of proinflammatory cascade activation, including reduction I STAT3 expression
Enhanced RBM3 protein expression, protein with antiapoptotic and cell proliferation functions
Biomarkers of HIE
Protein S100 beta - seen in cord blood or first urine of neonates
Glial fibrillary acidic protein levels likely elevated during first 2 days after delivery
NICU grads have normal HS, is this reassuring?
are at risk for delayed onset or progressive hearing loss
HIE - describe pathophysiology
increased synaptic release of glutamate and over-activation of glutamate neuronal receptors
1st phase: immediate cell death due to necrosis as result of interruption of substrate delivery
2nd phase: complex activation of several intracellular pathways including excitotoxicity (increased synaptic release of glutamate with over-activation of glutamate neuronal receptors, free radical production leading to increase in oxidative stress, and neuronal injury, inflammatory cascades
Maternal SSRI use increases risk for what as kids get older
ADHD
Myotonic dystrophy type 1 - prenatal findings that make you suspicious
AD, CTG trinucleotides in noncoding region of myotonic dystrophy protein kinase (DMPK) on chromosome 19
Prenatal findings that make you suspicious - polyhydramnios, VM/hydrocephalus, talipes equinovarus, decreased fetal movements
TNMG - pathophysiology
ACHr antibodies (85%), or Muscle specific receptor tyrosine kinase (15%)
PVL primary cell target is
pre-myelinating oligodendrocyte (high concentration b/w 23-32 weeks GA) - susceptible to H-I injury, free radicals, inflammation, excitotoxicity
What is developmental coordination disorder
milder form of motor disaibility than CP. Impairment of motor sufficient to produce functional performance not explicable by child’s age or intellect. Usually do not have problems with early milestone acquisition
Osteogenesis imperfecta gene
collagen 1A gene; abnormal collagen fibrils in type I collagen
brachial plexus injury recovery times
Most brachial plexus injuries recover by 1 month. If delayed to 2-3 months, full recovery unlikely (could be bc suboptimal cortical development due to prolonged paralysis at critical period of brain development)
Initial arm and hand involvement in BPI may affect subsequent cortical development even after full recovery
Residual deficits = 20-30%
Aicardi syndrome
agenesis of CC, infantile spasms, chorioretinal lacunae. X-linked dominant. 46 XXY
Benign familial neonatal convulsions
family hx, spontaneously resolve after few days or weeks
Benign neonatal seizures
onset of seizures b/w 4 days and 6 days after birth (fifth day fits), no family hx
Typically focal clonic, respond well to anti epileptics. Good prognosis.
nemaline myopathy
MC form of congenital myopathy, most encoding sarcomeric thin filament proteins
Topography of white matter injury in preterm neonate is best explained by
distribution of oligodendrocyte progenitors
SARNAT exam
LOC
Activity
Posture
Tone
Reflexes
Autonomic dysfunction
3-6 domains abnormalities = moderate/sever encephalopathy
Positive vs negative burst suppression
> 100 or <100 bursts/hour
S100 beta levels and mortality
Preterm newborns with high S100 beta levels have higher mortality rates than those who are of otherwise similar weight and gestational age without high S100 beta levels
Possible protective mechanism for EPO
Neuroprotective mechanism of EPO may result from prevention of N-methyl-D-aspartate receptor activation that can occur after hypoxic ischemic injury
Possible other manifestations of myotonic dystrophy
resp distress, arrhythmias (death in adulthood), GI dysfunction, endocrine problems
Dejerine-sottas disease
severe hereditary motor and sensory demyelinating neuropathy; significant decrease in myelinated fiber density, thin myelin sheaths, onion bulb formation
Seizure appearance on EEG
usually have an appearance of gradual buildup and decline in frequency ad an amplitude that includes repetitive spikes, sharp waves, or a single sinusoidal pattern that lasts 5-10 seconds
What length of seizure is not detected by aEEG
< 30 seconds
What type of imaging is very sensitive in detecting diffuse PVL
diffusion tensor imaging
Cystic vs diffuse PVL
Cystic PVL - focal cystic necrotic lesions in the periventricular white matter, can easily be identified on CUS. Incidence of cPVL has been decreasing over the past several years and occurs among less than 5% of preterm neonates <32 weeks GA
Diffuse PVL - most common brain injury in neonates born preterm. 17-25% of neonates < 32 weeks when using MRI at term.
Rate of recovery of brachial plexus injury
90%, but some have 20-30% residual deficits.
Recovery of biceps function within first month predicts full recovery by age 2. But if delayed to 2-3 months, full recovery less likely
Active receptors are _____
highly expressed in neuronal cells and preterm newborns with high serum activin A levels have higher risk of developing IVH
Zellweger syndrome
AR; PEX gene mutation; intracellular accumulation of VLCFA. Severe peroxisome biogenesis disorder including adrenoleukodystrophy.
Facial features (large fontanelle, high forehead), abnormal retinal pigmentation, marked hypotonia, poor feeding, HM, renal cysts, shortened proximal limbs, chondrodysplasia punctuate, cortical malformations, hypomyelination
aEEG area of brain that should be avoided
Frontal region should be avoided bc decreased sensitivity to seizure detection
Punctate white matter hyperintensities are predictive of
adverse ND outcomes depending on #, location, and timing (6+ is associated with abnormal motor development)
Corona radiata above posterior limb of internal capsule specific of motor disability
Punctate hyperintensities prior to term equivalent PMA have not beeen shown to be predictive of outcomes
Neurofilament and glial fibrillary acid protein (GFAP) is a
cytoskeletal filament protein specific to astrocyte, released after astrocyte death. GFAP high in neonates with posthemorrhagic ventricular dilatation
Seizures are common in neonates because
delay in maturation of GABA receptors. GABA receptor activation results in net influx of chlorie into cell resulting in decreased cellular membrane resting potential, inhibiting action potentials
Immature brain - higher intraneuronal chloride concentration, so GABA Inhibition is diminished or even net excitatory
This developmental asynchrony explains why neonatal seizures have incomplete responsses to medications that act via GABAergic mechanisms such as PHB and benzos
Germinal matrix involutes by
36 weeks
Congenital disorder of glycosylation
AR 2/2 abnormal synthesis of N-linked oligosaccharides (critical for synthesis of glycoproteins and glycolipids)
Present with microcephaly, hypotonia. abnormal distribution of fat (suprapubic, ilac, buttock), inverted nipples, strabismus
Cystic vs diffuse PVL
Cystic PVL - focal cycstic necrotic lesions in PV WM, easily seen on CUS at 2-4 weeks of age. <5% of neonates born at < 32 weeks
Diffuse - MC brain injury in preterms. 17-25% of neonates < 32 weeks GA at MRI at term.
Melatonin mechanisms of neuroprotection
reduces extent of neutrophil migration
Erbs vs Klumpke palsy
Erb’s palsy: C5-6
Klumbke palsy: C8-T1 (Horner syndrome when T1 injured)
Ehlers Danlos type 7 (arthrochalasis)
most likely to be recognized in newborn period (bilateral hip dislocation, congenital patellar dislocation, hpotonia)
Biomarker of early recognition of fetal alcohol syndrome
fatty acid ethyl esters
Most distinguishing feature of cell apoptosis in HIE is
chromatin aggregation
Riley- Day syndrome
autonomic neuropathy type 3; ashkenazi Jew parents; feeding difficulty, recurrent aspiration, nasal cry, jerky limb movements, hypotonia. corneal reflexes absent
Gene mutation on chromosome 9q31, truncated I kappa B kinase
Main cause of mortality after initial MMC repair is
2/2 Arnold-Chiari malformation type II progression and shunt malfunction
MMC Repair long term outcomes
47% ambulate, 80% social continence, 85% intermittent cath
men: 12-75% ED
70-75% normal IQ, 60% learning disability
Glucose levels in mild vs severe encephalopathy
Initial glucose levels in neonates with severe encephalopathy are likely to be lower than in neonates with mild
Structure of cerebellum most susceptible to injury is
external granular layer
PHB = phenytoin in efficacy, but PHB has lower protein binding and fewer interactions. What are phenytoin disadvantages
difficulty in maintaining therapeutic levels in oral meds, higher protein binding + more interactions, risk of irritation and tissue injury with extravasation (fospheny beter), posssible bradycardia
Teratogenic effects of alcohol in brain is mediated by
inhibition of sonic hedgehog signaling, increased free radical production, agonist to GABA and antagonist to NMDA (apoptosis)
Prader Willi Syndrome - inheritance, what features is present in nearly all affected males
Maternal disomy; cryptorchidism
CP is a _____ dx
clinical - lacks specific pathological or radiographic features, some have normal brain MRI
Recurrence risk of MMC
3%; high doses of folate (4000 mcg) recommended
Describe secondary energy failure in HIE
activation of microglia and inflammatory response, caspases release and activate apoptotic pathways, decrease growth factors and protein synthesis, further accumulatino of excitotoxic neurotransmitters
