Pediatric Flashcards
Features of Apert and Crouzon syndromes:
Apert (FGFR2 mutation) and Crouzon (FGFR3 mutation) syndrome commonly present with multiple cranial suture involvement and midface hypoplasia.
Syndactyly, however, is typical in Apert syndrome and presents only rarely in Crouzon syndrome. Also characterized by multisuture craniosynostosis (classically bicoronal), microviscerocranium, midfacial hypoplasia, and II-V finger syndactyly of hand and toes with proximal phalanx of bilateral thumbs “in delta”.
Hydrocephalus and developmental delay are present in the majority of children with Apert syndrome, compared to only approximately 1/3 of those with Crouzon syndrome.
Patients with Apert syndrome often have some degree of ventriculomegaly but without progressive hydrocephalus.
Apert and Crouzon syndrome have an autosomal dominant inheritance pattern, and most patients with either disease appear to have mutations in fibroblast growth factor receptor genes.
which pharmacologic agents reduces blood loss and transfusion requirements during routine craniofacial surgery in infants?
TXA
lysine analog that competitively inhibits the conversion of plasminogen to plasmin, thus inhibiting the proteolytic action of plasmin on the fibrin clot, thereby inhibiting fibrinolysis at the surgical site and promoting clot formation.
Which disorders are inherited via mitochondrial DNA?
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
Myoclonic epilepsy with ragged red fibers (MERRF)
Kearns–Sayre syndrome (KSS)
Leber hereditary optic neuropathy (LHON)
Developmental disorders of the nervous system: Gestational age, event, and pathology
3-4 weeks: primary neurolation
myelomeningocele
4-5 weeks: secondary neurolation
meylocystocele (abnormal dysjunction), dermal sinus, diastematomyelia
5-10 weeks: ventral induction
holoprosencephaly
2-5 months: migration
Corpus callosum agenesis, colpocephaly, cavum septum pellucidum, polymicrogyria, pachygyria, lissencephaly, megalencephaly, schizencephaly, porencephaly
At what gestational age does the posterior neuro pore close?
28 days
Hypothalamic hamartomas cause:
Gelastic seizures and precocious puberty
At what age does the neural tube, anterior neuropore, and posterior neuropore close?
The neural tube closure starts in the middle at 22 days, then the anterior neuropore at 24 days forming the lamina terminalis, and then the posterior neuropore at 28 days.
Holoprosencephaly occurs during what gestational age:
occurs at 5–10 weeks gestation and is caused by abnormal ventral induction
Process of primary neurolation:
Primary neurulation occurs at 3 to 4 weeks with formation of the neural plate, neural groove, and neural folds
primitive streak forms at postovulatory day 13
notochord forms at day 17 and induces the primitive streak to form the neural plate that later develops the neural groove and neural folds
neural folds fuse at day 22 to form the neural tube, with the proximal two-thirds forming the brain and the distal one-third forming the spinal cord.
anterior neuropore closing first at day 24 (forming the lamina terminalis)
posterior end closing second (to L1/2) at day 26-28
A problem at this stage causes neural tube defects and Chiari malformations.
Definition: Process of dysjunction
separation of ectoderm from neuroectoderm after the neural tube forms
The mesenchyme in between the two layers forms dura, neural arches, and paraspinal muscles
If dysjunction occurs too early, the mesenchyme can enter the neural tube and form lipomas and lipomyelomeningoceles
Focal failure of dysjunction causes an epithelial-lined dermal sinus tract
More widespread failure of dysjunction may cause a myelocele or a myelomeningocele.
What is the process of secondary neurolation? when does it occur?
occurs at 4–5 weeks as the mesoderm forms the dura, skull, vertebrae, and distal spine
Defects of secondary neurulation cause spinal dysraphism below L1/2. Lesions are from conus and below: caudal regression, terminal syrinx, fatty filum
What is ventral induction? When does it occur?
Induction is the growing brain’s influence on the overlying mesoderm causing it to grow
occurs at 5–10 weeks as the primary vesicles form from the neural tube.
Abnormalities at this stage cause holoprosencephaly, septo-optic dysplasia, and Dandy–Walker malformation.
When does Neuronal proliferation and differentiation occur and result of problems at this stage?
occurs at 2–4 months
A problem at this stage causes vascular malformations and neurocutaneous syndromes
When does Neuronal organization and myelination occur? What is the patterning?
Occur from 5 months to the postnatal period as the synapses form and completed by 2 years
Myelination begins in the fifth fetal month and proceeds caudad to cephalad, dorsal to ventral, central to peripheral, and sensory before motor
At birth, the cortex/white matter signals on MRI are reversed because of the paucity of myelination and increased water content of the cortex compared with the white matter.
When does the corpus callosum form?
8–17 weeks
forms from front to back except for the rostrum that forms last, so partial agenesis always includes the rostrum and splenium.
Definition: Neural crest
group of cells at the neural tube/somatic ectoderm junction
forms the leptomeninges, Schwann cells, sensory ganglia of the CNs, dorsal root ganglia (DRG), autonomic nervous system ganglia, the adrenal medulla, melanocytes, and amine precursor uptake and decarboxylation (APUD) cells
Dura is formed by:
mesoderm
pia/arachnoid are made from:
neuroectoderm
Definition: Exencephaly
occurs when the cerebral hemispheres are present but disorganized. There is also absent calvaria and abnormalities of the skull base
Risk factors include parental consanguinity, affected siblings, decreased vitamin A or folate, and use of valproic acid or carbamazepine
associated with Chiari II malformation (100%), hydrocephalus (80%), lipoma (75%), syringomyelia (50%), diastematomyelia (40%), scoliosis (20%), kyphosis (10%), orthopedic deformities, and callosal dysgenesis
Definition: Sincipital cephalocele
protrudes between the nasal and ethmoid bones and is not associated with neural tube defects
transsphenoidal cephaloceles are associated with:
associated with sellar abnormalities, endocrine dysfunction, and agenesis of the corpus callosum
Location of parietal cephalocele and associated conditions?
protrudes between the lambda and bregma
associated with midline anomalies, agenesis of the corpus callosum, lobar holoprosencephaly, Dandy–Walker malformation, and Chiari II malformations.
location and associated clinical syndromes of occipital cephalocele
protrudes between the foramen magnum and the lambdoid suture
associated with myelomeningocele (7%), diastematomyelia (3%), Chiari II and III malformations, Dandy–Walker malformation, and Klippel–Feil syndrome
location of sphenoethmoidal cephalocele? What is the result of dural diverticulum that doesn’t regress?
crista galli is absent or eroded and the foramen cecum is enlarged
dural diverticulum normally regresses, but if it does not, it may form a dermal sinus tract
Definition: Meckel–Gruber syndrome
cystic dysplastic kidneys, cardiac anomalies, orofacial clefting, and cephaloceles
associated with maternal hyperthermia on days 20–26 of gestation
Definition: Septooptic dysplasia (de Morsier syndrome)
occurs with mild lobar holoprosencephaly, absence of the septum pellucidum, schizencephaly, and hypoplastic optic nerves
associated with seizures, visual symptoms, hypothalamic–pituitary dysfunction (precocious puberty), enlarged ventricles, and hypotelorism
Definition and types of holoprosencephaly:
undivided or poorly divided forebrain
Definition: Cleidocranial dysostosis
occurs with retention of mandibular teeth, delayed closure of fontanelles, wormian bones, and midline defects
What is Lhermitte–Duclos disease? features on MRI? Associated with which syndrome/mutation?
hypertrophied cerebellar granular cell layer and increased myelin in the molecular layer of the cerebellum with thick folia
mass effect on the fourth ventricle
considered a hamartoma
may be calcifications, hydrocephalus, and folia with increased signal intensity on T2
associated with Cowden syndrome where patients have facial trichilemmomas, fibromas of the oral mucosa, hamartomatous polyps of the gastrointestinal (GI) tract and breast, and thyroid tumors
PTEN mutation
Describe Klippel–Feil syndrome:
congenital fusion of the upper cervical vertebrae
associated with Sprengel’s deformity (elevation of the scapula) and Chiari I malformation
Describe Trisomy 13 (Patau’s syndrome):
female predominance, hypotelorism, holoprosencephaly, microcephaly, microphthalmia, cleft palate and lip, polydactyly, dextrocardia, and ocular abnormalities
Death ensues before 9 months
Describe Trisomy 18 (Edward’s syndrome):
female predominance, gyral dysplasia, callosal agenesis, Chiari II malformation, dolichocephaly, cerebellar hypoplasia, hypertelorism, microphthalmia, syndactyly, rocker bottom feet, and ventricular septal defects
Less than 10% live up to 1 year.
Cause and sequelae of Kernicterus
caused by increased unbound unconjugated bilirubin staining the gray matter and causing neuronal necrosis
affects predominantly the GP, thalamus, subthalamus, and CNs III and VIII nuclei, causing symmetric cell loss with extrapyramidal motor signs.
Definition: Porencephaly
cavity that extends from the leptomeninges to the ventricles or superficial white matter lined by white matter (as opposed to schizencephaly, which is a cleft lined by gray matter)
Encephaloceles: associated with which syndromes, presentation, treatment
Eighty percent cranial (usually occipital), 15% frontoethmoidal (sincipital), others mainly basal
Associated with spina bifida, split cord, Chiari II and III malformations, Klippel–Feil, Dandy–Walker syndromes.
Presentation/natural history:
Generally identified prenatally, anterior can present later with facial/ocular manifestations or CSF leak.
Treatment:
Excision of sac and contents with watertight dural closure (generally combined intracranial and transnasal approach for basal), treatment of hydrocephalus if needed.
Chiari malformations: associated with which syndromes, presentation, treatment
Approximately 25% Chiari I are associated with other skeletal abnormalities (basilar invagination, Klippel–Feil syndrome, atlanto-occipital fusion, cervical spina bifida), not brain abnormalities.
Chiari II associated with many CNS abnormalities (myelomeningocele in 100%, migrational abnormalities, hindbrain abnormalities, aqueductal stenosis), lacunar skull, incomplete C1 arch, low-lying torcula - i. Approximately 50% both types associated with syringomyelia (generally improves with treatment).
Presentation/natural history:
Chiari I: cervical pain, suboccipital headache, Lhermitte’s sign, central cord syndrome. Worsening of symptoms with cough/Valsalva maneuver.
Hydrocephalus in 25% Chiari I cases and in 90% Chiari II cases.
Treatment:
Principle to treat from above down: hydrocephalus first if present, then posterior fossa decompression, and finally the syringomyelia.
5 year old with polyuria and polydypsia likely has?
LCH or germinoma
Treatment for hypothalamic hamartoma?
LITT or resection
What are the lipomas classification scheme?
Dorsal lipoma, terminal lipoma (at the conus), and transitional (anywhere between dorsal and terminal
what is the total blood volume in premature babies, full term, 1mo to 1year, and 1 year old to adult?
Total blood volume in premature babies 90–100 mL/kg, full term 80 mL/kg, 1 month to 1 year 75 mL/kg, >1 year to adult 70 mL/kg
What are the clinical symptoms of Congenital syphilis?
Hutchinson’s triad of notched teeth, deafness, and interstitial keratitis.
Bug associated with lyme disease, CNS symptoms? Treatment?
Borrelia burgdorferi,
aseptic meningitis, cranial neuritis (especially CN VII), encephalitis, myelopathy, radiculopathy, and peripheral neuropathy
treatment is with tetracycline.
Which bug is an opportunistic pathogen, infects lungs, CNS, with multiple abscesses and is AFB positive?
Nocardia
Which bacteria is branched and filamentous (looks like fungus), rare in the CNS, contains sulfur granules, and is acid-fast bacillus (AFB) negative?
Actinomyces
How are taenia and cysticercosis contracted? Treatment?
Taeniasis (tapeworm infection) is contracted by ingestion of undercooked pork, whereas cysticercosis is contracted by ingestion of food with fecal contamination. Treatment is with praziquantel or albendazole
What is the enzyme deficiency in Tay-Sachs disease?
Hexosaminidase A
Most common cranial synostosis?
Saggital
Which is the first-line drug of choice for simple partial and neonatal seizures?
Carbemazipime
Rathkes cleft cysts are derived from the persistence of what primary germ layer?
Ectoderm
canavans disease: inheritance, deficiency, symptoms, pathology
autosomal recessive iChromosome 17 defect,
N-acetylaspartoacylase
myelin degeneration
progressively suffer from milestone loss, hypotonia or spasticity, macrocephaly, blindness, epilepsy, and death, often by age 5-10
spongy degeneration of the central nervous system
