Child Neurology Flashcards
Alexander’s Disease
- characterized by diffuse rosenthal fibers (hyaline eosinophilic rods) present diffusely in brain
- gene mutation in glial fibrillary acidic protein (GFAP)
- leukodystrophy (problem in myelination)
- MRI with WM signal abnormality in frontal lobes + involvement of U fibers
- sx: early onset (<4), seizures, macrocephaly, motor/dev delay, FTT, encephalopathy
- type I is more severe then type II
Lesch-Nyhan
- x-linked recessive dx
- dx of purine metabolism due to absent hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) enz activity
- increased serum uric acid
- gout, self injurious behavior, intellectual impairment, hypotonia/dystonia, spasticity, choreoathetosis
Rett’s Syndrom
- mutation in MECP2 gene on Chromosome X
- error in modulation of gene expression
- usually affects females
- stereotypic hand movements, developmental arrest between 6-18 months, seizures, growth failure
Cri du chat
5 p monosomy
high pitched cry, moon facies, low set ears, small jaw, heart defect
Patau Syndrom
Trisomy 13
- intellectual disability, microcephaly, holoproencephaly, polydactyly, single palmar crease, cleft lip/cleft palate, coloboma/fusion into one eye
Edwards Syndrome
Trisomy 18
intellectual disability, rocker bottom feet, pointed ears, microagnathia, microcephaly, heart defects. most die shortly after birth
Down’s Syndrom
Trisomy 21
- intellectual disability, characteristic facial features, hypotonia, brushfield spots
- Increased risk of alzheimer’s, leukemias, and heart defects
Subcortical Band Heterotopia
“double cortex”
- mutation of DCX gene on X chromosome encoding doublecortin
- due to abnormal neuronal migration
- associated with lissenencephaly
Aicardi Syndrom
- triad of infantile spasms, corpus callosal agenesis, and retinal malformations
- x-linked dominant (lethal in males)
Galactosemia
- inability to metabolize galactose
- def in galactose-1-phosphate-uridyl transferase
- enlarged liver, cataracts, gram negative sepsis, and poor weight gain
- tx: galactose-free diet
Duchenne Muscular Dystrophy
- x-linked recessive (21p frame shift mutation)
- mutation in dystrophin gene (anchors contractile proteins to outside of muscle cell)
- proximal muscle weakness, elevated CK, calf pseudohypertrophy (muscle replaced by fat), gaucher walk (use hands to rise from floor), use hands to push on knees to rise (gower’s maneuver), scapular winging
- may experience some sx benefit from prednisone
- EMG with myopathic changes
- most die from complications due to cardiac muscle involvement (Dilated CM)
Rasmussen Syndrome
- intractable seizures (usu focal motor) and epilepsia partialis continua
- tx is hemispherectomy
Myotonic Dystrophy
- autosomal dominant
- CTG repeats on DPMK gene on Ch 19
- symptoms typically happen for >1000 repeats
Homocystinuria
- cystathionine-beta-synthase deficiency
- elevation of blood homocysteine and methionine
- asx at birth; later will have developmental delay and intellectual disability
- collagen metabolism is involved –> lens dislocation
- marfanoid habitus (pes cavus, osteoperosis)
- high incidence venous thromboembolism and cerebral infarcts
- tx: pyridoxine, folate/b12 supplementation, low protein diet (esp methionine with cysteine supplementation)
Benign epilepsy with centrotemporal spikes
- presents b/w age 3 and 13
- nocturnal seizures which start with unilateral facial paresthesias followed by clonic jerking and drooling
- may have secondary generalization
- typically remit during puberty
Othahara syndrome
severe epileptic encephalopathy which starts in infancy
- multiple clusters of tonic spasms
- infants become hypotonic and psychomotor development stops
- EEG with burst suppression pattern in both awake and asleep state. During tonic seizure, will show high amplitude spike and wave followed by generalized fast activity
Benign familial neonatal epilepsy
- autosomal dominant
- hypertonia and apnea followed by clonic movements of face and limbs
- interictal EEG may be normal or show multifocal abnormalities
West Syndrome
“infantile spasms”
age 3-7 months
triad: arrest and regression of psychomotor development, epileptic spasms, and EEG with hypsarrhythmia (high voltage slow waves and multifocal spikes followed by alternating periods of attenuation)
- epileptic spasms: mixed flexor/extensor spasms lasting <2 seconds; occur hundreds of times daily
Early myoclonic epilepsy
can be difficult to distinguish from Othahara syndrome
- seizures start prior to day 10 of life and are myoclonic
- EEG with burst suppression accentuated by sleep (unlike Othahara, where burst suppression is present in both sleep and wake state)
Landau-Kleffner syndrome
infrequent simple motor seizures, auditory agnosia (word deafness), and expressive aphasia
- EEG with bitemporal spike wave discharges
NARP syndrome
Neuropathy, ataxia, and retinitis pigmentosa
- proximal muscle weakness, sensory motor neuropathy, ataxia, and retinitis
- inherited due to mitochondrial dx on gene MT-ATP6
Sialidosis
lysosomal storage disease
- deficient levels of alpha- N acetyl neuraminidase
- prognosis varies by type of disease (stillborn, fatal, live up to 20)
- dx: a decrease in cultured skin fibroblast alpha-neuraminidase
- eeg: progressive slowing and bilateral, photosensitive fast spike-wave discharges
- myoclonic seizures, macrocephaly, coarse facial features, hypotonia, nystagmus, cherry red macula, night blindness, loss of color vision
Septo optic dysplasia
absence or dysgenesis of septum pellucidum with hypoplasia of the optic nerve + pituitary infundibulum. Associated with:
1) Schizenecephaly or
2) Diffuse white matter hypoplasia , ventriculomegaly, and abnormal hypothalamic/pituitary function (growth hormone def is most common)
- most patients have blindness or visual impairment
- intellectual disability, epilepsy, cerebral palsy, ADHD, autism
Krabbe Disease
Globoid cell leukodystrophy
- deficiency of galactosylceramide beta galactosidase which converts galcatosylceramide to ceramide
- globoid cells are MQ which phagocytize accumu galac
- autosomal recessive, CH 14
- infantile form: exagg startle, devel regression, hyporeflexia, seizures, peripheral neuropathy, spastic weakness
- juvenile form: cortical blindness, ataxia, dev regression, spasticity
- MRI with diffuse WM demyelination
- tx: BM tx before sx onset
DNET
mixed glioneural neoplasm, occurs in childhood
- most commonly presents with refractory temporal lobe epilepsy
- MRI with “bubbly” appearance, enhancement, and calcification
- good prognosis with complete resection
Oligodendrioglioma
IDH mutated with 1p/19q co-deletion
Astrocytoma
p53 and IDH mutation
Pilocytic astrocytoma
- cyst with an enhancing mural nodule
- histologically: bipolar astrocytes
McArdle’s disease
- deficiency of muscle phosphorylase
- mutation in Ch 11, autosomal recessive
- exercise intolerance: tire easily, muscles spasms/contractures and pain with excercise
- weakness is mild, and in proximal muscles and UE
- dark urine; elevated serum ammonia (normal lactate)
- can –> life threatening kidney problems
Chiari Type II malformation
caudal displacement of cerebellar tonsils, cervicomedullary junction, pons, 4th ventricle, and medullar
- associated with myelomeningocele and hydrocephalus
- tx: surgical decompression and CSF shunt for hydrocephalus
Miller Dieker syndrome
17 p chromosome deletion –> lissenencephaly
- most infants typically die during childhood
- seizures, cardiac/renal malformations and resp issues
NF1
- genetic testing with 2 of the following: 6 or more cafe au lait spots, at least 2 neurofibromas, axillary and inguinal freckling, optic gliomas, iris hamartomas (lisch nodules), bony lesion, first degree relative with NF1
- autosomal dominant
- pilocytic astrocytoma
Sturge Weber Syndrome
- angiomas of face, meninges, and brain (ipsilateral to facial lesion –> contralateral weakness and homonymous hemianopsia
- cutaneous angiomas are called “port wine stain” and usu occur in V1 distribution
- intellectual disability, seizes, glaucoma, hydrocephalus, cerebral atrophy, tram track gyral calcifications
- Ch 9 mutation (GNAQ)
- mneumonic: STURGE = Seizure, Tram track calcifications, Unilateral portwine stain, Retardation, Glaucoma, Epilepsy
Friedreich’s Ataxia
MC hereditary ataxia
- GAA trinucleotide repeat expansion of FXN gene on CH 9; autosomal recessive
- present b/w 2-6 years with dysarthria, ataxia, and posterior column signs (UE > LE), high arch (pes cavus), absent DTR
- most are wheelchair bound by 15
- axonal neuropathy with sparing of motor nerve conduction
- asso with cardiomyopathy, DM, and scoliosis
Pilocytic astrocytoma
- WHO grade I tumor, slow growth and good prognosis (90% survival rate)
- cerebellum is most common location
- cystic component with contrast enhancing mural nodule on MRI; bipolar hairlike processes on path
- associated with NF1
- tx is surgical resection; if incomplete, then follow with xrt
Fragile X Syndrome
most common genetic cause of intellectual disability
- x-linked dx; loss of function mutation due to CGG repeat expansion
- narrow, long face with prominent chin & forehead; large ears, testicular enlargement after puberty
- macrocephaly, hypotonia, flat feet, MVP, arched palate
- autism, ADHD, impulsivity, stereotyped movements, gaze aversion, unusual speech pattern
Fabry disease
x-linked, recessive, lysosomal storage disorder due ot def of alpha-galactosidase
- present with severe neuropathic limb pain, GI symptoms/pain, corneal opacity, angiokeratoma, tinnitus/hearing loss
- renal and cardiac involvement –> death
Leigh disease
caused by def in pyruvate DH
- infants with loss of motor skills, poor sucking, vomiting, and seizures
- develop weakness and lactic acidosis
- fatal
Medulloblastoma
- occur exclusively in posterior fossa (arise from cerebellar vermis and protrude into 4th ventricle) –> obstructive hydrocephalus
- potential for leptomeningeal spread
- contrast enhance, +/- calcification
- homer wright rosettes are pathognomonic
NF2
- Ch 22, merlin gene
- bilateral vestibular schwanommas, or unilateral with multiple tumor types (meningioma, ependymoma, glioma, neurofibroma)
- 85% have cataracts
Fabry Disease
- x-linked recessive, lysosomal storage disorder
- deficiency of alpha galactosidase A –> buildup of glycoprotein
- severe neuropathic limb pain, GI symptoms/pain, corneal opacities, hypohidrosis, angiokeratoma, tinnitus/hearing loss
Prader-willi
- caused by either paternal deletion of long arm of Ch 15, or maternal disomy (so there are no paternal copies of the chromosomes as both are inherited from the mother)
- characterized by: insatiable hunger, obesity, hypogonadism, intellectual disability, short stature
Angelmann Syndrome
- caused by maternal deletion of Ch 15 or paternal disomy (opposite of Prader Willi)
Giant axonal neuropathy
- autosomal recessive, childhood neurdegenerative dz
- frequent falls, cerebellar ataxia, ocular atrophy
- coarse, kinky red hair
- mutations in GAN gene, encodes cytoskeletal gene gigaoxin
- giant axonal swelling on nerve bx
- usually die from respiratory complications by 30
Doose syndrome
- myoclonic astatic epilpesy
- characterized by a myoclonic jerk, followed by an atonic seizure (brief loss of tone of neck, trunk, or limbs)
- EEG between seizures is normal
- age of onset 3-6 years; development is normal until onset of seizures
Leber’s Hereditary Optic Neuropathy
- mitochondrial dx which produces bilateral optic neuropathy
- onset between 15-35 years
- vision loss of painless, central, and permanent. starts in one eye before involving the second (within weeks-months)
- hyperemia of optic nerve head, with edema and focal hemorrhage
