Notes 4b Flashcards
Periventricular nodular heterotopia: inheritance and deficiency
XR
FLNA mutation
Periventricular nodular heterotopia: what is it and sx
disorder of neural migration (neurons failed to migrate and remained in periventricular area)
Characterized by nodules of grey matter lining the ventricles and extending into the lumen
presents with seizures
Disorders of cell proliferation (2)
megalencephaly, focal dysplasia
Disorders of cell migration (3)
lissencephaly
cobblestone complex malformations
all heterotopias
Disoders of cortical organization (4)
polymicrogyria
focal cortical dysplasia with normal cell types
microdysgenesis
schizencephaly
L hemispheric hemimegalencephaly: sx and tx
enlargement of only one hemisphere
presents with cranial asymmetry, epilepsy, developmental delay, contralateral hemiparesis
Tx: hemispherectomy
Lissencephaly
smooth brain, less sulci/gyri
Miller-Dieker syndrome: what is it, mutation, sx
Classic lissencephaly
malformation of cortical development from abnormal cell migration, LIS1 gene
microcephaly, typical facies including micrognathia, low set ears, thin upper lip, short nose, prominent forehead, bitemporal hollowing
Gene assoc with X linked lissencephaly
DCX (codes for protein doublecortin)
Neuronal migration disorders (4)
lissencephaly
polymicrogyria
schizencephaly
focal cortical dysplasia
hepomelanosis of Ito: sx
neurocutaneous disorder
hypo-pigmented patches at birth that follow Blaschko lines (skin lines), best detected under UV light.
p/w seizures, microcephaly, eye stuff (cataracts, retinal detachments),
subcortical band heterotopia: mutation, what is it and sx
mutation in DCX on chromosome X in females (same mutation can lead to lissencephaly in males).
malformation of cortical neuronal migration, causes the formation of double cortex
seizures and developmental delay
Neurofibromatosis Type 1: inheritance, mutation and chormosome, presentation
AD
NF1: neurofibromin gene (tumor suppressor gene) on chromosome 17
Skin: cafe au lait spots
Eye: Lisch nodules (usually benign)
Bone: sphenoid wing dysplasia
Can undergo malignant transformation: plexiform neurofibromas
Plexiform neurofibromas?
Seen in NF1 that undergoes malignant transformation. Consists of schwann cells.
Causes skin hyperpigmentation, hypertrophy and thickening
Homocystinuria: inheritance, mutation/chrom, pres, tx
AR
cystathionine-beta-synthase deficiency, CBS gene on chromosome 21
causes elevation in blood and urine homocystine, methionine
Eye: ectopia lentis
Body: marfanoid habitus
vascular: intimal thickening of blood vessel walls → inc risk of thromboembolisms
Tx: daily pyridoxine, folate, B12, low protein diet
Most common urea cycle disorder? sx
OTC
ornithine transcarbamylase
leads to hyperammonemia, encephalopathy, resp alk
Down Syndrome: finding in eye?
Brushfield spots (white depigmentation seen in iris)
Rett Syndrome: mutation/chrom, findings
MECP2 gene on X chromosome (encodes methyl CpG branding protein 2, involved in DNA methylation)
Normal development with subsequent regression
Arrest of head growth → seizures and spasticity
Tuberous sclerosis can be from which mutations on which chromosome? inheritance?
AD
mTOR pathway mutation
TSC1 (hamartin, chromosome 9)
TSC2 (tuberin, chromosome 16)
Findings in Tuberous Sclerosis?
Skin: ash leaf, angiofibromas, ungal fibromas, shagreen patch
Brain: tubers (non-premalignant), SEGA(subependymal giant cell astrocytoma), subependymal nodules.
Psych: assoc with autism, ADHD, learning disabilites
Treatment for cortical tubers assoc with TS?
Vigabatrin
Treatment for SEGA (assoc with TS)?
rapamycin (mTOR inhibitor)
surgical resection
Prader Willi Syndrome: mutation and sx
Paternal inherited chromosome 15 mutation
hypotonia, short stature, dysmorphic face, hypogonadism, hyperplasia and obesity
Angelman’s Syndrome: mutation and sx
maternally inherited chromosome 15 mutation
intellectual disability, microcephaly, intractable epilepsy, ataxia, inappropriate laughter
“happy puppet syndrome” wide based stance and flailing of the arms at the sides during ambulation
Williams Syndrome: mutation and sx
Chromosome 7 deletion
ID, happy affect, congenital heart defects, “elfin” facies
Cri-du-chat: mutation and sx
Chromosome 5 deletion
cat like cry, ID, presence of epicanthal folds, hypertelorism
Dandy Walker malformation
cerebellar vermis hypoplasia, 4th ventricle cystic dilation, elevation of torcula and tentorium cerebella
can cause hydrocephalus and macrocephaly
Canavan’s Disease: inheritance/mutation, sx
AR
deficiency in aspartoacylase, leading to accumulation of N-acetylaspartic acid
common in ashkenazi jews
Poor tracking, psychomotor arrest/regression, feeding difficulties, hypotonia
MRI findings in Canavans disease
diffuse symmetric T2 hyperintensities in the WM with characteristic involvement of U-fibers
Alexander disease: mutation/chromsome, sx
mutation in GFAP on chromosome 17
seizures, dev delay, spasiticity, bulbar findings as you get older, dysautonomia, ataxia
MRI findings in Alexander disease?
diffuse WM hyperintensity, predominantly in frontal lobe and anterior cerebral regions with involvement of u-fibers
Tadpole sign on sagittal MRI (dramatic thinning of upper C spine)
Histology for Alexander disease
Rosenthal fibers (assoc with severe myelin loss)
Sturge Weber Syndrome
Skin: port wine angioma of the face
Brain: seizures, contralateral hemiparesis, AVMs, venous thromboembolisms, leptomeningeal capillary-venous malformations
Cobb’s syndrome?
variant of sturge weber in which cutaneous angiomas occur in dermatome responding to spinal dural angioma
Glycine encephalopathy (nonketotic hyperglycemia): inheritance and sx?
AR
few hours after birth, poor feeding and hiccups → encephalopathy and seizures. If survives the acute phase, will have profound ID and intractable epilepsy
Dx of Glycine encephalopathy (nonketotic hyperglycemia)
high CSF glycine
both serum and CSF levels are elevated. ratio of CSF to plasma is >0.6, where usually it is 0.4 or lower
MRI in glycine encephalopathy (nonketotic hyperglycemia)?
hypoplastic or absent corpus callosum, gyral malformation or cerebellar hypoplasia
EEG in glycine encephalopathy (nonketotic hyperglycemia)
burst suppression or hypsarrhythmia
NF2: mutation and inheritance?
AD
mutation in Merlin gene (tumor suppressor gene on chromosome 22)
NF2: characteristic feature?
bilateral schwannomas on CN8
Epidermal nevus syndrome (ENS): characterized by?
epidermal nevi (raised patches of hyperpigmentation) + neurologic manifestation
Tangier Disease: inheritance and mut
AR familial neuropathy
mutation in adenoids triphosphate cassette transporter (ABCA1 gene), results in a deficiency of HDL with very low cholesterol and high triglyceride concentration
Tangier Disease (familial neuropathy) exam findings?
accumulation of cholesterol esters in tonsils, peripheral nerves, cornea, bone marrow
typical finding is enlarged orange tonsils, loss of pain/temp sensation
Menke’s disease: exam finding
“kinky hair syndrome”
presence of brittle and lightly pigmented hair (pili torti), hyperplastic skin and thin or absent eyebrows
MELAS (mitochondrial encephalopathy, lactic acidosis and strokes): features
normal at birth, around 2-10 yo p/w seizures, strokes, vomiting, weakness
Stroke like episodes: transient weakness, altered consciousness
MELAS (mitochondrial encephalopathy, lactic acidosis and strokes): labs
LA in blood and CSF
MELAS (mitochondrial encephalopathy, lactic acidosis and strokes): muscle bx
ragged red fibers
PKAN (pentothenate kinase-associated neurodegeneration): inheritance and mutation
PKAN2 gene
AR
PKAN (pentothenate kinase-associated neurodegeneration): MRI
eye of the tiger sign
hyperintensity in BL medial globus pallidus surrounded by hypointensity
Neuro- Lyme disease: dx
B. burgdorferi in the CSF and PCR
Neuro Lyme disease: weird finding
bilateral bells in some cases
If lyme is causing neuro sx, tx?
ceftriaxone or penicillin G
Infectious cause of cavernous sinus thrombosis?
Mucormycosis
Neuro sx assoc with West Nile virus
encephalitis, cranial neuropathies, tremors, can also invade spine and cause areflexia and flaccid weakness
cryptococcal meningitis: dx?
elevated OP on LP and (+) india ink smear
cryptococcal meningitis tx?
aphoterecin B + flucytosine for 2-3 w
CNS toxoplasmosis: MRI findings
multiple ring enhancing lesions with surrounding edema
Tx for CNS toxo?
sulfadiazine + pyrimethamine
Primary CNS lymphoma in AIDS is assoc with? Tx for Primary CNS lymphoma?
EBV
tx is steroids
Most common causes of bacterial meningitis in neonates?
E coli
Listeria
Group B strep
Pott’s Disease?
TB that spreads to the spine (usually T spine)
2 variants of leprosy?
spreads through resp system but affects the peripheral nerves typically
Lepromatous variant: causes skin and systemic manifestations
tuberculoid variant: asymmetric neuropathies, more localized skin lesions (happens in patients with better immunity), can resemble mononeuritis multiplex
Treatment for leprosy?
rifampin, dapson, clofazimine
Neuro sx in Whipple disease (tropheryma whipplei)? Dx?
dementia, supranuclear ophthalmoplegia, ataxia, oculomasticatory myorythmia, meningitis
Dx: positive PAS (periodic acid schiff)
CJD signs on MRI?
pulvinar sign (DWI hyperintensity in pulvinar nucleus of the thalamus)
Hockey stick sign: anterior and putamen hyperintensity
SSPE: complication of?
measles
EEG findings in SSPE?
periodic slow wave complexes at regular interval
MRI findings in SSPE?
hyperintensity in the grey and subcortical white matter greater in the posterior regions
Micro finding in aspergillus?
septate hyphae that tranche at acute angles
MRI findings in brain abscesses for T1? FLAIR? DWI?
T1: hypointense center, capsule that enhances with contrast surrounded by hypointense edema
FLAIR: hyperintense edema
DWI: restricted diffusion in the center (characteristic and differentiates from mets or primary brain tumors)
