Notes 4A Flashcards
MDD diagnosis can be made after the occurrence of?
2 major depressive episodes that occurred at least 2 months apart
Serotinin receptors acted on for SSRI?
5-HT1A
Serotonin receptors that has vasoconstrictive role?
5-HT1B
Serotonin receptor that inhibits neuronal transmission/trigeminal neurogenic inflammatory peptide release
5-HT1D
Serotonin receptor that triptans work on?
5HT1D (inhibits neuronal transmission and trigeminal neurogenic inflammatory peptide release)
Metabolic abnormality that can be caused by SSRIs?
HypoNa
The main embryonal layer giving rise to the nervous system
ectoderm
From the ectoderm, what induces formation of the neural plate?
notochord
The notochord gives rise to?
The vertebral column
The neural plate forms the _____ at around 3-6 weeks gestation
neural tube
Any disturbance during 3-6 weeks gestation will lead to?
Neural tube defects (NTD)
Anencephaly
complete absence of both hemispheres of the brain, not compatible with life
Encephalocele
herniation of the neural tissues into a midline defect in the skull.
Appear as round, protuberant, fluctuant masses covered by an opaque membrane or normal skin
Most common location of encephalocele?
occipital area
Encephaloceles are assoc with what disorders?
Trisomy 18 and 13
Encephalocele vs Meningocele?
In meningocele, only the leptomeninges and CSF are herniated through the skull
Holoprosencephaly
failure of the prosencephalon to form the telencephalon and diencephalon results in failure of the formation of two distinct cerebral hemispheres
Seen in trisomy 13 and 18
After neurulation, the neural tube undergoes segmentation into 3 vesicles?
Prosencephalon
Mesencephalon
Rhombencephalon
Prosencephalon gives rise to?
telencephalon + diencephalon -> both cerebral hemispheres, thalamus and hypothalamus
Mesencephalon gives rise to?
midbrain
Rhombencephalon gives rise to?
pons, medulla and cerebellum
The neural crest cells (derived from the neural tube) gives rise to?
PNS
chromatin tissue of the adrenals and melanocytes
Corpus callosum develops by week?
17
abnormalities of the ______ lead to defects in the corpus callosum (agenesis or dysgenesis)
commissural plate
MRI sign for agenesis of the corpus callosum
Steer horn sign if coronal, or racing car sign if axial imaging
Cerebral hemispheres form from?
a single layer of epithelium surrounding the lateral ventricles (ventricular zone)
All 6 layers of the cortex are identifiable by week?
27
galactosemia: which deficiencies can cause it (3)? Most common?
1. Galactose - 1 - phosphate uridyltransferase (MC)
- galactokinase deficiency
- uridine diphosphate galactose 4 epimerase
Galactosemia: Sx, Dx and Tx
feeding issues, vomiting, diarrhea, hepatomegaly, cataracts (due to accumulation of galactitol)
Dx: urine shows reducing substances
Tx with galactose and lactose restriction
Pyruvate Dehydrogenase Deficiency: inheritance, sx
X linked
severe neonatal lactic acidoses with death, episodes of ataxia, nystagmus
Pyruvate Dehydrogenase Deficiency: Dx and Tx
elevated LA and pyruvate, low LA: pyruvate ratio
KGD (ketoglutarate decarboxylase) and thiamine
Phenylketonuria (PKU): deficient enzyme? sx and tx
phenylalanine hydroxylase deficiency (converts phenylalanine to tyrosine) leads to accumulation of phenylalanine which is eventually metabolized to phenyl-acetic acid which is responsible for the musty odor of sweat and urine.
developmental delay, microcephaly, seizures, hypotonia, musty odor of sweat and urine.
diet restriction of phenylalanine and low protein
Maple syrup urine disease: deficient enzyme? Sx? Tx?
branched chain keto acid dehydrogenase complex deficiency: leads to accumulation of branched chain amino acids (leucine, isoleucine and valine)
lethargy, poor feeding, hypotonia, 2-3 days of life a progressive encephalopathy develops with opisthotonus (spasm of the muscles causing backward arching of the head, neck, and spine).
low protein diet is tx
Glucose Transporter Type 1 Deficiency (GLUT-1) sx? dx? tx?
glucose usually crosses the BBB through this transporter, so basically no glucose in the CNS, sx and dx makes sense
epileptic encephalopathy, developmental delay, microcephaly
Dx: low CSF glucose and normal serum
Tx: KGD (alpha-ketoglutarate dehydrogenase)
Sacral agenesis (absence of the sacrum) is assoc with
maternal insulin dependent DM
myelomeningocele?
protrusion of the spinal cord and meninges through a bony defect
Associated findings in tuberous sclerosis (other than neurologic ones)?
- cardiac: rhabomyomas, arrhythmias (can cause embolic strokes)
- Renal: angiomyolipoma
- Pulmonary: lymphangiomyomatosis
- Ophtho: retinal hamartomas, macular lesions leading to vision loss, retinal detachment
Spina bifida occulta
defect in bony components along the posterior vertebral column.
Can be asx or present with conus medullaris/flium terminale
patient presents with a tuft of hair that sometimes develops into motor delay but not always
Lesch Nyhan Disease: inheritance and enzyme
X linked
deficiency of hypoxanthine guanine phosphoribosyltransferase (HGPRT)
leads to accumulation of purine and conversion to uric acid.
Lesch Nyhan Disease: sx and tx?
hypotonia, motor delay, neck and limb rigidity with dystonia, choreoathetotic movements, seizures, aggressive behavior, self mutiliation and progressive dementia.
purine restricted diet, hydration, allopurinol
Treatment for neuropsychiatric manifestation of Lesch Nyhan Disease?
Levodopa and tetrabenazine can have some benefit
Risk factors for neural tube defects?
maternal folate deficiency, maternal diabetes, retinoic acid exposure, ASM exposure (especially VPA and CBZ)
Dx of neural tube defects?
prenatal US, high maternal serum AFP (leaks from fetal CSF into amniotic fluid)
higher level correlates with NTD severity
Niemann-Pick: inheritance and defect for each type?
AR
Type A/B: sphingomyelinase deficiency, leads to accumulation of sphingomyelin
Type C: defect in cholesterol circulation, so cholesterol builds up in perinuclear lysosomes.
Niemann Pick Type A: involves what systems? sx? dx?
CNS and viscera
cherry red spot, massive hepatosplenomegaly
Bone marrow bx: vacuolated histiocytes with lipid accumulation called foam cells.
most do not survive past 3y
Niemann Pick Type B: involves? sx? dx?
purely visceral (no CNS)
massive hepatosplenomegaly and interstitial lung disease
may survive into adulthood
Bone marrow bx: vacuolated histiocytes with lipid accumulation called foam cells.
Niemann Pick Type C: dx and sx
vertical gaze apraxia
dx by Filipin test (demonstrates impaired ability of cultured fibroblasts to esterify cholesterol)
Fabry disease: inheritance and deficiency?
X linked
alpha galactosidase, leads to accumulation of ceramide trihexoside
Fabry Disease: sx and tx?
NEURO:small fiber neuropathy→ dysesethesias,
SKIN: angiokeratomas
also cardiac, renal, vascular involvement (stroke)
OPHTHO: corneal opacity
Tx with enzyme replacement therapy
Krabbe Disease: Inheritance and deficiency?
AR
Mutation in galactocerebrosidase gene → accumulation of galactocerebrosides
MRI for Krabbe Disease?
demyelination, WM disease sparing the U fibers
Histo for Krabbe?
globoid cells (PAS+ multinucleate macrophages with cytoplasmic accumulation of galactocerebroside)
Krabbe: sx?
3 forms
Infantile: opisthotonos and blindness
Juvenile: vision problems, muscle weakness, gait changes
Adult: spastic paraparesis, vision loss, neuropathy
Metachromatic Leukodystrophy: inheritance and deficiency?
AR
arylsulfatase (lysosomal enzyme) → accumulation of cerebroside sulfate
Metachromatic Leukodystrophy: sx?
Infantile: clumsiness, falls, slurred speech. May progress to loss of vision and hearing, neuropathy and deterioration of mental function
Juvenile: same but slower progression
Adult: behavioral changes, psychosis and dementia
Metachromatic Leukodystrophy: MRI
T2 hyperintense changes in periventricular and subcortical WM, sparing the U fibers
Gaucher Disease: inheritance and deficiency?
AR def of glucocerebrosidase → accumulation of glucocerebrosides
Gaucher: histo?
“Gaucher Cells” With Linear Cytoplasmic Striations
These Gaucher cells demonstrate the characteristic fibrillary or striated cytoplasm reminiscent of wrinkled tissue paper
Tay Sachs Disease (GM2): inheritance and deficiency?
AR
hexosaminidase A deficiency
Tay Sachs Disease (GM2): presentations
Typically in Ashkenazi Jews
CNS is the only affected system (in contrast to Sandhoff’s disease which is cause by def in hexosaminidase A and B, presents with hepatosplenomegaly as well)
Increased startle response, motor regression, spasticity, seizures, blindness (optic atrophy → cherry red spot on the macula)
GM1 gangliosidosis: inheritance and deficiency
AR
beta-galactosidase deficiency
GM1 gangliosidosis: sx
weakness, spasticity, seizures, psychomotor arrest, cherry red spot on macula
Summary Table of Lysosomal Storage Diseases
Syringomyelia vs hydromyelia
- synringomyelia: fluid-filled cavity within spinal cord that is separate form the central canal and lined by gliotic tissue.
- Hydromyelia: enlargement in the central canal itself, and the cavity wall is, therefore lined by ependyma
Chiari 1 vs Chiari 2
- chiari I: displacement of cerebellum and cerebellar tonsils downward through the foramen magnum + syringmyelia
- Chiari 2: Chiari 1 + myelomeningocele (downward displacement of cerebellum + brainstem displacement, hydrocephalus, and tectal plate formation).
Chiari 3
cerebellar herniation into cervical or occipital encephalocele
Jouberts Syndrome: what is it?
When there is cerebellar vermis hypoplasia with 4th ventricle enlargement, interpeduncular fossa and abnormal superior cerebellar peduncles
Joubert’s Syndrome: inheritance and sx
AR
developmental delay, ataxia, oculomotor abnormalities, resp issues
Joubert Syndrome: sign on MRI
Molar tooth sign
Other than Joubert Syndrome, what else has the molar tooth sign on MRI?
COACH syndrome
Cerebellar vermis hypoplasia, oligophrenia (congenital dementia), congenital ataxia, coloboma, hepatic fibrosis.
Foramen of Monro connects
lateral ventricles to third ventricle
Cerebral aqueduct connects
3rd ventricle to 4th ventricle
Infantile Syndromes of peroxisomal dysfunction (3)
Zellweger Syndrome
Neonatal adrenoleukodystrophy
Infantile Refsum Disease
Zellweger Syndrome (VLCFA): mutation and sx
peroxisome disorder affecting the WM, PEX genes
Causes a cerebro-hepato-renal syndrome
High forehead, large fontanelle, flat supraorbital ridges, hypertelorism, epicanthal folds, broad nasal bridge, micrognathia, flat occiput.
Typical feature: chrondrodysplasia with bony stippling of the patella
Septo optic dysplasia: what is it and mutation?
group of malformations that include hypoplasia/absence of septum pellucidum, optic nerve or optic chiasm, dysgenesis of the corpus callosum/anterior commisure, and fornix detachment from the corpus callosum.
Can have vision issues, ataxia, hydrocephalus
mutation in HESX1, homebox, SOX genes
Leighs Syndrome: What is it
Mitochondrial disease that causes subacute encephalomyelopathy
affects brainstem, thalamus, BG, cerebellum
- In infancy, they present with hypotonia, loss of head control, poor sucking, vomiting, irritability, seizures
- If onset > 1 y—> present with gait disturbance, cerebellar ataxia, dysarthria, psychomotor retardation, external ophthalmoplegia, dystonia, resp failure
Kearns-Sayre Syndrome: what is it
mitochrondrial disease that causes this triad
- progressive external ophthalmoplegia
- Onset <20y
- One of the following: short stature, pigmentary retinopathy, cerebellar ataxia, heart block, inc CSF protein >100
Parry Romberg Syndrome
loss of facial tissue, cartilage, bone leading to hemifacial atrophy, ipsilateral loss of eyelashes, eyebrows and scalp hair
Neuro sx: headaches, horner syndrome, seizures and hemiparesis
Von Hippel-Lindau: inheritance and deficiency
AD
mutation in VHL gene on chromosome 3 that encodes a tumor suppressor protein
Von Hippel-Lindau: sx
multiple retinal, cerebellar, and spinal hemangioblastomas
(also at risk for renal cell carcinoma)
