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Neuro Recap > Child Neuro > Flashcards

Child Neuro Flashcards

1
Q

Ectoderm

A

Nervous system

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2
Q

Notochord

A

layer of mesodermal cells in contact with ectoderm induces formation of the neural plate. Later gives rise to spinal cord!

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3
Q

Neurulation

A

proliferation/migration of ectodermal cells for fusion of neural plate in a specific pattern forming fusion reaching the neuropore in an anterior to posterior direction–> neural tube formed

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4
Q

Mesodermal cells of notochord

A

ventral aspect of neural tube 2/2 sonic hedgehog protein

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5
Q

Neurulation process

A

occurs 3-6 weeks gestation and failure of crucial processes leads to NTD failing to fuse at each site results in specific defects.

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6
Q

Abnormal rostral fusion

A

anterior neuropore leads to encephalocele or anencephaly

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7
Q

Abnormal caudal fusion

A

posterior neuropore leads to spina bifida

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8
Q

After neuralation?

A

3 different segments form the prosencephalon, mesencephalon and rhombencephalon.

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9
Q

Prosencephalon

A

subsequently forms the telecephalon which gives rise to the cerebral hemispheres and diencephalon forming the hypothalamus/thalamus

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10
Q

Mesencephalon

A

gives rise to midbrain

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11
Q

Rhombencephalon

A

brainstem (pons/medulla) and cerebellum

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12
Q

Neural crest cells

A

form the peripheral nervous system derived from neural tube after it fuses. Also adrenal medulla/melanocytes

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13
Q

Galactosemia

A

autosomal recessive. 3 enzymes: galactose-1-phosphate uridyltransferase deficiency, galactokinase deficiency
Present with feeding diff, vomiting, jaundice, hepatomegaly, failure to thrive, hypotonia, cataracts d/t glactitiol, developmental delay, ataxia, tremor.
Dx of reducing substance in urine after feeding
Rx lactose/galactose restricted from diet

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14
Q

Pyruvate dehydrogenase deficiency

A

Oxidative decarboxylation of pyruvate to carbon dioxide and acetyl coenzyme A. X-linked gene. Since brain derives energy primarily from glucose oxidation, neurologic dysfunction manifests ranging from lactic acidosis, ataxia, nystagmus, lethargy, areflexia, hypotonia
Rx ketogenic diet

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15
Q

NF1

A

normal cognition or mild developmental delay, renal artery stenosis, pheochromocytoma, moyamoya, intracranial aneursyms, macrocephaly

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16
Q

Glut-1 deficiency

A

transportation past BBB. Manifest with epileptic encephalopathy with infantile onset seizures, developmental delay, microcephaly
Rx ketogenic diet

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17
Q

Phenylketonuria (PKU)

A

deficiency of phenylalanine hydroxylase converting phenylalanine to tyrosine leading to accumulation–> metabolized to phenylpyruvic acid/phenylacetic acid which gives it a musky smell. Children are blond hair, blue eyes, pale skin given lack of melanin pigment production.

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18
Q

PKU presentation?

A

appear normal at birth, however if untreated may lead to cognitive delays, microcephaly, seizures, hypotonia

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19
Q

Maple syrup urine disease

A

autosomal recessive. alpha ketoacid dehydrogenase complex deficiency leading accumulation of branched chain acids (leucine, isoleucine, valine)
Presentation includes progressive encephalopathy, hypotonia, opisthotonus then eventually coma and death
Rx low protient diet

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20
Q

Sacral agenesis

A

absence of sacrum rather than absence of sacral spinal cord. Associated with insulin-dependent diabetes

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21
Q

Tuberous sclerosis complex

A

Cardiac rhabdomyomas, most regress over time with manifestations including heart failure due to obstruction or cardiomyopathy,arrhtmias or stroke. Surveillance with periodic echos.

Renal angiomyolipomas benign tumors consisting of vessels, smooth vessel

Lymphangiomyomatosis of chest

Retinal hamartomas

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22
Q

Propionic acidemia

A

hematologic manifestations such as pancytopenia may occur. Autsomal recessive. Deficiency of propionyl-CoA carboxylase. Appear normal at birth, then develop hypotonia, dehydration, metabolic acidosis , hepatomegaly, seizures, incranial hemoorhage
Rx protein restriction , carnitine, biotin

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23
Q

Lesch-Nyhan disease

A

X-linked. Deficiency of hypoxanthine gaunine phosphoribiosyltranserase. Purine metabolism. Gene HPRT1, leading to uric acid accumulation. Leads to choreoathetotic movements.

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24
Q

Neiman Pick type A

A

Spingomyelinase deficiency leading to accumulation of sphingomyelin. Autosomal recessive. Involves CNS and manifests infancy with cherry red spot, hepatosplenomegaly. Histology shows vacolated histiocytes w/lipid accumulation called foam cells.

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25
Q

Neimann Pick type C

A

defects in intracellular cholestrol circulation accumulating in lysosomes

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26
Q

Metachromatic leukodystrophy

A

autosomal recesive disorder. Deficiency of lysosomal enzyme arylsulfatas A with accumulation of sulfatide resulting demyelination
MRI shows T2 hyperintense signal changes in periventricular and subcortical white matter, sparing U fibers

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27
Q

Krabbe disease

A

deficiency of glaactosylceramidase

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28
Q

Tay Sachs disease

A

deiciency of hexosaminidase

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29
Q

Hydromyelia vs syringomyelia

A

fluid filled cavity vs central canal diltation

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30
Q

Sialdosis

A

myoclonic epilepsy. Lysosomal storage disorders. Coarse facial features, skeletal abnormalities, psychomotor retardation. Deficiency of lysosomal alpha n-acetyl neuraminidase. Type I - cherry red spot develops in adulthood. Type II child form, severe neuro deficits

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31
Q

Jouberts syndrome

A

autosomal recessive. Molar tooth sign which results from cerebellar vermis hypoplasia with 4th ventricle enlargement, abnormal superior cerebellar peduncles.
Ataxia, oculomotor apraxia, resp diff,

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32
Q

Fabrys

A

X linked disorder deficiency of alpha-galactosidase resulting in accumulation of ceramide trihexoside.
small fiber neuropathy, autonomic dysfunction, renal failure, cardiomyopathy. Lysosomal storage of birefringent lipids on EM.

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33
Q

GM 1 gangliosidosis

A

B-galactosidase deficiency

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34
Q

Neuronal ceroid lipofuscinosis

A

autosomal recessive disorders characterized by progressive psychomotor retardation, seizures, blindness.

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35
Q

Congential aqueductal stenosis

A

narrowing of cerebral aqueduct that connects the third and fourth ventricle, disorder of neurulation

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36
Q

Zellwegers syndrome

A

peroxisomal disodrer in which white matter is involved, Very long chain fatty acids. Pachygyria or polymicrogyria

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37
Q

Fabry disease

A

X linked. Deficeincy of lysosomal enzyme alpha galactosidase. Purplish aniogkeratomas, small fiber neuropathy, stroke, multiple organ failure

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38
Q

Hereditary hemorrhagic telangiectasia

A

autosomal dominant. Recurrent epstaxis. Mutiple AVMs or cerebral embolisms

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39
Q

Septo-optic dysplasia

A

absence of septum pellucidum, optic nerve/chiasm, corpus callosum. Associated with lobar holopresechephaly.

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40
Q

Adrenoleukodystrophy

A

X-linked. ABCD1 gene mutation. Impaired transport of very long chain fatty acids into peroxisomes, preventing beta-oxidation with subsequent accumulation. Presents with bulbar sxs, spasticity, adrenal insufficiency. senosory neuropathy, elevated ACTH

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41
Q

Arrhinencephaly

A

agenesis of olfactory bulb/tract

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42
Q

Leighs syndrome

A

subacute encephalomyelopathy. Mitochondrial disorder. myoclonic jerks. Elevated CSF/blood lactate levels. MRI brain b/l symmetric hyperintense T2 signals of brainstem/basal ganglia

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43
Q

Kearns-Sayre syndrome

A

Mitochondrial DNA deletion. Triad of progressive external ophthalmoplegia, onset before 20, short stature, cerebellar ataxia, heart block

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44
Q

Congenital disorders of glycosylation (CDG)

A

Autosomal recessive. Affect multiple organs. Developmental delay/dysmorphic features. Abnormal processing of glycans of glycoproteins. Inverted nipples, fat pads in buttocks is distinctive.
Dx carbohydrate-deficient transferrin in serum/CSF

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45
Q

Corpus callosum development

A

commissural plate develops and abnormalities lead to agenesis/dysgenesis. Can be seen in aicardis.

46
Q

Cerebral hemispheres embryology

A

newly formed neuons migrate from a scaffold from radial glia to the cortical plate

47
Q

Phakomatoses

A

group of disorders with dysplastic lesions with tendency for tumor formation (NF, TSC, Sturge weber, hypomelanosis of Ito

48
Q

Neurocutaneous melanosis

A

congenital cutaneous lesions that are abnormally pigmented such as giant heair pigmented nevi in association with leptomeningial melanosis

49
Q

Parry romberg syndrome

A

progressive loss of facial tissure leading hemifacial atrophy. Present with horners, szs, hemiparesis

50
Q

Maffucci syndrome

A

mutiple enchondromas (cartilage tumors) with skin findings of vitiligo, hyperpigmented patches, cafe au lait spots. Associated with brain gliomas.

51
Q

Von hippel-Lindau

A

mutiple retinal, cerebellar and spinal hemangioblastomas occur. Renal cell carcinomas. VHL gene. No cutaneous features.

52
Q

Periventricular nodular heterotopia

A

neuronal migration disorder characterized by nodules of gray matter lining the ventricles extending to the lumen. MC presentation is seizures.

53
Q

4 categories of cortical developemental malformations?

A

disorders of cell proliferation, migration, cortical organization and malformations of cortical development

54
Q

Neuronal proliferation disorders?

A

megalencephaly, focal cortical dysplasia

55
Q

Neuronal migration disorders?

A

lissencephaly (agyria, pachygyria and subcortical dysplasia) , periventricular nodular hetrotopia

56
Q

Cortical organization disorders?

A

polymicrogyria, focal cortical dysplasia, schizencephaly

57
Q

Hemimegalencephaly

A

contralateral hemiparesis

58
Q

Microcephaly

A

head cirucumference more than 2 standard deviations below the mean. Causes include inutero infections, toxin exposure, hypoxia

59
Q

Macrocephaly

A

head circumference more than 2 SD above mean. Megalencephaly causes include storage disease (tay sach, canavan disease, alexander disease, sotos syndrome. Considered abnormality of neuronal proliferation.

60
Q

Lissencephaly

A

lissencephaly (4 layer vs normal 6 layer) which is a malformation of cortical developement from abnormal neuronal migration resulting in impaired formation of gyri and reduced cortical gyration.

61
Q

Cobblestone lissencephaly

A

neuronal migration disorders (not cortical organization) in which cortical gray matter has reduced number of gyri and sulci that appear like cobblestones with reduced white matter with associated hydrocephalus.

62
Q

Miller Dieker syndrome

A

form of lissencephaly variant characterized by microcephaly, small jaw, low set ears, thin upper lip, short nose, prominent forehead. Intractable seizures, quadriparesis and spasticity. Microdeletions on LIS gene

63
Q

Hypomelanosis of Ito

A

neurocutaneous disorder. hypopigmented streaks or patches that are present at birth and follow skin lines forming specific patterns such as a V line. Associated with seizures and cataracts.

64
Q

Subcortical band heterotopia “double cortex”

A

cortical development malformation (neuron migration disorder). Relatively normal cortex with an underlying band of white matter, underneath which is a band of gray matter. Encodes protein doublecortin, involved with microtubule organization and stabilization similar to lissencephaly

65
Q

NF1

A

cutaneous manifestations of cafe au lait spots vs ashleaf which are hypopigmented and seen in TSC, neurofibromas, axillary freckling. Lisch nodules, optic gliomasSeen on chromosome 17q11.2

66
Q

Legius syndrome

A

just like NF1, however NOT associated with optic gliomas, neurofibromas, lisch nodules or risk of malignancy

67
Q

Walker-warburg syndrome, fukayama muscular dystrophy and muscle eye brain disease

A

Cobblestone Lissencephaly spectrum. autosomal recessive syndromes sharing clinic features including microcephaly, global developmental delay, epilepsy, hypotonia, muscular dystrophy

68
Q

Homocystinuria

A

cystathionine-B-synthase deficiency. Elevated homocystine, homocysteine, methionine levels. Vit b6 response variant. Marfanoid habitus, tall, thin, pectus carinatum,
Rx Vit B6/low protein diet/folate/b12

69
Q

Schizencephaly

A

cleft that extends from the pial surface to the ventricle ependyma and lined with white matter

70
Q

Lisch nodules

A

iris melanocytic hamartomas (NF1) not found in legius syndrome!

71
Q

Periventricular nodular heterotopia

A

Most common heterotopia. result from abnormal neuronal migration. FLNA gene involved in cytoskeleton stabilization and cell migration impeding attachment of neurons to the radial glia. Epilepsy is common manifestation. X linked dominant.

72
Q

Plexiform neurofibromas

A

consist of schwann cells and fibroblasts, leading to hypertrophy, hyperpigmentation thickening of skin. Can transform to malignancy

73
Q

Ornithine transcarbamylase (OTC)

A

Mosst common urea cycle disorder. X linked recessive. Caused by OTC gene mutation. Hyperammonemia, encephalopathy and respiratory alkalosis. Ammonia leads to glutamine accumulation leads to astrocyte swelling/edema High ammonia levels, normal anion gap and glucose level
Rx Low protein diet, arginine supplementation except for arginase deficiency

74
Q

Arginase deficiency

A

Urea cycle disorder. No newborn sxs compared to others.

75
Q

Polymicrogyria

A

cortical organization defect. Excessive abnormal gyri that are small and separated y shallow sulci.

76
Q

Porencephaly

A

Cleft of schizencephaly is lined uniformly with gray matter. Proencephalic cysts are CSF-filled cysts most often result from in utero hypoxic insult.

77
Q

NF2 associated with?

A

schawannomas and epndymomas

78
Q

Down syndrome

A

frontal lobes small and underdeveloped. Varying degrees of intelligence . Brusfield spots.

79
Q

Pataus syndrome

A

Trisomy 13. Microcephaly, microphthalmia, iris coloboma, low set ears, cleft lip/palate, polydactyly

80
Q

Trisomy 18

A

microcephaly, rocker bottom feet umbilical hernia

81
Q

Retts syndrome

A

motor and cognitive regression with eventual severe disability. Mutation in MECP2 gene involved with metyhlating DNA

82
Q

TSC

A

angiofibromas of the nose, ash leaf spots, retinal hamartomas, ungual fibromas, cortical dysplasias, shagreen patch, subependymal nodules and astrocytomas. Autosomal dominat with variable penetrance. Hamartin/Tuberin form together neurocutaneous disorder.

83
Q

Fragile X syndrome

A

most common form of intellectual disabilty. Expansion of CGG trinucleotide repeat on FMR gene. Elongated face, high forhead, elongated jaw, protuberant ears and enlarged testes with varying intellectual disability in males.

84
Q

Metyhlmalonic acidemia

A

autosomal recessive. Deficiency of methylmalonyl-CoA mutase normally catalazes succinyl-CoA. Defect leads to accumulation of propionic acid/metylmalonic acid causing metabolic acidosis, hyperglycemia, hyperammonemia.
Rx B12, protein restriction, carnitine

85
Q

Biotinidase deficiency

A

BTD gene mutation leading to biotin deficiency due to inability to recycle biotin and 10-30% enzyme activity. Manifest as seizures, hypotonia, ataxia, developmental delay, hearing, vision loss, spastic paraparesis, alopecia. Ketoacidosis, hyperammonemia, organic aciduria

86
Q

Dandy-walker malformation

A

cerebellar vermis hypoplasia, fourth ventricular cystic dilation and elevation of tenorium cerebelli, posterior fossa enlargement and hydrocephalus are common.

87
Q

TSC uncommonly associated with what type of tumor?

A

Subependylmal giant cell astrocytoma (SEGA). Low grade w/sxs of mass effect and ventricular obstruction

88
Q

Betz cells

A

upper motor neurons of V Motor Cortex layer.

89
Q

Gaucher disease

A

autosomal recessive. Glucocerebrosidase deficiency leadin to lysosomal accumulation of glucocerebrosides in macrophages “wrinkeld tissue paper” Associated hepatosplenomegaly, spasticity, ataxia, limited horizontal gaze, retardation.

90
Q

Cortical tubers

A

cortical hamartomas, predominantly composed of astrocytes and demyelinated axons. Do not grow. Most common cause of infantile spasms. Quantity correlate iwth cognitive function or seizures unlike subependymal nodules.
Rx Vigabatrin

91
Q

Tay Sachs

A

hexosaminidase A deficiency. GM2 gangliosidosis vs GM1 caused by b-galactosidase deficiency. HEX A mutation affecting CNS only vs HEX A/B in sandhoff disease which causes visceralmegaly. Increased startle response , motor regression, spasticity, cherry red spot with optic atrophy, seizures

92
Q

Subependymal nodules vs SEGA?

A

nodules calcified and dont enchance unlike SEGA

93
Q

Canavan disease

A

autosomal recessive disorder. Deficiency of aspartoacylase leading to accumulation n-acetylaspartic acid in the brain. ASPA gene mutation. Sxs poor fixation and tracking and MEGALENCEPHALY PRESENT
Dx urine N-acteylaspartic acid elevated. MRI showing characterist involvment of the U fibers!

94
Q

Sturge weber syndrome

A

cutaneous angioma of face (port-wine nevus) often occuring at trigeminal distribution. Associated features ipsilateral leptomeningeal enhancement affecting parietal/occipital lobes. CT showing gyral calcifications

95
Q

NF1

A

NEUROFIBROMIN gene mutation on chrosome 17, which is a tumor suppresor protein which inhibits RAS involved in cell proleferation.

96
Q

NFII

A

MERLIN gene on chrosome 22 which encodes merlin which is a cytoskeeltal protein involved in cell growth control .

97
Q

Glycine encephalopathy

A

corpus callosum agenesis, high CSF glycine levels. Hypotonia, myoclonic seizures, respiratory failure.
Rx sodium benzonate to reduce levels.

98
Q

Krabbe disease

A

Galactocerebrosidase defiency leading to accumulation of galactocerebrosides in macrophages of the white matter in CNS, leading to formation globoid cells and demyelination due to its main role of myelination, Sparing U fibers.

99
Q

NF2 criteria

A

bilateral schawannomas, unilateral schwannoma with a first degree relative or associated meningioma. MERLIN gene mutation on chrosome 22

100
Q

Schwannomatosis

A

occurence of multiple schwannomas affecting various CNs, but not CN VIII.

101
Q

GM1 gangliosisdosis

A

accumulate in brain and viscera. Autosomal recessive.
lysosomal enzyme B-galactosisdase deficiency. Present with incooridination, weakness, spasticity, seizures, cherry red spot, dysmorphic features.

102
Q

Alexanders disease

A

progressive disorder of astrocytes. GFAP mutations. Megalencephaly, developmental delay, seizures, spasticity and qaudriparesis. MRI brain diffuse white matter changes involving U fivers. Rosenthal fibers on histo.

103
Q

Pelizaeus -Merzbacher disease

A

hypomyelinating leukodystrophy. X linked recessive. PLP gene mutation essential for myelination. Presents with pendular nystagmus, ataxia, spasticity, laryngeal stridor. MRI diffuse hypomyelination. “tigroid appearance”

104
Q

Hunters syndrome (MPS III)

A

X linked. Mucopolysaccharidosis (MPS) or sanfilippo syndrome. Idorante sulfatase deficiency. Accumulation of heparan sulfate. Impaired lysosomal degradation of glucosaminoglycans which are usually autosomal recessive except for hunters.

105
Q

Hurlers syndrome (MPS I)

A

MPS type I. L idoronidase deficiency. Accumulatoin of both dermatan and heparan sulfate.

106
Q

Sanfilipo syndrome (MPS III)

A

accumulation of heparan sulfate only. Intellectual disability mainly.

107
Q

Epidermal nevus sydnrome

A

epidermal nevi and neurologic manifestations. Slightly raised patches of hyperpigmenetation present at birth. May include intellectual disabilty, seizures, hemimegalencephaly. Increased for malignancy. Iris colobomas. Beckern nevus and proteus.

108
Q

acute intermittent porphyria

A

given lack of cutaneous manifestations and absence of coproporphyrin III. Attacks will show elevated aminolevulinic acid (ALA) and porphobilinogen (PBG). Can be triggered by barbiturates, solfonamides, infection, keto diet. Radial nerve wrist drop is MC. Present with seizures, abdominal pain

109
Q

Tangier disease.

A

Autosomal recessive familial neuropathy. ABCA1 gene mutation resulting in deficiency of HDL leading cholestryl accumulation in tonsils, peripheral nerves, cornea. ENLARGED ORANGE TONSILS and sensory peripheral neuropathy.

110
Q

Menkes disease

A

disorder of intracellular copper transport. Brittle coarse, lightly pigmented hair, hyper elastic skin, thin/absent eyebrows. Seizures, developmental delay, vasculopathy, sub dural hematomas/hygromas. X linked recessive disorder of ATP7A gene mutation, copper transporter vs ATP7B gene in autosomal recessive wilsons disese

111
Q

Mitochondrial encephalopathy, lactic acidosis and strokes (MELAS)

A

MTTL1 gene. Stroke like episodes occur, migraine headaches, growth retardation, progressive deafness. MRI multifocal infarcts not correlating to vascular territory. Lactate level is elevated in blood/CSF.

112
Q

Abetalipoproteinemia

A

autosomal recessive disorder. Microsomal triglyceride transfer protien (MTTP gene). Results in fat malabsorption and ADEK vitamins. Vitamin E deficiency is most pronounced with subacute dorsal column degeneration.

Neuro Recap (6 decks)

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