Developmental Diseases of the Nervous System Flashcards
Pediaaaaaa Neuroooooo
Hydranencephaly is hydrocephalus + ?
HCP + destruction or failure of development of parts of the cerebrum
A focal developmental defect in the wall of the cerebral mantle that is due to the localized failure of evagination is _______
Schizencephaly
Differentiate macrocephlay from macroencephaly.
Macrocephaly is enlargement of the head
Macroencephaly is a subtype characterized by a large head with normal or only slightly enlarged ventricles indivative of advancing metabolic disease like Alexander, Canavan and Tay sachs disease
The following neuroradiologic terms all pertain to what pathology: moose head, race car and bat wing
Corpus callosum agenesis
What kind of craniostenoses results from affected:
- Lambdoid and coronal sutures
- Sagittal suture
- Coronal suture
- Lambdoid and coronal sutures: tower skull, oxycephaly, turricephaly, acrocephaly
- Sagittal suture: scaphocephalic long and narrow head
- Coronal suture: Brachycephalic, wide and short head
When the maximum length of the skull is in the diagonal plane rather than the sagittal plane what type of craniosynostosis results?
Plagiocephaly
What tumor has a tigroid appearance on MRI?
Lhermitte-Duclos type of cerebellar gangliocytoma
What disorder of neuronal migration results from the mutation of the following genes:
- SHH
- TSC1 (hamartin) and 2 (tuberin)
- FCMD (fukutin)
- SHH: Holoprosencephaly, Lissencephaly
- TSC1 (hamartin) and 2 (tuberin): Tuberous sclerosis, heterotropia
- FCMD (fukutin): Fukuyama muscular dystrophy, heteroropia– will also have cobblestone lissencephaly
What are prenatal markers of anencephaly?
Elevated alpha fetoprotein and acetylcholinesterase in the amniotic fluid at 15-16 weeks
What would the brain of baby with one eye and no nose look like?
Holoprosencephaly– two cerebral hemispheres form a single telencephalic mass
What are the components of the Dandy walker syndrome?
- Cystic enlargement of the 4th ventricle
- Vermian hypoplasia
- +/- HCP
- +/- agenesis of the corpus callosum with cortical dysgenesis
RELN mutation causes lissencephaly with?
Cerebellar hypoplasia
ARX mutation is assocaited with X linked lissencephaly and?
Agenesis or the corpus callosum and hypogonadism
What are the 3 diseases associated with a cobblestone brain? Nodularity of the pial surface.
- Fukuyama musular dystrophy fukutin
- Muscle eye brain disease POMGNT1 gene
- Walker Warburg syndrome
(Lissencephaly, cortex, meninges and eyes fail to differentiate normally) POMT1 gene
All genes are for glycosyltransferase
What syndrome?
Craniofacial dysostosis, proptosis with shallow orbits, midline facial hypoplasia and short upper lip, malformed auditory canals and ears, moderate mental retardation
Crouzon syndrome
What type of dwarfism?
- AD, Hemihypertrophy
- Bird head, severe retardation , RAD3-realted protein mutation
- AR, DHCR7 mutation, microcephaly, ptosis, hypospadias
- AD, CREB binding protein defect, Grimacing smile, cataracts
- Generalized hirsutism and synophrys (eyebrows that meet across midline)
- AD, Hemihypertrophy: Russel silver syndrome
- Bird head, severe retardation , RAD3-realted protein mutation: Nanocephalic dwarphism
- AR, DHCR7 mutation, microcephaly, ptoris, hypospadias: Smith Lemli Opitz syndrome
- AD, CREB binding protein defect, Grimacing smile, cataracts: Rubinstein Taybi syndrome
- Generalized hirsutism and synophrys (eyebrows that meet across midline): De lange syndrome
When does the fusion of dorsal midline structures of the primitive neural tube take place?
First 3 weeks of post conceptional life
What is an eventration of brain tissue and its coverings through an unfused midline defect in the skull?
Encephalocoele
Differentiate spina bifida occulta VS meningocoele VS meningomyelocoele
SBO: cord inside canal, no external sac, subcutaneous lipoma or dimple or wisp of hair
Meningocoele: Dura and arachnoid protrusion
Meningomyelocoele: cord with the cauda equina is extruded
Unexplained meningitis with a tuft of hair at the back should prompt search for?
Sinus tract
What are the three most consistent anomalies that are associated with a Chiari Malformation?
- Extension of the tongue of cerebellar tissue posterior to the medulla and cord that extends into the cervical spinal canal
- Caudal displacement of the medulla and inferior part of the 4th ventricle into the cervical canal
- Frequent but not invariable association with syringomyelia or a spinal developmental abnormality
Describe the details of the different types of chiari malformation: Type 1 Type 2 Type 3 Type 4
Type 1: Cerebellar descent without meningomyelocele
Type 2: Cerebellomedullary descent with meningomyelocele
Type 3: High cervical or occipito cervical meningomyelocoele with cerebellar herniation
Type 4: Cerebellar hypoplasia
Type 0: no descent just “full” posterior fossa but with sxs
Type 1.5: Cerebellar descent with additional caudal brainstem displacement
What is them most common form of inherited mental retardation?
Fragile X syndrome
Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behavior such as fidgeting or impulsive actions. They may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have features of autism spectrum disorders that affect communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with fragile X syndrome.
Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty.
Identify which chromosomal dysgeneses is involved:
- Trisomy 13: death in childhood
- Trisomy 18: death at infancy
- Abnormal cry like a kitten, severe mental retardation, micrognathia
- XXY: Males with sparse facial and body hair, gynecomastia, small testicles
- XO: Female Webbed neck, short stature, mild dev delay
- Marked dilation of the occipital horns of the lateral ventricles with thickening of the overylying rim of cortical gray matter and thinning of white matter– spasticity, seizures– mosaicism for trisomy 8
- Patau Trisomy 13: death in childhood– ndividuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia).
- Edwards Trisomy 18: death at infancy– Affected individuals may have heart defects and abnormalities of other organs that develop before birth. Other features of trisomy 18 include a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers
- Cri-cu di chat syndrome Deletion in short arm of chromosome 5: Abnormal cry like a kitten, severe mental retardation, micrognathia
- Klinefelter syndrome: XXY: Males with sparse facial and body hair, gynecomastia, small testicles
- Turner syndrome: XO: Female Webbed neck, short stature, mild dev delay
- Colpocephaly: Marked dilation of the occipital horns of the lateral ventricles with thickening of the overylying rim of cortical gray matter and thinning of white matter– spasticity, seizures– mosaicism for trisomy 8
Identify which chromosomal dysgeneses is involved:
- Unstable repeat sequence in the CGG of X chromosome: Most common inherited form of dev delay, 1 in 1500 male births, 10% with severe dev delay, enlarged testes
- Combination of cerebral maldevelopement with cardiovascular abnormalities like supravalvular aortic stenosis traced to a microdeletion on chromosome 7
- At the first year, dev delay, obesity, hyperphagia, hypogonadism deletion in 15q11-q13
- Maternally inherited single gene defect, dev delay, inappropriate laughter, microcephaly, long tongue, thin upper lip,: HAPPY PUPPET SYNDROME
- Dominant defect on X chromosome, at 6-18 months slow steady regression in motor skills and mental abilities
Identify which chromosomal dysgeneses is involved:
- FRAGILE X SYNDROME Unstable repeat sequence in the CGG of X chromosome: Most common inherited form of dev delay, 1 in 1500 male births, 10% with severe dev delay, enlarged testes
- WILLIAMS SYNDROME Combination of cerebral maldevelopement with cardiovascular abnormalities like supravalvular aortic stenosis traced to a microdeletion on chromosome 7
- PRADER WILLI SYNDROME At the first year, dev delay, obesity, hyperphagia, deletion in 15q11-q13
- ANGELMAN SYNDROME Maternally inherited single gene defect, dev delay, inappropriate laughter, microcephaly, long tongue, tuhin upper lip,: HAPPY PUPPET SYNDROME
- RETT SYNDROME Dominant defect on X chromosome, at 6-18 months slow steady regression in motor skills and mental abilities
What is H3O mnemonic for prader willi syndrome
Hypomentia, hypotonia, hypogonadism, obesity
What is the teratogenic risk of AEDs in the general population?
3%
Those on AEDs approximately 5%
What are the 2 true phakomatoses?
- Tuberous sclerosis
2. Neurofibromatosis
What is the triad of tuberous sclerosis?
- Adenoma sebaceum: angiofibromas in the face (aka adenomas of Pringle)
- Epilepsy
- Developmental delay
What chromosomes are TSC 1 hamartin and TSC 2 tuberin located in?
TSC 1: Hamartin in (9q long arm)
TSC 2: Tuberin in (16 p short arm)
What is the initial seizure pattern of tuberous sclerosis?
In the first year or two they take the form of massive flexion spasms with hypsarrhythmia –> GTC and psychomotor attacks or petit mal
What is a phakoma?
A gliomatous tumor in the retina in or near the optic disc
If adenomas of Pringle are found in the face what diagnostic lesion of tuberous sclerosis is found in the trunk?
shagreeen patch
What are cortical tubers made up of?
plump fibrous astrocytes much like astrocytoma though lacking in glial fibrillar protein
What AED can be used for the flexor spasms of tuberous sclerosis at infancy? How about status epilepticus associated with TS?
ACTH
Everolimus– DON’T FORGET THIS!
Molluscum fibrosum (non-neural skin tumors) of NF is distinguished from lipomas by the phenomenon of?
“buttonholing”
What is a Lisch nodule?
small whitish spot representing an iris hamartoma
Diagnostic criteria for Tuberous sclerosis?
__ Major
__ Major + __ Minor
Besides shagreen patch, ash leaf spots 3 or more, cortical dysplasias more than 3, SEGA what are the other major signs
2 major
1 major 2 minor
Major:
Angiofibromas (3 or more) or forehead plaque
Hypomelanotic macules “ash leaf spots” (3 or more)
Ungual fibromas (2 or more)
Shagreen patch or multiple collagenomas
Multiple retinal hamartomas
Cortical dysplasias (more than 3). This includes tubers and cerebral white matter radial migration lines.
Subependymal nodule(s)
Subependymal giant cell astrocytoma(s)
Cardiac rhabdomyoma
Lymphangioleiomyomatosis (LAM)
Angiomyolipomas (2 or more)
Minor:
Dental enamel pits (more than 3) Intraoral fibromas (2 or more) Nonrenal hamartomas Retinal achromic patch “Confetti” skin lesions Multiple renal cysts
How to diagnose NF1?
Clinical diagnosis based on presence of two of the following:
- Six or more café-au-lait macules over 5 mm in diameter in prepubertal individuals and over 15mm in greatest diameter in postpubertal individuals.
- Two or more neurofibromas of any type or one plexiform neurofibroma.
- Freckling in the axillary or inguinal regions.
- Two or more Lisch nodules (iris hamartomas).
- Optic glioma.
- A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis.
- First-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.
Diagnostic criteria CAFE SPOt:[2]
Café-au-lait spots. Six or more. 5mm/15mm
Axillary or inguinal freckling.
neuroFibroma (two or more) or plexiform neurofibroma (one).
Eye hamartomas (Lisch nodules). 2 or more
Skeletal abnormalities, e.g. sphenoid dysplasia, leg bowing.
Positive family history. or Pamily (hehe)
Optic Nerve Tumour (optic nerve glioma).
What percentage of NF1 patients can be diagnosed with the presence of 6 or more cafe au lait spots?
80%
How to diagnose NF2?
Confirmed (definite) diagnosis of NF2:
bilateral vestibular schwannomas (may also be known as acoustic neuroma)
(Probable) diagnosis of NF2:
family history of NF2 AND
unilateral vestibular schwannomas or any 2 of the following tumor types: meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, juvenile cortical cataract
Mnemonic MESE2 (Meningioma, Ependysmoma, Schwannoma, Cataract, Lens opacity)
What ocular pathology is associated with NF2?
posterior subcapsular lenticular opacity, juvenile cortical cataract
What orthopedic pathology is associated with NF1?
A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis.v
Meningo-Encephalofacial angiomatosis with cerebral calcification is aka?
Sturge weber syndrome
The vascular nevus in sturge weber synrome is usually located in what part of the face?
Ophthalmic division
The calcifications seen in Sturge weber syndrome is seen in in what layer of the cortex?
2nd and third
2nd external granular
3rd external pyramidal
For sturge weber syndrome what pathologies are found in the:
- Brain
- Eye
- Leptomeningeal angioma and calcifications
2. Glaucoma and facial angioma surrounding the eye
Hereditary hemorrhagic telangiectasia is AKA
Osler Rendu Weber Disease
What are the key features of von Hippel lindau? VHL gene on chromosome 3
- Hemangioblastoma in the cerebellum, brainstem or spinal cord
- Retinal hemangioblastoma
- Renal Cell CA 60% of patients with 1/3 mortalities
- Polycythemia vera
- Pheochromocytoma
- Pancreatic tumors
What are the characteristic locations of telangiectasias in ataxia telangiectasia syndrome (AR)?
Outer parts of the bulbar conjunctivae (early) and over the years on exposed parts of the neck, on the bridge of the nose and cheeks
How do patients with ataxia telangiectasia syndrome die?
What is another name for the Ataxia telangiectasia? How is it inherited? What chromosome and arm is involved?
Usually from bronchopulmonary infection or neoplasia due to humoral immunodeficiency decrease in IgA IgE IgG2 IgG4
Louis Bar syndrome. AR. 11q long arm
Why are patients with ataxia telangiectasia syndrome at risk for post radiation lymphoma, leukemia and other tumors?
Mutations in the ATM gene cause ataxia-telangiectasia. The ATM gene provides instructions for making a protein that helps control cell division and is involved in DNA repair. This protein plays an important role in the normal development and activity of several body systems, including the nervous system and immune system. The ATM protein assists cells in recognizing damaged or broken DNA strands and coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell’s genetic information.
Mutations in the ATM gene reduce or eliminate the function of the ATM protein. Without this protein, cells become unstable and die. Cells in the part of the brain involved in coordinating movements (the cerebellum) are particularly affected by loss of the ATM protein. The loss of these brain cells causes some of the movement problems characteristic of ataxia-telangiectasia.
What are the two main symptoms that comprises Mobius syndrome? What are the others
Facial Diplegia and abducens palsies
Lingual palsy Clubfeet Complete ophthalmoplegia Clubfeet Mental defect Absent pectoral muscle
Describe the findings in Cogan’s oculomotor apraxia.
Lack of lateral gaze volitionally or on command– responds to caloric stimulation
In those born from 20-35W fatal brain bleeds can usually be found in what area?
Subependymal germinal matrix zone near the caudate nucleus at the level of the foramen of Monro
What are the 3 major etiologic sydnromes of CP?
- matrix hemorrhages in the immature infant
- HIE
- Other developmental motor abnormalities like intrauterine stroke
What proportion of subependymal hge patients will have periventricular leukomalacia?
1/3
What is the rate of mortality and neurodev disability for HIE bebes?
Neurodev 25%
Mortality 20%
What is the most commmon neuroimaging correlate for CP in the european cerebral palsy study?
Periventricular leukomalacia
What type of HIE? Fenichel et al.
- hyperaltertness and jittery baby first 24 hours
- EEG is normal
- irreg respirations needing MV at birth
- EEG is abnormal may improve from obtunded after 48 hours or may worsen
- Hypotonic limbs, no moro, depressed sucking and swallowing
- hyperaltertness and jittery baby first 24 hours 1
- EEG is normal 1
- irreg respirations needing MV at birth 3
- EEG is abnormal may improve from obtunded after 48 hours or may worsen 2
- Hypotonic limbs, no moro, depressed sucking and swallowing 3
Type 1 mild: Jittery baby in the first 24 hours. Normal tone except for head lag during traction. NORMAL EEG
Type 2 moderate: Obtunded hypotonic. post 72 hours may get better or worsen. EEG is abnormal.
Type 3 severe. Stupor and coma at birth. Hypotonic and motionless. Requiring MV. Abnormal EEG.
What is the classic position of the LE in spastic diplegia?
Scissors
What does the presence of statu marmoratus (etat marbre) say about the timing of a cerebral lesion? Seen in the basal ganglia and thalamus in patients with young patients with extrapyramidal syndromes
That the insult occurred BEFORE infancy before myelination has completed its early developmental cycle
Serum bilirubin level greater than ____ mg dl when kernicterus develops.
25
What should be suspected if extrapyramidal syndrome is accompanied by bilateral deafness and paralysis of upward gaze? Lesions in the GP, Thalamus, STN, CN3 and CN8
Kernicterus
What is the Crigler Najjar syndrome?
Hereditary hyperbilirubinemia due to deficiency in glucoronosyltransferase
What part of the cerebellum is missing in Jourbert syndrome?
Dysgenisis of the vermis causing the molar tooth sign on MRI
What tumor causes opsoclonus myoclonus ataxia?
Neuroblastoma
What two TORCH infections have calcifications?
Toxo (widely disseminated) and CMV (periventricular distribution)
What two TORCH infections cause deafness?
Rubella and CMV
Neurosyphillis also causes deafness
What is the tetrad of rubella congenital?
Cataracts
Deafness MOST COMMONW
Congenital heart disease
Developmental delay
What is the treatment for active infection of CMV and congenital rubella in then newborn?
What about toxoplasmosis?
None
Pyrimethamine and sulfadiazine
What are the eye lesions in toxoplasmosis?
Chorioretinitis
What is the Hutchinson triad of syphillis?
Keratitis
Dental deformity
Bilateral deafness
What age group do these epileptic states occur in:
- Febrile seizures
- Generalized temporal spike wave activity with benign motor and complex partial seizures
- Petit mal seizures
- Myoclonic or extensor spasms
- Febrile seizures 6 months to 6 years
- Generalized temporal spike wave activity with benign motor and complex partial seizures 6 years to 16 years
- Petit mal seizures 4-13
- Mid to late adolescent years
What may be the only physicla abnormality in Fragile X?
large testes
What is the cut off IQ for developmental delay that allows for independent living?
60 and up
What are the to somatic hallmarks of Prader Willi syndrome?
Obesity and hypogenitalism
What characteristics rhythmias or movement stereotypies are characteristic of the following syndromes?
- Autism:
- Rett syndrome:
- Down syndrome:
- Autism: hand flapping
- Rett syndrome: hand wringing
- Down syndrome: hand waving
What is the repeated unstable sequence in Fragile X syndrome that leads to breakage at the distal end of the long arm of X chromosome? How do the testes look?
CGG
Large testes
Remember the disease affects males mostly
Fragile premutation syndrome in adults can be described as?
Adult onset ataxia, tremor, midl retardation and autistic like behavior
What is the genetic basis for rett syndrome and why is it only seen in girls?
Defect at the chromosomal Xq28 gene MECP2– fatal outcome in boys and mosaic condition in girls
What are three characteristic features of Williams syndrome?
- Striking sociability and empathy
- Supravalvular aortic stenosis
- Memory for musical scores
Think Prince William! WIlliamStenosis
What is the eponym for autism? Asocial, lacking in communicative skills in both verbal and non verbal and committed to repetitive ritualistic behaviours
Kanner Asperger syndrome
What percentage of autistic patients have an IQ that is normal or superior?
1%
What are the 4 core elements of autism?
Social
Language
Cognitive
Behavioural
What are the serotonin levels in autism?
Increased in platelet but decreased in serum– SSRIs can be used for mood swings
