Post on 15-Dec-2014
description
November 25, 2008
Neurology Board Review
Neurocutaneous Syndromes
Neurofibromatosis 1AKA Von Recklinghausen Disease
1/3000 individuals
Autosomal Dominant50% sporadic
Chromosome 17qNeurofibromin – tumor supressor
Diagnostic Criteria NF 1At least 2 of the following:
Café au Lait Macules – 6 or more>5 mm in prepubertal children>15 mm in post pubertal children
2 or more neurofibromas of any type, or one plexiform neurofibroma
Axillary or inguinal frecklingOptic glioma2 or more Lisch nodulesFirst degree relative with NF1Osseous lesion (sphenoid dysplasia, thinning of
long bone cortex)
Café au Lait MaculesBrown hyperpigmented macules with
smooth margins
Lisch NodulesHamartomas of the iris
Skeletal AbnormalitiesShort statureMacrocephalySevere angular scoliosis with dysplasia of the
vertebral bodiesDefects of posterior-superior wall of the orbitCongenital bowing and thinnning of long bone
cortexPseudoarthrosis of the tibia, fibula, femur, clavicleDisorders of bone growthErosive bony defects by neurogenic tumorScalloping of posterior margins of vertebral bodies
Skeletal Abnormalities
NF 1 Tumors
Very commonOptic glioma 15%Ependymomas, meningiomas, astrocytomas
IntelligenceMR is rareLearning disabilitiesBehavior problems
Neurofibromatosis 2Autosomal Dominant
95% penetrance
1/50,000
Chromosome 22Merlin or Schwannomin – tumor suppressors
Symptoms in teens/twentiesHearing loss, tinnitus, unsteadiness, facial
weakness
Diagnostic Criteria for NF 2Bilateral 8th nerve masses seen with
imaging OR
First degree relative with NF 2 and unilateral 8th nerve mass OR 2 of the followingNeurofibromaMeningiomaGliomaSchwannomaJuvenile posterior subcapsular lens opacity
Tuberous SclerosisAutosomal Dominant
80% have seizuresInfantile spasms
TSC1 on Chromosome 9 qHamartin – tumor suppressor
TSC2 on Chromosome 16qTuberin – tumor suppressor
1/6000-9000 have gene1/150,000 - full expression of geneCarriers usually only have Ash-leaf macule
Major FeaturesFacial angiofibromas
(adenoma sebaceum)
Nontraumatic ungual fibroma
Hypomelanotic macules (Ash leaf spots)
Shagreen patch (connective tissue nevus)
Multiple retinal nodular hamartomas
Cortical tuber
Subependymal nodule
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma
Renal angiomyolipoma
Lymphangiomyomatosis
Minor FeaturesMultiple randomly distributed pits in dental
enamelHamartomatous rectal polypsBone cystsCerebral white matter radial migration linesGingival fibromasNonrenal hamartomaRetinal achromatic patch“confetti” skin lesionsMultiple renal cysts
Diagnostic Criteria for Tuberous SclerosisDefinite
2 Major Features1 Major and 2 Minor Features
ProbableOne Major + One Minor Feature
PossibleOne Major Feature2 or more Minor Features
Sturge – Weber SyndromeVascular Malformation over the face
covering ophthalmic cutaneous distribution of CN VPort wine stain to forehead and upper eyelidPink – purple and present at birth
Sturge – Weber SyndromeIpsilateral leptomeningeal angiomatosis
with intracranial calcificationsSeen on CT scan (though often normal at
birth)Seizures in 90%
Sturge – Weber SyndromeHigh incidence of mental retardation
Cognitive and behavioral problemsIpsilateral ocular complications
Buphthalmos – corneal enlargementColoblomaGlaucoma
Klippel-Trenaunay SyndromePort-wine stain over lateral aspect of the
leg (arm)Bilateral is rare
Underlying vascular lesion increases blood supply hemihypertrophy and lymphedema
Ataxia - TelangiectasiaAutosomal Recessive Degenerative
Ataxia – cerebellar degenerationOculocutaneous Telangiectasia – seen by age
6Immunodeficiency
Deficient cellular immunity , low IgA and IgMRecurrent sinopulmonary infections
NeoplasiaALL or lymphoma
AtaxiaStereotypic ProgressionInfant – tremors of headToddler- unsteady gaitSchool age child – global ataxia and
scanning, slurred, dysarthric speechBy 10 yo – loss of deep tendon reflexes,
impared position and vibratory senseAdolescence – choreoathetosis, dystonic
posturing, gaze apraxia, progressive dementia
Linear Sebaceous NevusPresent at birth
Can be anywhereYellow – tan waxy linear lesion
Excess of pappillomatous sebaceous glands15-20% risk of malignant degeneration
Association with seizure and mental retardation
CNS Malformations
Macrocephaly
> 2 standard deviations above the mean head circumference for age, gender, gestation
CausesHydrocephalusIntracranial massThickening of the skullMegalencephaly – increased brain substance
EvaluationSeries of measurements of head
circumferenceMeasurement of parental head
circumferenceDevelopmental historyFamily historyCT or MRI- assessment of ventricular size,
intracranial masses, chronic subdural effusions, calcifications, blood
HydrocephalusImbalance between CSF production and resorption
that results in a significant net accumulation of fluid in the ventricular system
Choroid plexus papilloma – CSF overproduction
Non-communicating HydrocephalusObstruction of CSF pathways within the ventricular
systemAqueductal Stenosis, tumors of posterior fossa, other
congenital malformations
Communicating HydrocephalusObstruction of CSF pathways in the subarachnoid spaceIntracranial hemorrhage, meningitis
Clinical Manifestations of HydrocephalusExcessively large head at birth OR rapidly
growingForehead is disproportionately largeFace appears smallScalp is thin with distended veinsAnterior fontanelle - large and tenseSutures splitOcular findings
Impaired upward gaze Sunsetting sign
Divergent strabismusAbducens nerve paresis
Hydrocephalus
Dandy-Walker MalformationProgressive cystic enlargement of the fourth ventricle
Enlarged posterior fossa
Upward displacement of the tentorium and transverse sinuses
Hydrocephalus – universal
60% with increased ICP by age 2
Bulging occiput, posterior fossa cyst
Ataxia, nystagmus, cranial nerve deficits
Dandy-Walker Malformation
HydrancephalyCharacteristics
Absence of cerebral hemispheresIntact meningesNormal skull
Appear normal at birth
First few weeksDevelopmental arrest, hypertonia, hyperreflexicSeizures
Die between 6-12 months
Hydrancephaly Pictures
MicrocephalyHead circumference more than 2 standard
deviations less than the mean for gender, age, gestation
Neurologic manifestationsMinor
Motor skills, mild MRMajor
Vegetative stateDiagnostic evaluation
Family, prenatal historyKaryotypeInborn error of metabolismSerologic studies for TORCH infectionsImaging
Causes of MicrocephalyGenetic defects
TrisomiesDeletionsTranslocations
Antenatal IrradiationIntrauterine
infectionsRubellaCMVToxoplasmosisCongenital syphilisHSV
Exposure to drugs or chemicals during gestationFetal alcohol syndromePhenytoin exposureTrimethadione
exposureMethyl mercury
exposureMaternal PKUPerinatal Insults
TraumaAnoxicMetabolic infectious
Microcephaly
Midline Defects/ Occult Spinal DysraphismMidline spinal cord and vertebral skeletal
defectsEncephaloceleDefective closure of caudal portion of neural
tubeMyelomeningocele spina bifida occulta
Occult Spinal DysraphismCutaneous/subcutaneous defects
Hairy patchLipomaSkin tagPort-wine stainHemangiomaSacral dimples
Radiologic Screening for Cutaneous StigmataUltrasound
Vertebrae do not ossify until 3 monthsCan assess cord motion
MRI
Neurosurgery referralEarly intervention can prevent progression of
defects
Clinical SymptomsSymptom-free interval
3 years- school age (periods of rapid growth)
Leg stiffness
Clumsiness
Weakness/numbness
Bowel/bladder dysfunction
Physical exam
Decreased tone
Decreased reflexes
Decreased sensation
Foot deformities
Pictures