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