Download Slide 1 - LSU School of Medicine

Neurology Board Review
November 25, 2008
Neurocutaneous Syndromes
Neurofibromatosis 1
 AKA Von Recklinghausen Disease
 1/3000 individuals
 Autosomal Dominant
 50% sporadic
 Chromosome 17q
 Neurofibromin – tumor supressor
Diagnostic Criteria NF 1
 At 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
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neurofibroma
Axillary or inguinal freckling
Optic glioma
2 or more Lisch nodules
First degree relative with NF1
Osseous lesion (sphenoid dysplasia, thinning of long bone cortex)
Café au Lait Macules
 Brown hyperpigmented macules with smooth margins
Lisch Nodules
 Hamartomas of the iris
Skeletal Abnormalities
 Short stature
 Macrocephaly
 Severe angular scoliosis with dysplasia of the vertebral bodies
 Defects of posterior-superior wall of the orbit
 Congenital bowing and thinnning of long bone cortex
 Pseudoarthrosis of the tibia, fibula, femur, clavicle
 Disorders of bone growth
 Erosive bony defects by neurogenic tumor
 Scalloping of posterior margins of vertebral bodies
Skeletal Abnormalities
NF 1
 Tumors
 Very common
 Optic glioma 15%
 Ependymomas, meningiomas, astrocytomas
 Intelligence
 MR is rare
 Learning disabilities
 Behavior problems
Neurofibromatosis 2
 Autosomal Dominant
 95% penetrance
 1/50,000
 Chromosome 22
 Merlin or Schwannomin – tumor suppressors
 Symptoms in teens/twenties
 Hearing loss, tinnitus, unsteadiness, facial weakness
Diagnostic Criteria for NF 2
 Bilateral 8th nerve masses seen with imaging OR
 First degree relative with NF 2 and unilateral 8th nerve mass
OR 2 of the following
 Neurofibroma
 Meningioma
 Glioma
 Schwannoma
 Juvenile posterior subcapsular lens opacity
Tuberous Sclerosis
 Autosomal Dominant
 80% have seizures
 Infantile spasms
 TSC1 on Chromosome 9 q
 Hamartin – tumor suppressor
 TSC2 on Chromosome 16q
 Tuberin – tumor suppressor
 1/6000-9000 have gene
 1/150,000 - full expression of gene
 Carriers usually only have Ash-leaf macule
Major Features
 Facial 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 Features
 Multiple randomly distributed pits in dental enamel
 Hamartomatous rectal polyps
 Bone cysts
 Cerebral white matter radial migration lines
 Gingival fibromas
 Nonrenal hamartoma
 Retinal achromatic patch
 “confetti” skin lesions
 Multiple renal cysts
Diagnostic Criteria for Tuberous
Sclerosis
 Definite
 2 Major Features
 1 Major and 2 Minor Features
 Probable
 One Major + One Minor Feature
 Possible
 One Major Feature
 2 or more Minor Features
Sturge – Weber Syndrome
 Vascular Malformation over the face covering ophthalmic
cutaneous distribution of CN V
 Port wine stain to forehead and upper eyelid
 Pink – purple and present at birth
Sturge – Weber Syndrome
 Ipsilateral leptomeningeal angiomatosis with intracranial
calcifications
 Seen on CT scan (though often normal at birth)
 Seizures in 90%
Sturge – Weber Syndrome
 High incidence of mental retardation
 Cognitive and behavioral problems
 Ipsilateral ocular complications
 Buphthalmos – corneal enlargement
 Colobloma
 Glaucoma
Klippel-Trenaunay Syndrome
 Port-wine stain over lateral aspect of the leg (arm)
 Bilateral is rare
 Underlying vascular lesion increases blood supply 
hemihypertrophy and lymphedema
Ataxia - Telangiectasia
 Autosomal Recessive
 Degenerative
 Ataxia – cerebellar degeneration
 Oculocutaneous Telangiectasia – seen by age 6
 Immunodeficiency
 Deficient cellular immunity , low IgA and IgM
 Recurrent sinopulmonary infections
 Neoplasia
 ALL or lymphoma
Ataxia
 Stereotypic Progression
 Infant – tremors of head
 Toddler- unsteady gait
 School age child – global ataxia and scanning, slurred,
dysarthric speech
 By 10 yo – loss of deep tendon reflexes, impared position
and vibratory sense
 Adolescence – choreoathetosis, dystonic posturing, gaze
apraxia, progressive dementia
Linear Sebaceous Nevus
 Present at birth
 Can be anywhere
 Yellow – tan waxy linear lesion
 Excess of pappillomatous sebaceous glands
 15-20% 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
 Causes
 Hydrocephalus
 Intracranial mass
 Thickening of the skull
 Megalencephaly – increased brain substance
 Evaluation
 Series of measurements of head circumference
 Measurement of parental head circumference
 Developmental history
 Family history
 CT or MRI- assessment of ventricular size, intracranial masses,
chronic subdural effusions, calcifications, blood
Hydrocephalus
 Imbalance 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 Hydrocephalus
 Obstruction of CSF pathways within the ventricular system
 Aqueductal Stenosis, tumors of posterior fossa, other congenital
malformations
 Communicating Hydrocephalus
 Obstruction of CSF pathways in the subarachnoid space
 Intracranial hemorrhage, meningitis
Clinical Manifestations of
Hydrocephalus
 Excessively large head at birth OR rapidly growing
 Forehead is disproportionately large
 Face appears small
 Scalp is thin with distended veins
 Anterior fontanelle - large and tense
 Sutures split
 Ocular findings
 Impaired upward gaze
 Sunsetting sign
 Divergent strabismus
 Abducens nerve paresis
Hydrocephalus
Dandy-Walker Malformation
 Progressive 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
Hydrancephaly
 Characteristics
 Absence of cerebral hemispheres
 Intact meninges
 Normal skull
 Appear normal at birth
 First few weeks
 Developmental arrest, hypertonia, hyperreflexic
 Seizures
 Die between 6-12 months
Hydrancephaly Pictures
Microcephaly
 Head circumference more than 2 standard deviations less than the
mean for gender, age, gestation
 Neurologic manifestations
 Minor
 Motor skills, mild MR
 Major
 Vegetative state
 Diagnostic evaluation
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Family, prenatal history
Karyotype
Inborn error of metabolism
Serologic studies for TORCH infections
Imaging
Causes of Microcephaly
 Genetic defects
 Trisomies
 Deletions
 Translocations
 Antenatal Irradiation
 Intrauterine infections
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Rubella
CMV
Toxoplasmosis
Congenital syphilis
HSV
 Exposure to drugs or
chemicals during gestation
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Fetal alcohol syndrome
Phenytoin exposure
Trimethadione exposure
Methyl mercury exposure
 Maternal PKU
 Perinatal Insults
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Trauma
Anoxic
Metabolic
infectious
Microcephaly
Midline Defects/ Occult Spinal
Dysraphism
 Midline spinal cord and vertebral skeletal defects
 Encephalocele
 Defective closure of caudal portion of neural tube
 Myelomeningocele  spina bifida occulta
 Occult Spinal Dysraphism
 Cutaneous/subcutaneous defects
 Hairy patch
 Lipoma
 Skin tag
 Port-wine stain
 Hemangioma
 Sacral dimples
Radiologic Screening for Cutaneous
Stigmata
 Ultrasound
 Vertebrae do not ossify until 3 months
 Can assess cord motion
 MRI
 Neurosurgery referral
 Early intervention can prevent progression of defects
Clinical Symptoms
 Symptom-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