CNS Pathology

Part 2. Developmental pathology

A. Neuro tube defects
a. Failure of neuropore to fuse during week 4
i. vertebral arches do not fuse resulting in a connection between
amnionic cavity and spinal canal
b. defect tends to occur in lumbosacral region
c. can be detected by testing maternal blood for -fetoprotein (AFP)
i. if elevated and neural tube defect is present, then
amniocentesis will show both -fetoprotein (AFP) and
acetylcholinesterase
d. associated with maternal folate deficiency commonly caused by:
i. low folic acid intake during pregnancy
ii. medications that interfere with folate utilization
1. Valproate, methotrexate, sulfasalazine, phenytoin
e. Spina bifida occulta (no increase in AFP)
i. least severe variation with dura intact and no herniation
ii. tuft of hair in lumbosacral region
f. Spina bifida with meningocele
i. only meninges herniate through spinal defect forming a CSF
filled sac, but spinal cord remains in spinal canal
g. Spina bifida with meningomyelocele
i. meninges and spinal cord herniate through defect

B. Forebrain
a. Anencephaly failure of anterior neuropore to close resulting in
failure of brain and calvarium to form
i. no swallowing center polyhydramnios
ii. AFP
 iii. most common cause of AFP is incorrect pregnancy
dating

b. Holoprosencephaly failure of prosencephalon to divide and form

cerebral hemispheres

i. single 3rd ventricle

ii. absence of olfactory bulbs and tracts

iii. cyclopia, cleft palate, cleft lip

iv. associated with

1. Patau syndrome (trisomy 13) and Edwards syndrome

(trisomy 18)

2. severe fetal alcohol syndrome

3. cleft lip/palate

c. Cerebral aqueduct stenosis

i. congenital stenosis of aqueduct b/t 3rd and 4th ventricles most

common cause of hydrocephalus in newborns

ii. CSF produced by the choroid plexus lining the ventricles

iii. Enlarging head circumference and paralysis of upward

gaze (Parinaud syndrome)

1. Also seen in the case of pineal tumor

2. Pressing on MLF (upward gaze center)

C. Posterior fossa

a. Dandy-Walker syndrome

i. dilation of 4th ventricle w/ absence/agenesis of

cerebellar vermis

ii. small cerebellar hemispheres

iii. posterior fossa cysts

 iv. enlargement of posterior fossa

v. associated with non-communicating hydrocephalus and

spina bifida

b. Arnold Chiari I

i. cerebellar tonsil herniation through foramen magnum

ii. often presents in adulthood with chronic headaches and ataxia

iii. associated with cervico-thoracic syringomyelia

iv. milder in severity in comparison to type II malformations

c. Arnold Chiari II

i. due to small posterior fossa, the cerebellar tonsils herniate

through foramen magnum causing

1. aqueductal stenosis and hydrocephalus

2. may present with syringomyelia, thoracolumbar spina

bifida with myelomeningocele

ii. symptoms present from compression of medulla oblongata

and CN IX, X, and XI

1. reduced gag reflex

2. vocal cord paralysis

3. laryngeal stridor

4. swallowing difficulty

5. spastic dysphonia

D. Spinal cord

a. Syringomyelia central canal of spinal cord enlarges

i. nerves closest to central canal affected first

 ii. spinothalamic tract: bilateral loss of pain and temperature
sensation in affected area, touch and positional sense not
affected

1. further expansion leads to LMN signs (anterior horn) of

upper extremities and Horners syndrome (lateral horn)

occurs most often at C8-T1 (both arms)

cape-like pattern loss

often associated with Chiari I, less frequently with Chiari II

E. Neurocutaneous syndromes
a. Disordered growth of ectodermal tissue +
malformations/tumors of the CNS
i. All associated w/ tumor
ii. Tuberous sclerosis and Sturge-Weber also associated w/ mental
retardation and seizure

b. Neurofibromatosis = Autosomal dominant tumor suppressor

mutation
i. NF-1 = chromosome 17
ii. NF-2 = chromosome 22
iii. NF type I

iv. Neurocutaneous disorder with widely distributed

neurofibroma (pigmented, pedunculated skin lesions
sparing palms and soles)

1. result of mutated NF-1 gene (chromosome 17) tumor

suppressor

v. Associated with

1. caf-au-lait spots

2. Lisch nodules (pigmented hamartomas of the iris)

3. Pigmented plexiform neurofibroma

4. Associated w/ pheochromocytoma or Wilms tumor

a. Both have HTN

vi. Recall: NF Type II is associated with bilateral acoustic

schwannomas (benign, hearing loss and tinnitus)

1. No widely distributed neurofibroma?

 vii. Mutated NF-2 gene (chromosome 22)

Caf-au-lait spots Lisch nodules

axillary freckling

c. Tuberous sclerosis: Neurocutaneous disorder with widespread

hamartomas in CNS, skin, and viscera mental retardation and
seizures beginning in infancy
i. Associated with
1. cardiac rhabdomyoma
2. renal angiomyolipoma
3. subependymal giant cell astrocytoma
4. hypopigmented "ash leaf spots"
5. Shagreen patches (connective tissue nevose)
6. sebaceous adenoma (angiofibroma on the face)

ii. AD inheritance

1. Proliferation of multinucleated atypical astrocytes forming

tubers

Angiofibroma Shagreen patch

leaflet spot

d. Sturge-Weber syndrome a sporadic neurocutaneous disorder

characterized by congenital port wine stains (aka nevus flammeus)

i. classically in trigeminal distribution though may involve other

distributions

1. due to vascular malformation

ii. Associated with

1. ipsilateral leptomeningeal capillary-venous malformation

2. pheochromocytoma
iii. complications include seizures and mental retardation