Nervous System and Special Sensory Disorders

(Adapted from Fishman RA: Brain edema. N Engl J Med 1975; 293: 706 in Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 862, Fig. 23-4.)

Subfalcine herniation: compression of ACA

a. Cingulate gyrus herniates under the falx cerebri.

b. Causes compression of the anterior cerebral artery (ACA)

3. Uncal herniation

a. Medial portion of temporal lobe herniates through the tentorium cerebelli.

b. Complications

Uncal herniation: compression CN III, PCA, parasympathetic fibers

(1) Compression of the midbrain

• Produces Duret’s hemorrhages

(2) Compression of oculomotor nerve

(a) Eye is deviated down and out.

Uncal herniation: eye deviated down and out; mydriasis

(b) Pupil is mydriatic (dilated).

• Compression of parasympathetic postganglionic fibers

(3) Compression of posterior cerebral artery (PCA)

• Causes hemorrhagic infarction of occipital lobe

4. Tonsillar herniation

a. Cerebellar tonsils herniate into the foramen magnum.

Tonsillar herniation: coning of cerebellar tonsils; cardiorespiratory arrest

b. Causes “coning” of the cerebellar tonsils (Fig. 25-4)

c. Produces cardiorespiratory arrest

D. Hydrocephalus

• Increase in the CSF volume causes enlargement of the ventricles.

25-4: Cerebellar coning. Note the notching in the cerebellar tonsils (arrows) due to downward displacement of the cerebellar tonsils through the foramen magnum.

(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 312, Fig. 39-2.)

Hydrocephalus: enlargement of ventricles

1. Production and movement of CSF

a. Produced by the choroid plexus in the ventricles

CSF: produced by choroid plexus; reabsorbed by arachnoid granulations

b. Exits fourth ventricle through foramina and enters subarachnoid space

c. Reabsorbed by the arachnoid granulations into the dural venous sinuses

d. CSF analysis (Box 25-1)

2. Communicating (nonobstructive) hydrocephalus

a. Open communication between ventricles and subarachnoid space

b. Causes

Box 25-1 Cerebrospinal Fluid (CSF) Analysis

CSF derives from the choroid plexus in the ventricles and enters the subarachnoid space. It cushions the brain and spinal cord and transmits chemicals to reach other parts of the brain. CSF is reabsorbed by the arachnoid granulations and drained into dural venous sinuses, which eventually drain into the jugular vein.

CSF normally is clear and colorless. Turbidity may be caused by an increase in protein, cells, microbial pathogens, or a combination of all three elements. Bloody CSF from spinal taps is most commonly iatrogenic but can also represent a pathologic hemorrhage into the subarachnoid space (e.g., ruptured berry aneurysm, intracerebral bleed near the surface of the brain or ventricles). If the bloody tap is iatrogenic, the supranate should be clear after centrifugation, particularly in the last tube collected in the spinal tap. In pathologic bleeds, there are sequential color changes that occur. CSF colors after centrifugation may be pink- or orange-tinged. A pink color is due to oxyhemoglobin (oxyHb) from ruptured red blood cells. It first occurs 2–4 hours post-bleed, peaks in 24–36 hours, and subsides in 4–8 days. A yellow to orange color (xanthochromia) is due to oxyHb breakdown into bilirubin. It first appears 12 hours post-bleed, peaks in 2–4 days, and subsides in 2–4 weeks. CSF protein normally is 15–45 mg/dL. CSF prealbumin and albumin derive from plasma; therefore, increased levels of these proteins must be due to increased capillary permeability (e.g., acute inflammation). CSF gamma (γ) globulins derive from the synthesis of IgG by plasma cells within the central nervous system (CNS). In a CSF electrophoresis, CSF γ-globulins account for <12% of the total protein. An increase in CSF IgG is due to either increased synthesis of IgG in the CNS (e.g., multiple sclerosis) or an increase in capillary vessel permeability in acute inflammation (e.g., meningitis). It is clinically important to make this distinction. A CSF IgG index (calculated with a formula) is useful in distinguishing acute inflammation from demyelinating diseases, the most common CNS disease producing an increase in IgG. An increase in the CSF IgG index correlates with a CNS origin of the IgG, and a decreased index indicates acute inflammation. Routine CSF electrophoresis quantitates the amount of γ-globulins that are present when CSF protein is increased. High-resolution CSF electrophoresis, however, is most useful in detecting demyelinating disease, of which multiple sclerosis is the most common cause. Other demyelinating diseases include neurosyphilis and Guillain-Barré syndrome. High-resolution detects oligoclonal bands in the γ-globulin region (see Fig. 25-27D). These are discrete, discontinuous bands originating from single clones of immunocompetent B cells. Another test for demyelinating disease is myelin basic protein (MBP), a protein that is normally present in myelin. An increased CSF MBP occurs with active demyelinating disease. CSF MBP is decreased when a demyelinating disease is in remission.

CSF glucose does not have the same concentration as serum glucose. A normal value for CSF glucose is 50–75 mg/dL, but a normal value in serum glucose is 70–110 mg/dL. A rough estimate of what the CSF glucose should be is to multiply a serum sample value obtained 30–90 minutes before the lumbar puncture by 0.66. For example, if the serum glucose is 100 mg/dL, then the CSF glucose should be around 66 mg/dL. A decreased CSF glucose (hypoglycorrhachia) is defined as a glucose level < 40 mg/dL. It implies that there has been increased uptake of glucose by cellular elements in the CSF (e.g., neutrophils in acute bacterial meningitis, malignant cells) or a defect in the glucose carrier system (frequently occurs in bacterial/fungal meningitis). CSF glucose is usually normal in viral meningitis, neurosyphilis, demyelinating disease, and a cerebral abscess. Exceptions in which viral infections of the CNS produce a decreased CSF glucose include infections associated with mumps, herpes simplex, and the lymphocytic choriomeningitis virus. CSF chloride is usually greater than the serum chloride (limited usefulness). The CSF white blood cell count normally is 0–5 mononuclear cells/mm³. Neutrophils are never normal in the CSF. An increased CSF WBC count is most often due to meningitis caused by microbial pathogens. Bacterial meningitis usually has a predominance of neutrophils, while viral meningitis initially has a neutrophil response in the first 24 hours that changes to a predominantly lymphocytic response in 2–3 days. Fungal meningitis is characterized by a predominance of lymphocytes and monocytes. A parasitic meningitis usually has a mixed inflammatory infiltrate (eosinophils suggest a helminth infection). A Gram stain is useful for detecting bacteria (75–80% sensitivity) in the sediment after ultracentrifugation of the CSF. Other tests include culture, India ink for Cryptococcus neoformans (sensitivity is 50%), antigen detection (sensitivity depends on the pathogen; specificity is 96–100%), enzyme immunoassay (96–100% sensitivity/specificity), and polymerase chain reaction studies that detect DNA (sensitivity 94%, specificity 96%).

Communicating hydrocephalus: ↑ production CSF; ↓ reabsorption CSF

(1) Increased CSF production

• Example—choroid plexus papilloma

(2) Obstruction in reabsorption of CSF by arachnoid granulations

• Examples—postmeningitic scarring, tumor

3. Noncommunicating (obstructive) hydrocephalus

Noncommunicating hydrocephalus: obstruction CSF outflow into ventricles

a. Obstruction of CSF flow out of the ventricles

b. Causes

(1) Stricture of the aqueduct of Sylvius

Blockage aqueduct of Sylvius: most common cause of hydrocephalus in newborns

(a) Most common cause in newborns

(b) Paralysis of upward gaze (Parinaud’s syndrome; Fig. 25-5)

(2) Tumor in the fourth ventricle

• Examples—ependymoma, medulloblastoma

(3) Scarring at the base of the brain

• Example—tuberculous meningitis

(4) Colloid cyst in the third ventricle

(5) Developmental disorders (see section II)

4. Clinical findings

a. Newborns

25-5: Hydrocephalus and Parinaud’s syndrome. Note the increased head circumference and paralysis of upward gaze in this newborn with stenosis of the aqueduct of Sylvius.

(Courtesy of Dr. Albert Biglan, Children’s Hospital of Pittsburgh.)

Hydrocephalus children: ventricles dilate and enlarge head circumference

• Ventricles dilate and enlarge the head circumference (see Fig. 25-5).

b. Adults

Hydrocephalus adults: no increase in head size; dementia, gait disturbance, urinary incontinence

• Ventricles enlarged but no increase in head circumference

5. Hydrocephalus ex vacuo

a. Dilated appearance of the ventricles when the brain mass is decreased

b. Example—Alzheimer’s disease

Hydrocephalus ex vacuo: dilated ventricles secondary to brain atrophy

6. Normal pressure hydrocephalus

a. Epidemiology

(1) Dilated ventricles + symptom complex of:

(a) Wide-based gait

(b) Urinary incontinence

Normal pressure hydrocephalus: dilated ventricles + triad—dementia, urinary incontinence, wide-based gait

(2) Dilated ventricles but normal CSF pressure

(3) Accounts for 5% of dementia cases

(4) Potentially reversible cause of dementia

b. Causes

Normal pressure hydrocephalus: potentially reversible cause of dementia with shunting

(1) Idiopathic (50%)

(2) Secondary causes

(a) Prior subarachnoid hemorrhage

(b) Prior intracranial surgery

c. Pathogenesis

(1) Increased subarachnoid space volume

(2) Ventricular dilation is out of proportion to sulcal atrophy (“ventriculomegaly”)

Wide-based gait/urinary incontinence: stretching of sacral motor fibers

(3) Wide-based gait and urinary incontinence due to stretching of sacral motor fibers near the dilated ventricle

Dementia: stretching of the limbic fibers

(4) Dementia due to stretching of limbic fibers near the dilated ventricle

d. Diagnosis

(1) MRI documents ventriculomegaly and sulcal atrophy.

(2) Large volume of CSF is removed at lumbar puncture.

• Symptoms improve with removal of the fluid.

e. Treatment

• Ventriculoperitoneal or ventriculoatrial shunting

II. Developmental Disorders

A. Neural tube defects

1. Pathogenesis

a. Failure of fusion of the lateral folds of the neural plate

Neural tube defects: failure of fusion of lateral folds of neural plate; ↑AFP

b. Rupture of a previously closed neural tube

2. Maternal findings

Maternal folate level must be adequate before pregnancy

• Increased maternal α-fetoprotein (AFP) in serum or amniotic fluid

3. Anencephaly

a. Complete absence of brain (Fig. 25-6)

25-6: Anencephaly showing absence of the brain and opening of the spinal canal.

(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 126, Fig. 5-23B.)

Anencephaly: absence of brain; maternal polyhydramnios

b. Frog-like appearance

c. Maternal polyhydramnios

4. Spina bifida occulta (Fig. 25-7A)

a. Defect in closure of the posterior vertebral arch

25-7: Types of spina bifida: spina bifida occulta (A), meningocele (B), meningomyelocele (C).

(From Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 12, Fig. 1-13.)

Spina bifida occulta: dimple/tuft of hair overlying L5–S1

b. Dimple or tuft of hair in the skin overlying L5–S1

5. Meningocele (Fig. 25-7B)

a. Spina bifida with cystic mass containing meninges

Meningocele: cystic mass with meninges

b. Most common in lumbosacral region

6. Meningomyelocele (Fig. 25-7C)

a. Spina bifida with cystic mass containing meninges and spinal cord

Meningomyelocele: cystic mass with meninges and spinal cord

b. Most common in lumbosacral region

B. Arnold-Chiari malformation

1. Caudal extension of medulla and cerebellar vermis through foramen magnum

2. Noncommunicating hydrocephalus

Arnold-Chiari: caudal extension medulla/cerebellar vermis through foramen; hydrocephalus; meningomyelocele; syringomyelia

3. Platybasia (flattening of base of skull)

• Decompression surgery

C. Dandy-Walker malformation

1. Partial or complete absence of the cerebellar vermis

Dandy-Walker: partial/complete absence of cerebellar vermis; cystic dilation of 4th ventricle; hydrocephalus

2. Cystic dilation of fourth ventricle

3. Noncommunicating hydrocephalus

4. Treatment

• Shunt to treat hydrocephalus

D. Syringomyelia

1. Degenerative disease of spinal cord

Syringomyelia: degenerative disease of spinal cord; usually cervical cord

a. Symptoms appear in the third and fourth decades.

b. Fluid-filled cavity (syrinx) within the cervical spinal cord (Fig. 25-8)

c. Produces cervical cord enlargement

d. Cavity expands and causes degeneration of spinal tracts.

25-8: Syringomyelia. Note the collapsed cystic cavity (syrinx) in the center of the cervical spinal cord.

(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 554, Fig. 11-70.)

Syringomyelia: cervical cord enlargment; fluid-filled cavity

2. Associated with Arnold-Chiari malformation

3. Pathogenesis

a. Obstruction of outflow from fourth ventricle

b. Birth injury

4. Clinical findings

Syringomyelia: ↓ pain/temperature sensation in hands; loss intrinsic muscles of hand

a. Disruption of the crossed lateral spinothalamic tracts

(1) Loss of pain and temperature sensation in the hands

• Tactile sense preserved

(2) Patient can burn hands without being aware of the burn.

b. Destruction of anterior horn cells

(1) Atrophy of intrinsic muscles of the hands

(2) Often confused with amyotrophic lateral sclerosis (ALS)

• No sensory changes in ALS

c. Charcot joint shoulder, elbow, wrist

5. Diagnosis

Syringomyelia: MRI shows cervical enlargement and cavity

• MRI shows enlarged cervical cord and cystic cavity.

6. Treatment

• Drainage of syrinx slows progression.

E. Phakomatoses (neurocutaneous syndromes)

Phakomatosis: neurocutaneous syndromes

1. Epidemiology

a. Neurocutaneous syndromes

b. Disordered growth of ectodermal tissue

c. Malformations or tumors of the CNS

d. Includes the following in descending order of incidence:

• Neurofibromatosis, tuberous sclerosis, Sturge-Weber syndrome

2. Neurofibromatosis (NF)

a. Autosomal dominant (AD) disorder with incomplete penetrance

NF: AD; incomplete penetrance

b. No gender predominance

c. Type 1 (NF1; most common) and type 2 (NF2) variants

(1) NF1—mutation on chromosome 17 coding for neurofibromin

(2) NF2—mutation on chromosome 22 coding for merlin

(3) Both proteins act as tumor suppressors.

d. NF1 (peripheral type) associated with:

(1) Café au lait coffee-colored macules (Fig. 25-9)

25-9: Neurofibromatosis showing café-au-lait macule (arrow) and numerous pigmented, pedunculated neurofibromas.

(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 104, Fig. 2-86.)

Both types: café au lait macules; neurofibromas

(a) Occur in both types

(b) Occur in 100% of children before 2 years of age

(2) Optic gliomas (2–5%); astrocytomas

NF₁: optic gliomas; Lisch nodules; axillary/inguinal freckling

(3) Lisch nodules (>90%)

• Hamartoma of the iris

(4) Axillary and inguinal freckling (70%)

(5) Mild scoliosis

(6) Pigmented plexiform neurofibromas (not in NF2)

• May progress into neurofibrosarcoma involving large nerves

(7) Pigmented cutaneous/subcutaneous neurofibromas

(a) Occur in both types

(b) Occur anywhere on the body except palms, soles

(d) Focal or diffuse

NF1 tumor associations: pheochromocytoma; Wilms’ tumor; CML (juvenile)

(8) Tumor associations

(a) Pheochromocytoma; Wilms’ tumor

• Both produce hypertension.

(b) Juvenile chronic myelogenous leukemia (CML)

(9) Neurodevelopment problems (30–40%)

e. NF2 (central type); associated with:

(1) Bilateral acoustic neuromas (schwannoma; >90%)

NF2: bilateral acoustic neuromas; juvenile cataracts; meningiomas

(a) Cranial nerve (CN) VIII tumor

(b) Benign tumor

(2) Meningiomas

(3) Spinal schwannomas

(4) Juvenile cataracts (∼︀80%)

f. Genetic testing available for both types

g. Treatment is mainly surgical.

3. Tuberous sclerosis

a. AD disorder

b. Second most common phakomatosis after neurofibromatosis

c. Mental retardation and seizures (infantile spasms) beginning in infancy

Tuberous sclerosis: AD; mental retardation; hamartomas in brain, kidneys

d. Angiofibromas (adenoma sebaceum) on the face (Fig. 25-10)

e. Hypopigmented skin lesions (“ash leaf” lesions; Fig. 25-11)

(1) Best identified with Wood’s lamp

(2) Occur in >80% of cases

25-10: Adenoma sebaceum (angiofibromas) in tuberous sclerosis. Note the reddish brown papules on the nose, cheeks, and chin.

(Courtesy of R.A. Marsden, MD, St. George’s Hospital, London.)

25-11: Shagreen patch in tuberous sclerosis. Note the irregular area of white skin (leukoderma) with the typical ash-leaf pattern of a shagreen patch.

(From Lookingbill DP, Marks JG: Principles of Dermatology, 3rd ed. Philadelphia, Saunders, 2000, p 234, Fig. 14-7.)

Key findings tuberous sclerosis: seizures, mental retardation, angiofibromas, ash leaf lesions

f. Hamartomatous lesions

(1) Astrocyte proliferations in subependyma

• Look like “candlestick drippings” in the ventricles

(2) Angiomyolipomas in the kidneys (80%)

g. Rhabdomyoma in the heart (50–60%)

Rhabdomyoma of heart: highly predictive of tuberous sclerosis

• Almost 100% predictive of tuberous sclerosis

4. Sturge-Weber syndrome (SWS; refer to Chapter 9; see Fig. 9-9D)

a. Somatic mosaicism or sporadic

b. Vascular malformation on the face

• In a trigeminal nerve distribution

SWS: vascular malformation of face; ipsilateral arteriovenous malformation in meninges in some patients

c. Some patients have ipsilateral arteriovenous malformation in the meninges.

III. Head Trauma

A. Cerebral contusion

1. Permanent damage to small blood vessels and the surface of the brain

2. Most often secondary to an acceleration-deceleration injury

3. Coup injuries occur at the site of impact (Fig. 25-12).

25-12: Brain contusion. The contrecoup injury involves the frontal and temporal lobes (left arrows), while the coup lesion (site of impact) involves the cerebellum (right arrow).

(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 403, Fig. 9-6.)

Coup injuries: site of impact

Contrecoup injuries: opposite site of impact

4. Contrecoup injuries occur opposite the site of impact.

• Common sites are at the tips of the frontal and temporal lobes.

B. Acute epidural hematoma

1. Epidemiology

a. Occurs in 1% to 2% of head injuries

b. Arterial bleed creates a blood-filled space between the bone and dura (Fig. 25-13A and B).

c. Caused by a fracture of the temporoparietal bone

25-13: A, Schematic of epidural hematoma and subdural hematoma. B, Epidural hematoma. Note the blood is located on top of the dura (arrow). C, Subdural hematoma. The reflected dura shows the outer membrane of an organized venous clot covering the convexity of the brain.

(A from Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 871, Fig. 23-13A; B courtesy of Dr. Raymond D. Adams, Massachusetts General Hospital, Boston; C from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 405, Fig. 19-20.)

Epidural hematoma: temporoparietal skull fracture; tear of middle meningeal artery

(1) Causes—hammer; baseball bat; any focused blow to head

(2) Severance of the middle meningeal artery

(3) Vessel lies between the dura and inner table of bone.

2. Some patients have lucid interval after trauma followed later by neurologic deterioration.

3. Intracranial pressure increases, leading to herniation and death.

4. Diagnosis

a. Head CT scan is the imaging test of choice.

CT scan: imaging test of choice

b. Hematoma rarely crosses the suture line due to firm attachment of dura at these sites.

5. Treatment consists of creating burr holes to relieve pressure.

C. Subdural hematoma