3-Pathology

Question 1

Describe Guillain-Barré syndrome

Answer 1

active inflammatory demyelinating polyradiculoneuropathy.
Features:
1. Ascending paralysis (starts in feet; normally).
2. Segmental demyelination of spinal and peripheral nerves (primary lesion).
3. Weakness (distal limbs first).
4. Life threatening (respiratory arrest; cardiac electrical system).
5. Decreased conduction velocity; increased CSF protein.

Onset: acute. Preceded by “flu-like” symptoms.
Causes: Campylobacter jejuni, CMV, Mycoplasma pneumoniae, vaccination.

Treat: plasmapheresis.
Lymphocyte and macrophage mediated

Question 2

Define wallerian degeneration and its etiology

Answer 2

Degeneration of dorsal columns after a spinal cord injury.

Question 3

Describe the various reactions of astrocytes to injury

Answer 3

Astrocytosis: local proliferation of glial cells in response to injury

Congenital hydrocephalus: gestational viral infection of ependymal cells

Question 4

Red Neurons

Answer 4

Ischemic/Dead neurons at the site of injury

Question 5

Astrocytes

Answer 5

Astrocytes: support neurons and promote repair. Star shaped. Outnumber neurons throughout CNS.
Fibrillary astrocytes (white matter).
Protoplasmic astrocytes (grey matter).
Glial Fibrillary Acidic Protein (GFA): stain specific for astrocytes.
Function: BBB (metabolic buffers); repair and scar formation.

Question 6

Gliosis

Answer 6

Astrocytosis (reactive gliosis): proliferation locally in response to injury (trauma, abscess, tumors, infarcts, hemorrhage).

Most important histopathalogic indicator of CNS injury!

Question 7

Rosenthal Fibers

Answer 7

bright, thick, elongated eosinophilic structures associated with long standing gliosis.

Also associated with pilocytic astrocytoma and reactive structures adjacent to craniopharyngioma

Question 8

Corpora Amylacea

Answer 8

Astrocytes make and store these proteins

When slow turnover of these processes

Proteins tagged with stuff and stored

Question 9

Differentiate between vasogenic and cytotoxic edema

Answer 9

Vasogenic edema: due to disruption of BBB (increased permeability). May be focal or generalized.

Cytotoxic edema: increase intracellular volume (hypoxia/ischemia inhibiting active pumps).
White matter more edematous. Increased salt due to pump inhibition. Affects ponds and midbrain more.

Question 10

Define hydrocephalus

Answer 10

Hydrocephalus: increased CSF in the ventricular system.

Non-communicating: there is an obstruction in the normal path of CSF flow.

Communicating: no obstruction. Removal via subarachnoid granulations (into venous system) is insufficient to keep up with production.

Aqueduct of Sylvius: most common location of obstruction (congenital malformation; viral ependymitis during emgryogenesis results in stenosis).

Question 11

Describe Chiari Type I and Type II (Arnold-Chiari) malformations.

Answer 11

CM: brainstem (medulla) and cerebellum compacted into bowl-shaped posterior fossa (flattening of base of skull; enlarged foramen magnum).

Associated with: syringomyelia; lumbar meningomyelocele.

Type I: NO meningomyelocele. Present infant to adolescence.

Type II, III: adults. Meningomyelocele.

Question 12

Define concussion and its immediate and long term effects

Answer 12

Transient loss of consciousness due to trauma (mainly brainstem reticular formation). Mildest type of spinal cord injury (transient/reversible).

“Knock-out”: quick deflection of head up and posteriorly places torque on brainstem and causes functional paralysis of neurons of reticular formation.

Temporal-parietal blow: skull fracture (generally not a concusision; lateral movement prevented by Falx).

Question 13

Epidural vs Subdural Hematoma

Answer 13

Epidural: convex tear-drop shape, MMA hemorrhage usually from fracture

Subdural: rupture of bridging veins slow bleed, concave with contour of head.

Question 14

Charcot-Bouchard microaneurysms

Answer 14

Charcot-Bouchard aneurysm: occur in small blood vessels.

Cause: chronic hypertension.

Pathogenesis: thickened vascular walls; lipid deposits.

Location: brainstem.

Prognosis: thrombus in ICA sends emboli into MCA.

Question 15

Describe congenital saccular “berry” aneurysms

Answer 15

arterial defect that arises during embryogenesis. 90% of secular aneurysms occur at branch points in carotid system.
Younger women. Saccular.

Rupture: life-threatening subarachnoid hemorrhage. ~35% mortality.

Question 16

AV malformations, discuss them

Answer 16

ArterioVenous Malformation (AVM): most common congenital vascular malformation. Onset 2nd-3rd decade.
Features: seizures; intracranial hemorrhage (subarachnoid).
Location: cerebral cortex (typically).

Pathology: abnormal vessesl replace cortical grey matter and extend deeply into white matter.

Question 17

4 main routes of entry for infection in the CNS

Answer 17

Hematogenous spread: most common. Usually via arterial route, or retrogradely (veins).
Direct implantation: trauma; iatrogenic (rare; lumbar puncture); congenital (meningomyelocele).
Local extension: secondary to established infections. Most from mastoid and frontal sinuses.
PNS to CNS: viruses (rabies, herpes zoster).

Question 18

Acute pyogenic meningitis and the causative organisms

Answer 18

Neonates: streptococcus agalactiae; E. Coli; Listeria monocytogenes.

Adolescents and young adults: Neisseria meningitidis (most common); Haempohilus influenza (reduced due to immunization; most common in infants is no S. pneumoniae).

Children and adults: Strep. Pneumonia.

IV Drug Users with HIV: Staph aurues.

Question 19

Brain abscesses and their possible sources/causing agents

Answer 19

Brain abscess: produces ring enhancement lesion on imaging.

Routes: movement from primary infected site (heart; lungs; tooth decay; bones).

Causes: staph, strep.

Pathogenesis: destructive lesions (central liquifactive necrosis surrounded by fibrous (collagenous) cap; edema surrounding).

Location: frontal lobe; parietal lobe; cerebellum.
Presentation: progressive focal deficits (increased ICP).

CSF: increased pressure; increased WBC; increased protein; glucose normal.

Thrombophlebitis: result of abscess. Develops in bridging veins, leading to occlusion (infarct).

S&S: febrile; headache; neck stiffness; lethargy/coma (if untreated).
CSF: similar to abscess.

Extradural abscess: associated with osteomyelitis (arise from adjacent site of infection).

Sources: sinusitis; surgical procedure.

Question 20

Tabes Dorsalis

Answer 20

demyelination of sensory neurons (ataxia; weakness; loss of coordination).

Result of neurosyphilis 3rd degree.

Question 21

List the most common sites of primary thrombosis.

Answer 21

MCA

Question 22

18. List and describe the two groups of infarcts.

Answer 22

Ischemic

Hemorrhagic

Question 23

19. Discuss lacunar infarcts and their etiology.

Answer 23

noncortical infracts caused by occlusion of penetrating arteries.

Question 24

20. Describe hypertensive encephalopathy and Binswanger disease

Answer 24

Fibronoid necrosis: hypertensive encephalopathy. Malignant hypertension.
Petechiae: minute hemorrhages.

Binswanger disease: subcortical arteriosclerotic encephalopathy (multiple infarcts in white matter).

Question 25

21. List the major cause of nontraumatic intraparenchymal hemorrhages

Answer 25

Most commonly seen in systemic hypertension. i.e. charcot-bouchard aneurysm

Question 26

30. Describe the types of neurologic dysfunction associated with HIV infections

Answer 26

~60% of patients develop neurologic dysfunction. Aseptic meningitis within 1-2 weeks of seroconversion in ~10% of patients. HIV meningoencephalitis (subacute encephalitis): dementia (mental slowing; memory loss; mood disturbances); ataxia; bladder/bowl incontinence; seizure. Chronic inflammatory reaction: microglial infiltrates (nodules); multinucleated giant cell. Vacuolar Myelopathy: spinal cord. 20-30% of paitients in US. Similar to subacute combined degeneration (Vit B12 deficiency; Vit B12 levels are normal). Myopathy and Peripheral Neuropathy: inflammatory myopathy. Most described disorder in patients with HIV. S&S: proximal weakness; pain; increased serum creatine kinase. Most commonly reported syndromes: acute/chronic inflammatory ~60% of patients develop neurologic dysfunction. Aseptic meningitis within 1-2 weeks of seroconversion in ~10% of patients. HIV meningoencephalitis (subacute encephalitis): dementia (mental slowing; memory loss; mood disturbances); ataxia; bladder/bowl incontinence; seizure. Chronic inflammatory reaction: microglial infiltrates (nodules); multinucleated giant cell. Vacuolar Myelopathy: spinal cord. 20-30% of paitients in US. Similar to subacute combined degeneration (Vit B12 deficiency; Vit B12 levels are normal). Myopathy and Peripheral Neuropathy: inflammatory myopathy. Most described disorder in patients with HIV. S&S: proximal weakness; pain; increased serum creatine kinase. Most commonly reported syndromes: acute/chronic inflammatory

Question 27

31. Describe progressive multifocal leukoencephalopathy (PML)

Answer 27

Demyelination of CNS due to destruction of oligodendrocytes. Associated with JC virus. Usually fatal. Rapidly progressive

Question 28

32. Define kuru plaques.

Answer 28

Kuru: prion disease. Ritualistic cannibalism. | S&S: symptomatic coordinative malfunctions; inappropriate episodes of laughter (“laughing death”).

Question 29

33. Describe CJD.

Answer 29

Prion disease rapidly progressive dementia with myoclonus Spongiform cortex

Question 30

36. Describe Pick’s disease

Answer 30

Dementia, aphasia, parkinsonian aspects, personality changes, Spares parietal lobe. Find pick bodies on histo, spherical tau protein aggregates.

Question 31

37. List the four major classes of brain tumors

Answer 31

Gliomas Neuronal Tumors Poorly Differentiated Meningiomas

Question 32

38. List the three major types of gliomas.

Answer 32

Astrocytoma Oligodendroglioma Ependymoma

Question 33

39. Describe astrocytomas and glioblastomas.

Answer 33

Fibrillary astrocytoma: most common (80% of adult primary tumors). Onset 20-40s (rare after). Location: cerebral hemispheres. Presenting signs: seizures; headache; no focal neurological dificits. Prognosis: WHO classification; grades 1-4. Glioblastoma multiformes: death sentence (8-10 months after diagnosis). 2 distinct clinical histories: 1. Short, rapidly progressive, arising without preexisting low grade tumor. Typically in older patients (primary glioblastoma). 2. Previously diagnosed low grade astrocytoma (secondary astrocytoma). Young. P53 mutation. Pathology: necrosis (well-circumscribed).

Question 34

40. Describe pilocytic astrocytomas

Answer 34

young adults, children. Relatively benign. Rare p53 mutation. Location: cerebellum; anterior optic pathway; floor of 3rd ventricle; cerebral hemispheres. Features: cystic appearance (solid, brightly contrast-enhancing mural component and associated cyst); grows slowly; WHO grade 1. Diagnosis: labeled by antisera to B-crystallin; immunoreactive for α-1-antitrypsin.

Question 35

41. Describe oligodendrogliomas.

Answer 35

young, middle-aged adults. 5-15% of gliomas. Location: frontal and temporal lobes (mainly within white matter). Features: calcification. Pathology: loss of chromosome 1p and 19q (80% of patients). Prognosis: 5-10 year survival.

Question 36

42. Briefly describe general ependymomas

Answer 36

young (ventricular system); adults (spinal cord). Location: next to ependymal-lined ventricular system. Central canal of spinal cord. 4th ventricle: young (1st 2 decades). Spinal cord: adults. Associated with Neurofibromatosis-2. Pain. Clinical features: posterior fossa ependymoma with hydrocephalus secondary to obstruction. Histology: form rosettes or perivascular pseudorosettes.

Question 37

43. Describe primary brain lymphoma

Answer 37

Primary CNS lymphomas: most common CNS neoplasm in immunosuppressed (HIV; SLE) patients. Elderly (> 60; nonimmunosuppresed). Location: brain; spinal cord; meninges. Pathology: B-cell origin (EBV). Pathogenesis: invades deep structure of brain (cerebral hemispheres; corpus callosum; basal ganglia); cerebellum; brainstem; spinal cord (rarely). Crosses corpus callosum. Features: perivascular localization (rosettes).

Question 38

44. Briefly describe schwannomas

Answer 38

Schwannomas: benign. Arise from neural crest cells. SOL (brainstem, spinal cord). NF2 gene: inactivating mutations of chromosome 22. Merlin: product of 22. Loss of expression consistent finding in schwannomas. Normally controls/restricts actions of cell surface growth factor (EGFR). Absence results in hyperproliferation. Acoustic neuroma: occur in cerebellopontine angle (attached to CN VIII). Features: tinnitus; hearing loss.