Pathology High-Yield Topics

1. Hydrocephalus – types and sequellae

- defn:

- increased volume of CSF in cranial cavity à ventricles and subarachonoid spaces are dilated

- types:

- internal – increased volume of CSF just in ventricles

- external – increased volume confined to subarachnoid space

- communicating – free flow of CSF between ventricles and subarachnoid space but problem of absorption

- equal dilation of ventricles

- non-communicating – obstructed flow of CSF from vent à SA space

- causes:

- obstruction of CSF circulation b/c congenital malformations, inflammation, and tumors (common)

- overproduction of CSF by choroid plexus papilloma (rare)

- low pressure differential – if CSF pressure is lower than venous pressure

- hydrocephalus ex vacuo – not a true hydeocephalus

- brain reduction à dilation of fluid spaces/increased CSF to maintain constant brain volume

- sequellae/signs and symptoms

- increased ICP

- h/a,

- n/v

- bradycardia

- elevated BP

- Cushing’s reflex = bradycardia + inc. BP + altered respirations

- papilledema à blindness

- altered consciousness

- urinary retention

- changes in head diameter (in children)

- setting-sun sign – oculomotor difficulties

- diplopia

- hyperreflexia

2. CNS manifestations of viral infections

- can be limited to meninges or involve whole brain and spinal cord

Virus	Infection	Clinical manifestations	Histologic features	Other
Viral meningitis	Viral agents (especially enteroviruses like echo and coxsackie), hematogenous spread	Fever, h/a nuchal rigidity, photophobia, minigitis, encephalitis, seizures,		CSF: increased WBC, mod inc protein, nl glucose, Tx – supportive only
Encephalitis		Inflammations of brain substance à fever, seizures, altered consciousness, disordered thinking May also have brain abscess	Inclusion bodies in neurons or glial cells, perivascular cuffing
Arbovirus (St. Louis, Eastern or Western Equine, West Nile)	Horse/bird reservoir, mosquito vector	Meningitis, fever, h/a, encephalomyelitis, optic neuritis, radiculitis		CSF: decreased WBCs, inc protein, pleocytosis
Arena/White Water Arroyo/ Hantaviruses	Rodents (rats and mice) carry virus, can be transmitted person-to-person as well	Hanta – fatal Arena (Lassa fever) – mild (conjunctival exudates, 8^th nerve damage) or severe (hemorrhagic fever)	White Water (with clinical) – fever, hemorrhagic manifestations
HSV	Virus sits in nerves à no viral antigens made, spreads retrograde to CNS	Acute onset: meningitis, encephalitis, fever, confusion, personality changes, seizures, lethargy		Most common in teens and young adults, uncommon complication of HSV Tx – acyclovir (only treatable encephalitis)
Rabies	Saliva of dogs, bats, raccoons, foxes, etc à multiplies in muscle à moves along nerves to CNS	Violent muscle contractions and convulsions, fever, malaise, h/a, increased salivation	Negri bodies in neurons	Fatal once clinical signs/symptoms appear
CMV	Affected immunosuppressed	Encephalomyelitis, lesions of kidney, lungs, liver, salivary glands, retintis Infants: severe mental retardation, microcephaly, chorioretinitis, hepatosplenomegaly	Eosinophilic inclusions	Tx with ganciclovir or foscarnet
HIV	Can affect brain, spinal cord, or PNS by direct HIV infection, opportunisitic	AIDS dementia (progressive), difficulty concentrating and w/memory, lethargy, balance and motor coordination problems		Zoster à can be activated as shingles (sometimes 1^st sign of HIV)
Creutzfeldt-Jakob	Infection by prions	Ataxia, rapidly progressive dementia, early death	Spongiosis, especially in gray matter

3. Spinal muscular dystrophies (degenerative)

Spinal Muscular Dystrophy	Genetics/Anatomy	Type of neuron/muscle involved	Clinical aspects	Other
ALS	Loss of anterior horn cells, corticospinal tract involvement, degeneration of peripheral motor nerves, neurogenic muscular atrophy	Both LMN (see symmetric atrophy and fasciculations), UMN (see hyperreflexia, spasticity, pathologic reflexes) involved	Rapidly progressive LMN and UMN failure, death often from respiratory failure	“Lou Gehrig’s disease”, most common form of motor neuron disease
Friedrich’s ataxia	Familial (AD), onset under 20, Dorsal root and spinocerebellar involvement	PNS and CNS involved	No deep tendon reflexes, gait ataxia, hand clumsiness, dysarthria à eventual paralysis	Opposite of ALS
Werdnig-Hoffman Syndrome	AR, manifests in infancy, linked to chr. 5q	Large Type I fibers are the hallmark of disease	“floppy baby”, tongue fasciculations, death from respiratory failure	Babies don’t survive longer than 1-2 years
Duchenne/Becker	X-linked, Complete (Duchenne) /Partial (Becker) lack of dystrophin	All muscles affected à atrophy	Very arched back, hypertrophied calves and butts	Affects only boys (X-linked), only live to 18-20 years
Myotonic Dystrophy	AD, gene on chr. 19	Systemic à all muscles affected, will see inc # of internalized nuclei, ring fibers on bx	Muscle weakness, cataracts, testicular atrophy, heart disease, dementia, baldness
Polio	Poliovirus invades CNS	LMN	Paralysis
Progressive bulbar palsy		Brainstem and cranial nerve involvement	Difficulty swallowing and speaking, death by respiratory failure