Pathology

Question 1

Dementia

Answer 1

A decrease in cognitive ability, memory, or function with intact consciousness

Question 2

Alzheimer disease

Answer 2

Most common cause in elderly. Down syndrome patients have an incr risk of developing Alzheimer.
Familial form (10%) associated with the following altered proteins (respective chromosomes in parentheses):
-Early onset: APP (Chr 21), presenilin-1 (Chr 14), presenilin-2 (Chr 1)
-Late onset: ApoE4 (Chr 19) ApoE2 (Chr 19) is protective.

Widespread cortical atrophy. Narrowing of gyri and widening of sulci.
Decreased ACh

Senile plaques: extracellular β-amyloid core; may cause amyloid angiopathy–> intracranial hemorrhage; Αβ (amyloid-β) synthesized by cleaving amyloid precursor protein (APP)

Neurofibrillary tangles: intracellular, hyperphosphorylated tau protein = insoluble cytoskeletal elements; tangles correlate with degree of dementia

Question 3

Pick disease (frontotemporal dementia)

Answer 3

Dementia, aphasia, parkinsonian aspects; change in personality. Spares parietal lobe and posterior 2 ⁄3 of superior temporal gyrus.
Pick bodies: spherical tau protein aggregates Frontotemporal atrophy

Question 4

Lewy body dementia

Answer 4

Initially dementia and visual hallucinations followed by parkinsonian features.
α-synuclein defect

Question 5

Creutzfeldt-Jakob disease

Answer 5

Rapidly progressive (weeks to months) dementia with myoclonus (“startle myoclonus”).
Spongiform cortex Prions (PrPc-->PrPsc sheet [β-pleated sheet resistant to proteases])

Question 6

Other causes of dementia

Answer 6

Multi-infarct (2nd most common cause of dementia in elderly); syphilis; HIV; vitamins B1, B3, or B12 deficiency; Wilson disease; and NPH.

Question 7

Multiple Sclerosis

Answer 7

Autoimmune inflammation and demyelination of CNS (brain and spinal cord). Patients can present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils)
internuclear ophthalmoplegia, hemiparesis, hemisensory symptoms, or bladder/bowel incontinence. Relapsing and remitting course.
Most often affects women in their 20s and 30s; more common in whites.

Charcot classic triad of MS is a SIN:

• Scanning speech
• Intention tremor (also Incontinence and Internuclear ophthalmoplegia)
• Nystagmus

Dx: Incr protein (IgG) in CSF. Oligoclonal bands are diagnostic. MRI is gold standard. Periventricular plaques A (areas of
oligodendrocyte loss and reactive gliosis) with destruction of axons. Multiple white matter lesions separated in space and time.

Tx: β-interferon, immunosuppression, natalizumab.
Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABA receptor agonist), pain (opioids).

Question 8

Acute inflammatory demyelinating polyradiculopathy

Answer 8

Most common variant of Guillain-Barré syndrome. Autoimmune condition that destroys Schwann cells

Question 9

Progressive multifocal leukoencephalopathy

Answer 9

Demyelination of CNS due to destruction of oligodendrocytes. Associated with JC virus. Seen in 2–4% of AIDS patients (reactivation of latent viral infection). Rapidly progressive, usually fatal. Incr risk associated wtih natalizumab

Question 10

Acute disseminated (post infectious) encephalomyelitis

Answer 10

Multifocal perivenular inflammation and demyelination after infection (commonly measles or VZV) or certain vaccinations (e.g., rabies, smallpox).

Question 11

Metachromatic leukodystrophy

Answer 11

Autosomal recessive lysosomal storage disease, most commonly due to arylsulfatase A deficiency. Buildup of sulfatides–> impaired production of myelin sheath.
Findings: central and peripheral demyelination with ataxia, dementia.

Question 12

Charcot-Marie-Tooth disease

Answer 12

Also known as hereditary motor and sensory neuropathy (HMSN). Group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath. Typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches).

Question 13

Krabbe disease

Answer 13

Autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase. Buildup of galactocerebroside and psychosine destroys myelin sheath. Findings: peripheral neuropathy, developmental delay, optic atrophy, globoid cells.

Question 14

Adrenoleukodystrophy

Answer 14

X-linked genetic disorder typically affecting males. Disrupts metabolism of very-long-chain fatty acids–>excessive buildup in nervous system, adrenal gland, and testes. Progressive disease that can lead to long-term coma/death and adrenal gland crisis.

Question 15

Partial (focal) seizures

Answer 15

Affect 1 area of the brain. Most commonly originate in medial temporal lobe. Often preceded by seizure aura; can secondarily generalize. Types:

• Simple partial (consciousness intact)— motor, sensory, autonomic, psychic
• Complex partial (impaired consciousness)

Question 16

Generalized seizures

Answer 16

Diffuse. Types:

• Absence (petit mal)—3 Hz, no postictal confusion, blank stare
• Myoclonic—quick, repetitive jerks
• Tonic-clonic (grand mal)—alternating stiffening and movement
• Tonic—stiffening
• Atonic—“drop” seizures (falls to floor); commonly mistaken for fainting

Question 17

Epilepsy

Answer 17

a disorder of recurrent seizures (febrile seizures are not epilepsy).

Question 18

Status epilepticus

Answer 18

continuous seizure for > 30 min (also heard 5 mins?) or recurrent seizures without regaining consciousness between seizures for > 30 min (or 5 mins?)
Medical emergency.

Question 19

Seizure causes by age

Answer 19

• Children: genetic, infection (febrile), trauma, congenital, metabolic
• Adults:tumors, trauma, stroke, infection
• Elderly:stroke, tumor, trauma, metabolic, infection

Question 20

Cluster headaches (description, localization, duration, treatment)

Answer 20

Localization: Unilateral 15 min–3 hr; repetitive
Description: Repetitive brief headaches. Excruciating periorbital pain with lacrimation and rhinorrhea. May induce
Horner syndrome.
More common in males
Tx: Inhaled O2, sumatriptan

Cluster headaches can be differentiated from trigeminal neuralgia based on duration. Trigeminal neuralgia produces
repetitive shooting pain in the distribution of CN V that lasts (typically) for < 1 minute. The pain from cluster headaches lasts considerably longer (> 15 minutes

Question 21

Tension headaches (description, localization, duration, treatment)

Answer 21

Bilateral > 30 min(typically 4–6 hr); constant
Steady pain. No photophobia or phonophobia. No aura.
Tx: Analgesics, NSAIDs, acetaminophen;
amitriptyline for chronic pain

Question 22

Migraine headaches (description, localization, duration, treatment)

Answer 22

Unilateral 4–72 hr
Pulsating pain with nausea, photophobia, or phonophobia. May have “aura.” Due to irritation of CN V, meninges, or blood vessels (release of substance P, CGRP, vasoactive
peptides).
Abortive therapies (e.g., triptans, NSAIDs) and prophylactic (propranolol, topiramate, calcium channel blockers, amitriptyline).

POUND–Pulsatile, One-day duration, Unilateral, Nausea,
Disabling

Question 23

Other causes of headache

Answer 23

subarachnoid hemorrhage (“worst headache of life”), meningitis, hydrocephalus, neoplasia, and arteritis.

Question 24

Trigeminal neuralgia

Answer 24

Trigeminal neuralgia produces repetitive shooting pain in the distribution of CN V that lasts (typically) for < 1 minute.

The pain from cluster headaches lasts considerably longer (> 15 minutes)

Cluster headaches can be differentiated from trigeminal neuralgia based on duration.

Question 25

Vertigo

Answer 25

Sensation of spinning while actually stationary. Subtype of “dizziness,” but distinct from “lightheadedness.”

Question 26

Peripheral vertigo

Answer 26

More common. Inner ear etiology (e.g., semicircular canal debris, vestibular nerve infection, Ménière disease). Positional testing–>delayed horizontal nystagmus.

Question 27

Central vertigo

Answer 27

Brain stem or cerebellar lesion (e.g., stroke affecting vestibular nuclei or posterior fossa tumor). Findings: directional change of nystagmus, skew deviation, diplopia, dysmetria. Positional testing–>immediate nystagmus in any direction; may change directions. Focal neurological findings.

Question 28

Sturge-Weber syndrome

Answer 28

Congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ectoderm) due to activating mutation of GNAQ gene.

• Affects small (capillary sized) blood vessels –>Port-wine stain of the face (non-neoplastic “birthmark” in CN V1/V2 distribution);
• Ipsilateral leptomeningeal angioma–>seizures/epilepsy; -Intellectual disability; and episcleral hemangioma–> incr IOP –>early-onset glaucoma.

STURGE-Weber: Sporadic, port-wine Stain; Tram track Ca2+ (opposing gyri); Unilateral; Retardation, Glaucoma, GNAQ gene; Epilepsy.

Question 29

Tuberous sclerosis

Answer 29

HAMARTOMAS: 
Hamartomas in CNS and skin; 
Angiofibromas; 
Mitral regurgitation; 
Ash-leaf spots; 
cardiac Rhabdomyoma; 
(Tuberous sclerosis); 
autosomal dOminant; 
Mental retardation; 
renal Angiomyolipoma D; 
Seizures, Shagreen patches.
Incidence of subependymal astrocytomas and ungual fibromas.

Question 30

Neurofibromatosis type I (von Recklinghausen disease)

Answer 30

Café-au-lait spots, Lisch nodules (pigmented iris hamartomas), neurofibromas in skin, optic gliomas, pheochromocytomas. Mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of Ras) on chromosome 17. Skin tumors of NF-1 are derived from neural crest cells.

Question 31

von Hippel-Lindau disease

Answer 31

Cavernous hemangiomas in skin, mucosa, organs; bilateral renal cell carcinomas; hemangioblastoma (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum; and pheochromocytomas. Autosomal dominant; mutated VHL tumor suppressor gene on chromosome 3, which results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors.

Question 32

Glioblastoma multiforme (grade IV astrocytoma)

Answer 32

Common, highly malignant 1° brain tumor with ~ 1-year median survival. Found in cerebral hemispheres A. Can cross corpus callosum (“butterfly glioma”). Stain astrocytes for GFAP. “Pseudopalisading” B pleomorphic tumor cells—border central areas of necrosis and hemorrhage.

Question 33

Meningioma

Answer 33

Common, typically benign 1° brain tumor. Most often occurs in convexities of hemispheres (near surfaces of brain) and parasagittal region. Arises from arachnoid cells, is extra-axial (external to brain parenchyma), and may have a dural attachment (“tail”). Often asymptomatic; may present with seizures or focal neurological signs. Resection and/or radio surgery. Spindle cells concentrically arranged in a whorled pattern; psammoma bodies (laminated calcifications).

Question 34

Hemangioblastoma

Answer 34

Most often cerebellar. Associated with von Hippel-Lindau syndrome when found with retinal angiomas. Can produce erythropoietin–>2° polycythemia. Closely arranged, thin-walled capillaries with minimal interleaving parenchyma F .

Question 35

Schwannoma

Answer 35

Usually found at cerebellopontine angle. Schwann cell origin H, S-100 “; often localized to CN VIII–>acoustic schwannoma (aka acoustic neuroma). Resectable or treated with stereotactic radio surgery. Bilateral acoustic schwannomas found in NF-2.

Question 36

Oligodendroglioma

Answer 36

Relatively rare, slow growing. Most often in frontal lobes I . Chicken-wire capillary pattern. Oligodendrocytes = “fried egg” cells—round nuclei with clear cytoplasm J . Often calcified in oligodendroglioma.

Question 37

Pituitary adenoma

Answer 37

Most commonly prolactinoma K. Bitemporal hemianopia ( L shows normal visual field above, patient’s perspective below) due to pressure on optic chiasm. Hyper- or hypopituitarism are sequelae.

Question 38

Pilocytic (low-grade) astrocytoma

Answer 38

Childhood primary brain tumor
Usually well circumscribed. In children, most often found in posterior fossa A (e.g., cerebellum). May be supratentorial. GFAP “. Benign; good prognosis.
Rosenthal fibers—eosinophilic, corkscrew fibers B. Cystic + solid (gross).

Question 39

Medulloblastoma

Answer 39

Childhood primary brain tumor.
Highly malignant cerebellar tumor. A form of primitive neuroectodermal tumor. Can compress 4th ventricle, causing hydrocephalus. Can send “drop metastases” to spinal cord.
Homer-Wright rosettes. Solid (gross), small blue cells (histology).

Question 40

Ependymoma

Answer 40

Childhood primary brain tumor.
Ependymal cell tumors most commonly found in 4th ventricle. Can cause hydrocephalus. Poor prognosis.
Characteristic perivascular rosettes. Rodshaped blepharoplasts (basal ciliary bodies) found near nucleus

Question 41

Craniopharyngioma

Answer 41

Benign childhood tumor, may be confused with pituitary adenoma (both can cause bitemporal hemianopia).
Most common childhood supratentorial tumor.
Derived from remnants of Rathke pouch. Calcification is common (tooth enamel–like).

Question 42

Brain herniation sydromes

Answer 42

-Cingulate (subfalcine) herniation under falx cerebri
Can compress anterior cerebral artery.

-Downward transtentorial (central) herniation

• Uncal herniation Uncus = medial temporal lobe. Compresses ipsilateral CN III (blown pupil, “down-andout”
  gaze) , ipsilateral PCA (contralateral homonymous hemianopsia), contralateral crus cerebri (ipsilateral paralysis, “false localization” sign).

-Cerebellar tonsillar herniation into the foramen magnum
Coma and death result when these herniations compress the brain stem (and inhibit respiration).