CIS

Question 1

Increased ICP is due to what?

Answer 1

1) Generalized brain edema
2) Expanding mass lesion

Question 2

Transtentorial herniation is due to what and will lead to compression of which CN?

Answer 2

Transtentorial is due to uncal/medial aspect of the temporal lobe compressed against the tentorium

CN 3 affected which leads to dilation of pupil and impaired eye movement

Question 3

Tonsilar herniation?

Answer 3

Tonsillar: cerebellar tonsils displaced through the foramen magnum; life threatening due to respiratory & cardiac center compression

Question 4

Kernohan’s notch phenomenon is what and involves which CNs?

Answer 4

is a result of the compression of the cerebral peduncle against the tentorium cerebelli due to transtentorial herniation. This produces ipsilateral hemiparesis or hemiplegia

CN3 and CN6

CN6 signs

Clinical features of abducens nerve palsy include diplopia, the affected eye resting in adduction (due to unopposed activity of the medial rectus), and inability to abduct the eye

Question 5

Embolic stroke, from what?

Due to what?

Answer 5

Hemorrhagic (red): intra-cerebral or subarachnoid hemorrhage

• Hemorrhage secondary to reperfusion of damaged vessels

Question 6

Thrombotic stroke features?

Can cause what?

Answer 6

• Ischemic (pale, bland, anemic) infarction: bloodless

Hygroma and liquifactive necrosis

Question 7

Multiple system atrophy has what kind of deposit and what are it’s 3 cardinal effects?

Answer 7

Deposition of alpha synuclein in oligodendrocytes

1) Straitonigral circut is disrupted causing parkinsonism
2) Olivopontocerebellar circuit which causes ataxia
3) Autonomic dysfunction leading to hypotension

Question 8

What is periventricular leukomalacia and what can it lead to?

Answer 8

Infarcts in the supratentorial white matter

Premature infants, chalky yellow plaques which leads to necrosis and calcification

Leads to multicystic encephalopathy: extensive ischemic damage of both white & gray matter → large destructive cystic lesions

Question 9

Vasogenic edema is primarily due to the disruption of what? Due to what?

Answer 9

↑extracellular fluid due to BBB disruption & ↑vascular permeability

Usually due to neoplasm and often follows ischemic injury

Question 10

CMV presents in who, where, and what does it cause?

Answer 10

Presents as an oppurtunistic infections in aids patient (immunocompromised) and fetuses

• In utero → periventricular subependymal necrosis → severe brain destruction → microcephaly & periventricular calcification

Question 11

Toxoplasmosis presents in who and how?

Histo?

Answer 11

HIV/ immunocomp

Brain absess near the gray-white junction and deep gray nuclei

Histo: Central foci of necrosis, petechial hemorrhages and vascular proliferation

Free tachyzoites and encysted bradyzoites at the periphery of necrotic zones

Question 12

HIV presents with what symptoms and how does it present in the chronic stages?

Cancer associated?

Answer 12

Aseptic meningitis

Acute: perivascular inflammation

Chronic: microglial nodules with multinucleated giant cells

Associated with dementia

*Primary CNS lymphoma*

Question 13

What is CJD? Tell me about the proteins involved

Answer 13

Prion protein (PrP)

• Abnormal forms of cellular proteins → rapidly progressive

Turns to abnormal beta pleated sheet

Characterized by spongiform changes: intracellular vacuoles

Question 14

Tell me about neisseria and what it causes? Where do people get it?

Answer 14

It’s a gram negative diplococci that is transmitted in crowded populations

• Rapidly progressive septicemia with fever, hypotension, DIC, petechial and purpuric lesions
• Purpura fulminans: hemorrhagic skin lesions which progress to gangrene; occurs in distal portions of limbs
• Hemorrhagic infarction of adrenal glands: Waterhouse Friderichsen syndrome

Question 15

Where are most anneurysms and where do they start?

Answer 15

Most frequent cause of clinically significant subarachnoid hemorrhage (SAH) is rupture of saccular (berry) aneurysm

• Circle of Willis, therefore begins as basilar SAH

develop over time due to underlying defect in the media of the vessel​

About 90% saccular found near major branch points of the anterior circulation

Question 16

AVMs and their most common locations?

Answer 16

AVM: subarachnoid space, may extend into brain parenchyma or may be exclusively in parenchyma

• Tangle, worm-like vascular channels with prominent pulsatile arteriovenous shunting with high blood flow
• Arteriovenous shunting: arteries →veins without intervening capillaries
• MCA & posterior branches most common

Question 17

Lacunar infarcts are caused by what and affect what portions of the brain?

Answer 17

• Lacunar infarcts: deep penetrating arteries & arterioles develop arteriolar sclerosis (lenticulostriate arteries) affecting caudate and putamen

Question 18

What causes hypetensive encephalopathy? And chronically can lead to what?

Answer 18

Malignant HTN • HTN risk factor most commonly assoc with deep brain parenchymal hemorrhages

• Charcot-Bouchard microaneurysms: assoc with chronic hypertension
• Minute (<300 m) aneurysms in the basal ganglia

Question 19

What happens in CADASIL and what is it positive for?

Answer 19

• Recurrent strokes and dementia • first detectable ~35yo: Infarcts typically occur 10-15 years later in other cases
• Autosomal dominant NOTCH 3 gene

Thickening of the media & adventitia, loss of smooth muscle cells, & basophilic PAS+ deposits

Question 20

Huntington Dz Pathogenesis

Answer 20

• Loss of medium spiny striatal neurons that usually dampen motor acticity lead to chorea and what not

Toxic gain of fxn on Huntingtin gene

**Striking atrophy of caudate nucleus; putamen later**

*Atrophy in the frontal lobes* and severe loss of striatal neurons mostly in the caudate nucleus

Question 21

Huntington dz pattern of inheritance, gene locus, and symptoms?

Answer 21

• Autosomal dominant
• Progressive movement disorder & dementia; histologically by degeneration of striatal neurons
• Jerky, hyperkinetic, sometimes dystonic movements involving all parts of the body = chorea
• HD: polyglutamine trinucleotide repeat; chr 4p16.3 encodes Huntingtin protein (HTT)
• Anticipation: repeat expansions during spermatogenesis leads to earlier onset (juvenile form)

Question 22

Multiple sclerosis characteristics and symptoms

Answer 22

• Autoimmune demyelinating DO

• Distinct episodes of neurologic deficits, separated in time, attributable to white matter lesions that are separated in space
• Relapsing & remitting episodes of variable duration
• Unilateral visual impairment: frequently initial symptom (optic neuritis, retrobulbar neuritis)
• 10-50% pts with optic neuritis develop MS

Question 23

CJD

Answer 23

• CJD: 90% of cases, seventh decade • Iatrogenic transmission: corneal transplant, brain implantation of electrodes & human growth hormone
• Rapidly progressive dementia with startle myoclonus, 7 months • So rapid, little if any gross evidence of brain atrophy
• Spongiform changes microscopic

Question 24

What is vCJD and what is it positive for?

Answer 24

• Behavioral changes early in dz
• Slower progression
• Exposure to bovine spongiform encephalopathy
• Kuru plaque: extracellular deposits of aggregated abn protein;

+ Congo Red & + PAS

Question 25

ALS, gene, presentation

Answer 25

• Loss of **lower motor** neurons in spinal cord & brainstem, & **upper motor neurons** that project into corticospinal tracts **SOD1**: superoxide dismutase • Early sx: asymmetric weakness of hands; dropping objects, difficulty with fine motor tasks, cramping & spasticity of arms & legs Fasiculations, URIs

Question 26

Progressive bulbar palsy (bulbar ALS)

Answer 26

• Progressive bulbar palsy (bulbar ALS): degeneration of lower brainstem cranial motor nuclei occurs early & **_progresses rapidly_**; **deglutination & phonation difficulties** (Speaking & Swallowing)

Question 27

What is the organism for neuro syphillis? Symptoms of meningococcal neurosyphillis?

Answer 27

Meningovascular neurosyphilis: chronic meningitis involving **base of the brain,** communicating hydrocephalus • **_Obliterative endarteritis_** = **_Heubner arteritis_**; perivascular plasma cells & lymphocytes

Question 28

What is paretic neurosyphillis? What deposits do you see?

Answer 28

• Paretic neurosyphilis: insidious, but progressive mental deficits assoc with mood alterations (**delusions of grandeur**) that terminate in severe dementia (**general paresis of the insane**); **perivascular _iron_ deposits**

Question 29

What is tabes dorsalis associated with and what is it?

Answer 29

**Tabes dorsalis**: damage to the **sensory nerves** (loss of myelin & axons) in the dorsal roots; impaired joint position sense & resultant ataxia (locomotor ataxia); _loss of pain sensation_; **joint damage** (**Charcot joints**); “lightening pains”; _absence of deep reflexes_

Question 30

what does Basal Cell Carincoma look like and where does it manifest?

Answer 30

Nodulo-ulerative: **pearly nodules, telangiectatic vessels, central ulcer (“rodent ulcer”), rolled edges** • **Lower eyelid** \> inner canthus \> upper lid \> outer canthus • nests of basaloid cells that show **peripheral palisading** of nuclei

Question 31

Melanoma genes and manifestations?

Answer 31

Uveal melanoma most common primary intraocular tumor in adults (~5% of US melanomas) * **GNAQ & GNA11** uveal melanoma oncogenes, in 85% of uveal melanomas * nevi with GNAQ & GNA11 rarely transform to melanoma * Morph: spindle: fusiform • **\*Epithelioid: spherical, greater cytological atypicality, worse prognosis\*** • _Large nuclei, prominent nucleoli, infiltrating plasma cells & lymphs_ • Uveal melanoma spreads first to the liver

Question 32

Neuromyelitis optica

Answer 32

**_Synchronous (or near synchronous) bilateral optic neuritis & spinal cord demyelination_** **• 10-50% pts with optic neuritis develop MS** • CSF: **neutrophils** & increased opening pressure, can be turbid • Vascular deposition of immunoglobulin & complement • **Antibody to _aquaporins_** (maintain astrocyte foot processes; thus integrity of blood-brain barrier) • TX: attempt to decrease antibody burden via **plasmapheresis**

Question 33

Open angle glaucoma

Answer 33

complete _open access_ to trabecular meshwork, ↑ resistance to aqueous outflow → **↑intraocular pressure** • Primary open angle: most common form of glaucoma, **MYOC** gene mutations for juveniles & adults, some adults with OPTN mutation instead • Secondary open angle: **pseudoexfoliation** most common form, deposition of fibrillary material thruout ant segment, **LOX1** gene

Question 34

•Von Hippel-Lindau disease

Answer 34

* **AD inheritance** • VHL, chr 3p25.3, tumor suppressor gene * downregulates HIF-1 which regulates expression of **VEGF** * Involved in regulating expression of erythropoietin → **_polycythemia_** * **_hemangioblastomas_** of the CNS (**cerebellum & retina**) * **Cysts of pancreas, liver & kidneys** **_• RCC (renal cell carcinoma) • pheochromocytoma_**

Question 35

V H L

Answer 35

V-VHL gene H- Hamngioblastoma L- Lots of catecholamines VHL 3 letters = RCC three letters VHL 3 letters = Chromosome 3

Question 36

• ICU myopathy

Answer 36

AKA myosin deficit myopathy * **Critical illness with corticosteroid tx; profound weakness affects clinical course** * _Prolonged corticosteroid tx & Disuse: Type II fiber atrophy, sparing Type I fibers​_

Question 37

Myasthenia Gravis (MG)

Answer 37

85% have circulating autoantibodies to AChR • Strong assoc between AChR autoAb & **thymic abnormalities** • 10% of pts with MG have **thymoma; 30% Thymic hyperplasia**

Question 38

Diabetes and neuropathy

Answer 38

Diabetes is the most common cause of **peripheral neuropathy** • Several patterns: **ascending distal symmetric sensorimotor polyneuropathy** **symmetric neuropathy involving distal sensory & motor nerves​** * **Numbness, loss of pain sensation, difficulty with balance​** * Paresthesias & dysesthesias

Question 39

Guillain-Barre

Answer 39

**Acute inflammatory demyelinating polyneuropathy** Weakness beginning in distal limbs, but rapidly advancing to proximal muscles: **“ascending paralysis”** • **Deep tendon reflexes disappear** • Inflammation & demyelination of spinal nerve roots & peripheral nerves (**radiculoneuropathy**) • Acute onset **immune-mediated** demyelinating neuropathy

Question 40

Guillan barre is preceded by what? Caused by what? What does the demyelination look like?

Answer 40

• ⅔ cases preceded by **acute influenza-like illness**; recovered when neuropathy starts • **_Campylobacter jejuni_**, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae perivenular & endoneurial infiltration by lymphs, macrophages & few plasma cells **Segmental demyelination** affecting _peripheral_ nerves = primary lesion • **Anti-myelin antibodies**

Question 41

Neurofibromatosis type 2

Answer 41

• Less common (1 in 40-50,000), AD • Much less common than NF 1 • _**Bilateral schwannomas (CN VIII)** Tinnitus and hearing loss_, cerebellopontine angle • Increased **meningiomas**, **_ependymomas_** **_NF2= loss of merlin_**

Question 42

Tuberous sclerosis and genes

Answer 42

AD **_Angiofibromas_** **_TSC1/2_** * **Hamartomas: cortical tubers** * Renal angiomyolipomas Pulmonary lymphangioleiomyomatosis • Cardiac rhabdomyomas _“candle guttering”: drop-like masses bulge into the ventricles_

Question 43

• E coli, Pseudomonas & Klebsiella osteomyelitis is found in who

Answer 43

ore often isolated in pts with genitourinary tract infections (UTIs) or intravenous drug users (IVDA)

Question 44

• C5,6,7,8 & 9 (MAC) deficiency causes osteomyelitis in who

Answer 44

→ Neisseria susceptibility

Question 45

Acute osteomyelitis causes what kind of infiltration? What happens specifically with kids?

Answer 45

* Acute: bacteria proliferate & neutrophils. Necrosis of bone cells & marrow 48 hrs * Kids: periosteum loosely attached, sizable **subperiosteal abscesses** may form & dissect for long distances along the bone surface • Lifting the periosteum impairs blood supply & contributes to necrosis

Question 46

What is sequestrum and when does it become a draining sinus (osteomyelitis)

Answer 46

* Sequestrum: **dead bone following subperiosteal abscess** • Rupture of periosteum → soft tissue abscess which can channel to become a **_draining sinus_** * Sequestrum may crumble & release fragments through the sinus tract

Question 47

Osteomyelitis in infants can cause what?

Answer 47

• Infants (rare in adults): epiphyseal infection spreads through the articular surface or along capsular & tendoligamentous insertions into joints → **septic or suppurative arthritis**

Question 48

What is the ewing sarcoma genes? What is an importnant prognostic feature?

Answer 48

• The amount of **chemotherapy-induced necrosis** (more necrosis better, indicative of sensitivity to tx) is an important prognostic finding. Gene: **t(11;22)(q24:q12)**

Question 49

What is a blood feature of osteopetrosis?

Answer 49

**ANEMIA**

Question 50

Auto dom vs auto recessive in ostepetrosis?

Answer 50

1. **Severe infantile type is autosomal recessive** (Children of Mediterranean and Arab race ) • Cranial nerve deficits: optic atrophy, **deafness,** facial paralysis • Postpartum mortality: fractures, anemia & hydrocephaly 2. Mild autosomal dominant form: dx in adolescence or adulthood • Repeated fractures • **Mild cranial nerve deficits and anemia**