CPC3,4 &5

Question 1

what is differential dx of a single and/or multiple enhancing lesions?

Answer 1

brain metastases
multiple brain abscesses
multifocal tumors such as lymphoma or high-grade glial tumors
demylinating lesions
multiple infarcts (from emboli)
vascular malformations

Question 2

biologic Processes of Pseudo-Palisading Necrosis

Answer 2

Thrombosis of tumor vessels leads to hypoxic centers within the tumor. Most tumor cells die within these hypoxic regions. Smaller populations of cells that are capable migrate outward, away from the hypoxic core along cellular processes. This leads to “pseudo-palisading,” piling of tumor cells, around necrotic cores. Simultaneously, HIF-mediated transcription of factors such as VEGF in response to these hypoxic centers leads to microvascular proliferation and further outward expansion of tumor cells that have been selected for their mobility.

Question 3

molecular markers of glioblastoma

Answer 3

EGFR is amplified in 30-40%

p53 is altered in 25 - 30%

Question 4

clinical characteristics of primary GBM

Answer 4

• Majority of cases in older individuals (mean age 55 yrs)
• Manifest de novo following a short clinical history
• Not associated with radiological precursor lesions in most cases
EGFR overexpression in >60%

Question 5

clinical characteristics of secondary GBM

Answer 5

characterized molecularly by IDH1 and p53 mutations.
• Majority of cases in younger patients (less than 45 years)
• Develop due to progression from lower grade astrocytomas (hence the term secondary)
• Progression usually occurs over several years (mean 4-5 years)

Question 6

how do you treat High-grade glial tumors?

Answer 6

Resection, followed by radiation and chemotherapy. The most recent standard of care for GBM is surgery followed by 6 week of external beam radiation with concurrent low-dose daily chemotherapy (“chemo-irradiation”) followed by at least 6 months of high dose cyclical (5 days/mo) chemotherapy.

Question 7

what are the molecular markers for oligodendrogliomas?

Answer 7

loss of heterozygosity of chromosomes 1p and 19q associates with increased sensitivity to chemo and radiation and longer survival
about 60-70% of malignant oligodendrogliomas have these deletions

Question 8

what are the molecular markers for malignant astrocytomas?

Answer 8

methylation of the MGMT promoter (results in gene silencing) is associated with increased response to alkylating chemos and improved survival

Question 9

what is a positive marker for prognosis of secondary GBM?

Answer 9

mutated IDH1 is associated with better outcome (median survival time 4x longer than those without this mutation)

Question 10

what are distinctive features of oligodendrogliomas?

Answer 10

round, regularly appearing neoplastic cells with obvious cytoplasmic processes in the background
small, branching, delicate capillary processes in background = chicken wire

Question 11

what is striking about oligodendrogliomas under high power?

Answer 11

hese tumors are also characterized by a striking fixation artifact: perinuclear clearing or halos, giving the cells a so-called “fried egg appearance.” This is thought to be due to swelling and vacuolization of the cytoplasm, and only occurs after formalin fixation.

Question 12

what are the most common organisms that cause meningitis in HIV population?

Answer 12

Cryptococcosis
HIV (aseptic meningitis that may occur with seroconversion) 
Coccidioidomycosis
Listeria
Histoplasmosis
CMV
Treponema pallidum  (Syphilis)
Mycobacterium Tuberculosis
Community-acquired bacterial and viral meningitis also occur more commonly in the HIV population.

Question 13

what is the most feared complication of a LP?

Answer 13

cerebral herniation

Question 14

what are clinical characteristics that increase likelihood of intracranial space-occupying mass lesion or severely elevated intracranial pressure (and thus require CT scan before LP)?

Answer 14

1. Focal neurological deficits (including altered mental status)
2. Seizure
3. Immunocompromised patient
4. Elderly patients (over the age of 65)

Question 15

what causes decerebrate posturing?

Answer 15

corticospinal and rubrospinal tract dysfunction

Question 16

what kind of inclusions does CMV cause?

Answer 16

both intranuclear and intracytoplasmic (in HIV patients/immunocompromised)
typical CMV intranuclear inclusions are brightly eosinophil and compared to owl’s eye

Question 17

what is crazy about herpes encephalitis?

Answer 17

it is an aggressively necrotic disease - temporal lobes

Question 18

how common is optic neuritis in MS?

Answer 18

it is presenting feature in 15-20% of patients and occurs in 50% during the course of the dz

Question 19

describe relapsing-remitting MS

Answer 19

Occurs in approximately 80% of MS patients (starting between the ages of 20-40) of whom 50-70% demonstrate secondary progression during the ensuing 10 years (requiring gait assistance after 15 years). Approximately 25% remain non-disabled and 15% demonstrate a rapidly deteriorating course.

Question 20

describe primary progressive MS

Answer 20

Later onset, frequently manifests with spinal cord dysfunction

Question 21

what kind of bladder dysfunction occurs in MS?

Answer 21

UMN dysfunction - frequency, urge in continence and predisposition to infection

Question 22

what is significance of oligoclonal banding in MS?

Answer 22

Found in approximately 90% of patients with MS, oligoclonal banding represents the intrathecal synthesis of immunoglobulins of restricted specificity. Increased synthesis of IgG is also frequently observed.

Question 23

how do you treat acute exacerbations of MS

Answer 23

high dose prednisone

Question 24

what other symptomatic conditions frequently occur in MS pts and require directed therapy?

Answer 24

fatigue and sleep disturbance
cognitive loss and depression
spasticity and pain
gait and balance dysfunction
speech and swallowing dysfunction
urinary dysfunction and urosepsis