CNS Infections and Neoplasms Flashcards
1
Q
How can infectious agents reach the CNS? Which route its the most common?
A
- most common: hematogenous spread
- other routes: direct implantation (due to trauma), local extension (from the skull or spine), and via the peripheral nerves (rabies and herpes zoster)
2
Q
What is meningitis? What are the three major types? Which is a major medical emergency?
A
- meningitis is the inflammation of the leptomeninges (pia mater and arachnoid mater) within the subarachnoid space; it also involves the ventricular system
- major types: pyogenic/bacterial, aseptic/viral, and tuberculous (chronic)
- pyogenic meningitis is a major medical emergency (fatal if left untreated); luckily, viral meningitis is much more common and less severe
3
Q
What are the major agents involved in bacterial/pyogenic meningitis for different groups of patients?
A
- neonates: Escherichia coli, group B streptococci (mainly Strep agalactiae), Listeria monocytogenes, HiB, Streptococci pneumoniae, Neisseria meningitidis
- children: HiB (especially if unvaccinated), Neisseria meningitidis
- young adults: N. meningitidis, Strep pneumoniae
- older adults: Strep pneumoniae, L. monocytogenes
- open head trauma/surgery: Staphylococcus aureus
- (L. monocytogenes in age extremities, pregnancy, and immunocompromised; ingested from foods)
- (note that in neonates, the E. coli and group B strep are from the vaginal canal)
4
Q
What causes brain abscesses? What symptoms and signs result?
A
- these are focal, discrete, walled-off lesions that are nearly always due to a bacterial agent (commonly, they occur secondary to bacterial endocarditis)
- these are SOLs (space occupying lesions) leading to progressive focal deficits and general signs related to raised ICP (morning headaches, papilloedema)
5
Q
What is encephalitis?
A
- inflammation of the brain parenchyma; is usually viral
- this nearly always occurs with a meningeal inflammation (rarely occurs on its own) = viral meningo-encephalitis
- tends to be less severe and more self-limiting than bacterial meningitis
- common agents: HSV-1, CMV (in fetuses and immunocompromised), rabies, HIV (affects microglial cells and can progress from there), JC virus (causes progressive multifocal leukoencephalopathy/PML)
6
Q
What is Creutzfeldt-Jakob Disease (CJD)?
A
- this is a rapidly progressive, deadly “infection” of the CNS with a prion
- initial subtle changes in memory progress to coma and death in just 7 months
- consider this in patients with rapidly developing and progressing dementia
7
Q
Are primary or metastatic tumors more common in the CNS? Which primary malignant tumor is the most common? Most common benign?
A
- in the CNS, primary tumors are more common! (prevalence of each is actually about 50%)
- glioblastoma multiforme is most common malignant tumor in adults
- meningioma is the most common benign tumor in adults
8
Q
Where does the CNS receive most of its metastases from? Where do malignant CNS tumors metastasize to?
A
- CNS gets metastatic disease from lungs, breasts, kidneys, skin, and GIT
- even the most highly malignant CNS tumors rarely metastasize outside the brain, let alone the CNS
- (however, medulloblastomas and ependymomas may seed into the CSF and enter the spinal cord/spine)
9
Q
What are the key clinical features of pyogenic meningitis? What is the classic triad of symptoms for meningitis in general?
A
- classic triad: nuchal rigidity/stiff neck, headache, and photophobia
- also: rapid onset (12-24 hours), systemic signs of infection (fever, rash), altered mental state, seizures (20-40%) and increased ICP (raised ICP occurs in more than 90% of cases)
10
Q
Major investigation for meningitis is lumbar puncture and CSF analysis - compare the CSF in bacterial and viral meningitis.
A
- bacterial: yellow and cloudy, raised pressure, MANY neutrophils, LOTS of protein, LOW glucose (less than 50% plasma levels)
- viral: clear, normal/raised pressure, raised lymphocytes, raised protein, normal glucose
11
Q
What is the mortality rate of bacterial meningitis? How do we treat it? What are the most common residual deficits?
A
- mortality rate of 10-20% (20% w/ S. pneumoniae; 15% w/ L. monocytogenes; 3-7% w/ HiB, N. meningitides, or group B strep)
- immediately treat empirically (and then specifically if organism is found) with Vancomycin and Ceftriaxone w/ adjunctive Dexamethasone (to stabilize the BBB)
- add doxycycline during tick season, and ampicillin if neonate, elderly, immunocompromised (for Listeria monocytogenes)
- most common residual deficits are deafness, cognitive defects (retardation), and epilepsy
- note that there are vaccines for HiB, Strep. pneumoniae, Mycobacterium tuberculosis, Neisseria meningitidis, Strep. agalactiae
12
Q
Neisseria meningitidis
A
- spread via saliva or aerosol droplets
- this organism is responsible for meningitis epidemics
- colonizes the nasopharynx and then spreads hematogenously to the CNS
- meningitis is commonly preceded by a sore throat
- associated with purpura fulminans (this severe rash is seen in any severe case of sepsis though) and with Waterhouse-Friderichsen syndrome (adrenal hemorrhage resulting in adrenal gland failure)
- there is a vaccine
13
Q
What is the major cause of aseptic/viral meningitis?
A
- enterovirus (85-90%); specifically the coxsackievirus
- others: HIV, HSV, mumps
14
Q
How common are noninfectious causes of meningitis? What are some major examples?
A
- these are very rare
- drugs (NSAID hypersensitivity)
- autoimmune disorders (SLE)
- neoplasm (metastatic carcinoma)
- chemical agents (anesthetics)
15
Q
Why do neonates have the highest risk of developing meningitis? What are some other high-risk groups?
A
- neonates have poorly developed immune systems and relatively permeable BBBs
- other high-risk groups: children and immunocompromised patients
16
Q
Which organisms cause acute meningitis (fulminant, progresses in a few hours)? Which cause subacute/chronic meningitis (gradual onset of symptoms over days)?
A
- acute: viruses; Strep pneumoniae (50%), Neisseria meningitidis (25%), group B Streptococci (mainly Strep agalactiae, 13%), Listeria monocytogenes (8%), Hib (7%)
- subacute/chronic: Mycobacterium spp, spirochetes (such as Borrelia burgdorferi), Cryptococcus neoformans, Candida spp, Coccidiodes spp
17
Q
What are the major common and serious complications of pyogenic meningitis?
A
- septic shock, coagulation disorders (especially involving the adrenal glands in Waterhouse-Friderichsen syndrome), endocarditis, pyogenic arthritis, fever
18
Q
What is the pediatric assessment triangle?
A
- assessment of appearance, breathing, and circulation to skin
- appearance: “TICLS” tone, interactivity (mental state), consolability, look/gaze, speech/cry strength
- breathing: body position, pattern of breathing, abnormal sounds
- circulation to skin: skin color (reflects cardiac output and vital organ perfusion)
19
Q
What is the most common suppurative CNS infection?
A
- unfortunately, it is bacterial meningitis
20
Q
What is a major potential complication of brain tumors? How do we treat this complication?
A
- brain herniation due to the raised ICP (because tumors are space occupying lesions)
- treat herniation and raised ICP/edema with corticosteroids (dexamethasone and mannitol)
21
Q
What is the major chemotherapy drug used to treat malignant gliomas? What about primary cerebral lymphoma?
A
- Temozolomide for gliomas
- Methotrexate for CNS lymphoma
22
Q
What symptoms and signs are associated with malignancy of the brain?
A
- general: headache (usually worse upon waking up), cognitive defects, personality changes, gait disorders (usually due to raised ICP/hydrocephalus)
- focal: hemiparesis, aphasia, visual field defects, seizures
23
Q
What investigations are indicated for patients with suspected CNS malignancy? How can you tell different lesions apart?
A
- MRI w/ gadolinium contrast (and CT if MRI is contraindicated); the contrast will emphasize lesions that are highly malignant
- low-grade glioma: no enhancement on contrast, hypointense on T1 and hyperintense on T2/FLAIR
- meningioma: adjacent to bone, diffuse pattern of enhancement on contrast
- high-grade glioma (GBM): irregular ring-like enhancement on contrast
- metastases: multiple, well-circumscribed lesions in the white-grey matter junction, avid and clear enhancement on contrast
- (follow up the MRI with a biopsy if a lesion is found)
24
Q
Management of Patient with Brain Tumor
A
- steroids (dexamethasone) for edema and raised ICP and to prevent herniation and mass effect; the return to normal ICP will improve neurologic function
- anticonvulsants in patients presenting with seizures (however, avoid carbamazepine and phenytoin if patient is on chemo agents)
- anticoagulation prophylaxis to ALL patients (20-30% develop venous thromboembolism)
- benign tumors are usually easily resectable, while malignant tumors benefit from radiation and chemo
25
Q
Compare the prevalence of symptoms/signs and the prognosis for high-grade gliomas, low-grade gliomas, meningiomas, and metastatic disease.
A
- high-grade glioma: 12-15 mo; most prevalent symptoms are headache (50%), cognitive impairment (50%), and hemiparesis (40%); less common are seizures (20%) and aphasia (20%)
- low-grade glioma: 7-12 yr; most prevalent are seizures (more than 70%) and headache (40%); less common are cognitive impairment (10%), hemiparesis (10%), and aphasia (less than 5%)
- meningioma: 10-yr survival is 60%; most prevalent are headache (37%), hemiparesis (35%), and cognitive impairment (30%); less common are seizures (17%); aphasia is not seen
- metastatic: 2-7 mo; most prevalent are cognitive impairment (60%), hemiparesis (60%), and headache (50%); less common are seizures (18%) and aphasia (18%); visual field loss is uncommon (7%), but relatively unique to metastatic disease
26
Q
Glioblastoma Multiforme (GBM)
A
- a high-grade glioma originating from astrocytes (diffuse astrocytoma vs. pilocytic astrocytoma)
- most common malignant primary CNS tumor in adults
- arises in cerebral hemisphere, rapidly progressive, crosses to opposite hemisphere via the corpus callousm(“butterfly glioma”)
- histo: dense area of necrosis surrounded by high density of highly pleomorphic cells; GFAP positive (because of astrocytic origin)
- poor prognosis (12-15 months) as surgical resection is usually not possible and chemo/radiotherapy are more palliative than curative
27
Q
Meningioma
A
- a benign tumor of arachnoid cells
- most common benign primary CNS tumor in adults; females at greater risk (related to estrogen)
- these compress underlying parenchyma rather than invading them
- histo: classic whorled appearance w/ psammoma bodies (collections of calcium)
- prognosis: 5-year survival is 70%, 10-year is 60%
28
Q
Schwannoma
A
- a benign tumor or Schwann cells (involves cranial or spinal nerves); usually arising at the cerebellopontine angle
- CN VIII is the most commonly affected; and in neurofibromatosis type II, bilateral Schwannomas of CN VIII occur
- prognosis: 7-12 years (low-grade glioma)
29
Q
Oligodendroglioma
A
- a malignant tumor of oligodendrocytes
- this is a calcified tumor of the white matter, usually involves the frontal lobe
- histo: classic “fried-egg” appearance (nucleus surrounded by a halo of clear cytoplasm) and chicken-wire fence capillary pattern
- prognosis: 7-12 years (low-grade glioma); better prognosis than astrocytomas
30
Q
Pilocytic Astrocytoma
A
- a benign tumor of astrocytes (pilocytic astrocytoma vs. diffuse astrocytoma)
- most common CNS tumor in children, usually arising in the cerebellum
- histo: Rosenthal fibers (thick eosinophilic corkscrew processes), GFAP positive (because astrocytic origin)
- prognosis: 7-12 years (low-grade glioma)
31
Q
Medulloblastoma
A
- a highly malignant tumor of cerebellar granular cells
- usually occurs in children
- histo: many small, round blue cells w/ Homer-Wright rosettes (blue cells surrounding pink neuritic processes)
- poor prognosis because of rapid growth (but does respond well to radiotherapy), tendency to seed into the SAS/CSF, causing “drop metastases” in the spinal cord
- granular cells are NOT glial cells - they are neurons; neurons rarely divide in adults, but DO divide in children
32
Q
Ependymoma
A
- a malignant tumor of ependymal cells
- usually seen in children, and usually of the 4th ventricle
- histo: perivascular pseudorosettes (tumor cells line the blood vessels, giving off the “fake” rosette pattern)
- poor prognosis
33
Q
Craniopharyngioma
A
- a benign tumor of EPITHELIAL origin (from remnants of Rathke’s pouch, which give rise to the sella turcica)
- these classically compress the optic chiasm, leading to bitemporal hemianopsia; classically occur in children
34
Q
Which primary CNS tumors are malignant? Which are benign?
A
- malignant: glioblastoma multiforme, medulloblastoma, ependymoma, oligodendroglioma
- benign: meningioma, pilocytic astrocytoma, Schwannoma, craniopharyngioma
35
Q
Poliomyelits damages what part of the CNS? If these symptoms are present at birth, what disorder may the patient have?
A
- poliovirus targets the anterior horns of the spinal cord, resulting in LMN lesions
- if this occurs at birth, the child most likely has Werdnig-Hoffman disease (an inherited degeneration disorder of the anterior horns); the neonate is a “floppy baby” and death usually arises within a few years
