Both can result in headache in and fever.

Generally, meningeal syndromes (diffuse) will have altered sensorium and focal syndromes will induce seizures. However, focal findings and seizures can occur late in diffuse syndromes.

Inflammation predominantly in the subarachnoid space

Characterized by headache, altered mental status, signs of meningeal irritation (nuchal rigidity-Kerni's, Brudzinski's)

What is the most likely bacterial agent for meningitis in...

1. Adults with impaired immunity?
2. A patient with a break in the skull?
3. A patient experiencing head trauma?
4. An HIV patient?
5. Someone returning from a visit to the Southwest?

1. Listeria monocytogenes; M. tubercolosis; fungi
2. S. pneumonia, S. aureus, S. epidermidis 
3. Gram negative bacilli
4. Cryptococcus
5. Coccidiomycosis

• Pili or fimbriae (N. meningitidis and H. influenzae); polysaccharide capsule, IgA protease production
• Polysaccharide capsule (resist complement mediated activity and neutrophil phagocytosis)

1. Household and nursery contacts
2. N. meningitidis, H. influenze
3. H. flu (all infants), S. pneumo (all infants), N. meningitis (children and health care providers)
   

• N. meningitidis
• H. influenzae, S. pneumoniae

1. Neutrophil pleocytosis [Induced by S. pneumo cell wall components (techoic acids) and H. flu lipopolysaccharide]
2. Destruction of intercellular tight junction, increased CSF outflow resistance, cerebral vasculitis
3. Vasogenic edema (from increase in BBB permeability), increased ICP (from hydrocephalus and edema), infarction (from vasculitis), decrease in cerebral blood flow

[image][image][image] [image]

Indicative of nuchal rigidity.

A mass lesion or some other pathology causing herniation

Check for papilledema, focal neurological defecits, prior history of CNS disease, HIV status. If any of these conditions are present, check with CT scan

1. Group B strep, E. coli
2. Neisseria meningitidis
3. S. pneumo and Listeria monocytegenes

Those with bacterial endocarditis, congenital heart disease (R --> L shunt), bronchiestasis, sinusitis, dental excrations

Typically seen with Staph and Strep

CSF profile: mononuclear cells or mixture of lymphocytes/neutrophils, elevated protein, normal-low glucose

Histology: Giant cells (Langhans cells), caseating necrosis

Note: typically secondary to a primary focus found somewhere else in the body

• Blastomyces
• Aspergillus (narrow angle branching), Mucor (diabetics with ketoacidosis, have right angled branching and non-septate hyphae), sometimes Candida (associated with microglial nodules)

• Infiltration of plasma cells into the CSF, associated with obliterative endarteritis (Heubner's)
• Tabes dorsalis = Dorsal column inflammation (radiculitis) leading to degeneration of sensory
• Syphilitic gummas
• CNS involvement --> general paresis presenting as dementia (rare)

• Toxoplasma gondii - immunosuppressed patients, often involving the basal ganglia. Can be injgested from cat feces, incompletely cooked meals
• Naegleria fowlerii- bathing in infected waters (invades through nasal cavity/cribriform plate)
• Acanthamoebae- Immunosuppressed individuals

• Atherothrombotic and embolic infarctions (embolic more common in young)
• Hypertension (followed by amyloid angiopathy)
• Ruptured aneurysm (followed by aretiovenous malformations)

1. Pallor and vacuolization (due to edema); big to see "red nuclei" (eosinophilic, pyknotic, no nucleolus)
2. PMNs from 24-72 hrs
3. Maximal edema @ 3-4 days (vasogenic and cytotoxic)
4. Macrophages peak and liquifactive necrosis occurs @ 10-14 days
5. Cystic changes @ 3 weeks; cortex becomes gliotic, with superficial area preserved

What are will the clinical presentation of a patient with occluded...

• MCA (including lenticulostriate vessels)
• Superior division of MCA?
• Inferior division of MCA?

• Global aphasia and hemipalegia (as well as other deficits brought on by basal ganglia ischemia) 
• Broca's aphasia (expressive)
• Wernicke's aphasia (receptive)

• tPA within 3 hours to preserve penumbra.
• Aspirin to prevent further accumulation of thrombus.
• Check for hernation (papillary edema)
• Control of blood pressure
• Neuroprotection (R-glutamate antagonists, nirtric oxid)

• Glioblastoma multiforme
• Melanoma, choriocarcinoma, renal cell carcinoma (lung cancer has highest incidence due to propensity to metastasize)

• Saccular aneurysm
• Bifurcation in Circle of Willis (most likely MCA), due to lack of intima
• Alpha-1 antitypsin deficiency (congenital or induced by smoking), Ehlers-Danlos syndrome, Marfan syndrome, polycystic kidney disease

• Reduced perfusion pressure (global ischemia)
• Vasospasm
• Hypothalmic dysfunction (mass effect)
• Rebleed
• Extension of hemorrhage

Clipping of aneurysm at the neck

• Immunosuppresed patients
• Infection with EBV
• HTLV1 (?)

Increased ICP (either by mass effect or associated edema)

• Example 1- formen magnum meningioma --> tonsillar herniation --> compression 
• Example 2- Colloid cyst of third ventricle --> acute hydrocephalous

AA and Glio = adults

LGA, Pilo A = children

• Schwannoma
• Pilocytic astrocytoma in children, hemangioblastoma in adults
• Medulloblastoma (and others...)

Fibrillary processes; grading is performed using four criteria (AMEN): atypia, mitosis, endothelial proliferation, necrosis

• One criteria = grade 2
• Two criteria = anaplastic (grade 3)
• Three to four criteria = glioblastoma (grade 4)

• Primary glioblastoma = appears de nova from EGFR amplification. 95% of cases
• Secondary glioblastoma = derived from astrocytoma grade 2 from p53 mutation. 5% of cases

Rosenthal fibers (strands of alpha-beta crystallin positive fibers) located in cerebellum, and sometimes optic nerve. Shows biphasic pattern (alternating cystic and dense tissue)

DO NOT RADIATE

Oligodendroglioma

LOH in 1p19q suggests chemosensitivity. Brisk mitosis, mitotic figures, necrosis and endothelial proliferation suggest anaplastic oligodendrogliomas (low survival)

• Lysosomal structures
• Ganglioglioma
• Biological malignant potential is limited

Medullablastoma (primitive neuroectroderm tumor)

Ependymoma

Identify the tumor associated with the following histological features:

• Homer Wright Rosettes (no lumen in center)
• Hyperchromatic, rounded, carrot-shaped cells
• Rosenthal fibers
• Eosinophilic granular bodies
• Perivascular pseudorosettes

• Medulloblastoma
• Medulloblastoma
• Pilocytic astrocytoma
• Ganglioglioma
• Ependymoma

• Meningioma
• Similar to papillary thyroid tumors (Orphan Annie eye nuclei, psammoma bodies, whorls)

Neurofibroma, from NF1. Involves thick and bundled neural roots, typically pilocytic astrocytoma or optic glioma

NF2 = Chromosome 22

NF1 = Chromsome 17

NF1 occurs 1:3000-4000

NF2 is much more rare (1:40000)

Tubular sclerosis

Angiomyolipomas in the kidney and subependymal giant cell astrocytomas (SEGA) in the brain.

• The inflammatory cells are lymphocytes
• Blood vessels are ringed by lymphocytes in viral encephalitis
• Microglial cells clump into microglial nodules (note: also present in Rickettsia infection)
• Neuronophagia (phagocytosis of neuronal cells by microglial cells)

Negri bodies are pathognomonic for what virus? where would you expect to see them?

[image]

Which diseases will typical induce Cowdry type A inclusion body?

[image]

• Herpes Simplex encephalitis 
• Subacute sclerosing panencephalitis

HSV Type 1, which is predisposed to the inferior frontal lobe and temporal gyrus

Diagnosis confirmed by PCR. CSF will show mononucleor pleocytosis, with possible red cells (hemorrhagic lesion)

Similar to infarct; cortical necrosis, with lymphocytes infiltrating the subarachnoid space

Cowdry type A inclusions, lacy chromatin out of the periphery of the nucleus. On EM, nuclear capsids

HSV1 has frontotemporal propensity, HSV2 is more widespread.

Childbirth through an infected birth canal

• CMV- infects ependymal regions of the brain, (around the ventricle), opportunistic
• EBV- associated with CNS lymphoma in immunosuppressed patients

• Gross pathology / CT = dilation of Sylvian fissure, big ventricles
• Microscopic pathology = multinucleated giant cells surrounding blood vessels, accumulation of microglial cells
• Gross pathology suggests to Alzheimer's, microscopic pathology and history suggest to TB

Subacute sclerosing pancencephalitis, caused by a "defective" measles virus (an RNA virus)

Slow developing virus (harbor virus for years)

• CJD of the cortex
• Neurons (spongy change in gray matter)
• Can attack cerebellum (causing ataxia), occipital lobe (visual problems), basal ganglia (motor problems).