CNS Infections.txt

• Acute purulent type
• Chronic types: tuberculosis, syphilis, fingal
• Viral

• Fever
• headache
• nuchal rigidity
• Kernig sign: thigh at 90, can't extend leg without pain
• Brudzinski sign: neck flexion causes pain and knees to flex

• clear to inspection (like water)
• opening pressure: 80-180 mm/H2O
• protein: 20-40 mg/dL
• Glucose: 45-65 mg/dL (60% blood glucose)
• Cells: 0-5 lymphocytes

• Proinflammatory cytokines: vasodilatation - NO, PGI2, PAF; brain edema (C3a, C5a, histamine)
• Tissue invasion: brain and ventricles; blood vessels

• Exudate in meninges
• ploys in subarachnoid space
• vascular dilatation part of acute inflammation
• Brain edema
• ventriculitis and abscess formation - if meningitis is untreated
• Infection spread to vessels with vasculitis may lead to
• Multiple small infarcts

• Declining incidence in US except AIDS patients
• infection begins in the lung: reinfection TV with spread via blood
• Dx using CSF exam and/or PCR
• Complications are those of chronic basilar fibrosing meningitis (like cryptococcus and syphilis)

• thick exudate at base of brain leading to meningeal fibrosis
• Tuberculoma: extension from meninges - can get a Tb infiltration of brain

obstruction of Luschka, decreased reabsorption of CSF in arachnoid villi

• Occurs in tertiary disease
• Meningovascular syphilis: chronic fibrosing meningitis; obliterative arteritis with infarcts
• Tabes dorsalis: dorsal root disease

• Chronic fibrosing meningitis: especially over the convexities
• Infarcts due to obliterative arteritis

tabes dorsalis

• dorsal root disease with loss of axons in posterior columns
• Spirochetes seldom seen in tertiary syphilis
• Impaired proprioception (+Romberg) and loss of sensation in lower extremities

• Caused by fungus cryptococcus: found in bird excreta, rotting vegetation
• Underlying debilitating disease, 50% cases - but not just in the immunocompromised
• Primary focus in the lung
• Headache, low grade fever, cranial nerve palsies
• CSF exam important in Dx
• Chronic, progressive course

• Chronic fibrosing meningitis at the base of the brain
• Meningeal fibrosis traps cranial nerves causing cranial neuropathies
• Meningitis may etend along Virchow-Robin spaces,but organisms do not invade the brain
• Noncommunicating hydrocephalus due to chronic meningitis
• Meningitis obstructs foramina and restricts subarachnoid CSF flow
• Organisms with thick unstained capsule
• Capsule around organisms stained with mucin stain
• CSF showing organisms outlined by India ink

• Usually viral in origin, culture negative
• Patients present with clinical findings of meningitis
• Causes: Enterovirus 80%; HSV-2, LCM
• Often no definite Dx is made
• Infection is usually self-limited: no treatment is given

• Sources: local or distant infection
• Etiology usually bacterial - mixed flora
• Signs of mass lesion with fever: headache, seizures, elevated WBC
• CSF exam not useful: 10% mortality; 50% morbidity

• early abscess without a capsule
• may also have an early abscess with unilateral edema
• Early abscess without capsule; necrotic tissue with many ploys
• Two week old abscess with early capsule formation shown in trichrome stain for collagen (blue)
• Mature abscess: with fibrous capsule
• Abscess with ring enhancement
• this is the only instance ein which there's a fibrous scar forms in the brain - with an abscess
• will get a ring-enhancing lesion and a lot of edema around the abscess

• Mycotic aneurysms: involve small arteries beyond circle; due to bacteria, less often fungi - origin often endocarditis
• Septic infarcts: infected emboli from heart; infarcts are small, multiple cortical

• wall of aneurysm with inflammation
• multiple hemorrhagic septic infarcts
• septic infarct with numerous ploys and clusters of bacteria

• Opportunistic infection: HIV, cancer, immunosuppression
• Invasive disease
• May originate from pneumonia
• Angiocentric infection: and hemorrhagic infarction

• bacteria: meningococci, pseudomonas, leptospira
• Rickettsiae
• Fungi: aspergillus, mucomycosis
• viruses: HIV, varicella/zoster

• Typical lesion deep, can have multiple lesions
• with a deep hemorrhagic infarct
• organisms can be seen invading vessel wall
• Silver stain showing acute angle branching hyphae

• Opportunistic infection, esp. AIDS
• Caused by parasite T gondii
• Reactivated from dormant sites
• Presents as massl lesion or infection
• ring-enhancing lesion by imaging

• toxoplasma abscess
• abscess with necrotic cells and numerous ploys
• cyst containing many bradyzoites
• also looks like trypanosome cruzii

• represents the typical viral encephalitis: actually CNS viral infection is meningoencephalitis
• many agents usually in summer, warmer weather
• sudden onset, fever, headache, drowsiness, stupor, coma
• Course variable

• Brain is diffusely swollen and congested
• lymphocytic perivascular cuffing b/c started in the blood
• death of neurons are phagocytized (not specific, can also be caused by apoptosis or be seen in Rickettsial disease
• Glial nodules: primarily of microglial cells and lymphocytes - scattered

• was confined to Middle East
• First US case in summer of 1999
• Reservoir in crows and other birds
• Culex mosquito
• Dx: based on IgM Ab in CSF
• Sudden onset, fever, headache:rash, muscle weakness, myalgia
• most cases are mild - 15-20% mortality with encephalitis, risk greater after age 50

• Usually due to animal bite: rabid animal is aggressve; dogs, cats, wild carnivores
• Contact with bats less common: spread in aerosol
• Find the rabid animal and test it
• Long incubation period: shorter when bite is closer to head
• Human Dx can be made with corneal smear: show rabies antigen with IF

• headache, fever, paresthesias or pain at wound site
• Patients then become restless, develop seizures
• Have laryngeal muscle spasm with hydrophobia - can't swallow
• Nearly 100% mortality without Tx!!: vaccine available - can be given after bite along with human rabies Ig
• Tx: vaccine and antibodies

• Lymphocytic perivascular cuffing: especially brainstem
• Negri bodies=cytoplasmic viral inclusions: especially in hippocampus and Purkinjie cells

• Most common sporadic encephalitis in US
• Usually due to HSV-1: HSV-2 causes meningitis
• 90% adult population has HSV-1 antibodies
• primary infection occurs in childhood: often subclinical
• Encephalitis = recurrent infection

• 15% pts. have history of oral lesions
• Sudden onset of headache, fever: may present as a mass lesion
• CSF contains ploys and red cells early: xanthocromia later, PCR has replaced brain biopsy for diagnosis
• Rapidly progressive; 20% mortality: Rx with antivirals such as acyclovir - inhibits viral DNA polymerase
• Inferior frontal or temporal lobe and almost always unilateral: hemorrhagic or necrotizing
• Tends to produce marked brain edema: patients in danger of cynic from herniation

Neutrophils - predominate early: Cowdry inclusion body, EM shows herpes virus: can see virus particles

• Varicella - worldwide, highly contagious, usually in children; ages 2-8
• Rash begins on trunk: spreads to mouth, face, limbs
• Usually benign course - some get encephalitis

• nonseasonal
• latent infection: trigeminal ganglion, posterior root ganglia especially; reactivation with lower immunity, HIV, aging, cancer
• Worldwide, sporadic, nonseasonal
• Usually in adults
• Neuropathy, rash: very painful with fever; permanent nerve damage common
• Vesicular rash following intercostal nerves, rash often unilateral

• Inflammation in nerve root and ganglia
• Inclusions in neurons (like simplex)
• May be necrosis or hemorrhage in ganglia

• Cause is papovavirus, DNA virus, 40nm: three known strains; JC is major strain
• 80% population has antibodies: no clinical disease in vast majority; virus latent in lymphoid organs, bone marrow
• Opportunistic infection: AIDS, lymphoma, immunosuppression - after MS treatment with natalizumab , Poor cell-mediated immunity

• Onset 45-65 years: younger patients have AIDS
• Gradual development of symptoms
• Dementia, focal findings, especially loss of visual acuity
• CSF exam often normal
• Subacute course with 3-6mo. survival

• Multiple small foci of demyelination
• many lesions located in occipital white matter
• tiny demyelinating lesions: a lot smaller than in MS
• Demyelination with many gitter cells
• Bizarre atypical astrocytes: BIG
• Intranuclear inclusions: wine-colored in oligodendroglia
• Composed of numerous viral particles
• infected olives dies - myelin no longer made nor maintained

• Most common in developing countries: especially Latin America
• Caused by cestode, taenia solium
• Eat uncooked pork -> adult tapeworm: release proglottid segments with eggs in stool
• Fecal-oral route: eat eggs -> larvae hatch and penetrate gut: spread via blood to brain

• CNS symptoms: meningitis, seizures, focal signs
• Intraventricular lesions may cause hydrocephalus
• Rx: Surgery, Albendazole

• Cysts in brain often multiple
• cysts are thin-walled and contain parasites
• thin-walled cyst with SCOLEX: organism in the middle
• Intact cyst does not produce inflammation
• Rx and death of parasite may induce an inflammatory response:
• scolex have hooklets

• Subacute spongiform encephalopathy
• Disease both genetic and infectious
• Agent is an abnormal protein or prion
• PrPsc derived from normal protein PrPc
• Results from conformational change
• about 10% are inherited: PRNP gene on short arm of chromosome 20; point mutations in gene coding for PrPc

• Human disease is a varian of CJD: vCJD
• Most cases in britain
• prions found in appendix in mad cow disease in animals
• Clinical picture: young adults, longer course, behavioral symptoms
• Pathologically extensive cortical plaques: !

• Onset in middle-aged patients
• Severe dementia with memory loss
• Myoclonus
• Ataxia
• CSF contains excessive amount of protein: ***
• Fatal in 6-24 months: !

Spongiform change with marked cellular edema in neurons and neuropil

• Cerebral atrophy: large ventricles, large sulci
• Striking fliosis (PTAH) and marked neuronal loss: brain is totally gliotic

• Prion protein undergoes a conformation change into a beta-pleated sheet
• becomes insoluble amyloid: amyloid (congophilic) plaque
• can see amyloid plaque with silver stain as well
• EM shows amyloid as masses of filaments