• hematogenous
  • arterial- heart (esp. valves), lungs
  • venous- centripetal spread from veins of face and head
• local extension
  • air sinus (paranasal, mastoid)
  • intraoral (teeth, gingivae)
  • craniospinal surgical/traumatic site
• direct inoculation
  • trauma- open head injury
  • iatrogenic
    • lumbar punctures
    • surgery
• retrograde spread from PNS

• acute pyogenic (pyogenic bacteria)
• aseptic (viruses)

hrs/days

• Mycobacteria
• spirochetes
• fungi

1. chemical irritant in subarachnoid space
   • keratin from ruptured intracranial epidermoid (benign cyst arising from misplaced squamous epithelium trapped inside devloping skull durin fetal development)
2. noninfectious inflammation

• metastatic cancer/lymphoma spreads to subarachnoid space
  • meningeal carcinomatosis
  • meningeal lymphomatosis

• Streptococcus agalacticae (GBS)
• E. coli (other gram negatives)
• Listeria monocytogenes
• Staph aureus

• Strept. pneumo
• Hib (among unimmunized)
• Neisseria meningitidis

• S. pneumoniae (all ages, sporadic)
• N. meningitidis (young adults, crowded living conditions)
• gram negative rods (E coli, Klebsiella, Pseudomonas)
• Listeria monocytogenes
• S. aureus

• systemic
  • fever, chills, anorexia, vomitting
• neurologic
  • headaches
  • photophobia
  • irritability
  • decreased level of consciousness
  • stiff neck
• infection progresses rapidly
  • agent may disseminate in blood (septicemia)
    • Waterhouse-Friderichsen syndrome
      • adrenal septic hemorrhagic necrosis
      • skin petechiae
      • systemic collapse

• depends on early/rapid dx
  • essential to salvage patient
  • up to 90% fatal if patient shows severe neurological impairment on presentation

• increase ICP
• increase neutrophils
• increase protein
• decrease glucose

• microscopy
  • gram tain
  • India ink prep
• serology (Ab against specific microbial agents)
• culture (provide material for antibiotic sensitivity studies)

• gross
  • pus (white, yellow, green) in subarachnoid space
    • pus obscure view of underlying brain surface
  • pus may collect at base of brain
• microscopic
  • subarachnoid space filled with PMN's
  • possible inflammation w/ or w/o thrombosis of bv's passing through subarachnoid space

• no organism by gram stain or culture of CSF
• causative agents: usually viral
  • enterviruses
  • HIV, HSV-2, mumps, measles

• clinical presentation
  • less fulminant than acute pyogenic
  • spontaneous remission
• CSF finding
  • normal/increase ICP
  • increase lymphocytes
  • increase proteins
  • normal glucose
  • negative microscopy
  • negative bacterial/fungal Ab
  • negative cultures
• viral ID
  • viral culture of throat, stool
  • 4 fold serum titer rise against specific agent

• definition- localized pus forming infection of brain
  • cerebritis- early stage before suppuration
• multiple sources of infection
  • hematogenous (cardiac, pulmonary)
  • local extension (oro, sino, naso, facial)
• common causative agents
  • immunocompetent
    • staphylococcal and streptococcal 
      • anaerobic and microaerophilic species
  • immunocompromised
    • Toxoplasma gondii
    • Nocardia asteroides
    • L. monocytogenes
    • gram negative bacteria
    • mycobacteria
    • fungi

• clinical presentation
  • variable: indolent to fulminant
  • fever, headache, focal neuro deficit, seizures
• lumbar puncture
  • rarely needed
  • CI: elevated ICP
  • CSF findings
    • increased ICP
    • increase cells (neutrophils, lymphocytes)
    • increase protein
    • normal glucose
    • negative cultures

• course
  • dx- radiographic imaging, biopsy with cultures
  • potentially fatal without tx
    • complications
      • rupture into
        • ventricle
        • subarachnoid space
      • dural venous sinus thrombosis
• tx- surgery, antibiotics (less than 10% mortality)

• gross
  • early cerebritis
    • first 1-3 wks
    • hyperemic softened focus
  • developed purulent abscess
    • suppurative cavity with fibrous capsule and surrounding edema
      • often based at junction of cortical gray matter and subcortical white matter
• microscope
  • central core of suppurative liquefactive necrosis
  • intermediate zone of proliferating granulation tissue
    • only instance of inracerebral fibrous proliferation
      • fibroblasts derived from granulation tissue bv walls
  • outer ring of gliotic edematous brain

• definition- pus forming infection between inner dural surface and arachnoid
• pathogenesis
  1. spread of skull or sinus (paranasal, mastoid) infection
  2. organized by fibroblasts from dura
• complications
  • thrombophlebitis of dural venous sinus or bridging veins with cerebral venous thrombosis

• definition- pus forming infection between bone (skull, vertebrae) and outer dural surface
• origin- spread from osteomyelitis, sinusitis
• complication- spinal epidural hematoma may compress the spinal cord
  • surgical emergency requiring decompression and drainage

• meninges
• parenchyma
• spinal vertebrae

• histopathology- chronic granulomatous meningitis
  • basilar
  • reactive fibrosis of arachnoid
    • adhesive arachnoiditis
    • traps basilar vessels, CN's
• CSF findings
  • increase lymphocytes
  • increase protein
  • normal/slight decrease glucose
  • acid fast bacteria on mycroscopy
  • M TB on culture

• parenchyma
  • brain abscess with caseous necrosis surrounded by granulomatous inflammation
    • tuberculoma
• spinal vertebrae
  • TB spondylitis (Pott's disease) leading to:
    • vertebral destruction
    • spinal deformity
    • epidural abscess

• early symphilitic CNS infection limited to meninges with or without symptoms
  • "assymptomatic neurosyphilis)
  • CSF findings
    • normal/increase cells (lymphocytes)
    • increase protein
    • normal glucose
    • positive CSF serology for VDRL
  • symptomatic: acute syphilitic meningitis presenting like aseptic meningitis
• late symphilitic involvement of CNS
  • CNS mesodermally derived tissues (meninges and arteries)
  • CNS mesoderm + neuroectoderm (meninges, arteries, neural parenchyma) = parenchymatous neurosyphilis

meningovascular syphilis

• chronic fibrosing meningitis
  • meningeal gummas
• fibrosing vascular infection of meningeal and parenchymal arteries occluding lumens
  • obliterative endarteritis (infection of arterial intima) with plasma cells
  • leads to parenchymal ischemia/infarcts

• general paresis of the insane
  • chronic meningoencephalitis with neuronal loss, microglial activation (rod cells), gliosis
  • progressive mental deterioration leading to dementia
• tabes dorsalis (dorsal columns of spinal cord waste away)
  • infection of dorsal roots and sensory ganglia of spinal nerves
    • degeneration of spinal dorsal columns
      • loss of joint position sense leading to ataxia
    • loss of pain sensation leading to unfelt joint damage = Charcot joint

• gumma
  • granulomatous tissue reaction of syphilis
  • necrosis with preservation of tissue reticulin
  • plasma cells prominent
  • location- meninges, including dura
    • may extend into brain cortex from meninges
  • may occur in brain parenchyma in late tertiary syphilis aka gummatous neurosyphilis

multisystem disorder involving skin, CV system, joints, PNS, CNS

• causative agent: Borrelia burgdorferi (spirochete)
  • transmitted by Ixodes tick
• systemic manifestation
  • aseptic meningitis
  • CN VII palsy
  • peripheral neuropathy
  • encephalopathy
• histopath
  • microglial activation
  • granulomas
  • vasculitis

• Herpesvirus
  • HSV-1,2
  • VZV
  • CMV
• arboviruses
• poliomyelitis
• rabies

• measles (SSPE)
• JC polyomavirus (PML)
• HIV

• perivascular and parenchymal mononuclear cell infiltrates
  • perivascular lymphocytic cuffing
    • collection of lymphocytes in the parenchyma around bv's
  • microglial nodules
    • loosley aggregated collections of mononuclear inflammatory cells in CNS gray and white matter
• microglial cell activation
  • nuclei of activated microglia enlarge and become long and thin (cytoplasm not distinctly visible)
  • rod cells found in microglial nodules and scattered in parenchyma
• neuronal death and phagocytosis, often in a microglial nodule = neuronophagia
• gliosis
• viral inclusions may or may not be present
  • depend on specific virus, infection time course, antiviral tx

• CNS cell types
  • motor neurons of spinal cord and brainstem- poliovirus
  • oligodendrocytes: JC virus (PML)
  • ganglion cells of dorsal root and CN ganglia
    • VZV
    • HSV-1,2
• CNS regions
  • medial temporal/inferior frontal lobes: HSV-1
  • subventricular region: CMV

• VZV
• HSV-1,2
• measles (SSPE)

ToRCHeS

• Toxoplasma gondii
• Rubella
• CMV
• HIV
• HSV-2
• Syphilis