CNS Infections Flashcards
Host response to Bacteria
- Elicits neutrophilic & pyogenic response
Labs:
- Neutrophils
- Decreased CSF glucose
- gram stain/culture to ID causative organism
Complications:
- Death: herniation secondary to cerebral edmea
- Hydrocephalus
- Hearing Loss
- Seizures
Host response to Viruses
- generally elicits lymphocytes and activate microglials (the resident macrophages in the nervous system).
Labs:
- Lymphocytes
- Normal CSF glucose
Host response to Mycobacteria & Fungi
- elicit granulomas, which is an aggregation of epithelioid histiocytes with multi-nucleated giant cells.
Labs:
- Lymphocytes
- Decreased CSF glucose
Host response to Treponemal organisms, especially syphilis:
- elicits a special granuloma called a gumma
Routes of CNS Infection
- Hematogenous (most important):
- Arterial: Heart (esp cardiac valves) & Lungs
– Venous: Centripetal spread from veins
of face - Local extension (more chronic)
- Direct innoculation
– Traumatic: Open head injury
– Iatrogenic: Lumbar puncture; Surgery - Retrograde spread from peripheral nervous
system (PNS)
Meningitis
- general definition
- classic clinical symptoms
- Dx
Inflammation of Leptomeninges (Arachnoid and pia matter) and CSF
Classic Triad:
- Headache
- Nuchal Rigidity
- Fever
- Photophobia
- Vomiting
- Altered Mental Status
Dx: Lumbar Puncture (sample CSF) btw L4 & L5 (level of iliac crest)
- DO NOT PIERCE THE PIA MATER
Meningitis + Brain involvement
Encephalitis/Cerebritis
Meningitis + Spinal Cord
Myelitis
Meningitis + Spinal Nerve Roots
Radiculitis
Acute Pyogenic Meningitis
- Leptomeninges infected by pus (PMN)-eliciting bacteria
- Systemic Sx: Fever, chills,, anorexia, vomiting
– Neurologic: Headache, photophobia, irritability, loss of consciousness, stiff neck
– Infection progresses rapidly (septicemia)
– Rapid/early diagnosis essential for
patient salvage
CSF findings: – Increased Opening pressure (lumbar tap) – Increased CSF cells (mostly PMNs) – Increased CSF protein – Large decrease in CSF glucose Causative agent: Microscopy: – Gram stain (bacteria) – India ink prep (Cryptococcus) Serology: – Antibodies against specific microbial antigens Culture: – Provides material for antibiotic sensitivity studies
Waterhouse-Friderichsen syndrome
- Acute Primary Adrenal Insufficiency due to adrenal septic hemorrhagic necrosis, with skin petechiae and systemic collapse
Associated with:
- Neisseria meningitidis
- Septicemia
- DIC
- Endotoxic shock
Common causative agents of Acute Pyogenic Meningitis in Neonates
- – Group B streptococcus – E. coli and other GNRs – Listeria monocytogenes - H. influenza - Staphylococcus aureus
Common causative agents of Acute Pyogenic Meningitis in Children
- Streptococcus pneumoniiae (pneumococcus)
– Hemophilus infflluenzae type b
• Among uniimmuniized: Neisseria meningitidis (meningococcus)
Common causative agents of Acute Pyogenic Meningitis in Adults
- S. pneumoniae: All ages, sporadic
– N. meningitides (meniingococcus): Young adults, epidemiic in crowded living conditions
– Gram negative rods (E.. coli, Klebsiella, Pseudomonas)
– L. monocytogenes - S.. aureus
Acute Aseptic Meningitis
- “Aseptic”: No organism by Gram stain or
(bacterial) culture of CSF - usually Viral: esp. Enteroviruses (70 serotypes): Polio, echo, coxsackieviruses
– Less fulminant than acute pyogenic meningitis; w/ Spontaneous remission
CSF findings – Normal to increased opening pressure – mosttlly lymphocytes – Increased protein – NORMAL GLUCOSE - Viral identification: Serum Titer
Brain Abscess
- Definition
- causative organisms
- Dx
- Localized pus-forming infection of brain parenchyma
- Multiple sources of infection: Hematogenous (cardiac, pulmonary); Local extension (oro-sino-naso-facial)
Common organisms in Immunocompetents:
- Staphylococcal and streptococcal bacteria
– Anaerobiic and microaerophilic species
Common organisms in Immunocompromised:
- Toxoplasma gondi
- Nocardia asteroides
- L. monocytogenes
- Gram negative bacteria, mycobacteria, fungi
Diagnosed by imaging and biopsy with culture:
– Potentially fatal without treatment
– Treated with surgery and antibiotics
Lumbar puncture rarely warranted; Contraindicated with ICP
– CSF findings: Increased Openiing pressure; PMNs or lymphocytes, increased Protein; NORMAL GLUCOSE
- Negative cultures
Brain Abscess Morphology
Gross
- Early cerebritis (First 1-3 weeks): Hyperemic softened focus
– Development of purulent abscess: Suppurative cavity with fibrous capsule and surrounding
edema; Often based at gray-white
cortical junction
Microscopic:
– Central core of suppurative liquefactive necrosis
– Intermediate zone of proliferating granulation tissue (reticulin stain positive) –> Only instance of intracerebral fibrous proliferation, where fibroblasts are derived from granulation tissue blood vessel walls
– Outer ring of gliotic edematous brain
Subdural Empyema
- Pus-formiing infection between dura and
arachnoid, from Spread of skull/sinus infection
– Organiized by fibroblasts from dura
– Complication: Thrombophlebitis of dural
venous sinus or bridging veins with cerebral
venous thrombosis
Epidural Abscess
- Pus forming infection between bone (skull,
vertebra) and outer dural surface, Spreading from osteomyelitis or sinusitis
– Spinal epidural abscess may compress spinal cord –> Surgical emergency requiring decompression/drainage
Chronic Bacterial Meningoencephalittis
- Mycobacterial Infections
- Neurosyphilis
3. Neuroboreliosis (Lyme Disease)
CNS Mycobacterial Infections
Mycobacterium tuberculosis may infect meninges, parenchyma, spinal vertebrae (Pott Disease)
- CSF findings: increased cells (mostly lymphocytes); increased protein; Normal or slightly elevated gllucose
- Acid-fast bacteria on microscopy
- M. tuberculosis on culture
- Gross: cheesy caseating material at the base of the brain
- Histo: typical granuloma with multi-nucleated giant cells, central caseation, and epithelioid histiocytes
M. avium-intracellulare may infect immunocompromised
Neurosyphilis
Treponema pallidum may spread to meninges
- Early: limited to meninges
– Asymptomatic: CSF findings: Normal to cells (lymphocytes); increased protein; NORMAL GLUCOSE
– Symptomatic: Aseptic meningitis presentation
- Secondary Dormant phase
- Late (tertiary) Phase:
- Meningovascular Syphillis: Involvement limited to CNS mesodermally-derived tissues (meninges + arteries); Meningeal gummas
- Parenchymatous Neurosyphillis: Involves mesoderm + neuroectoderm
- General Paresis of the Insane
- Tabes Dorsales: infection of dorsal roots & sensory ganglia of spinal nerves; result in Charcot Joint (loss of pain sensation)
Gumma
- Granulomatous tissue reaction of syphilis
- like a granuloma, there is Necrosis, but with preservation of tissue reticulin
– Plasma cells prominent
– Occurs in meninges, including dura; May extend into brain cortex from meninges
– May occur in brain parenchyma in late tertiary syphilis
Neuroborreliosis
- CNS infection by spirochete Borelia burgdorfi; Transmitted by Ixodes ticks
Lyme disease
– Multisystem disorder involving skin, cardiovascular
system, joints, PNS, CNS with Variable manifestations: Aseptic meningitis, CN VII palsy, peripheral neuropathy,
encephalopathy
– Histo: Microglial activation (rod cells), granulomas, vasculitis
Viral Meningoencephalitis
- Def: Viral infection of meninges and brain parenchyma
All have:
– Perivascular and parenchymal mononuclear cell infiltrates; MICROGLIAL NODULE FORMATION, i.e., lymphocytes, plasma cells, monoctyes, macrophages, and microglia
– Microglial cell actiivation: Microglia transform into ROD CELLS
– Neuronophagia: Neuronal death and phagocytosis
– Gliosis
Viral tropism
- Targetiing of specific cell types or CNS regions by specific viruses
CNS cell types:
– Poliovirus: Motor neurons of spinal cord
and brainstem; anterior horns
– JC virus: targets Oligodendrocytes
– VZV, HSV-1 &2: Ganglion cells of dorsal root and cranial nerve ganglia
CNS regions:
– HSV-1: Medial temporal/inferior frontal lobes
– CMV: Subventricular region
Latent Viruses
– Dormant viral persistence in specific CNS cell types
- VZV
- HSV-1,2
- Measles (SSPE)
Transplacental passage of Viruses
“toRCH”
- Rubella
- CMV
- HSV-2
HSV-1 CNS Infection
– Important cause of sporadic viral encephalitis – Involves CNS on primary infection (lips, face) or by reactivation from trigeminal (CN V) ganglion – Targets: Medial temporal lobe, limbic regions – Necrotizing, hemorrhagic infection with Intranuclear viral inclusions in neurons and glia
HSV-2 CNS Infection
Adults - Retrograde spread to CNS from sacral dorsal root ganglia - Aseptic meningitis in healthy adults Necrotiziing encephalitis in immunocompromised
Neonates
- Acquired during birth through vaginal canal with primary HSV-2 infection, or transplacentally
- Necrotizing encephalitis
VZV CNS Infection
– Childhood viral exanthem (Varicella) - Latency established in dorsal root and trigeminal ganglia – Reactivation after many years with anterograde axonal transport to skin in dermatome distribution: Herpes zoster (shingles)
– With primary infection or reactivation,
VZV may travel retrograde to spinal
cord/brain, especially in immunosuppressed, causing Encephalitis, Myeloradiculitis, or CNS vascular infection
– Micro: intranuclear inclusions in neurons
and glia
CMV CNS Infection
− Intrauterine infection
• Targets periventricular regions with severe necrosis → periventricular calcification, microcephaly, CNS malformations
− Infection in immunosuppressed
• Encephalitis
• Retinitis
• Myeloradiculitis
− Cellular enlargement with prominent intranuclear (± cytoplasmic) inclusions in neurons, glia, endothelial cells
Arbovirus CNS Infection
Arbovirus = ARthropod BOrne (commonly mosquitos, rarely ticks)
− Important causes of epidemic viral encephalitis
− Viruses endemic in birds and small mammals
• Transmitted by insects to horses and humans as incidental hosts
• Names reflect geographic distribution, insect vector, or incidental host
• West Nile virus: Birds normal reservoir; May cause meningoencephalitis when transmitted by mosquitoes to human as incidental host
• Incidence of human encephalitis coincides with season of vector (mosquito) activity, e.g., Summer through early fall
CNS Poliovirus Infections
− Enteroviruses that infect gut and spread to blood
− A few strains can invade CNS from blood
• Neurovirulence
• Produce aseptic meningitis picture ± acute myelitis
− In myelitis, virus targets motor neurons of spinal cord (anterior horn cells) and brainstem
• Flaccid areflexic paralysis major clinical manifestation
• Respiratory muscle involvement may be fatal
− Vaccination has reduced world-wide incidence
CNS Rabies Virus Infection
• Virus endemic in small mammals (Dogs, bats, wild animals) transmitted to human by bite of infected animal
− Virus inoculated at bite site
− Travels retrograde through axons of PNS to reach CNS
• Time to disease onset reflects bite distance from CNS
• Fulminant encephalitis
− Negri bodies: Neuronal cytoplasmic inclusions that are round or oval, pink; Seen best in Purkinje cells and hippocampal pyramidal neurons
Subacute Sclerosing Panencephalitis (SSPE)
− Rare complication of early-age (<2 years) measles infection
− Non-productive (= i.e. no viral replication) CNS latency of altered measles virus after primary infection
− Onset of progressive behavior, cognitive, motor disturbances months to years after initial measles infection
− Encephalitis with widespread neuronal and white matter destruction
• Intranuclear inclusions in neurons, oligodendrocytes
Progressive Multifocal Leukoencephalopathy (PML)
− Reactivation during a period of immunocompromise of latent JC polyomavirus infection acquired earlier in life
• Primary JC virus infection asymptomatic
• Latency in lymphocytes, kidney
− JC virus infects glia on reactivation
• Oligodendrocyte involvement → myelin loss
• Astrocyte involvement → enlarged bizarre astrocyte nuclei
− Progressive neurologic syndrome due to CNS white matter destruction
• Multiple foci of secondary demyelination in cerebral, cerebellar, brainstem white matter
• Viral intranuclear inclusions in oligodendrocyte nuclei
CNS HIV Infection
• HIV may directly infect CNS early or late
− Early/seroconversion: Aseptic meningitis
− Late: Subacute meningoencephalitis: Direct HIV infection of cerebral microglia and macrophages (→ multinucleated giant cells) ± Infection of astrocytes, endothelial cells; Neurons destroyed by cytokines, blood-brain barrier failure
- results in Clinical dementia, motor disturbances, seizures
- Direct CNS infection by HIV: More commonly seen in pediatric HIV/AIDS
- Opportunistic CNS infections and malignancies: More commonly seen in adult HIV/AIDS
CNS Rickettsial Infection
- e.g., Rocky Mountain Spotted fever; Typhus
− Unicellular organisms between viruses and bacteria
• Possess cell walls, antibiotic-sensitive (like bacteria)
• Live and reproduce only inside host cells (like viruses)
− Spread by insect vectors: Ticks, lice, mites
− Infection of CNS vascular endothelium → Vasculitis, hemorrhage, thrombosis, infarction
Fungal Meningoencephalitis
• Fungal infection of meninges ± brain parenchyma
− Associated with immunocompromise
− Hematogenous dissemination or local extension of extracranial (pulmonary, sinonasal) infection to CNS
− Common organisms: Candida albicans, Aspergillus fumigatus, Mucor species, Cryptococcus neoformans
Three infection patterns
- Chronic meningitis: Cryptococcus
- Septic vasculitis: Aspergillus, Mucor
- Parenchymal invasion: Candida, Cryptococcus
- Inflammatory response granulomatous or minimal
- Cryptococcus may elicit little inflammatory response to large organism burden
Parasitic Meningoencephalitis
- CNS protozoan (unicellular) parasitic diseases
− Malaria, amebiasis, trypanosomiasis, toxoplasmosis
− Cerebral toxoplasmosis: Meningocerebral infection by Toxoplasma gondii
• Cat definitive T. gondii host
Sexual stage of parasite reproduction
• Human intermediate host
Acquires disease from food tainted by oocyst-containing cat feces →
GI cyst digestion and liberation of tachyzoites → tachyzoites infect GI macrophages → hematogenous and lymphatic dissemination of tachyzoites → CNS invasion
Parasitic Meningoencephalitis
- CNS metazoan (multicellular) parasitic diseases
− Cysticercosis, echinococcosis
− Neurocysticercosis: Larvae of Tenia solium (pork tapeworm) encyst in human CNS
• Human (definitive host) ingests eggs meant for pig (intermediate host); Human functions as dead-end intermediate host
CNS Toxoplasmosis
Two forms of CNS toxoplasmosis
− Intrauterine/neonatal infection (“ToRCH”)
− Primary/reactivation CNS infection in immunocompromised
Intrauterine infection
− Transplacental passage of tachyzoites during primary maternal infection
− Fetal meningoencephalitis: Targets subpial and subventricular regions; Widespread gray and white matter destruction
• Diffuse (contrast with subventricular [in CMV]) brain calcification, hydrocephalus, CNS malformations
CNS toxoplasmosis in immunosuppresion
− Toxoplasmosis abscess most common mass lesion in brain of AIDS patient
− Ring-enhancing cerebral abscess(es) gray/white cortical junction, deep gray matter
• ± Meningitis, vasculitis, retinitis
− Free tachyzoites and encysted bradyzoites on microscopy
Transmissible Spongiform Encephalopathies: Infectious proteins
- Prion Disease
− Normal neuronal protein PrPc converted from usual alpha-helix isoform to beta-pleated sheet PrPsc
• Single aberrant molecule of PrPsc serves as template for conversion of other PrPc molecules (Cascade effect)
• PrPsc resistant to usual cellular degradation mechanisms and normal techniques of sterilization and tissue fixation
• Aberrant PrPsc in brain may arise spontaneously: Inherited amino acid substitutions in polypeptide sequence predispose PrPc to abnormal folding
• PrPsc accumulates in brain tissue
• Neuronal cell bodies and axons acquire vacuoles (spongiform change)
• Aberrant PrPsc does not contain nucleic acid (No DNA or RNA)
Creutzfeldt-Jacob disease (CJD)
- Rapidly progressive (weeks to few months) dementia with myoclonic jerks (myo = muscle + clonus = rapidly alternating contraction and relaxation)
- Fatal in < 1 year
- Widespread neuronal loss, gliosis, and spongiform change in brain gray matter
- No inflammatory response
Variant CJD (vCJD) • BSE crossing species barrier from infected cattle to humans ingesting BSE-infected beef
