Download Viral Meningitis

Pathology of
Nervous System (I) -3
2016
Dr. Mohammed Alorjani, MD. EBP.
INFECTIONS OF CNS
IMPORTANT FACTORS
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Route: Hematogenous (most common),
Direct (trauma & iatrogenic…), Local
extension from adjacent focus, e.g. air
sinuses & congenital malformations,
Peripheral nerves
Agent: Bacteria, Viruses, Fungi, Parasites,
or immune process
Normal or immunocompromised host
SITES of INFECTIONS
Epidural & Subdural infections
 Meningitis
 Cerebral abscess
 Encephalitis, mainly viral
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Epidural & Subdural Infections:
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Staph., Strep., Gram neg. bacilli, Mixed.
Direct local spread
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Epidural Localized space occupying lesion
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Subdural empyema  Spreading infection &
↑ICP
Involvement of subdural vessels may lead to
cerebral cortical thrombophlebitis and
arteritis  infarction
Meningitis:
Inflammation of leptomeninges & CSF
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1- Acute Bacterial Meningitis:
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Neonates: Group B Streptococci & E. coli
 6M: H. influenza, S. pneumoniae
Adolescents & young adults: N. meningitidis
Elderly: S. pneumoniae & L.monocytogenes
Shunt operations: Staphylococci
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Clinical picture:
Fever, headache, vomiting, photophobia,
neck rigidity.
In N. meningitidis, may be accompanied
by skin rash & complicated by septicemic
shock
Waterhouse Friderichsen Syndrome
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C.S.F. findings:
↑Pressure, ↑Protein, ↓sugar, numerous
neutrophils, demonstrable bacteria
Morphology:
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Exudate in subarachnoid space, especially
around base, full of neutrophils & organisms
Severely congested meningeal vessels,
surrounded by neutrophils
Sometimes superficial cerebritis &
ventriculitis
Abscesses may occur
May show phlebitis, venous occlusion &
hemorrhagic infarction of underlying brain.
PURULENT (BACTERIAL) MENINGITIS
Thick exudate over base of brain in pyogenic meningitis
PURULENT MENINGITIS
2- Acute Aseptic Meningitis
(Viral Meningitis):
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Enterovirus, echovirus, coxackie & mumps v.
EBV, HIV
Hematogenous spread
Mild self-limiting often seasonal
Brain edema, mild mononuclear cell
infiltration of meninges & superficial brain
cortex
CSF is clear, slight protein, normal sugar,
 lymphocytes
ASEPTIC (VIRAL) MENINGITIS
3. CHRONIC Meningitis/meningoencephalits
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TB, brain and meninges
SYPHILIS, gummas in brain
LYME DISEASE (Neuro-borreliosis)
transmitted by ticks.
– aseptic meningitis
– facial nerve palsies
– polyneuropathies
– mild encephalopathy.
Chronic Meningitis:
1- Tuberculous Meningitis:
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Hematogenous spread from lung → brain
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Direct spread from Tuberculous vertebra
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Result: meningitis or tuberculoma
Morphology:
 Thick cheesy exudate, thick meninges,
tubercles on surface.
( Caseating Granulomas)
 Basal cisterns & sulci most affected
 May show obliterative endarteritis &
infarction
 CSF: Protein, lymphocytes, sugar N or 
TUBERCULOMA
2- Neurosyphilis: caused by spirochete
(T. pallidum)
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Meningovascular syphilis: Meningeal chronic
infection with obliterative endarteritis & cerebral
gummas. – usually base of brain
Plasma cells characteristically in lesions
Paretic neurosyphilis: Invasion of frontal lobe by
spirochetes, loss of neurons & proliferation of
microglia (ROD CELLS) & gliosis ± granular
ependymitis
Result: progressive mental deficits, mood
alteration → severe dementia – General Paresis of
the Insane (GPI)
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Tabes Dorsalis:
Involves spinal cord → damage to sensory nerves
in dorsal columns:
loss of pain sensation and joint position sense &
locomotor ataxia → skin and joint damage (Charcot
joints), characteristic "lightning pains” & absence of
deep tendon reflexes
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Acute syphilitic meningitis:
HIV infected patients who have ↑risk for
neurosyphilis & may develop severe rapidly
progressive disease
Complications of Bacterial
Meningitis
1- Obstructive hydrocephalus
2- Cerebral infarction
3- Cerebral abscess
4- Epilepsy
5- Cranial nerve palsy
6- Deafness
** Prognosis depends on rapidity of proper
antibiotic therapy
Parenchymal Infections:
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Localized: abscess, tuberculoma,
toxoplasmosis, parasites
Diffuse: encephalitis, usually viral
Brain Abscess:
– Usually bacterial but may be fungal
– Direct implantation
– Local extension: from paranasal sinusitis,
mastoiditis & middle ear infection 
Frontal or temporal lobes
– Hematogenous route: usually with
predisposing conditions...
 May be multiple
– Morphology:
Localized suppuration & liquefactive
necrosis, surrounded by granulation
tissue, reactive astrocytes & severe
edema leading to  ICP.
Later Fibrous capsule & gliosis
– CSF: protein, cells, normal sugar
– Complications:
Meningitis, Venous sinus thrombosis,
Ventriculitis, Focal neurological defects,
epilepsy.
PURULENT CEREBRAL ABSCESS
VIRAL Encephalitis
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ARBO VIRUSES (West Nile, Equines,… etc)
HSV1 & HSV2
Herpes Zoster
CMV
POLIO
RABIES
HIV
Progressive Multifocal Leukoencephalopathy (JC)
Subacute Sclerosing Panencephalitis (Measles)
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May be sporadic in healthy subjects
May only affect immunocompromised
subjects
Some are selective to the CNS while
others affect other tissues
VIRAL ENCEPHALITIS & MYELITIS:
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Sporadic infection: HSV encephalitis
Latent infections: Herpes Zoster
Neurotropic: Poliovirus, Rabies
Antenatal: CMV, Rubella
Immune deficiency:
HIV, CMV, PML, Herpes Zoster
Some systemic viral infections do not infect
the CNS, but initiate immune mechanisms in
CNS e.g. Influenza virus
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Some viruses have selective sites:
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CMV -Ventricles
HSV -Temporal lobe & orbital frontal area
Polio - Anterior horn cells of spinal cord
Herpes Zoster - Thoracic dorsal root
ganglia
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Features common to most viral
infections:
1- Perivascular mononuclear infiltrate
2- Cell lysis, neuronophagia
3- Microglial nodules
4- Nuclear or cytoplasmic inclusions
e.g. Cytoplasmic negri bodies in rabies,
nuclear inclusions in CMV …etc.
Microglia showing neuronophagia
Perivascular cuffs of lymphocytes
Microglial nodules
RABIES
CMV
1- Herpes Simplex Virus type 1 & 2
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Normal host: children or adults
Hemorrhagic necrotizing inflammation in
temporal lobe & orbital gyri of
frontal lobe
HSV-2 in adults may cause meningitis
All common features of viral encephalitis
seen with eosinophilic intranuclear viral
inclusions (Cowdry type A) in neurons &
glial cells.
HERPES ENCEPHALITIS
2- Varicella –Zoster Virus (Herpes-Zoster)
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Chicken pox in children but latent infection
in dorsal root ganglia in adults
Self-limited skin eruption along a dorsal
nerve dermatome (Shingles) or Postherpetic
Neuralgia
In immunosuppressed patients, may show
acute encephalitis.
Lesion is typical of viral infection
± granulomatous arteritis & infarction
3- Cytomegalovirus (CMV)
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AIDS patients: subacute encephalitis any
region & any cell but mainly ependymal &
subependymal cells.
There is hemorrhagic periventricular
necrosis with large cytoplasmic &
intranuclear inclusions
Fetus: intrauterine infection.
Changes similar to above + brain
destruction, microcephaly & calcification
4- Rabies
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Severe often fatal, encephalitis
– bite of a canine or others
– ascending along peripheral nerve from bite,
incubation period may last months
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Neuronal degeneration and inflammatory
reaction, most severe in
midbrain, & floor of 4th. Ventricle
Presence of Negri bodies: cytoplasmic,
eosinophilic inclusions in pyramidal neurons
of the hippocampus & Purkinje cells of
cerebellum
5- Poliovirus
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Enterovirus causing mild gastroenteritis
Involvement of CNS in the non-immunised
Acute:
mononuclear cell perivascular cuffs and
neuronophagia of the anterior horn motor
neurons of the spinal cord
Chronic:
Atrophy of the anterior (motor) spinal
roots, and neurogenic atrophy of denervated
muscle. Postpolio syndrome
Rare cases develop paralysis of respiratory muscles
6- Human Immunodeficiency Virus (HIV)
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At least 60% of AIDS pts. develop CNS dis.
Early: aseptic viral meningitis in 10%
Chronic HIV: Meningoencephalitis:
Progressive → HIV encephalopathy, affecting
motor control, memory, incontinence
Commonest cause of dementia in the young
(HAND)
Demyelination: Vacuolar myelopathy affecting
spinal cord nerve tracts.
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Pathology:
– Mainly white matter & basal ganglia,
& spinal cord.
– Demyelination, microglial nodules with
multinucleated giant cells …
– Brain atrophy
7- JC virus →PML
(Progressive Multifocal Leukoencephalopathy)
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Caused by JC virus (a polyomavirus)
exposure during childhood
AIDS patients & other immunosuppressed
patients
Infect oligodendrocytes: Enlarged
nuclei with inclusions. Large astrocytes
are also seen. RESULT:
Progressive demyelination of white matter
PRION DISEASES
SPONGIFORM ENCEPHALOPATHIES:
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Caused by prion variants not containing
RNA nor DNA
TRANSMISSIBLE FATAL Disease, NO Rx
Prion proteins are present in normal brains
( PrP)
Abnormal folding (mutation) of PrP →
(PrPsc ) → (PrPsc, PrPsc, PrPsc …etc)
Mutation can be sporadic, familial or
iatrogenic acquired via infected material
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Include a variety of conditions:
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Kuru
Creutzfeldt-Jacob Disease
‘New Variant’ CJD
Fatal Familial Insomnia
Scrapie in sheep
Bovine spongiform encephalopathy (Mad
Cow Disease)
CJD (Creutzfeldt-Jakob)
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1 per million incidence, 7th decade
Sporadic cases, not epidemic
Iatrogenic Transmitted ! Contaminated
material
Familial cases well documented – PRNP
mutation (15%)
Rapidly progressive dementia
FATAL, no treatment known, like ALL
prion diseases
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Creutzfeldt-Jacob Disease:
– Rapidly progressive
– Usually older people
– Younger in familial cases
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Variant CJD = Mad Cow Disease
– usually acquired through cattle & recently,
blood transfusion.
Pathology:
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Multifocal spongiform transformation of
cortex & deep grey matter→ multiple
cysts, most in caudate & putamen.
No inflammatory response.
Microscopic findings:
– Neuronal loss
– Gliosis
– Atrophy
– Amyloid deposits may be present (v.CJD)
FUNGAL ENCEPHALITIS:
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Candida, Cryptoccocus, Aspergillus, & Mucor
Normal or Immunocompromised patient sp.
Cryptoccocus
Hematogenous or direct spread
Diabetics with ketoacidosis are especially
prone to Mucormycotic infection from nose
or sinuses
AIDS patients are prone to cryptococcal
meningoencephalitis
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Blood vessel invasion with hemorrhagic
infarction especially found in Aspergillus
Morphology of fungal infections:
Microabscesses in brain or poorly
formed granulomas ± meningitis.
Fungi can be demonstrated by PAS or
Silver stain
OPPORTUNISTIC INFECTIONS
Fungal cerebritis: Aspergillus
OPPORTUNISTIC INFECTIONS
Fungal cerebritis: Aspergillus
Other infections:
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Cerebral Toxoplasmosis:
occurs in immuno-compromised patients
(AIDS), produces small, usually multiple,
abscesses & necrotic foci which contain
toxoplasma pseudocysts in microglial
nodules
Toxoplasma Pseudocyst
 Amebic meningoencephalitis
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Cysticercosis: Tapeworm Tenia Solium
– Man is the intermediate host: Ova are
ingested  Larvae  Cysts
– Anywhere in the body !
– Mass lesion
– Death  intense inflammation &
eosinophils
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Echinococcosis: Echinococcus
granulosus Tapeworm
Hydatid Cyst
Hydatid Cyst Wall