CNS infections (1 of 2)

How can microbes enter the nervous system?

• Hematogenous…the most common

…mostly arterial

…can be from facial veins (through anastomoses with venous sinuses of the skull)

• Direct implantation

…penetrating (open) trauma

…lumbar puncture, surgery…etc.

…congenital problems such as myelomeningocele

• Local extension…from infected sinuses (most common: mastoid, frontal), teeth, skull, or vertebrae

• Some viruses can be transported through peripheral nervous system

…rabies

…herpes zoster

Bacterial infections

Meningitis Localized infections

Chronic

Acute pyogenic

Abscess …mostly bacterial but can be also caused by fungi or parasites

Subdural empyema …rarely can be caused by fungi

Meningitis = inflammation of leptomeninges and subarachnoid space…mostly due to infection but may be: chemical meningitis

Meningoencephalitis = meningitis + inflammation of brain parenchyma

May be also caused by fungi

Bacterial acute pyogenic meningitis

*Systemic signs of infection

*Headache, photophobia,

phonophobia, irritability, clouding of

consciousness

*Neck stiffness

*In spinal tap (lumbar puncture):

-Cloudy/purulent (too many

neutrophils) CSF

-Increased pressure

-As many as 90,000 neutrophils

per cubic millimeter

-Increased protein concentration

-Markedly reduced glucose content

-Bacteria may be seen on a smear

or may be cultured

…sometimes a few hours before the neutrophils appear

*Klebsiella and anaerobes more in immunosuppressed …atypical clinical course and CSF findings

Symptoms/signs of meningeal irritation

Bacterial acute pyogenic meningitis, cmplications

• Severe involvement of leptomeningeal veins (phlebitis) may lead to venous occlusion and hemorrhagic infarction of the underlying brain

• Extension into brain substance…focal cerebritis…sometimes formation of abscess

• Extension into ventricles…ventriculitis

• Waterhouse-Friderichsen syndrome…adrenal hemorrhage due to meningococcal meningitis-associated septicemia (along with petechial rash)…also with pneumococcus

Bacterial acute pyogenic meningitis, morphology

**On microscopic examination:

*Neutrophils may fill the entire subarachnoid space or, in

less severe cases, may be confined to regions adjacent

to leptomeningeal blood vessels

*In untreated meningitis, Gram stain reveals varying

numbers of the causative organism

Elsevier. Kumar et al. Robbins and Cotran pathologic basis of diseases 9th

Viral infections

Meningitis

Brainstem and spinal cord syndromes

Acute aseptic

Rhombencephalitis Spinal poliomyelitis

Encephalitis

Encephalitis (not arthropod-borne)

Arthropod-borne encephalitis

Of viral infections, we will only discuss this in this lecture …other viral pathologies will be discussed in the next lecture

Acute aseptic (viral) meningitis

• “Aseptic” is a clinical term that means: No organisms in bacterial culture are found in a patient with a picture of meningitis

…also meningeal irritation, fever, and alterations of consciousness…but

less fulminant than pyogenic meningitis…self-limited

• Viral etiology (in about 80% of cases enteroviruses), but may be bacterial, rickettsial, or autoimmune in origin

Acute aseptic (viral) meningitis, cont’d

• CSF finding are different from pyogenic meningitis:

…the pleocytosis (increased WBC count) here

is lymphocytic not neutrophilic

…the protein elevation is only moderate

…the glucose content is nearly always normal

• Viral aseptic meningitides are usually self-limited and are treated symptomatically

On microscopic examination, there is either no

recognizable abnormality or a mild to moderate

leptomeningeal lymphocytic infiltrate

Aseptic meningitis-like picture

…due to chemical irritant or rupture of epidermoid cyst into

subarachnoid space (chemical meningitis)

• No organisms isolated (sterile CSF)

• Neutrophils

• May be increased protein

• Normal glucose

Chronic meningitis • Mainly: mycobacteria, some spirochetes, and fungi

…may also involve the brain parenchyma

Tuberculous meningitis Spirochetal infection

Fungal meningitis …see next slide *General symptoms: headache,

malaise, mental confusion, and vomiting

*Moderate increase in WBCs

(mononuclear or mononuclear +

polymorphonuclear)

*Protein is markedly high

*Glucose is moderately reduced

or normal

*May cause a well-defined mass

(= tuberculoma)

*May cause arachnoid fibrosis…hydrocephalus

*Neurosyphilis …tertiary (occurs in 10% of the untreated) …more and more severe in AIDS …3 patterns (isolated or in combination)

Meningovascular neurosyphilis …obliterative endarteritis …base of brain

Paretic neurosyphilis …progressive parenchymal loss and increased microglial cells…loss of mental and physical functions …psychiatric problems …eventually severe dementia

Tabes dorsalis …damage to the sensory nerves in the dorsal roots …impaired joint position sense and ataxia …loss of pain sense…skin & joint damage (Charcot joints) …lightning pains …absence of deep tendon reflexes

*Neuroberreliosis

Remember: -sensory ataxia …positive Romberg test …Stamping gait

Fungal meningitis

• Cryptococcus neoformans

• Histoplasma capsulatum

• Coccidioides immitis

Especially in immunocompromised …can be associated with high fatality

Parenchymal infections

• Brain abscess

• Viral encephalitis…will be discussed in the next lecture

• Fungal encephalitis

• Parasitic encephalitis

Brain abscess • Mostly bacterial

• Of the predisposing conditions:

-Acute bacterial endocarditis, from which septic emboli are released …multiple abscesses

-cyanotic congenital heart disease

…right-to-left shunt and loss of pulmonary filtration of

organisms

-chronic pulmonary infections, as in bronchiectasis

• Discrete destructive lesion with liquefactive necrosis surrounded by granulation tissue/fibrosis…outside: gliosis

Elsevier. Kumar et al. Robbins basic pathology 10th

Check http://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.html for references

http://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.htmlhttp://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.html

Brain abscess, clinical manifestations

• Like a tumor: focal neurological deficit and increased intracranial pressure

• CSF white blood cell count and protein may be elevated

…However, lumbar puncture has little role in the diagnosis of brain

abscess since organisms are more reliably cultured by draining the

abscess directly

• A systemic or local source of infection may or may not be apparent

• Abscess rupture can lead to ventriculitis, meningitis, and venous sinus thrombosis

• If untreated, progressive and can result in fatal herniation

Fungal encephalitis

• Usually granulomas or abscesses, often with meningitis

• Candida albicans

…multiple microabscesses, with or without granulomas

• Mucormycosis

…infection of nose/sinuses in diabetics with ketoacidosis is a risk

• Aspergillus fumigatus

…widespread septic hemorrhagic infarctions because of its marked

predilection for blood vessel wall invasion with subsequent thrombosis

Parasitic parenchymal infections • Cerebral toxoplasmosis (by Toxoplasma gondii):

-immunosuppressed adults

or

neonates (transplacentally)

…triad of chorioretinitis, hydrocephalus, and intracranial calcifications

-inflammation and breakdown of the blood-brain barrier at sites of

infection…imaging studies often show edema associated with ring-

enhancing lesions

-abscesses, frequently multiple, most often involving the cerebral

cortex (near the gray-white junction) and deep gray nuclei

-both free tachyzoites and encysted bradyzoites may be found at the periphery of the necrotic foci

Giemsa

Check https://emedicine.medscape.com/article/229969-overview for references...modified

Check https://www.cdc.gov/dpdx/toxoplasmosis/index.html for references...modified

Tachyzoites

Bradyzoites in cyst

https://emedicine.medscape.com/article/229969-overviewhttps://emedicine.medscape.com/article/229969-overviewhttps://emedicine.medscape.com/article/229969-overviewhttps://emedicine.medscape.com/article/229969-overviewhttps://emedicine.medscape.com/article/229969-overviewhttps://www.cdc.gov/dpdx/toxoplasmosis/index.htmlhttps://www.cdc.gov/dpdx/toxoplasmosis/index.htmlhttps://www.cdc.gov/dpdx/toxoplasmosis/index.html

Parasitic parenchymal infections, cont’d

• Cysticercosis:

-It is the consequence of an end-stage infection by the tapeworm Tenia solium

-Cysticercosis typically manifests as a mass lesion and can cause seizures. Symptoms can intensify when the encysted organism dies, as occurs after therapy

• Amebiasis

-Naegleria species…rapidly fatal necrotizing encephalitis

-Acanthamoeba…chronic granulomatous meningoencephalitis