CNS infections (1 of 2)

1. CNS infections(1 of 2) Ali Al Khader, MD Faculty of Medicine Al-Balqa Applied University Email: ali.alkhader@bau.edu.jo

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

3. Bacterial infections Meningitis Localized infections Chronic Subdural empyema …rarely can be caused by fungi Abscess …mostly bacterial but can be also caused by fungi or parasites Acute pyogenic May be also 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

4. Bacterial acute pyogenic meningitis *Klebsiella and anaerobes more in immunosuppressed …atypical clinical course and CSF findings Symptoms/signs of meningeal irritation *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

5. 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

6. Bacterial acute pyogenic meningitis, morphology Elsevier. Kumar et al. Robbins and Cotran pathologic basis of diseases 9th **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

7. Viral infections Brainstem and spinal cord syndromes Encephalitis Meningitis Spinal poliomyelitis Arthropod-borne encephalitis Encephalitis (not arthropod-borne) Rhombencephalitis Acute aseptic Of viral infections, we will only discuss this in this lecture …other viral pathologies will be discussed in the next lecture

8. 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

9. 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 asepticmeningitides 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

10. 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

11. Chronic meningitis • Mainly: mycobacteria, some spirochetes, and fungi …may also involve the brain parenchyma Spirochetal infection Fungal meningitis …see next slide Tuberculous meningitis *Neuroberreliosis *Neurosyphilis …tertiary (occurs in 10% of the untreated) …more and more severe in AIDS …3 patterns (isolated or in combination) *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 Remember: -sensory ataxia …positive Romberg test …Stamping gait 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 Paretic neurosyphilis …progressive parenchymal loss and increased microglial cells…loss of mental and physical functions …psychiatric problems …eventually severe dementia Meningovascular neurosyphilis …obliterative endarteritis …base of brain

12. Fungal meningitis Especially in immunocompromised …can be associated with high fatality • Cryptococcus neoformans • Histoplasma capsulatum • Coccidioidesimmitis

13. Parenchymal infections • Brain abscess • Viral encephalitis…will be discussed in the next lecture • Fungal encephalitis • Parasitic encephalitis

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

15. 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

16. 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

17. Parasitic parenchymal infections Check https://emedicine.medscape.com/article/229969-overview for references...modified • 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 tachyzoitesand encysted bradyzoites may be found at the periphery of the necrotic foci Tachyzoites Giemsa Check https://www.cdc.gov/dpdx/toxoplasmosis/index.html for references...modified Bradyzoites in cyst

18. Parasitic parenchymal infections, cont’d • Cysticercosis: -It is the consequence of an end-stage infection by the tapeworm Tenia solium -Cysticercosistypically manifests as a mass lesion and can cause seizures. Symptoms can intensify when the encysted organism dies, as occurs after therapy • Amebiasis -Naegleriaspecies…rapidly fatal necrotizing encephalitis -Acanthamoeba…chronic granulomatous meningoencephalitis

19. Thank You