CNS Pathology Inflammatory and Infectious Disorders

1. CNS PathologyInflammatory and Infectious Disorders

3. Classification of CNS INFECTIONS ETIOLOGY 1. BACTERIAL 2. VIRAL 3. FUNGAL 4. Others - PROTOZOAL - METAZOAL ANATOMY 1. MENINGES 2. PARENCHYMA 3. VENTRICLES meningitis, empyema encephalitis, cerebritis, abscess ventriculitis, ependymytis

4. Terminology: • Dura mater  Pachymeningitis • Meninges  meningitis (leptomeningitis), empyema • Parenchyma  encephalitis, cerebritis, abscess • Meninges&Brain  Meningoencephalitis • Ventricles  ventriculitis, ependymytis Etiology: • Infective – Septic & Aseptic • Chemical – Drugs • Carcinomatous – metastasis

5. CNS INFECTIONS(Pathogenesis) 1.BLOOD STREAM 2. DIRECT EXTENSION (sinuses, middle ear) 3. PENETRATING WOUNDS 4. PERIPHERAL NERVES 5. IATROGENIC (surgery)

6. Complications: • Encephalitis • Infarction • Abscess • Empyema • Raised ICP (Herniation & Hydrocephalus)

7. MAJOR CATEGORIES of CNS INFECTIONS • Bacterial: meningitis and abscess • Fungal: meningitis and abscess • Tuberculosis: tuberculoma and meningitis • Neurosyphilis • Parasitic • Viral • acute • chronic • Unconventional transmissible agents

8. Risk groups • The very young and the very old • Alcoholics • Patients with neural tube defects • Patients with CNS trauma, or after neurosurgical intervention • Patients who are immunocompromised for any reason • Patients with sickle cell anemia • Patients with cardiac and pulmonary anomalies

9. BACTERIAL INFECTIONS • Meningitis • Intracranial thrombophlebitis • Brain abscess • Epidural abscess • Subdural empyema

10. Variables: Systemic Manifestations • Meningococcus:Massive derangement (bacteriemia, shock, DIC, etc.) • Other organisms: CNS problems predominate(next slide) • Epidemic outbreaks: Meningococcus is the predominant organism (dorms, military barracks, etc.)

11. Variables: Age of onset • Neonatal: Coliforms, Group B Streptococci • Toddlers:Hemophilus influenzae B (decreasing in incidence, due to HIB vaccine) • Children, young adults: Meningococcus (vaccine available, routinely given to military recruits) • Young and adults: Pneumococcus (vaccine available for both age groups)

12. Common features: Effects on CNS • Purulent exudate • Cerebral edema • Cortical damage • Vascular damage (vasculitis) • Ventriculitis

13. Acute Pyogenic LeptomeningitisPurulent meningitis • An acute inflammation of the leptomeninges and subarachnoid space • Usually the infection is diffuse, since the CSF is a good culture medium & rapidly disseminates bacteria throughout the subarachnoid space

14. Origin • Hematogenous(bacteremia, infected emboli, septic thrombophlebitis) • Direct extension(otitis, sinusitis, mastoiditis, brain abscess) • Penetrating wounds • Developmental anomalies (neural tube defects)

15. Common organisms vary depending on the age of the patient • Infancy • E. coli • Group B Strep • Staphylococcus • L. monocytogenes • Childhood • H. influenzae • Pneumococcus • Meningococcus • Adulthood • Meningococcus • Pneumococcus

16. Pathology • The CSF is cloudy and contains many neutrophils • Protein is increased and glucose is reduced • Gram stain may demonstrate the causative organism (Gram negative diplococci = meningococci) • The meninges are opaque due to a covering of exudate, which often extends along the arachnoidal vessels • exudate tends to concentrate over the cerebral hemispheres in S. Pneumoniae meningitis • tends to be basal in location in H. Influenzae infection

17. Pathology • Hyperemia of meningeal vessels • Exudation of polymorphonuclear (PMN) leukocytes • Location of the subarachnoid exudate- pus tends to accumulate along the course of cortical veins • Neutrophils are present in the subarachnoid/Virchow - Robin spaces and sometimes fill these spaces • Secondary invasion of the brain produces a meningoencephalitis • In fulminant cases, there may be involvement of the leptomeningeal veins - which may develop a septicthrombophlebitis with secondary venous infarction of the brain • Cerebral edema (slight to moderate)

18. CSF mostly PMN, high protein, low sugar, high pressure, and positive cultures • Healing • complete resolution • fibrosis  hydrocephalus • Meningococcal meningitis frequently accompanied by • meningococcemia • myocarditis • adrenal hemorrhage (W-F) • sudden death

19. Complications • 1.Brain swelling: An important early step in meningeal inflammation is the local release of cytokines by host cells. This release is induced by bacterial cell wall material. These cytokines initiate meningeal inflammation and brain swelling, which may be rapid and fatal (especially in meningococcal and pneumococcal infections). • 2.Hypoxic brain damage:In Gram negative infections, endotoxic shock may lead to severe hypotension and hypoxic brain damage.

20. 3.Septicemia • 4. Waterhouse-Friderichsen syndrome: In meningococcal infection, organisms and/or toxins initiate the vascular damage and DIC, resulting in widespread petechial hemorrhages, which may affect many organs, including the brain. • An important complication of this process is hemorrhagic necrosis of the adrenal glands. • 5. Hydrocephalus:Organization of the subarachnoid exudate can produce adhesions (adhesive arachnoiditis) - obstructing the flow of CSF and producing a communicating hydrocephalus. • Early: Empyema acute hydrocephalus; • Late: Blockage of CSF pathwaysobstructive hydrocephalus.

23. SEPTIC MENINGITIS(after 24-36 hours) LEPTOMENINGITIS MENINGOENCEPHALITIS SUBARACHNOID SPACE PURULENT EXUDATE VENTRICLES

27. VENTRICULITIS VENTRICULAR EMPYEMA

29. Brain Abscess • Bacterial and fungal organisms • Sources of brain abscesses • Otogenous (temporal lobe or cerebellar) • Rhinogenic (paranasal sinuses) • Traumatic (e.g., stab wound) • Metastatic, hematogenously spread from • Bacterial endocarditis, septicemia • Lung abscess or bronchiectasis • Intestinal flora in congenital heart disease with a right to left shunt • Osteomyelitis

30. Pathogenesis of brain abscess • Preexisting necrosis: • Direct extension from adjacent focus (thrombophlebitis  venous infarct) • Infected emboli (occlusion of a small artery or arteriole arterial infarct) • Necrosis leads to frank suppuration • After a week or two, a fibrous wall (derived from the vasculature) that may be several mm thick after 4-5 weeks forms • Outside the fibrous wall, there are perivascular, chronic inflammatory cells and white matter edema (perifocal edema) • An intense astrocytic gliosis takes place with formation of a glial scar

31. Location • Mastoiditis  temporal lobe or cerebellar abscess • Frontal sinusitis and ethmoiditis  frontal lobe abscess • Metastatic (hematogenously derived) abscesses  anywhere Disseminated (metastatic) microabscesses are usually due to sepsis or acute bacterial endocarditis, and are multiple • Common organisms are Staph, Candida, and anaerobes (Bacterioides Fragilis) • Patients always have underlying immunosuppression

32. Complications of brain abscesses • Destruction of vital centers (e.g., medulla oblongata) • Rupture of the abscess causes empyema: • Meninges (leptomeningitis) • Ventricles (ventriculitis) • Increased intracranial pressure, due to: • Mass effect from large abscess • Perifocal inflammatory edema

33. Pathogenesis&Complications

34. BRAIN ABSCESS

35. BRAIN ABSCESS

40. EPIDURAL & SUBDURAL EMPYEMA • A subdural empyema is usually secondary to sinus or middle ear infection • It is a neurosurgical emergency since antibiotics do not penetrate the subdural space, and surgical drainage of the pus is necessary • The CT scan is diagnostic • The adjacent cerebral hemisphere is usually swollen (perifocal edema)

42. ACUTE SUBDURAL EMPYEMA

43. FUNGAL MENINGITIS • Cause a chronic meningitis, in some instances, granulomatous • Brain and cord may be involved • Most fungi produce infection of the CNS in either immunosuppressed or debilitated hosts

44. CRYPTOCOCCUS NEOFORMANS • Most common fungal infection • Produces a chronic basilar meningitis • Mononuclear inflammatory cells, foreign body giant cells, and the characteristic yeasts (mucicarmine- positive) are present within the subarachnoid and Virchow - Robin spaces • Produce the characteristic "soap bubble" appearance • India Ink stains of the CSF often demonstrate the encapsulated yeasts

45. Round capsulated fungal organisms • Lymphocytic infiltrate around  

46. Aspergillus infection

47. MUCOR • Infects the sinuses of diabetic patients with ketoacidosis • with direct invasion of the orbits and CNS (rhinocerebral mucormycosis) • Mucor has a propensity for • vascular invasion with secondary thrombosis • hemorrhagic cerebral infarction

48. TUBERCULOSIS • Pathologic response is a typical granulomatous inflammatory response of tuberculosis • Four main CNS lesions: • Solitary tuberculoma: caseous encapsulated large mass • Multiple tuberculomas of brain and meninges • Miliary tuberculosis (children) • Microscopic or a few mm in size • Tuberculous meningitis: produces a chronic basilar meningitis • Spinal:extension from vertebrae (Pott’s disease)

49. TUBERCULOMA • A focal tuberculous infection • Forming an expanding mass lesion • Occur in brain, cord or meninges • Simulates a neoplasm • May require surgical removal

50. Solitary tuberculoma