Pathology of the CNS PDF

Pathology of the CNS Reactions of neurons in the CNS to injury - Acute injury: ➔ Necrosis: ▪ Evident within 12 hours of irreversible ischemia/hypoxia ▪ Red neurons: shrinkage of the cell body, pyknosis of the nucleus, disappearance of the nu...

Pathology of the CNS Reactions of neurons in the CNS to injury - Acute injury: ➔ Necrosis: ▪ Evident within 12 hours of irreversible ischemia/hypoxia ▪ Red neurons: shrinkage of the cell body, pyknosis of the nucleus, disappearance of the nucleolus, & intense eosinophilia of cytoplasm ▪ Spheroids: axonal injury leads to cell body enlargement and rounding, and peripheral displacement of the nucleus & Nissl bodies (central chromatolysis) ➔ Apoptosis: in development and aging processes - Chronic or subacute injury (degenerative diseases): ➔ Neuronal loss & replacement by gliosis in progressive diseases (selective) ➔ Some neurodegenerative diseases show intracellular inclusions ➔ Neuronal processes may be thickened & tortuous (dystrophic neurites) ➔ Examples: Alzheimer disease, Parkinson disease - Axonal injury leads to: ➔ Cell body swelling ➔ Central chromatolysis: ▪ Peripheral displacement of the nucleus ▪ Enlargement of the nucleolus ▪ Peripheral dispersion of Nissl substance - Inclusions: ➔ Nuclear or cytoplasmic ➔ Mainly seen in viral infections ➔ Cytoplasmic Negri bodies in rabies - Accumulations: ➔ Abnormal proteins & complex lipids ➔ Lipofuscin with age (aging pigment = wear and tear pigment) ➔ Tay-Sachs disease: ganglioside (lipid) accumulation Glial cells (supporting cells) 1- Astrocytes ➔ Respond by ↑number & size in gliosis ➔ Commonest reactive change is gliosis ➔ Gemistocytes: ▪ Swollen reactive astrocytes with acidophilic cytoplasm ▪ ↑ Glial fibrillary acid protein (GFAP) ▪ May lead to fibrillary astrocytes ▪ In chronic conditions such as brain tumors ➔ Rosenthal fibers: ▪ Aggregates of thick eosinophilic astrocytic fibers ▪ In old gliosis or some low-grade glial tumors 2- Oligodendrocytes ➔ Synthesis & maintenance of myelin ➔ Deranged in demyelinating diseases ➔ Inclusions in specific viral infections – PML (JC virus) 3- Ependymal cells ➔ Line the ventricles and detoxify CSF ➔ Ependymal granulations ▪ Areas in ventricles of sloughed ependymal lining ▪ Could be normal or pathologic (ventriculitis) ➔ Inclusions characteristic of CMV 4- Microglia (Scavengers of the brain) ➔ Macrophages in infarction: (Gitter cells) ➔ Elongated cells in syphilis: (Rod cells) ➔ Aggregates of microglia around injured cells: (Microglial nodules) ➔ Aggregate around dead neurons: (Neuronophagia) CNS infections - Routes of infection ➔ Hematogenous (most common) ➔ Direct (trauma & iatrogenic) ➔ Local extension from adjacent focus (air sinuses & congenital malformations, peripheral nerves) - Epidural & Subdural Infections: ➔ Staph, Strep, Gram-negative bacilli, Mixed, or fungal ➔ Direct local spread ➔ Epidural abscess ✓ Arise from an adjacent infection: sinusitis or osteomyelitis ✓ Produces localized space occupying lesion ➔ Subdural empyema → Mass effect & ↑ICP ➔ Subdural vessels → cerebral cortical thrombophlebitis → infarction - Meningitis 1- Acute Pyogenic (Bacterial) Meningitis: ➔ Neonates: Group B Streptococci & E. coli ➔ Adolescents & young adults: N. meningitidis ➔ Elderly: S. pneumoniae & L.monocytogenes ➔ Clinical picture: ▪ Fever, headache, vomiting, photophobia, neck rigidity ▪ N. meningitides: skin rash & complicated by septicemic shock & Waterhouse Friderichsen Syndrome (Adrenal hemorrhage and failure) ➔ CSF findings: ↑Pressure, ↑Protein, ↓Sugar, ↑Neutrophils and bacteria ➔ Morphology: ▪ Exudate in subarachnoid space (around base) = neutrophils & MOs ▪ Severely congested meningeal vessels, surrounded by neutrophils ▪ Sometimes focal cerebritis & ventriculitis & abscesses may occur ▪ May show phlebitis, venous occlusion & hemorrhagic infarction 2- Aseptic (Viral) Meningitis: ➔ Hematogenous spread ➔ Mild self-limiting often seasonal ➔ Brain edema, mild mononuclear infiltrate (meninges & superficial cortex) ➔ CSF is clear, slight protein, normal sugar,  lymphocytes 3- Chronic Meningitis/meningo-encephalitis ➔ TB: brain and meninges ➔ Syphilis: gummas in brain (meningovascular neurosyphilis) ➔ Lyme disease (Neuro-borreliosis) transmitted by ticks ▪ Aseptic meningitis ▪ Facial nerve palsies ▪ Polyneuropathies ▪ Mild encephalopathy  ➔ Tuberculous Meningitis: ▪ Hematogenous spread from lung → brain ▪ Direct spread from tuberculous vertebra (Pott's disease) ▪ Result: meningitis or tuberculoma ▪ Thick cheesy exudate & thick meninges ▪ Caseating granulomas ▪ Basal cisterns & sulci most affected ▪ May show obliterative endarteritis & infarction ▪ CSF:  protein, lymphocytes, sugar is normal or  ➔ Neurosyphilis: caused by spirochete (T. pallidum) ▪ Meningovascular neurosyphilis: Neurosyphilis = tertiary syphilis: ✓ Meningeal chronic infection ✓ Obliterative endarteritis & cerebral gummas - 10% of untreated syphilis patients - More serious with HIV ✓ Usually at the base of the 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 ✓ Progressive mental deficits, mood alteration → severe dementia ▪ Tabes dorsalis (tertiary syphilis): ✓ Involves SC → 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 ▪ Acute syphilitic meningitis: ✓ HIV infected patients who have ↑risk for neurosyphilis ✓ May develop severe rapidly progressive disease - Complications of Bacterial Meningitis ➔ Obstructive hydrocephalus ➔ Cerebral infarction ➔ Cerebral abscess ➔ Epilepsy ➔ Cranial nerve palsy ➔ Deafness - Prognosis depends on rapidity of proper antibiotic therapy Parenchymal Infections: ➔ Localized: abscess, tuberculoma, toxoplasmosis, parasites ➔ Diffuse: encephalitis, usually viral 1- Brain Abscess: ➔ Usually bacterial ➔ Direct implantation ➔ Local extension from paranasal sinusitis, mastoiditis & middle ear infection → frontal or temporal lobes ➔ Hematogenous: 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 ▪  ICP 2- Fungal encephalitis: ➔ Candida, Cryptococcus, Aspergillus, & Mucor ➔ Normal or immunocompromised patient esp. Cryptococcus ➔ Hematogenous or direct spread ➔ Diabetics with ketoacidosis are especially prone to Mucormycotic infection from nose or sinuses ➔ Candida albicans produces multiple micro-abscesses +/- granuloma ➔ AIDS patients are prone to cryptococcal meningoencephalitis ➔ Blood vessel invasion with hemorrhagic infarction found in Aspergillus ➔ Morphology of fungal infections: ▪ Microabscesses in brain or poorly formed granulomas ± meningitis ▪ Fungi can be demonstrated by PAS or Silver stain Viral encephalitis - Sporadic infection: HSV encephalitis - Latent infections: VZV - Neurotropic: Poliovirus, Rabies  - Antenatal: CMV, Rubella - Immune deficiency: HIV, CMV, PML, VZV - Some systemic viral infections do not infect the CNS, but initiate immune mechanisms in CNS (Influenza virus) - Some viruses have selective sites: ➔ CMV - Ventricles ➔ HSV - Temporal lobe & orbital frontal area ➔ Polio - Anterior horn cells of spinal cord ➔ VZV - Thoracic dorsal root ganglia - Features common to most viral infections: ➔ Perivascular mononuclear infiltrate ➔ Cell lysis & neuronophagia ➔ Microglial nodules ➔ Nuclear or cytoplasmic inclusions (Cytoplasmic negri bodies in rabies, nuclear inclusions in CMV) Herpes Simplex Virus type 1 & 2 - Normal host: children or adults - Hemorrhagic necrotizing inflammation - In temporal lobe & orbital gyri of frontal lobe - HSV-2 in adults may cause meningitis - Eosinophilic intranuclear viral inclusions (Cowdry type A) in neurons & glia Varicella–Zoster Virus (Herpes-Zoster) - Chicken pox in children but latent infection in dorsal root ganglia in adults - Self-limited skin rash along dermatome (Shingles) or Post-herpetic neuralgia - In immunosuppressed patients, may show acute encephalitis - Lesion is typical of viral infection ± granulomatous arteritis & infarction Cytomegalovirus (CMV) - AIDS patients: ➔ Subacute encephalitis any region & any cell ➔ Mainly ependymal & subependymal cells ➔ Hemorrhagic periventricular necrosis ➔ Large cytoplasmic & intranuclear inclusions  - Fetus: intrauterine infection ➔ Changes similar to above ➔ Brain destruction ➔ Microcephaly ➔ Calcification Rabies - Severe often fatal, encephalitis ➔ Bite of a canine or others ➔ Ascending along peripheral nerve from bite ➔ Incubation period may last months - 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 Poliovirus - Enterovirus causing mild gastroenteritis - Involvement of CNS in the non-immunized - Acute: ➔ Mononuclear cell perivascular cuffs ➔ Neuronophagia of the anterior motor neurons of the spinal cord - Chronic: ➔ Atrophy of the anterior (motor) spinal roots → paralytic poliomyelitis or Postpolio syndrome (>20 yrs) ➔ Rare cases develop paralysis of respiratory muscles Human Immunodeficiency Virus (HIV) - At least 60% of AIDS patients develop CNS disease - Early: aseptic viral meningitis in 10% - Chronic HIV: Meningoencephalitis: ➔ Progressive → HIV encephalopathy (HIVE), affecting motor control, memory, incontinence ➔ Commonest cause of dementia in the young (HAND= HIV-associated neurocognitive disorder) ➔ Demyelination: vacuolar myelopathy affecting spinal cord nerve tracts - Pathology ➔ Mainly white matter & basal ganglia& spinal cord ➔ Demyelination, microglial nodules with multinucleate giant cells ➔ Brain atrophy JC virus → PML - Progressive Multifocal Leukoencephalopathy - 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: - Caused by prion variants not containing RNA nor DNA - Transmissible fatal disease, with no treatment - Prion proteins are present in normal brains (PrPc) - Abnormal folding (mutation) of PrP → (PrPsc) → (PrPsc, PrPsc, PrPsc …etc) - Mutation can be sporadic, familial or iatrogenic acquired via infected material - Include a variety of conditions: ➔ Kuru ➔ Creutzfeldt-Jacob Disease (CJD) ➔ ‘New Variant’ CJD = Variant CJD ➔ Fatal Familial Insomnia ➔ Scrapie in sheep ➔ Bovine spongiform encephalopathy (Mad Cow Disease) - CJD (Creutzfeldt-Jakob disease): ➔ 1 per million incidence, 7th decade ➔ Etiology: ▪ Sporadic cases, not epidemic (usually older people) ▪ Iatrogenic (transmitted by contaminated material) ▪ Familial cases well documented: PRNP mutation (15%): occurs at younger age ➔ Rapidly progressive dementia ➔ FATAL, no treatment known ➔ Variant CJD = Mad Cow Disease (first discovered in UK in 1995): ▪ Acquired through cattle, and recently acquired through blood transfusion ▪ Younger patients, prominent behavioral disorder, slower progression - Pathology: ➔ Multifocal spongiform transformation of cortex & deep grey matter ➔ Multiple cysts, most in caudate & putamen ➔ No inflammatory response ➔ Microscopic: Neuronal loss, Gliosis, Atrophy, Amyloid deposits may be seen (V-CJD)