Central Nervous System Infections Infectious Agents leading to CNS Infections Bacterial Acute Pyogenic (Bacterial) Infection Neonates Eschericia coli B Streptococci Streptococcus pyogene Streptococcus agalactiae Infant Hemophilus influenza (before vaccination) Streptococcus pneumoniae Adolescent and young adults Nisseria meningitidis Elderly Streptococcus pneumoniae Listeria monocytogene Chronic Granulomatous Infection Mycobacterium spp Spirochete Treponema pallidum Fungal Chronic Meningitis Cryptococcus spp. Vasculitis Aspergillus spp. Parenchymal Infection Granulomatous Cryptococcus spp. Abcess Candida spp. Unclassified (in Diabetic Ketoacidocis) Viral (Asceptic) Echovirus Coxsackievirus Nonparalytic poliomyelitis Herpes simplex Rabies Protozoal Malaria Toxoplasma spp. Entameoba histolytica Trypanosome spp.
Bacterial Infections Disease Pathogenesis Morphology Clinical Manifestation Macroscopic Microscopic Brain Abscess Local extension Sinusitis Mastoid sinus Frontal sinus Infected Osteomyelitis of the Cranium Spine Heamatogenous spread (the most common) The etiological agents spread from distant area of the body and lodged at the CNS Direct implantation of organisms Trauma Post meningitis Evolution of the Abscess The brain undergoes acute inflammatory response after come into contact with foreign agents, characterized with Neutrophilic infiltration Cerebritis When the tries to heal the lesion, granulation tissue forms at the peripheral of the lesion; middle zone undergoes liquefactive necrosis Sattellite abscess has a very poor capsulation at the medial side; therefore it is easily rupture and the pus may enter the ventricle Descrete lesion with liquefactive necrosis Edema Presented with expanded white matter adjacent to the abscess Dense aggregates of neutrophils Necrotic area surrounded with granulation tissue Neovascularization Outside the capsule of abscess is the zone of gliosis With numerous Gemistocytic Astrocytes Most commonly affected area Frontal lobe Parietal lobe Cerebellum Features Progressive focal deficit Loss of neurological function due to destruction of the brain tissue Subsequent increased in ICP Progrssive herniation If the abscess ruptures, it will lead to Ventriculitis Meningitis Venous sinous thrombosis Disease Pathogenesis Etiological agents Clinical Manifestation Epidural Abscess Ussually occurs due to complication of vertebral osteomyelitis Sometimes due to complications of Spinal surgery Trauma Spinal anesthesia Staphylococcus aureus (most cases) Gram negative rods Bacteroides Streptococci spp. Mycobacterium tuberculosis Initially presented with Fever Back pain Progression Weakness of the lower extremities Impaired Bowel function Bladder function Ends up with paralysis Subdural Abscess Extension of bacterial or fungal infection of the Cranium Sinuses Middle ear Headache Fever Neck stiffness Signs and symptoms of origin infection Ultimately will lead to mass effect if the pus is massive
Bacterial Infections Disease Pathogenesis Morphology Clinical Manifestation Laboratory Findings Microscopic Macroscopic Tuberculous Infection of CNS Spreaded through heamatogenous and usually comes about from disseminated pulmonary tuberculosis Mixture of Lymphocytes Plasma cells Macrophages Florid show granulomas Often presented with caseating necrosis and giant cells Mimicking the morphology of pulmonary tuberculosis Obliterative endarteritis of artery running through subarachnoid space Same appearance for Tuberculoma Subarachnoid space contains Gelatinous Fibrinous exudate This exudate most often finds at the base of brain, obliterating Cisterns Encasing cranial nerves May present with descrete white granules scattered over the Leptomeninges Tuberculoma may have a bigger lesion Generalized Headache Malaise Mental confusion Vomiting Lumbar puncture Elevated protein Glucose may be Moderately reduced Normal Complications Hydrocephalus Exudate may organize and form arachnoid fibrosis which may occlude the arachnoid granulation leading to communicating hydrocephalus Obliterative Endarteritis Artery may become occluded during healing and subsequently leads to cerebral infarction
Bacterial Infections Disease Pathogenesis Morphology Clinical Manifestation Microscopic Macroscopic Neurosyphilis Types Meningovascular neurosyphilis Paretic neurosyphilis Tabes dorsalis Happens during the tertiary syphilis This occurs in about 10% of syphilitic patients who didn’t have proper treatment It is caused by spirochete Treponema pallidum Meningovascular Neurosyphilis (Meninges) Meningovascular Neurosyphilis Apathy Seizures General paresis with dementia Paretic Neurosyphilis Insidious loss of mental and physical function Mood alteration Delusion of grandeur Terminating with severe dementia Dorsalis Impaired joint position sense Locomotor ataxia Loss of pain sensation Charcot’s joint Skin and joint damage Lightning pains Loss of deep tendon reflex Lymphocytes and plasma cells appeared at the peripheral to blood vessels Heubner Arteritis Marked endothelial thickening, thickened Tunica Tunica adventitia Primarily involved the meninges of the Base of the brain Subarachnoid space Blood vessels Paretic Neurosyphilis (Brain Parenchyma) Loss of neurons with microglial (rod cells) proliferation Gliosis Loss of Ependymal lining with subependymal gliosis Granular ependymitis appeared Shrunken Firm Frontal lobe is atrophic Leptomeninges is thickened With or wihout hydrocephalus Tabes Dorsalis (Spinal Cord) Loss of axons and myelin sheath at the Dorsal Column Pallor and atrophy of the Dorsal Column
Fungal Infections Primarily happens in Immunocompromised patients HIV patients Debilitated patients Patients undergoing chemo Characterized by 3 patterns Chronic fungal meningitis Cryptococcus spp. Vasculitis Mucor Aspergillus spp. Invasion of the blood vessel leading to Heamorrhage Thrombosis Branching of hyphae can be seen invading the cerebral vessels Parenchymal Invasion Abscess forming lesion Candida spp Granulomatous lesion Cryptococcus Disease Pathogenesis Morphology Clinical Manifestation Laboratory Findings Microscopic Macroscopic Chronic Fungal Meningitis Usually caused by Cryptococcus spp. Brain usually one of the latest organs to infected after disseminated fungal infection Spreaded through heamatogenous route Usually well-formed granuloma is hardly seen Infiltration of chronic inflammatory cells including Fibroblasts Mononuclear giant cells With presence of Cryptococci spp. Tubercle like nodule on the Leptomeninges at the base of the brain The infections can be Fulminant and fatal within 2 weeks Indolent and evolving up to months or years CSF findings High protein Few Presence of mucoid encapsulated yeast in Indian Ink
Infections Disease Pathogenesis Morphology Clinical Manifestation Laboratory Findings Microscopic Macroscopic Acute Aseptic Meningitis Generally viral in origin Echovirus Coxsackievirus Nonparalytic poliomyelitis Sometimes can be non-viral in origin (drug-induced) NSAIDs Antibiotics Usually no abnormalities can be found Sometimes mild to moderate lymphocytic infiltration of the Leptomeninges No distinctive changes can be seen on the brain Sometimes, brain appears edematous Less fulminant, and usually self-limiting CSF findings Increased in pressure Clear color Increased numbers of Lymphocytes Slightly increased protein Normal glucose level Smear and culture appear negative for bacteria Viral Encephalitis Nervous system tropism Certain virus affects certain cells Others have preference towards particular area of the brain Temporal lobe/ limbic system Herpes simplex Capacity of latency Varicella-zoster may remain dormant at the dorsal root ganglia It may also follow an immune mediated disease pathway This has no evidence of direct viral invasion For example Acute Disseminated Encephalitis Intrauterine infection May lead to congenital malformation May follow a slowly degenerating disease Postencephalitic Parkinsonism General characteristics Perivascular and parenchymal mononuclear infiltration Lymphocytes Plasma cells Macrophages Gliosis with/out nodules Neurophagia Nuclear/cytoplasmic inclusion bodies can be found Herpex Simplex Encephalitis Large eosinophilic intranuclear inclusion Rabies Negri bodies Round to oval in shape Eosinophilic cytoplasmic inclusion Found in Neurons in Hippocampus Pyramidal cells of the Cerebellum CMV Owl eyes Intranuclear and cytoplasmic inclusion Measles Warthin Finkeldey Bodies in Subacute Sclerosing Panencephalitis (SSPE) JC Virus Progressive Multifocal Leucoencephalopathy (PML) General characteristics Almost invariably with meningeal inflammation Sometimes with the involvement of the spinal cord Herpex Simplex Encephalitis Petechiae are seen on the Temporal lobe Rabies Intense edematous brain Vascular congestion
Protozoal Infections Disease Pathogenesis Morphology Clinical Manifestation Microscopic Macroscopic Toxoplasmic Encephalitis Cerebral Toxoplasmosis can be either Acquired Toxoplasmosis Congenital Toxoplasmosis Ingestion of the cysts will lead to infection The initial infection takes place at the intestion and regional lymph nodes The formation occurs at the CNS Eyes Cardiac muscle Skeletal muscle Toxoplasma pseudocyst with bradyzoites With/out granuloma Abscess formation Often present with multiple foci of calcification During an acute infection, patients usually appear assymptomatic But when the cysts forms in the CNS, patients will develop Fever Headache Lethargy Altered mental status neurological deficits Convulsions May end with fatality Single or multiple lesions can be seen at the Basal Ganglia Junction between the white and gray matter Prions Diseases Disease Pathogenesis Morphology Clinical Manifestation Microscopic Macroscopic Prions Diseases Disease (CJD) Syndrome (GSS) Fatal familial insomnia Kuru Groups of diseases with abnormal form of a specific protein, Prion Protein (PrP) It is itself transmissable particles Can be directly inoculated PrP undergoes conformational change from Normal α-helix-containing isoform (PrPc) Abnormal β-helix-pleated sheet isoform (PrPsc) PrPsc is located at the Chromosome 20 Accumulation of PrPsc in the neurons appear to be the cause of pathology Largely how does this happens, remains unknown Spongiform cerebral cortex Small vacoules in dendritic cytoplasm cluster Astrocytocis Neuronal loss atrophy The progression of disease can be either Very slow Rapid Most patients develop Dementia
Cause Appearance Polymorphonuclear cell Lymphocyte Protein Glucose Pyogenic Yellowish, turbid Markedly increased Slightly increased or Normal Markedly increased Decreased Clear fluid Slightly increased or Normal Markedly increased Slightly increased or Normal Normal Yellowish and viscous Slightly increased or Normal Markedly increased Increased Decreased Yellowish and viscous Slightly increased or Normal Markedly increased Slightly increased or Normal Normal or decreased