Infectious Diseases in the Nervous System Meningoencephalitis: diffuse meningeal and parenchymal process Myelitis: localized to spinal cord,

rd, immune mediated process Encephalomyelitis: viral or immune mediated involved the gray and white matter

Routes of infection: Blood stream (hematogenous) most common Direct implantation traumatic or iatrogenic (surgical) Local extension from skull, sinuses, middle ear Axonal transport CSF pathways Immunologic considerations: Brain lacks lymphatics and formed lymphoid tissues Lymphocytes and monocytes circulate in CNS only in small #s BBB may hinder drugs to pass through Manifestations of infections: Direct tissue damage Inflammatory edema Involvement of blood supply ischemia/thrombosis infarction/hemorrhage Immunologic damage Toxic effects Commensalism Neoplastic transformation EBV in primary CNS lymphoma of HIV pts

Acute purulent (pyogenic,bacterial) leptomeningitis Subarachnoid space due to virulent bacteria, fungi, protozoans Non-specific, systemic Meningeal irritation Direct CNS involvement Acute inflammation in subarachnoid space Common agents: Bacteria: Fungi: . Other: toxoplasma, ameba CSF findings: Increased pressure Increased protein Decreased glucose Leukocytosis Detectible by gram stain or culture

Acute lymphocytic (viral, aseptic) meningitis Viral agents (common viruses of upper GI or respiratory infections), noninfectious agents (cancer cells leptomeningeal carcinomatosis, chemicals/drugs chemical meningitis) Milder than acute purulent leptomenigitis and does not result in alteration of consciousness Clinical course mild with full recovery. Common syndrome but commonly missed. CSF findings: Increased protein,

Chronic meningitis Indolent persistent agent (TB, syphilis, sarcoidosis, low grade tumors, foreign substances) Non specific, slowly evolving Basal meningitis with mononuclear inflammation, fibrosis (at base of brain) CSF findings: Increased pressure of blockage of CSF flow Increased protein Decreased glucose Leukocytosis

Empyemas and abscesses -subdural/epidural empyema -brain parenchymal abscess (Cerebritis) RFs: -infection elsewhere -trauma to skull, spine, -presence of foreign body (Catheter, gauze pad, bullet fragment)

Acute viral encephalitis Acute viral infection of brain parenchyma/meninges Most viral infections display tissue tropism (specific virus infects a specific cell) Infections: lytic or non-lytic CSF findings: Increased protein, normal glucose, leukocytosis with PMNs EEG, imaging studies (CT, MRI) Serology, culture, PCR assay specific virus List specific examples!!!!

Chronic (slow) viral encephalitis Slowly progressing dementia or neurologic syndrome AIDS dementia brain atrophy, demyelination, encephalitis with monocytes and giant cells PML (progressive multifocal leukoencephalopathy) destruction of oligodendrocytes usually in immunocompromised. Papovavirus (JC strain) SSPE (subacute sclerosing panencephalitis) measles virus TSP (tropical spastic paraparesis) HTLV1, progressive spastic leg weakness and sensory loss due to involvement of lower spinal cord.

Localized area of tissue damage and acute/chronic inflammation surrounded by reactive layer; brain parenchyma may show Chronic prominent edema inflammation in Complications: subarachnoid space mass effect leads to leads to progressive increased ICP and meningeal fibrosis, herniation, vasculitis, infection can

Requires prompt diagnosis and treatment to prevent irreversible brain damage and optimize outcome Pathogenetic sequence: Primary colonization elsewhere in body, disseminate to CNS (hematogenous), infection of meninges, acute inflammatory response in subarachnoid space, consequence (brain swelling, damage, dissemination)

normal glucose, root/parenchymal leukocytosis involvement (early: few PMNs, later: lymphocytes) Complications: hydrocephalus, increased ICP, infarcts, focal deficits, cognitive decline. Difficult to diagnose due to indolent chronic course and nonlocalizing findings

spread (sepsis), focal permanent neurologic deficits, abscess may rupture into ventricles or disseminate into subarachnoid space as acute purulent leptomeningitis Tx: drainage or surgical removal of lesion Lumbar puncture may be CI due to increased ICP

HIV infection: Acute lymphocytic meningitis during primary infection Chronic HIV encephalitis progressive demntia (AIDS dementia) Vacuolar myelopathy degeneration of posterior and lateral columns of spinal cord in patis with chronicn AIDS. (Resembles subacute combined degeneration in Vit B12 deficiency) Peripheral neuropathy Inflammatory myopathy Opportunistic CNS infections: Toxoplasma cerebritis

PML CMV encephalitis Crytoptococcus meningitis Other complications: o Primary CNS lymphoma o Drug toxicity to neuromuscular system from anti-retrovirals