Infections Diseases in the Nervous System Flashcards
Characteristic syndromes
Pattern of infection/typical agents
Bony coverings
Pattern of Infection
Osteomyelitis
Typical agents
Bacteria, fungi
Characteristic syndromes
Pattern of infection/typical agents
Meninges
Epidural/subdural empyema
Bacteria, fungi
Meningitis (leptomeningitis):
Acute purulent - Bacteria, fungi
Aspetic, Viral - Viruses, chemical agents, cancer,
Subacute/chronic - Some bacteria or fungi, viruses
Granulomatous - TB, syphilis, fungi, sarcoidosis
Characteristic syndromes
Pattern of infection/typical agents
Parenchyma
Cerebritis (Abscess)
Bacteria, fungi, parasites
Encephalitis
Bacteria, fungi, viruses, protozoa
Demyelinating encephalitis Some viruses (papovavirus)
Infectious vasculitis
Bacteria, fungi
Spongiform encephalopathies
Prion agents
Meningoencephalitis/myelitis/encephalomyelitis
def
MENINGOENCEPHALITIS: diffuse meningeal and parenchymal process
MYELITIS: localized to spinal cord, often immune-mediated process
ENCEPHALOMYELITIS: usually viral or immune-mediated process involving gray and white matter throughout nervous system
Routes of infection to the CNS
BLOODSTREAM (hematogenous) - most common route
DIRECT IMPLANTATION - traumatic or iatrogenic (surgical)
LOCAL EXTENSION - e.g., from skull, sinuses, middle ear
AXONAL TRANSPORT - used by some viruses
CSF PATHWAYS – often important means of dissemination
Pathogenesis of NS infections
Important immunologic and vascular considerations
- Brain lacks lymphatics and formed lymphoid tissues. * Lymphocytes and monocytes normally circulate through CNS in small numbers.
- Microglial cells serve as resident CNS macrophages and may enlarge or proliferate in response to CNS injury. Macrophages also come from blood-borne monocytes.
- Blood-brain barrier may hinder access to CNS by therapeutic drugs.
Manifestations of infections
list
- DIRECT TISSUE DAMAGE - may produce irreversible deficits
- INFLAMMATORY EDEMA - mass effect, increased intracranial pressure
- INVOLVEMENT OF BLOOD SUPPLY – ischemia/thrombosis —> infarction/hemorrhage
- TOXIC EFFECTS - substances produced by infectious agent causing tissue damage or dysfunction
- IMMUNOLOGIC DAMAGE - both direct and “innocent bystander” damage
- COMMENSALISM - infectious agent persists in host with or without significant tissue damage and symptoms
- NEOPLASTIC TRANSFORMATION - e.g., EBV is involved in pathogenesis of primary CNS lymphoma in HIV patients
Acute purulent leptomeningitis
def
acute infection in subarachnoid space caused by virulent bacteria, fungi, some protozoans
Acute purulent leptomeningitis
Acute manifestations include
- non-specific, systemic: fever, nausea/vomiting, irritability, lethargy
- signs of meningeal irritation (meningismus): nuchal rigidity, Brudzinski sign (passive flexion of neck → flexion of hip and knee), Kernig sign (starting from flexed knee/thigh, extension of knee is resisted)
- direct CNS involvement: headache, photophobia, alteration of consciousness, seizures, focal localizing signs
Acute purulent leptomeningitis
Basic pathology
acute inflammation (neutrophils) in subarachnoid space: presence can be ascertained by examining CSF
Acute purulent leptomeningitis
CSF findings
elevated pressure (200-500mm H2O) elevated protein (> 50mg/dl) decreased glucose (often < 40mg/dl) leukocytosis (predominantly PMN’s) organism may be detectible by Gram stain or culture
Acute purulent leptomeningitis
Spectrum of organisms
spectrum of organisms causing acute purulent leptomeningitis varies with age and clinical circumstances, but common agents include:
a. bacteria: Streptococci, Staphylococci, Hemophilus, Neisseria, Gram negative rods, Listeria, anaerobes
b. fungi: immunosuppressed patients: Aspergillus, Candida, Mucor environmental exposure: Coccidioides, Histoplasma
c. other: Toxoplasma, ameba
Acute purulent leptomeningitis
Pathogenic sequence
primary colonization/infection elsewhere in body →
dissemination to CNS, usually hematogenous → infection of meninges → acute inflammatory response in SA space → consequences: brain swelling, focal damage,spread, etc. → outcome
NOTE: The inflammatory and overall response to infection may be modified by the immune status of the patient, the virulence of organism, effects of treatment, etc.
Acute purulent leptomeningitis
dx
Acute purulent leptomeningitis requires prompt diagnosis and treatment to prevent irreversible brain damage and optimize outcome.
Acute lymphocytic (viral, “aseptic”) meningitis
Def/causes
Definition: acute, usually self-limiting viral infection in subarachnoid space characterized by lymphocytic inflammation; syndrome is produced by
a. viral agents: common, includes common viruses causing upper respiratory or upper GI infections
b. some less virulent bacteria or other agents
c. non-infectious agents (cancer cells—“leptomeningeal carcinomatosis”, chemicals/drugs–“chemical meningitis”) can produce similar syndrome
Acute lymphocytic (viral, “aseptic”) meningitis
Clinical findings
Syndrome includes fever, headache, signs of meningeal irritation, lethargy, and rash but is milder than acute purulent leptomeningitis and usually does not result in significant alteration of consciousness.
Acute lymphocytic (viral, “aseptic”) meningitis
CSF findings
Elevated protein (mild)
Normal glucose
Leukocytosis (very early: a few PMNs, later: mostly lymphocytes)
Acute lymphocytic (viral, “aseptic”) meningitis
Clinical course
Clinical course is usually self-limited and mild with full recovery; although the syndrome is common, the diagnosis is often missed.
Chronic meningitis
def
chronic inflammatory process in leptomeninges due to relatively indolent/persistent agent (e.g., TB, meningovascular syphilis; sarcoidosis, some low-grade tumors, some foreign substances cause a similar picture)
Chronic meningitis
Clinical sx
Syndrome: often non-specific/non-localizing, slowly evolving (+/- headache, +/- stiff neck, low-grade fever, seizures, cognitive dysfunction)
Chronic meningitis
pathology
commonly “basal meningitis”, with mononuclear inflammation, fibrosis, +/- granulomas (depends on agent), most prominent at base of brain
Chronic meningitis
CSF findings
elevated pressure or blockage of CSF flow
elevated protein (100-200mg/dl or even higher with CSF flow blockage)
decreased glucose (less dramatic than in acute purulent meningitis)
leukocytosis (predominantly lymphocytes, monocytes)
agent (organism, tumor cell, etc.) may be detectible
Chronic meningitis
pathophysiology
chronic inflammation in subarachnoid space leads to effects: progressive meningeal fibrosis, vasculitis, root/parenchymal involvement
consequences: hydrocephalus (non-obstructive),
↑ ICP, infarcts, focal deficits, cognitive decline
Chronic meningitis
dx
Chronic meningitis can be very difficult to diagnose due to the relatively indolent chronic course and often non-localizing findings.
Empyema and abscesses
Def/main patterns
Definition: acute/chronic localized purulent or necrotizing infections due to destructive bacteria, fungi, or other organisms fall into two main patterns:
- subdural/epidural empyema
- brain parenchymal abscess (“cerebritis”)
Empyemas and abscesses
Clinical syndromes result from…
- infection/inflammatory process: fever, malaise, etc. 2. mass effect: headache, increased intracranial pressure
- localizing signs, if brain parenchyma is involved: e.g., seizures, focal deficits
- CSF findings may be minimal if lesion does not involve CSF pathways, and lumbar puncture may be contraindicated because of ↑ ICP.
Empyemas and abscesses
Pathogenesis
Predisposing factors
a. infection elsewhere (especially osteomyelitis, dental infection, sinusitis, otitis media, endocarditis, congenital heart disease)
b. trauma to skull or spine, including surgery
c. presence of foreign body (catheter, gauze pad, bullet fragment, etc.)
Empyemas and abscesses
Organisms/pathology
organisms: bacteria, fungi, others
pathology: localized area of tissue damage and acute/chronic inflammation surrounded by reactive layer; brain parenchyma may show prominent edema.
Empyemas and abscesses
Complications include
mass effect may lead to increased ICP and herniation
abscess may rupture into ventricles or disseminate in subarachnoid space as acute purulent leptomeningitis
infection can spread to other organs or become systemic (sepsis)
focal permanent neurologic deficits may develop.
Empyemas and abscesses
tx
May require drainage or surgical removal of lesion
Acute viral encephalitis
def
Definition: acute viral infection of brain parenchyma +/- meninges
- most viral infections display tissue tropism, i.e., a particular virus infects a particular cell type: requires specialized cell surface receptors
- infections may be lytic or non-lytic to infected cell
Acute viral encephalitis
Clinical presentation
Syndrome: prodrome of infection involving nervous system (fever, headache, malaise, etc.) followed by acute onset of neurologic symptoms including seizures, focal deficits, and alteration of consciousness: the specific syndrome varies with virus and specific location of infection
Herpes Zoster
Agent/preferential site of involvement
Varicella-Zoster
Trigeminal or DRG, with pain, dermatomal distribution of vesicular rash
Acute poliomyelitis
Agent/preferential site of involvement
Poliovirus
Anterior horn cell destruction leads to lower motor neuron paralysis
Acute (meningo)encephalitis
acute necrotizing
Agent/preferential site of involvement
Herpes Simplex I
Medial temporal lobes (cowdry type A nuclear viral inclusions in infected cells)
CMV Periventricular tissues (cytomegalic cells) occurs as congenital infection (recall TORCH syndrome) and in immunocompromised hosts
Acute (meningo)encephalitis
Epidemic, seasonal
Agent/preferential site of involvement
Arboviruses
Deep gray nuclei, cortex; syndromes are variable; often transmitted by arthropod bites
Acute (meningo)encephalitis
Rabies
Agent/preferential site of involvement
Rabies virus
Brainstem (cytoplasmic viral aggregates – Negri bodies – in infected cells); usually lethal
Acute viral encephalitis
dx
- high index of suspicion based on history and exam
- CSF exam shows
protein: mild-moderate increase
glucose: normal
leukocytosis: +/- PMN’s (early acute phase)
lymphocytes (50-500/ul)
NOTE: more destructive infections show more dramatic changes. - electroencephalography (EEG): may help to localize lesion
- imaging studies (CT, MRI): help to localize and characterize lesion
- serology, culture, or PCR assay for specific virus, based on index of suspicion
Acute viral encephalitis
pathogenesis
- infection of host with transport of virus to CNS.
* hematogenous
* some viruses use axonal transport - host response cells: lymphocytes, plasma cells microglial cell proliferation is prominent edema and vascular response tissue or cellular (neuronal) necrosis
- outcome depends of virulence of virus, availability of appropriate anti- virals, degree of tissue damage, etc.
Chronic (“slow”) viral encephalitis
Def/clinical findings
Definition: progressive viral infection, with prolonged incubation following initial exposure, insidious onset, slow progression of symptoms, due to conventional viral agents: NOTE: prion diseases are not included in this category
Syndrome: usually slowly progressive dementia or neurologic syndrome.
Chronic (“slow”) viral encephalitis
Examples
AIDS dementia
PML: progressive multifocal leukoencephalopathy
SSPE: subacute sclerosing panencephalitis
TSP: tropical spastic paraparesis
Chronic (“slow”) viral encephalitis
Agent/special features
AIDS dementia
HIV
Brain atrophy
Demyelination
Encephalitis with monocytes and giant cells
Chronic (“slow”) viral encephalitis
Agent/special features
PML
Papovavirus (JC strain)
Infection and destruction of oligodendrocytes → progressive demyelination, usually in immunocompromised host
Chronic (“slow”) viral encephalitis
Agent/special features
SSPE
Measles Virus
Diffuse brain involvement, children/adolescents, ? related to unusually early primary measles infection (this disease is very rare)
Chronic (“slow”) viral encephalitis
Agent/special features
TSP (tropical spastic paraparesis)
HTLV-1
Progressive spastic leg weakness & sensory loss due to involvement of lower spinal cord; endemic or common in particular geographic areas
Chronic (“slow”) viral encephalitis
Non-viral agents
Non-viral agents can also occasionally cause slowly progressive conditions such as syphilis (paretic neurosyphilis or tabes dorsalis) or borrelia (neuroborreliosis: Lyme disease).
HIV infection
Neurologic syndromes
- acute lymphocytic meningitis: often during primary infection.
- chronic HIV encephalitis with progressive dementia (AIDS dementia)
- vacuolar myelopathy: uncommon degeneration of posterior and lateral columns in spinal cord in patients with chronic AIDS resembles subacute combined degeneration seen in vitamin B 12 deficiency.
- peripheral neuropathy (various types)
- inflammatory myopathy (polymyositis-like)
HIV
Opportunistic CNS infections
Opportunistic CNS infections related to immunodeficiency common in poorly controlled HIV infection include
- Toxoplasma cerebritis
- PML
- CMV encephalitis
- Cryptococcus meningitis
HIV
Other risk complications include…
- risk of developing primary CNS lymphoma
- drug toxicity to neuromuscular system from anti-retroviral drugs.
- Treatment of HIV sometimes results in an acute encephalitic syndrome due to return of immunologic function (immune reconstitution inflammatory syndrome –IRIS), often triggered by residual infections such as PML or Toxoplasma
