Central Nervous System Infections

p. 323 – 341

Introduction

p    Infection of the CNS by microbes is uncommon.

p    CNS well protected anatomically

p    Routes of invasion:

n    Blood

n    peripheral nerves

n    local invasion

Invasion of the central nervous system

•              bloodborne invasion (fig. 24.1, 24.2)

n           invasion of blood-brain barrier

p         causes encephalitis

n           invasion of blood-cerebrospinal fluid

n          causes meningitis

p        inflammation of the arachnoid and pia mater of brain and spinal cord and the cerebrospinal fluid

Fig. 24.2: Invasion by Poliovirus
          - Invade CNS across blood-brain barrier

microbes invade by

n            infecting and growing across cells that comprise barrier

n            being passively transported across in intracellular vacuoles

n            being carried across by infected white cells

–             generally things don’t cross

–             invasion via peripheral nerves

n            culprits are rabies, HSV and VZV

The body’s response to invasion

•            CSF cell counts increase in response to infection

•           “Aseptic meningitis” à Viral infections – CSF remains clear

•          self-limiting and client recovers

•           “Septic meningitis” à bacterial infection

•          cerebrospinal fluid becomes visibly turbid

•          a medical emergency with a mortality rate of approximately 25%

•            cell types present and chemistries indicate infection type (fig. 24.3)

•             pathological consequences depend on type of pathogen

•             CSF usually not involved in transmission process

•           Dead end for most pathogen except:

p        HSV and VZV

§       Latent in neurons

§       Reactivated à lesions

p        Rabies

§       spread to peripheral nerves à salivary glands à transmission

Bacterial meningitis

•              More severe but less common than viral meningitis

•             Fig 24.5 Causative agents

•              More severe but less common than viral meningitis

•             Fig 24.5 Causative agents

•             Before Hib vaccine

•           H. influenzae responsible for most cases

•             Now caused mainly by N. meningitidis and S. pneumoniae

•             All 3 organism have virulence factors in common (Fig 24.6)

p          Includes possession of a capsule (fig 24.7)

•              meningococcal meningitis

–           Neisseria meningitidis

–          Gram negative diplococcus

–          polysaccharide capsule

–           frequents young adults

–          Spread person to person by droplet infection

–          Overcrowding and confinement contribute to frequency of infections

–             clinical features (fig. 24.9)

•            hemorrhagic rash (petechiae)

•            sore throat, headache, drowsiness

•            fever, irritability, neck stiffness

•            fulminating septicemia leads to DIC (disseminated intravascular coagulation), endotoxemia, shock and renal failure

•            bleeding into brain and adrenal glands

•            100% mortality if untreated

–             Diagnosis

–           Cerebrospinal fluid analysis

–          microscopy and gram stain of CSF

–           Blood cultures

–           Polymerase chain reaction

–           Complete blood count

–             Immediate emergency treatment

–            Penicillin or ampicillin treatment

–             close contacts treated prophylactically with rifampin

•             Haemophilus meningitis

–           Cause: Haemophilus influenzae

–           Small gram negative rod

–           Originally thought to cause influenza

–           Capsulated type b

–          commonly in respiratory tract of infants and small children

–          Causes infection à invades blood à meningitis

–           Septicemia and subsequent meningitis is not common

–          Hardest on infants and young children

–          Severe neurologic sequelae, but less frequently fatal

–       Hearing loss, delayed language development, mental retardation and seizure

–          Treatment: ampicillin

–           Vaccine (Hib) available

•            Pneumococcal meningitis

–          Cause: Streptococcus pneumoniae

–          Encapsulated gram positive diplococci

–          Carried in throat of many healthy individuals

–         Rarely cause septicemia and subsequent meningitis

–         Affects infants and the elderly

–      children < 2 years of age, elderly or compromised individuals

–      Susceptibility associated with low levels of antibodies

–          Vaccine available

•            Listeria monocytogenes meningitis

–          Small gram positive rod

–          Psychrophile

–          Affects immunocompromised, fetuses and neonates

•            Neonatal meningitis

•           Pre-term: Low birth weight, immature immune system

–          Most frequently caused by Escherichia coli and Streptococcus agalactiae (Group B streptococci) (fig. 24.10)

–         Infants infected as nosocomial infection or from infected mother during delivery

–         Neurologic sequelae:

–      cerebral or cranial nerve palsy, epilepsy, mental retardation, or hydrocephalus

–         Diagnosis:

–      fever, poor feeding, vomiting, respiratory distress or diarrhea

–          Neonatal meningitis has a 35% mortality rate

•              Tuberculosis meningitis

–           caused by Mycobacterium tuberculosis or other mycobacterium species

–           Patients have a focus of infection somewhere (fig. 24.11)

•           25% may have no clinical presentation or history of infection

•           50% have acute miliary tuberculosis

–           onset is slow

–          presentation variable

–       Begins with malaise, apathy, anorexia, proceeding to photophobia, neck stiffness and unconsciousness

–          Prompt diagnosis and treatment required to avoid complications and sequelae

–       Spinal tuberculosis à destruction of intervertebral disks à paraplegia

Fungal meningitis

•          Cryptococcus neoformans

–        Found in patients with depressed cell-mediated immunity

–        Slow onset, days to weeks

–        Encapsulated yeast

–        Diagnosed by:

–       India ink stained of CSF specimen

–       Culture and antigen detection by ELISA or latex agglutination

–        Treatment with antifungal medications

•            Coccidioides immitis 

–          Meningitis occurs in less than 1% of infected individuals

–          Fatal unless treated

–          Diagnosed by

–         Complement-fixation of antibodies in serum

–         Stains and cultures are usually negative

–          Treated with antifungal medications

Protozoal meningitis

•            caused by free-living amoebae

•           Naegleria – rapid onset

•           Acanthamoeba spp. – chronic infections

•            infection is via the olfactory tract à meninges

•            Diagnosis:

•           amoebae on wet mount of CSF

•            treatment

•           iffy à unsatisfactory

•            high mortality rate

Viral meningitis

•             most frequent cause of meningitis

•             milder disease than bacterial meningitis

•            Similar symptoms but:

p         Less neck stiffness

p         CSF is clear

p         Cells involved are PMNs

•             many viruses associated with meningitis (fig. 24.13)

•             seldom cultured

•            Genome detection by PCR

•             patients usually completely recover

Encephalitis

p          Inflammation of brain parenchyma and often meninges à affects cerebrum, brainstem, and cerebellum

n           Degeneration of neurons of the cortex

n           Hemorrhage, edema, necrosis, small lacunae develop in cerebral hemispheres

•             symptoms are signs of cerebral dysfunction

•            Abnormal behavior, seizures and altered consciousness with nausea, vomiting and fever

•             usually caused by viruses (fig. 24.14)

•            other causes: bacteria, fungi, protozoan

•           Toxoplasma gondii, Cryptococcus neoformans, Plasmodium falciparum, Borrelia burgdorferi  and Legionella pneumophilia

•            frequently fatal

•            Herpes simplex virus is the most common cause of encephalitis

–          in infants – acquired from mother (HSV-2)

–          in adults – reactivation or primary infection (HSV-1)

–          skin or mucosal lesions may be present

–          diagnosed by:

–         scan (CT, MRI) of lesions on brain

–         brain biopsy

–         HSV genome detection by PCR

–          70% mortality in untreated cases

–          treatment – acyclovir (intravenous)

–          other herpes viruses

–          VZV or CMV - less common causes

•             Mumps virus can cause a mild encephalitis

•             Rabies encephalitis

–           35,000 human cases worldwide annually

–           cause is a rhabdovirus, a ss RNA virus

–           many animals are infected

–           transmission to humans is through saliva (bite)

–           infection is fatal in animals

–           spread has had some “unnatural” help in many instances

–          Importation of infected raccoons for sporting purposes

5. Poliovirus - used to be most common cause

•            Mumps virus can cause a mild encephalitis

•            Rabies encephalitis

–          35,000 human cases worldwide annually

–          cause is a rhabdovirus, a ss RNA virus

–         many animals infected (fatal)

–         transmission to humans through saliva (bite)

–         “unnatural” help in spread

–        Importation of infected raccoons for sporting purposes

•               Rabies encephalitis

–            incubation is 4-13 weeks but may take up to six months

–            clinical features

–           muscle spasms, convulsions and hydrophobia

–           Fatal due to cardiac and respiratory arrest

–          Less than 10 people known to survive rabies

–            diagnosed by detection of viral antigen or detection of genome by PCR

–            following exposure to a potentially infected animal:

•           clean wound with alcoholic iodine and debride

•           determine whether animal is rabid

Clinical observation, brain biopsy

•           rabies immunoglobulin, passive immunization, 50% intramuscularly and 50% directly into the wound

•           active immunization with killed vaccine – immediately

•             Togavirus meningitis and encephalitis

•            Reservoirs à birds and reptiles

•            Vectors à arthropods

•            <1% infected humans develop neurologic disease

•              West Nile virus and other Flavivirus

•            infects birds and mosquitoes

•            Humans are incidental hosts

•            No treatment, no vaccine

•            Prevented by mosquito control

•             Retrovirus meningitis and encephalitis

•            HIV causes subacute encephalitis often with dementia

Neurological diseases of possible viral origin

•            encephalopathy due to Scrapie-type agents (prion)

–          virus like but appear not to contain RNA or DNA

–         Convert normal proteins to abnormal forms

–         Results in spongiform appearance of nerve tissue

–         Originated from sheep and goats with scrapie

–          resistant to heat, chemicals and radiation

–          cannot be cultured

–          no treatment, no vaccine, always fatal

•            Creutsfeldt-Jakob disease

–          Rare, chronic encephalopathy

–          Mode of natural transmission unknown

–         transmitted by:

–      consuming BSE infected beef

–       vCJD – more rapid onset, younger patients

–      neurosurgical instruments

–      corneal grafts

–      growth hormones

–            May be hereditary – somatic mutations in prion gene

•             Kuru

•            Exclusive to Fore tribe in Papua New Guinea

•            Associated with ritual cannibalism

•            Incubation of 4-20 yrs

•            No new cases since cannibalism was stopped

•            Origin – consumption of a missionary who died of CJD

•             other prion diseases (rare neurologic diseases)

–           GSS syndrome (Gerstmann-Straussler-Scheinker syndrome)

–           Fatal familial insomnia

–          Results in loss of sleep

–          Death within 1-2 years

•             Brain abscess

–           associated with trauma or other predisposing factor

–           Diagnosed by clinical presentation and scan

–           Treat by draining abscess and long-term antibiotic treatment

•             CNS disease due to helminth parasite

•            Toxoplasmosis, cerebral malaria, roundworm and tapeworm infections

•             Tetanus and botulism

•            Due to toxin production be C. tetani and C. botulinum, respectively.