CNS infections I & II

Meningitis, encephalitis, meningo-encephalitis, intracranial abscesses

Slow diseases of nervous system

 Progressive multifocal lencoencephalopathy (PML)

 Subacute sclerosing panencephalitis (SSPE)
 Progressive rubella encephalitis
 Transmissible spongioform encephalopathies
 Familial Gerstmann-Straussler-Scheinker disease
 Kuru
 Creutzfeldt-Jakob disease

Meningitis (bacterial, meningococcal,H. influenza, pneumococcal,tuberculous, viral)

Causes

 Bacteria (significant morbidity)

 Viruses (common but no significant morbidity)
 Fungi
 Protozoa

Bacterial meningitis
Acute
 Onset of S&S over hours to days
Chronic  Investigations
 Onset of S&S over weeks to months  Dx rests on lab examination of
 Causes  CSF
 Mycobacterium tuberculosis (most common)  Blood culture
 Treponema pallidum  Lumbar puncture
 Brucella spp.  For dx of meningitis
 Borrelia spp.  Distinguish bacterial from viral meningitis or other causes
 Leptospira spp.  Rapid aetiological dx of causative bacteria
 Indications for CT scan prior to LP
Acute bacterial meningitis (ABM)
 Raised ICP
 Predominant organisms in specific age groups
 Role of lab in dx & tx  depressed consciousness
 Medical emergency  papilloedema (optic disc swelling)
 Mortality:  focal neurological signs •
 H. influenzae 5%  LP can be performed safely w/o prior CT scan if pt does not present any of the 3 causes
 N. meningitidis 7-10% of raised ICP
 S. pneumoniae 20-30%
 Morbidity:
 Preventable if pt gets tx earlier
 Abscesses, ventriculitis, hydrocephalus, cranial nerve palsies (sensorineural hearing loss), seizures,
 hemiplegia, spasticity, mental retardation, learning difficulties
 Causes

 CSF
 opening pressure ( Normal <18 cm H2O).
 Macroscopic appearance (Normal clear and colourless).
 3 specimens into numbered containers and one into blood sugar estimation bottle.
 Lab examination
 Cell count
 Common neurologic sequelae of BM  Cell type –
 Neutrophils/lymphocytes
 Biochemistry
 Glucose & protein concentration
 Gram stain
 Culture
 Blood agar, chocolate agar
 Identification & antibiotic sensitivities
 Composition of normal CSF vs ABM’s CSF

Normal CSF ABM CSF

Appearance Clear, colourless Turbid/cloudy

 Predominant organisms in each age group
Cell count <6 200 – 20,000
(mm3) - predominantly
- all lymphocytes polymorphs
- no RBCs - pleocytosis;
increased cell count

Protein (g/L) 0.1 – 0.4 > 1.0

Glucose 60% blood < 50% blood glucose

glucose

 Lab examination
 Blood culture
 Pathogenesis  Rapid antigen detection by latex agglutination
 Haematogenous spread**  Not routine
 most common  False-positive & false-negative results
 foci in nasopharynx, lung, intestines, urinary tract, heart valves
  Contiguous spread  Useful when CSF gram stain & culture are negative
 septic foci in head  Test for
 e.g. sinusitis, otitis media, mastoiditis, facial or skull infections, dental infections, osteomyelitis  N. meningitidis
in bones and skull  S. pneumoniae
 Direct implantation
 H. influenzae
 trauma - fractured skull
 Group B streptococcus
 neurosurgical procedures
 Purpuric rash
 pathogenic & pathophysiologic mechanisms in BM
1. Attachment and colonisation of nasopharyngeal mucosal epithelium.  scrappings for gram stain and culture
2. Penetration through the mucosa.  PCR
3. Invasion and survival in bloodstream.  Multiplex PCR can detect N. Meningitis, S. Pneumoniae etc
4. Translocation across BBB and entrance into CSF  High sensitivity & specificity
5. Survival and replication in the cerebrospinal fluid.  Helpful in monitoring pts pre-treated with Abx
 Management
 2 main goals of tx
 Eradication of infecting organisms
 Management of CNS & systemic complications
 Prompt tx with Abx is essential
 Pt should be treated with IV abx for 30 mins as soon as symptoms appear
 Empirical abx based on age & predisposing factors
 Empirical abx

 Presentations

 Rash
 Not skin haemorrhage, but clotting of small vessels in skin resulting in ischaemia of endothelium  Duration of abx therapy in bacterial meningitis
leading to necrosis of skin
 Variable in extent & severity
 Erythematous macule -> petchiae -> purpura/ecchymosis
 Start in trunk & spread to extremities


 Common bacterial pathogens based on predisposing factor

 Adjunctive steroid therapy in ABM

 Primary tx is abx, adjunct tx is steroid, all to deal with SAS inflammation & the complications
it causes. Less inflammation = less side effects
 Inflammatory responses within enclosed spaces lead to destructive secondary effects.
 Outcome correlates with severity of inflammatory response
 Steroid reduces inflammation:
 In adults:
 Decrease in mortality & neurological sequalae
 Significant only in pneumococcal meningitis
 In children
 Beneficial effect on severe hearing loss in Hib (haemophilus influenzau type B)
 Therapy
 IV dexamethasone given before or with 1st dose of abx
 Continue for 4 days
 Indications
 Recommended in all previously well & non-ICed adults & children > 3 mths old
 Should not be given to IC-ed pts or pts who have alrdy received animicrobial therapy

Meningococcal meningitis H. Influenza meningitis Tuberculous meningitis Viral meningitis

Pneumococcal meningitis
Epidemiology H. Influenza meningitis Clinical presentations Features
 80-85% due to serogroup B in Ireland Epidemiology Features  Commonest type of meningitis
 5% due to serogroup C  predominantly 6 months to 5 years old  TM is a basilar type of meningitis  Most mild/inapparent
 Peak at 6 months with decline until age 5 to 10 yrs  peak 6 months to 1 year  M. Tuberculosis causes chronic TM  Usually self-limiting, < 1 week
 a smaller peak in teenagers  H. influenzae capsular type b causes 90% of cases  Manifestation of primary tuberculosis in  Exception for those with
 Sporadic outbreaks  decreased incidence since routine vaccinations children or later in life  Agammaglobulinaemia
 Increased risks if  Rupture of subependymal tubercle into SAS  Chronic enteroviral
 Asplenia Management meningoencephalitis
 Third-generation cephalosporin causing intense inflammation
 Complement deficiency  Enteroviral symptoms:
 Terminal complement components (C5-C8).  Dexamethasone  Pleurodynia: severe
Clinical presentations
 Acquire infection at later age.  decrease incidence of nerve deafness pain in muscles btwn
 General ill health
 Frequent recurrences.  For close contacts ribs/diaphragm
 Meningeal symptoms, changes in
 Serogroups Y and W135.  Chemoprophylaxis  These pts present with severe
 Rifampicin for 4 days consciousness, seizure and focal neurological
 Milder disease and lower mortality. form of viral meningitis
 Hib vaccine signs, particularly cranial nerve palsies.
 Importance
Clinical features  If unvaccinated  Differentiating dx from other
 short incubation period (2-5 days).  3 doses if age < 1 y/o infective causes
 Develop rapidly over 24 hours.  1 dose of age > 1 y/o  Supportive tx needed for most cases
 Treatment  No vaccination after 4 years  Common cause of aseptic meningitis
 Benzylpenicillin  (-)
 Cefotaxime Pneumococcal meningitis  Gram stain
 Chloramphenicol  All age groups  Routine bacterial culture
 Mortality 7%.  Most frequent cause of bacterial meningitis in: Causes (all are self-limiting except that in
 children < 2 y/o bold;)
Control & prevention  Adults > 19 y/o  Echovirus
 Antibiotic chemoprophylaxis  Susceptible  Coxsackievirus
 rationale is to eliminate carriage from close
 Poliovirus
contacts (household members, day care
 centre,direct exposure to pt’s oral secretions;  Asplenia  Mumps virus
kissing/mouth-to-mouth  Alcoholic  Arbovirus
resuscitation/endotracheal intubation)  Chronic liver/renal disease  Epstein-Barr virus
 and reduce subsequent spread to other  DM  HSV-2, Varicella-zoster virus (requires
susceptible persons  Multiple myeloma anti-viral)
 Close contacts at elevated risk of secondary  Chronic otitis media/ sinusitis  Measles
disease  Tx  Influenza
 Risk of disease highest during first few days after  Benzylpenicillin
onset of disease in index case or Enteroviruses
 Chemoproph should be given as soon as third-generation cephalosporin  85% to 95% of all cases.
possible or  more common in summer and
 Prescribed: vancomycin + third-generation cephalosporin autumn.
 Rifampicin for 2 days depending on resistance  commonest in children
 Contraindicated during pregnancy  Prevention  under 4 years of age most at risk,
 Ceftriaxone (safe mor pregnant mothers)  Pneumococcal polysaccharide vaccine (PPV23) highest risk = < 1 y/o
 Ciprofloxacin  indicated for at risk patients  outbreaks in nurseries, boarding
 Vaccine  Pneumococcal conjugate vaccine (PCV) schools and residential institution.
 (1) Meningococcal polysaccharide vaccine  No chemoprophylaxis
 effective against serogroup A, C, Y and W- Investigation
135 Formation of exudate (hallmark of TM) CSF of viral meningitis
 Indications  From rupture of subependymal tubercle into  clear
 travellers, household contacts, military SAS  100 - 1000 cells/ mm3
recruits, asplenia, complement  Contains lymphocytes, plasma cells,  predominantly lymphocytes
deficiency macrophages, fibrin  protein : 0.5 - 1 g/L
 Drawbacks  Subsequent neurological pathology:  glucose : normal
 not effective in < 2 year olds  Adhesion formation
 no long term memory (protection 3 to  Results from dense basal meningeal
5 years only) exudatethat develops after
 (2) Meningococcal C conjugate vaccine (MenC) inoculation of bacilli into SAS
 serogroup specific polysaccharide antigen  Causing blockage which results in
conjugated to carrier proteins. obstruction of CSF
 immunogenic in children < 2 y/o.  Consequences
 long-term protection.  cranial nerve palsies (VI, III, IV,
 childhood immunisation schedule in Ireland VII)
from 2000.  hydrocephalus (excess CSF
 Indications building up within ventricles,
 routine childhood immunisation increase ICP)
 all infants at 6 months with  Obliterative vasculitis
booster doses at 13 months & 12-  Can result in infarction/stroke
13 years  Infarction through vasculitis
 (3) MenB vaccine (Bexsero) contributes to irreversiblee
 4 antigenic components neurological sequelae
 Factor H binding protein
 Neisserial heparin-binding antigen
 Porin A
 In Ireland, given at 2, 4 & 12 months Clinical staging of TM

CSF findings
 cell/mm3: 10 - 1,000.
 Lymphocytic pleocytosis.
 Raised protein.
 Low glucose.
 AFB on Z-N stain (10-22%)
 Acid fast stain. Positive AFB culture means
M. Tuberculosis is present
 Culture positive (38-88%)
Investigations
 PCR
 greatest benefit if Z-N stain negative
 low sensitivity
 (-) test do not rule out tuberculous
meningitis
 CT or MRI (observed)
 Thickening of basal meninges
 Infarcts
 Hydrocephalus
Tx
 Early dx & tx vital
 Fatality rate high in developing countries bcs dx

is difficult
 Adjunctive tx: corticosteroid given for stage 2 &
3
 Encephalitis

Causes Clinical features Investigations Herpes simplex encephalitis

Viruses (as the most Protozoa and fungi Bacteria  usually begins with nonspecific CSF Features
common cause of • Toxoplasma gondii • Borrelia burgdorferi acute febrile illness  10 - 2,000 cell/mm3  most common sporadic encephalitis.
encephalitis) • Plasmodium falciparum • Borrelia recurrentis  fever, malaise, headache,  lymphocytic  HSV-1.
 Arboviruses • Trypanosoma spp. • Treponema pallidum nausea, vomiting  protein elevated  Adults.
 Seasonal & • Cryptococcus • Rickettsia rickettsii  confusion.  glucose  acute onset of fever, deterioration of
geographical neoformans • Rickettsia prowazekii  irritability, personality change.  normal consciousness, seizures and focal
distributions • Mycoplasma pneumoniae  drowsiness, coma.  viral neurological signs.
depend on  seizures.  rickettsial  acute asymmetrical necrotising infection
habitat & life  focal neurological signs.  low (haemorrhagic & necrotising) primarily of
cycle of vectors  tuberculous temporal/frontal lobes.
 Herpes simplex virus**  fungal  mortality 80% if untreated; 90% survivors
 Enteroviruses  bacteria have long-term sequelae.
 Mumps, measles,  amoebic
rubella Dx
 Varicella-zoster virus, Other investigations  MRI
CMV, EBV  Electroencephalography (EEG)  EEG
 Rabies  Magnetic Resonance Imaging  Highly suggestive but not
 Influenza (MRI) pathognomonic
 HIV  PCR on CSF  Include focal slowing, spiking
 Viral cultures  CSF
 10-200 cells/mm3
 lymphocytic
 red blood cells
 bcs of haemorrhaging lesion
 moderate elevation of protein
 normal glucose
 HSV DNA by PCR **
 do PCR on CSF specimen
 (Brain biopsy)

Tx
 Intravenous acyclovir
 reduces mortality and morbidity if
given early
 low toxicity
 use empirically in acute sporadic
encephalitis
 for 14 to 21 days
 mortality in treated reduced to 20%
 50% recover completely
 Brain abscess

Intro+pathogenesis, site+microbiology, clinical features, dx, management,

Pathogenesis Site & Microbiology Clinical features Dx Management

Intro Site - Direct involvement or destruction of  2 main aims - Usually a combination of antibiotics,
 a focal suppurative process of the brain parenchyma;.  Determined by proximity to brain.  to demonstrate and surgery and
 functional tissue in the brain that is made up of contiguous foci - Raised intracranial pressure. localise lesion treatment for cerebral oedema
neurons and glial cells  otitis media and mastoiditis  to identify causative
 1 in 10,000 hospital admissions in USA. with temporal lobe and The triad of main symptoms, if present organisms  (1) Abx
 age distribution depends on predisposing conditions. cerebellum assume brain abscess until proven  Contrast-enhanced  parenteral
 sinusitis with frontal and otherwise: computerised tomography  bactericidal
Pathogenesis temporal lobe  headache (CT)  in adequate concentrations
 (1) Contiguous focus of infection  all close in proximity to original  fever or  have activity against likely
 e.g. otitis media, mastoiditis, sinusitis site of infection  focal neurological deficits  Magnetic resonance range of pathogens
 direct extension through infected bone or  Haematogenous spread from a + imaging (MRI).  Empirical therapy based on
haematogenous spread through emissary veins distant focus  nausea & vomiting  Avoid lumbar puncture as predisposing conditions
(connect the extracranial venous system with the  often multiple  seizures risk of herniation after abscess material
intracranial venous sinuses) or diploic veins  occur in distribution of MCA at  altered consciousness considerable. obtained for microbiologic
(thin-walled, valveless veins lying in diploe of junction of grey and white  Blood culture. studies
skull which is between inner & outer tables of matter Other features depend on location of  Pus by aspiration for  Penicillin or a third
bones of skull) or spread through lymphatics abscess  gram stain generation
Microbiology  temporal lobe  culture. cephalosporin
 Caused by  memory defects, aphasia +
 Streptococci  frontal lobe Ring-enhancing lesion in right metronidazole
 aerobic and anaerobic  altered personality fronto-parietal region  Penicillinase-resistant
 Anaerobes  drowsiness with cerebral oedema and mass penicillin if S. aureus
 Enterobacteria  cerebellum effect suspected
 Staphylococcus aureus  ataxia  Vancomycin if
 Fungi methicillin resistance
 Candida, Aspergillus, suspected
Cryptococcus neoformans  Change in abx guided by
 polymicrobial in 30-60% microbiological results &
 Nocardia clinical and radiographic
 Toxoplasma gondii progress.
 (2) Haematogenous spread from a distant focus  Mycobacterium  4 to 6 weeks treatment.
 e.g. pyogenic lung diseases (pus-producing  Causes  (2) aspiration (surgery approach)
infection), infective endocarditis, dental  Otitis media or mastoiditis  CT-guided
procedures  Caused by  drainage of pus
 (3) Trauma  Streptococci  allows bacteriologic dx
- contrast injected, lesion lights
 e.g. penetrating head injury or post-  Bacteroides  Gram stain positive
up
neurosurgery  enterobacteria 82%
- cerebral oedema seen around 
 direct inoculation into brain parenchyma  Trauma or neurosurgery Culture positive 88%
lesion
 Caused by:
- mass effect causing midline
Main pathogenic factors  S. aureus Outcome of brain abscess
shift & obliteration of ventricles  Mortality
 source of virulent microorganisms
 presence of ischaemic or devitalised tissues  S. epidermidis
(deprived of a normal supply of nutrients and oxygen.  P. aeruginosa
)  enterobacteria
 Dependent on
 site of initiating infection
 patient’s underlying condition
 less than 10% with prompt
treatment
 10-20% in most studies
 Long term sequelae in one-third
 Seizures
 mental retardation
 focal neurological deficits