MB15 CNS Infections Flashcards
In terms of CNS infections, why are these particularly dangerous?
The brain has a critical function
The brain is within a solid container
The brain is relatively inaccessible (immune elements and anti-microbial) (antimicrobial elements penetrate the CSF poorly unless the meninges are inflamed) (BBB limits blood-bourne invasions)
How do bugs get into the CNS?
- Contiguous: Sinus, Ear, Mastoid, Face
- Trauma: Direct Inoculation
- Haematogenous: Via bloodstream
- Via Nerves
What is the name for inflammation of the
- meninges
- Brain substance
- Meningitis
- Encephalitis
What is the name for infection of
- The meninges
- The brain substance
- The spinal cord
- Meningitis
- Encephalitis, Brain Abscess
- Myelitis
What are the symptoms of Meningitis
- Fever
- Stiff neck
- Photophobia
- Headache
- Vomiting
- Irritable
- Drowsy
Compare the two types of meningitis
- Viral
- Bacteria
Give an example of what causes VIRAL meningitis
- More common, more benign - usually a complete recovery to norm
- Less common, more severe: mortality, morbidity, residual problems
Enteroviruses, Mumps Virus, HSV
What are the causes of meningitis?
- Bacterial
- Viral
- Fungal
- Neisseria meningitidis, Haemophilus influenzae type b, Streptococcus pneumoniae (MEDICAL EMERGENCY) Special groups = Group b streptococci, Echerichia coli, Listeria monocytogenes, Mycobacterium tuberculosis
- enteroviruses (most common) & others
- Cryptococcus neoformans
Compare the cell counts in bacterial, TB, and viral meningitis
Bacterial = massive white cell count (neutrophils), greatly lowered glucose, increased protein
TB= similar to above, but more lymphocytes instead of neutrophils
Viral= raised lymphocytes, slightly raised protein, 50% serum glucose
What are the ‘big three’ in terms of bacterial meningitis?
Remember = NHS
N = Neisseria Meningitidis
H = Haemophilius Influenza (capsule type B)
S = Streptococcus Pneumonia
What is this infection?
Gram negative intracellular diplococci in neutrophils
Neisseria meningitidis in CSF
What is the disease burden of Neisseria meningitidis in Africa?
‘Meningitis Belt’ in Africa
December to June peak.. Massive burden of disease. Waves can last 2 or 3 years
What is the commonest type of meningitis?
Who is most likely to present with this type?
What will a typical presentation include?
What capsule types exist?
For which do vaccines exist?
Neisseria Meningitidis (meningococcus)
Children (<5y) and young adults (15-20y)
Sudden onset, Meningitis and rash (Haemorragic rash, Purpura, Non blanching on tumbler test) Mortality 10%
A, B, C and D and others
A and C (B vaccine is new this year)
How is Neisseria Meningitis spread?
When is it more common?
Where can clusters be seen?
- Person to person via respiratory droplets, 10- 20 % of adults have throat carriage at any time. Goes via blood to brain
- Disease more common in winter
- Schools
What can the rash in meningococcal disease be associated with?
Meningitis
Septicaemia
How can Neisseria Meningitis be controlled?
- Public health notification
- Control measures for Clusters/ close contacts
–Antibiotic prophylaxis (Ciprofloxacin or Rifampicin)
Vaccine
What Vaccines are available for Neisseria Meningitis?
- Tetravalent vaccine serotypes A, C, Y & W135 (but not B)
- Men C conjugate vaccine
–In UK childhood immunization schedule
•Men B vaccine licensed for use in 2013 & now being introduced.
A and C are now rare in UK
NHS
What can Strepococcus pneumoniae be called?
Who does it tend to infect?
What are the concerns?
How is it prevented?
Pnemococcal Meningitis
Older age, Babies, Head Trauma, after splenectomy
Penicillin resistant pneumococci are becoming a problem world wide
Vaccines
NHS
What is Haemophilus meningitis caused by?
What age group is it most common in?
It is rare now thanks to what vaccine?
There is a high rate of what associated?
What is the prevention?
Haemophilus influenzae (capsule type B)
Children 1-5 years old
HIB vaccine
neurologic sequelae
prophylaxis for close contacts, Hib vaccine (UK childhood immunization schedule)
What is TB meningitis caused by?
What is the source of this bacteria?
What is the treatment?
Meningitidis Tuberculosis (acid fast bacilli)
Usually elsewhere on pt (lung)
It has a gradual progression, so prolonged treatment with anti-TB drugs (combination of 3 drugs)
- What are the causes of neonatal meningitis?
- Who is sucepible?
- What is the onset like?
- What are the consequences?
- What is diagnosis like?
- What is the treatment?
- Group B haemolytic streptococci (GBS) -10-30% of pregnant women colonized- (normal inhabitants of female genital tract). Also E. coli & L. monocytogenes. Other routes such as nosocomial infection
- Neonates & low birth weight (immature immunological status)
- Early or later onset disease. <1wk or >1wk age
- Permanent neurological sequelae- cerebral or cranial nerve palsy, mental retardation, hydrocephalus
- Clinical diagnosis is difficult - no specific signs
- Blind antibiotic treatment
What is the most common type of meningitis?
What is it characterised by?
What will investigations show?
What causes it?
How can viruses be identified?
What is the treatment?
VIRAL meningitis
Benign course, complete recovery
CSF: clear no bacteria, cells are mainly lymphocytes
Enteroviruses mainly (Coxsackie or Echovirus), VZV , Mumps, Others
When isolated from CSF (<50% of cases) PCR is useful
No specific treatment
What causes fungal meningitis?
What is it associated with?
What is it’s onset like?
How is it diagnosed?
How is it treated?
C. neoformans encapsulated yeasts
Associated with meningitis in patients with depressed cell-mediated immunity (AIDS)
Slow
India-ink-stained preparations of CSF- antigen detection
antifungal drugs
How can a diagnosis of meningitis be made?
Lumbar Puncuture: check for intracranial pressure
CSF examination:
–Cell counts: WBCs (lymphocytes & polymorphs)
–Chemistry: glucose & protein
–Stained films : gram & Ziehl Neelson (if relevant for TB)
–Culture /Antigen detection/ PCR
Blood culture
What is the management for Bacterial Meningitis?
What about meningococal disease?
And bacterial meningitis of an unknown cause?
- Antibiotic therapy - give first dose before urgent transfer to hospital
- benzyl penicillin IV or IM
- cefotaxime or ceftriaxone - these will cover the main 3 bacterial causes
What can indicate infection type?
Cell types present & chemistries
What is Encephalitis?
What is a main cause?
What are the symptoms?
What is the treatment?
Inflamation of the brain substance
herpes simplex (HSV-1) in the temporal lobe brain (reactivation infection)
–Stroke like signs and memory loss
–Behavioural changes
–Reduced consciousness
–Seizures
aciclovir – early – high dose – IV
•
What are the CSF findings of Ecephalitis?
CSF findings as viral meningitis
What are the viral causes of Encephalitis?
(sporadic outbreaks)
•HSV: commonest- infant & adult forms distinguished
- Mumps : much less common than meningitis
- VZV: a rare complication of opthalmic zoster
- CMV: in utero & immunosuppressed
- Rabies
What are the viral causes of Encephalitis?
(outbreaks)
Enteroviruses
Arboviruses:
- numerous- e.g. Japanese encephalitis virus, West Nile virus (now widespread in North America)
- region specific-
- cause meningitis or encephalitis
What SLOW viruses cause Encephalitis?
-
Measles:
- Subacute sclerosing encephalitis (SSPE) after interval of up to 10 years;
- Measles inclusion body encephalitis (MIBE)- several months after measles infection in immunocompromised individuals
-
JC virus (polyomavirus) :
- Progressive multifocal leucoencephalopathy (PML)- in immunocompromised (AIDS)
What is PML?
What is it caused by?
Who is it most likely to affect?
What is it characterised by?
Progressive multifocal leukoencephalopathy (PML)
JC Virus (polyoma virus)
Immunosuppressed patients
Infection of oligodendrocytes - causes demyelination
Multiple white mater lesions
What is Rabies Encephalitis transmitted by?
What is the incubation period?
What are the clinical features?
Cases worldwide per year?
via bite of infected animals
few weeks to years
muscle spasm, convulsions & pharyngeal spasm
60 000 human cases
How does Rabies progress through the human body?
- Virus enters tissue through saliva of biting animal
- Virus replicates in muscle near the bite
- Virus moves up PNS to CNS in spinal cord
- Virus ascends spinal cord
- Virus reaches brain and causes fatal encephalitis
- Virus enters salivary glands and other organs of victim
What are the predisposing factors for a Brain Abscess?
Otitis media (middle ear infection)
Sinusitis
Dental abscess
Trauma
Endocarditis
What is a Brain Abscess?
What causes it?
What is it’s clinical presentation?
What is the treatment?
Focal infection - a collection of pus
Bacteria (Streptococci, anaerobes, others)
Similar to encephalitis - Focal neurological signs especially.
–Stroke like signs and memory loss
–Behavioural changes
–Reduced consciousness
–Seizures
Surgical drainage or excision in addition to antibiotics
What can a cause cranial nerve palsy of the facial nerve? (CN VII)
What is Ramsay Hunt syndrome?
Zoster (VZV reactivation)
Facial paralysis and shingles rash
What are Prions?
Infectious agents that are much smaller than viruses
No nucleic acid
resistance to heat, disinfection and UV radiation
Very long incubation period
No immune response
What is a classic example of the transmissible Spongiform encephalopathies? (prion diseases)
Creutzfelt-Jakob Disease
–Genetic, sporadic, infectious
–Transmitted folding event
Normal prion protein (Prpc) undergoes abnormal folding into different form (Prpsc)
What does TSE stand for?
transmissible Spongiform encephalopathies
(prion diseases)
What is the presentation of TSE?
(transmissible Spongiform encephalopathies)
- Dementia
- Ataxia
- Other features
- Progressive & fatal
Why does this folding event occur in prions?
Is it infectious afterwards?
- Sporadic
- Genetic predisposition defined mutations in PrP
Infectious person to person
In what way can Prpsc induce more abnormal folding?
By an autocatalytic process
What is the significance of ‘Encephalopathy’ in terms of Spongiform encephalopathies?
pathology without inflamation (ie not .. “itis”)
full of holes = spongiform
Causes neuronal loss
Sporadic, genetic, iatrogenic
What is CJD?
How does it come about?
What is variant CJD?
Creutzfeldt-Jakob disease, a transmissible Spongiform encephalopathy (TSE)
–Spontaneous
–Genetic (Defined mutations in PrP)
–Iatrogenic CJD (E.g neurosurgical transmission – dura mater grafts) (Human growth hormone)
cCJD = Bovine spongiform encephalopathy (Epidemic in 80s – 90s in UK) (from COWS) There are worries that a proportion of the population carry this
How are Prions transmitted?
- CNS tissue- neurosurgical instruments brain electrodes.
- Tonsil is infectious in vCJD
- Transfusion – cases – a worry
- Human Growth hormone harvested from brains
- Worries about nerve tissue generally
- including gingival tissue and dental pulp
e. g concern about endodontic files
difficult to quantify risks
How is Rabies Encephalitis diagnosed?
How is it treated?
Observation of inclusions
Antigen detection/ PCR
–Passive/ active immunization – vaccine
–Rabies immunoglobulin (RIG) from donors who have been vaccinated
- What are the clinical features of Tetanus (lockjaw)
- How is it diagnosed?
- How is it transmitted?
- muscle rigidity & spasms
- diagnosis is mainly clinical- organisms rarely isolated
- Exposure to Cl. tetani (Clostridium tetani) spores from environment
Infection of umbilical stump→ neonatal tetanus
Spores enter a wound - necrotic tissue permit anaerobic growth of bacteria - toxin tetanospasmin is produced
Toxin spread to CNS- blocks release of inhibitory neurotransmitters
What is the prophylaxis for a tetanus infection?
- Tetanus toxoid (childhood vaccination)
- After injury
–Clean wound thoroughly
–For tetanus prone wound: give human tetanus immunoglobulins with a tetanus containing vaccine if necessary ( according to vaccination history)
•A 45 year old man suddenly collapsed while walking with a friend in the street and then had a seizure, his friend said he has been complaining of headache for the past few days and has been acting in a slightly strange way. No relevant past history, and has not had a seizure before.
On examination he is drowsy, confused and has a temperature of 38°C, no focal neurologic signs although his reflexes were brisk, the rest of his examination was normal.
- What urgent investigation would you perform?
•A CT scan shows an area of low density in the left temporal lobe.
Results of LP are: CSF clear- white cell counts 50/ml (n 0-5) (all lymphocytes) - protein 90 mg/dl (n 15-45) ; CSF glucose 60 mg/dl (n 45-85) ; no organisms seen on gram stain
- What diagnosis would you consider in the light of these results?
- How can you manage and treat him?
- Neuroscanning, Want to get CSF (lumbar puncture)
Looks like it could be an encephalitis. Would be worried it could be a herpes simplex encephalitis
- WBCs ok, proteins a little up, no organisms.
Would worry it is a herpes simplex encephalitis.
- Always intravenous acyclovir
Do PCR for herpes simples, varicella.
Classic presentation of Herpes Simplex Encephailitis
