Meningitis and Encephalitis

Question 1

what is the difference b/w meningitis and encephalitis?

Answer 1

meningitis - inflammation of the meninges

encephalitis - inflammation of the brain (parenchyma)

Question 2

what is the carriage and transmission of neisseria meningitis?

Answer 2

• throat carrier in approx. 10% population: 25% of 15-19yrs
• person-person spread
• inhalation of respiratory secretions
• lose prolonged contact e.g. household members
• direct contact (kissing)
• disease in minority (patients needs to be immune-susceptible and the strain of bacteria needs to be present in the throat)

Question 3

what are the types of meningococcal disease and how prevalent are they?

Answer 3

1. septicaemia (25%) - blood stream infection, symptoms like fever, hypothermia, headache (may be), low BP, rapid spreading rash at periphery (e.g. toes)
2. meningitis (15%) - similar symptoms as septicaemia but no rash
3. both septicaemia and meningitis (65%)

Question 4

1. what are the rate of prognosis (or fatality) of meningococcus (meningitis, septicaemia and if left untreated)?
2. if survived what are morbidity cases? and
3. what is impact of antibiotics?

Answer 4

1. fatal in
   - meningococcal: 10%
   - with meningitis: 5%
   - septicaemia: 50%
   - untreated: 100%
2. if survived, 1 in 8 suffer from long term morbidity like headache, joint stiffness, epilepsy, learning loss and learning difficulties
3. early antibiotics improve prospect of recovery

Question 5

why is hearing loss a common long term neurological problem in meningococcal diseases?

Answer 5

because the cranial nerves pass through the meninges which gets inflamed and damaged

Question 6

what is the treatment for bacterial (Neisseria) meningitis?

Answer 6

• antibiotics: IV ceftriaxone or cefotaxime, after blood cultures or lumbar puncture
• Aurburtin M et al. 1993, Proulx et al. 2005 showed delayed administrations associated w increased mortality
• role of corticosteroid unclear?

Question 7

how common is neisseria meningitides?

Answer 7

• England: groups B,C,W,Y
• common in children <4yrs
• at peak in 5-6m olds
• 2nd highest incidence in teens (15-19yr)
• meningococcal cases in England:
• 1999/00: 2595 cases
• 2016/17: 747 cases
• significant reduction since meningococcal C vaccine introduction in 1999/2000

Question 8

at what age is meningitis B and ACYW given?

Answer 8

since 2015

• Men B:2-4m, booster: 1-3yrs
• MenACYW-135: teenagers + uni students

Question 9

how common is meningitis in foreign countries?

Answer 9

• African meningitis belt
• Saudi Arabia, Hajj (Men ACYW-135), travellers going to hajj need to present vaccination certificate (medical cases exempted)

Question 10

pneumococcal meningitis

1. Prevalent in which age
2. Mode of spread
3. Treatment

Answer 10

1. Elderly: main cause of bacterial meningitis
2. contiguous spread: sinuses (infection) -> middle ear
   - (sequel) previous history of neurological condition
3. similar to meningococcal meningitis i.e cephalosporins: IV ceftriaxone or cefotaxime (antibiotics)
   - alternative meds for penicillin resistant pneumococcus like vancomycin

Question 11

are corticosteroids helpful in treating bacterial meningitis?

Answer 11

• dexamethasone for 4 days if organism unknown or streptococcus pneumonia confirmed
  A. De Gans J et al. 2002, RCT of 301 pts w bacterial meningitis in Europe,
  1. dex significantly reduced mortality + neurological disability at 8wks in pts with Strep pneumonia w GCS<11 on admission
  2. meningococcal meningitis: much lower mortality + morbidity rates independent of the use of dex
• no diff in groups for hearing loss
• effective: intermediate>mild neurological problems
  3. dex reduced mortality + incidence of deafness in children w Haemophilus influenzae meningitis + pneumococcal meningitis
• dex safe except cerebral malaria cases, therefore, the use of steroids could be beneficial
  B. Scarborough M et al. 2007, contrastingly a Malawi study w 95% HIV +ve pts had
  1. no benefits from dex even for pneumococcal meningitis
  C. Van de Beek D et al. 2010, metaanalysis w 81% bacterial meningitis, 29% HIV +ve + 41% <15yrs does not significantly reduce death or neurological disability and benefit for all or any subgroup of patients remains unproven
• highlighting,
  1. variance of efficacy across race (cross-check?)
  2. poor/some evidence to reduce mortality + morbidity in step. pneumonia meningitis but not in other bacterial meningitis

Question 12

listeria monocytogenes

1. how common is it?
2. causes
3. which are the risk groups
4. likelihood of developing of meningitis
5. mortality rate
6. treatment

Answer 12

1. 60 cases/year in England + Wales, third common cause in adults in UK
2. acquired by ingestion for meats or dairy
3. high risk groups (via blood)
   - >55yrs
   - immunocomprised
   - pregnant women
   - neonates
4. can develop meningitis in 55-70% (if enters the blood)
5. mortality rate: 25%
6. treatment: IV amoxicillin +/- gentamicin

Question 13

what are the viral and non-viral causes of meningitis?

Answer 13

1. viral: enterovirus, herpes simplex virus (HSV 1 +2 - recurrent) (mollaret’s syndrome), mumps, measles (rash), adenovirus, HIV
2. non-viral: Lyme disease, syphilis, drugs (used to treat UTI, mostly benign and self-limiting)

Question 14

enterovirus meningitis

1. days of incubation
2. location of replication
3. mode of transmission
4. diagnosis
5. prognosis
6. treatment

Answer 14

1. incubates for 2-5days
2. replication in reparatory or GI epithelial cells
3. transmission via respiratory or conjunctival secretion, face-oral
4. diagnosis: PCR (CSF (most common),throat swab, faeces)
5. prognosis: self limiting
6. treatment: symptomatic

Question 15

gram stain is useful for which meningitis and why?

Answer 15

for bacterial meningitis because viruses too small to be seen

Question 16

TB meningitis

1. days of presentation
2. risk factors
3. diagnosis (imaging?)
4. treatment

Answer 16

1. presentation: chronic days-wks (unlike bacterial meningitis)
2. risk factors - HIV (immunosuppressed -> increases the likelihood of heamatogenous TB spread), alcoholism, diabetes, steroids, anti-TNF agents (anti-TNF -> switcher off cytokine, essential for immune control to TB, thus inactive TB -> active -> replicate +spreads), immigration to area of high prevalence (India)
3. diagnosis: imaging used
   - chest x-ray: suggestive of active or previous pulmonary TB in 50%
   - contrast CT head: hydrocephalus, basal enhancement, infarction, tuberculoma
4. treatment:
   - 12m (pulmonary TB6m but CNS TB longer): antibiotics used to treat TB, rifampicin, isoniazid, pyrazinamide, ethambutol
   - dexmeth (Thwaites regimen)
   - communicating hydrocephalus: acetazolamide + frusemide or repeated LP
   - non-communicating hydrocephalus: consider early ventriculo-peritoneal shunting

Question 17

cryptococcal meningitis

1. symptoms
2. commonly found in
3. cause
4. CD4 count that results in disease
5. treatment

Answer 17

1. classic meningitis symptoms usually absent
2. global distribution - bird dropping (breathing it all the time but does not cause disease)
3. cause: inhalation of Yeats
4. CD4 >100cells/μL otherwise disease rare
5. treatment
   - uniformly fatal if left untreated
   - controlling raised ICP: major factor in reducing mortality and morbidity

Question 18

True or False

1. Neisseria meningitis infection is always associated with a non-blanching rash
2. Neisseria meningitis serogroup C is vaccine preventable
3. Listeria meningitis can be treated with ceftriaxone
4. Enterovirus is the commonest cause of viral meningitis
5. Cryptococcal meningitis should be treated with adjuvant corticosteroids

Answer 18

1. FALSE, N. meningitis may present rash but not always
2. TRUE since introduction of vaccine in
3. FALSE, listeria is resistant to cephalosporins (class of ABs w ceftriaxone) thus, combination of amoxicillin + gentamicin is used
4. TRUE
5. FALSE corticosteroids may be effective only for step. pneumococcal meningitis

Question 19

how does the lab results differ for bacterial and viral meningitis?

Answer 19

refer

Question 20

how to distinguish meningitis and encephalitis?

Answer 20

• by brain abnormalities in brain function, encephalitis associated w
  1. altered mental status
  2. motor or sensory deficits (frontal)
  3. altered behaviour/personality (parietal)
  4. speech or movement disorder
  5. may be lethargic or have seizures
• distinction blurred if features of both preset - meningoencephalitis
• markers: inflammatory cells in CSF or inflammation on imaging

Question 21

what are the causes of encephalitis?

Answer 21

1. viruses
   - direct invasion of CNS: herpes virus, arboviruses (arthropod borne viruses)
   - immune mediated post infection/vaccination: ADEM (acute disseminated encephalomyelitis) and mumps, measles, rubella, influenza
2. bacteria: listeria, mycoplasma, lyme, syphilis
3. TB
4. parasites: cerebral malaria (topical areas)
5. fungi

Question 22

what are the causes of viral encephalitis?

Answer 22

1. herpes virus: HSV 1 +2 (common in industrialised), Epstein-Barr virus, HHV 6 + 7
   - HSV2 encephalitis neonates and immunocompromised
   - HSV2 meningitis in adults
2. enteroviruses: coxsackie, poliovirus
   - normally do not cause encephalitis but not possible
3. paramyxoviruses: weasels, umps
4. rarer: influenza, adenovirus, parvovirus, rubella

Question 23

why is it essential to enquire the travel history off patients while examining viral encephalitis? what is significance the west nile virus?

Answer 23

• geographically restricted
• west nile encephalitis in America, supre, Middle East, Africa and Asia
• Murray valley is Australasia
• all arboviruses except rabies
• therefore, essential to ask the travel history
• west nile virus: mosquito borne infection -> kills birds

Question 24

HSV encephalitis

1. number of cases per year
2. age group affected
3. mortality rate in untreated
4. neuropsychiatric sequelae

Answer 24

1. 1-2 cases/ 250,00/ year
2. all age groups
3. 70% mortality in untreated
4. 2/3 survivors
   - 70% memory impairement
   - 45% personality/behavioural change
   - 40% dysphasia
   - 25% seizures (risk of those w seizure during acute period higher)
   - disinhibition/depression

Question 25

what are the clinical presentation of HSV encephalitis?

Answer 25

``` Acute presentation Flu-like prodrome Fever (90%) Headache Altered consciousness Disorientation (76%) Seizures in 1/3 of patients with HSV-1 encephalitis Focal neurological signs common Speech disturbance (59%) Behavioural change, e.g. hypomania, irritability (41%) Memory impairment ```

Question 26

what are the common misdiagnosis of encephalitis?

Answer 26

1. fever + confusion - urinary/chest infection 2. fever + seizures (febrile) - post-octal pyrexia (febrile illness - CNS infection investigation) 3. altered consciousness or behaviour - drugs/alcohol/psychiatric illness

Question 27

how is HSV diagnosed?

Answer 27

1. lab tests - CSF HSV-1 DNA PCR: sensitivity >95% within 10days from onset but can be -ve initially - CSF antibody: sensitivity 50%, detection from 10days 2. Imaging: MRI > CT, imaging could be normal initially, MRI w DWI might help - unilateral temporal abnormality suggest HSV encephalitis 3. EEG: non-specific focal findings in >80% HSV encephalitis, periodic lateralised epileptiform discharges

Question 28

1. what is aciclovir? 2. what are the pros and cons associated 3. when to administer it?

Answer 28

1. antiviral used for treating HSV encephalitis 2. pros: reduces mortality from 70% to 28% + limits postendephaltiic impairment cons: poor outcome if delay>2days b/w admitting and starting the treatment 3. in suspected EC, first perform LP (proving no contradictions) then start acyclovir antibiotics - if LP likely to delayed or patient deteriorating start presumptive aciclovir at once

Question 29

when to stop acicclovir for HSV encephalitis ?

Answer 29

1. confirmed HSV E: stop at 14-21 days 2. high suspicion but initial CSF PCR -ve, continue acyclovir and repeat LP after 48hrs 3. if PCR again -ve but suspicion persists then continue IV acyclovir for 10 days 4. low suspicion or alternative diagnosis apparent then stop after 2.d -ve PCR

Question 30

what is the significance of corticosteroids in HSV encephalitis?

Answer 30

- retrospective non-randomised data – corticosteroid administration improved outcome in 22 of 45 patients with HSV encephalitis w combination therapy for aciclovir and corticosteroids - Efficacy not yet proven - Optimal timing unclear - Often used if significant brain oedema or if deterioration despite appropriate antiviral treatment - however, mannitol and decompressive hemicraniectomy sometime preferred - prospective RCT 2015, following standard treatment w IV ACV for PCR-confirmed HSE, an additional 3-month course of oral (valacyclovir) VACV therapy did not provide added benefit