25 Central nervous system infections Flashcards
CNS infection occurs usually via blood vessel (polio/ neisseria) or nerves (HSV/ VZV/ rabies) of CNS
What are innate barriers to CNS infection?
Blood-brain barrier - tightly joined endothelial cells with thick basement membrane, surrounded by glial processes
Blood- CSF barrier - endothelial cells with fenestrations, tightly joined to choroid plexus epithelial cells
How do infections traverse barriers of CNS?
Infecting cells that compromise the barrier, so they can cross
Passively transported in intracellular vacuoles
Passively transported across by infected white blood cells
What is clinical presentation of:
Meningitis - meninges/ membrane surrounds brain
Encephalitis - brain itself
Meningitis - fever, headache, neck stiffness, photophobia, nausea/ vomiting. Strictly speaking it is a pathological diagnosis, but we use other tests as surrogate markers.
Meningism - triad headache/ neck stiffness/ photophobia. May be due to infection. Can also be SAH/ migraine
Encephalitis - fever, confusion, seizure, focal neurological feature e.g weakness, visual disturbance, dysphasia. Usually viral cause
Meningoencephalitis - mixture of both, inflammation of meninges and adjoining brain parenchyma
Myelitis - inflammation spinal cord
Name some examples of viruses which cause encephalitis
Arbovirus - Yellow Fever West nile Tick borne encephalitis Japanese encephalitis Equine encephalitides St Louis encephalitis Zika
Enterovirus -
Coxsackievirus
Echovirus
Poliomyelitis
Myxovirus infections Measles - subacute scleorsing panencephalitis Mumps Rubella Influenza Hendra Nipah Rabies
Herpesvirus infections HSV VZV CMV HHV6
Polymoavirus
JC virus
There are many other causes of encephalitis, including bacteria, rickettsia, fungi, parasites (malaria) and AI
Travel history dictates further investigations e.g malaria
What is life cycle of polio?
Similar life cycle to mumps, haemophilus, pneumococci, meningococci
Infection by ingestion - taken up by GALT to local lymph nodes
Lymph nodes then spreads via blood to liver and throughout bloodstream, causing viraemia/ fever
Invades meninges after infecting vascular endothelial cells at blood-CSF barrier
Invades neurones by infecting vascular endothelial cells at blood-brain-barrier
How do HSV/ VSV and rabies spread to CNS?
HSV/ VZV in skin/ mucosal lesions travel up axons using normal retrograde transport mechanisms at rate 200mm/day to reach dorsal root ganglion (similar to tetanus toxin)
Rabies infects muscle fibes after bite, and binds to nicotinic acetylcholine receptors. Travels in retrograde fashion until reaches CNS glial cells and neurones
What are glial cells?
The glial cells surround neurons and provide support for and insulation between them. Glial cells are the most abundant cell types in the central nervous system.
CNS - astrocytes oligodendrocytes ependymal cells microglia
PNS -
Schwann cells
satellite cells
What is role of these glial cells in CNS?
astrocytes
oligodendrocytes
astrocytes - involved in physical structure of brain. Formation of synapses, formation of BBB
oligodendrocytes - involved in physical structure of brain. Support and insulate neurones - myelinating cells of CNS
What is role of these glial cells in CNS?
ependymal cells
microglia
ependymal cells - line ventricles of brain, and central canal of spinal cord. Assist production and monitoring of CSF
microglia - macrophage like cells remove microbes, cell debris
What is role of these glial cells in PNS?
Schwann cells
satellite cells
Schwann cells - myelin sheath
satellite cells - surround neurone cell bodies in ganglia. Provide structure and protection as cushions. Can express receptors to interact with neurotransmitters
What is definition of aseptic meningitis?
Meningitis but CSF is sterile on regular bacteriological culture/ molecural diagnostics
Means another cause e.g viruses, TB, leptospira, fungi, brain abscess, partially treated bacterial meningitis
In septic meningitis what changes would you expect in CSF?
Cell count
Protein
Glucose
Causes by bacteria, TB, leptospira, amoebae, fungi, brain abscess
Normal cell count <5
Normal protein 150-450
Cell count 200- 20 000 mostly neutrophils
Protein >1000
Glucose <4.5
In aseptic meningitis what changes would you expect in CSF?
Normal cell count <5
Normal protein 150-450
Cell count 100-1000 mostly lymphocytes
Protein 500-1000
Glucose normal
What are ways in which viruses can damage CNS?
Direct damage to neurones - polio/ rabies
Direct damage to oligodendrocytes - loss of myelin sheath JC virus
Perivascular infiltration with lymphocytes/ monocytes can cause damage
Oedema in “closed box” of skull, can rapidly be life threatening
Rabies can descend from CNS to salivary glands. It also affects limbic system, and changes behavior to make animal more aggressive and bite
Bacterial meningitis is more severe, but less common than viral meningitis.
What are common causes?
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae
E. Coli
Listeria
TB
Cryptococcus
Since Hib vaccine introduced, it has gone from most common, to third. After neisseria and strep
What is general treatment for bacterial meningitis?
Ceftriaxone 2g QDS
Cefotaxime 2g QDS
If suspect listeria (immunocompromised/pregnant/ age >60/ diabetes/ alcohol)
Add amoxicillin 2g 4hourly
Penicillin allergy -
Chloramphenicol 25mg/kg QDS
If suspect listeria (pregnant/ age >60)
Co-trimoxazole 20mg/kg QDS
If penicillin resistance expected (foreign travel) start -
vancomycin 20mg/kg BD
Rifampicin 600mg BD
dexamethasone 10mg QDS IV. Start initially. If strep pneumoniae, continue for 4 days. Otherwise can stop if other pathogen
TB - specific agents
Cryptococcus - amphotericin B + flucytosine
For these causes of bacteria meningitis, what treatment/ vaccine is available for prevention or following close-contact exposure?
Although 20% asymptomatic colonised with these bacteria anyway, risk of meningitis is 1000x higher after exposure compared to background population.
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis - ciprofloxacin prophylaxis for close contacts, polysaccharide vaccine
Streptococcus pneumoniae - polyvalent (23 serotypes) polysaccharide vaccine. Treat any respiratory infections/ otitis media promptly
Haemophilus influenzae - polysaccharide vaccine against type B (Hib)
Occupational health organises it for staff - those at risk e.g intubation/ CPD
PHE organises prophylaxis for contacts
For these causes of bacteria meningitis, what treatment/ vaccine is available for prevention or following close-contact exposure?
E. Coli
Listeria
TB
Cryptococcus
E. Coli - no vaccine
Listeria - no vaccine
TB - BCG vaccine. Isoniazid prophylaxis for close contacts recommended in USA
Cryptococcus - no vaccine
Neisseria meningitidis is carried by approximately 20% of population asymptomatically. Attached by pili to epithelial cells of nasopharynx. Invasion of blood/ meningies poorly understood
What is mode of transmission?
Droplet spread - often facilitated by other respiratory infection, such as viral causes, which cause increased respiratory secretions.
Outbreaks seen in conditions of overcrowding such as prison, military barracks, university dormitories
Peaks occur early spring and late winter. Carrier rate may reach 60-80%
What are virulence factors for bacterial meningitis?
Capsule IgA protease Pili Endotoxin Outer membrane proteins
Neisseria meningitidis/ haemophilus have all of these
Strep pneumoniae just has capsule/ IgA protease
Which groups of people are at high risk of infection with neisseria meningitidis?
Outbreaks seen in conditions of overcrowding such as prison, military barracks, university dormitories
C5-C9 complement deficiencies
Children who have lost maternal antibodies, but not yet developed their own immune response
Which menigococcal serotypes predominate in resource-rich countries, and which pre-dominate in resource-poor countires?
resource-rich countries
B, W, Y, C in that order
resource-poor countries
A, W-135
What vaccines are available for meningococcal?
Important strains: A, B, C, Y, W-135
Polysaccharide A, C, Y, W quadrivalent vaccine
B vaccine
Quadrivalent vaccine introduced 1999 routine childhood immunisation, and recently for school-leavers. Men B vaccine introduced 2015 for infants
What vaccines are available against these causes of meningitis?
Haemophilus influenzae
Streotococcus pneumoniae
Group B Strep
E. Coli
Haemophilus influenzae - B is most important type. Polysaccharide Hib for <1 year olds
Streotococcus pneumoniae - many strains. Polysaccharide pneumovax works against 23 different types
Group B Strep - Ia, Ib, II, III - many types. Vaccine in development
E. Coli - KI type causes meningitis. No vaccine
What are different clinical features/ groups seen in these causes of bacterial meningitis?
Neisseria meningitidis
Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitidis - children/ adolescents. Skin rash. Acute onset <24 hours
Haemophilus influenzae - children <5. Onset 1-2 days
Streptococcus pneumoniae - children <2 and elderly. Onset follows pneumonia/ sepsis
Approximate mortality rates for these diseases, and sequelae (deafness, seizures, mental retardation)
Neisseria meningitidis
Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitidis - 10% mortality, sequelae <1%
Haemophilus influenzae - 5% mortality, sequelae 10%
Streptococcus pneumoniae - 25% mortality, sequelae 20%
What are symptoms of neisseria menigitis?
Sore throat Headache Drowsiness Fever Neck stiffness Photophobia Rash - petechiae
Septicaemia causes DIC, endotoxaemia, shock and renal failure.
In severe cases, bleeding into brain/ adrenal glands can cause addisonian crisis termed Waterhouse-Friedrichsen syndrome
What are investigations for meningitis?
Bloods - CRP/ WCC/ coag/ platelets
CT/ MRI
LP
Serology not helpful as disease too acute for antibody response to occur
Haemophilus influenzae has six types (a-f), what is unique about type b which causes meningitis?
Why are children most at risk?
Capsulated type b can occasionally invade blood/ meninges
Uncapsulated other strains are common, and present in throat of most healthy people
Maternal antibodies protect infant until 4 months of age, but this weakens, and there is a window of susceptibility before child produces own antibodies.
What are risk factors for strep pneumoniae?
<2 years old Elderly Sickle cell Splenectomy patients Head trauma
Immunity is type specific, and there are over 85 capsular types of strep pneumoniae
Vaccine recommenced in childhood, and those high risk - sickle cell, splenectomy, HIV, immunodeficiency.
Which groups are at risk of listeria meningitis?
Why is treatment different for listeria than empirical treatment?
Children
Elderly
Immunocompromised
Use ceftriaxone and amoxicillin because listeria is less susceptible to penicillin, so combination therapy better
Why are neonates at increased risk of meningitis?
Higher risk if premature/ LBW
Immature innate and adaptive immune systems
Difficult diagnosis - may only have lethargy, poor feeding
Often leads to permanent neurological sequelae such as cerebral palsy, cranial nerve palsy, epilepsy, mental retardation, hydrocephalus
What is empirical treatment for neonatal meningitis?
Benzylpenicillin and gentamicin
Antibiotics given in pregnancy to eliminate carriage, but does not guarantee this
How does TB meningitis present?
25% have no history of previous TB
50% of cases present with acute miliary TB
Insidious onset over weeks
If high TB prevalence - presents in children aged 0-4
If low TB prevalence - presents in adults
How does pulmonary TB lead to TB meningitis?
Primary lesion in lung
Bacilli move to lymph nodes
Lymphatics drain into lymphatic duct/ SVC
Moves in bloodstream to CNS causing tubercles
Tubercle ruptures into subarachnoid space
Bacilli spread in CSF
What are fungal causes of meningitis?
Cryptococcus neoformans - immunocompromised
Coccidioides immitis
How does fungal meningitis present?
Slow, over days or weeks
How to diagnose cryptococcal infection
Treatment cryptococcal infection?
Cryptococcal antigen in blood/ CSF
India ink stain CSF
Amphotericin B + flucytosine
Which geographical areas at risk of coccidioides immitis meningitis?
CNS infection occurs <1% of those infected
What is treatment for coccidioides immitis?
North/ South america
Rarely visible in CSF, cultures positive <50% cases
Detect antibodies in serum
Amphotericin B or fluconazole
What are causes of protozoal meningitis?
Amobes:
- Naegleria fowleri
- Acanthomoeba
- Balamuthia madrillaris
Can infect healthy individuals
- plasmodium
- toxoplasmosis
Where does naegleria fowleri live?
How does it reach CNS?
Fresh warm water - lakes, swimming pools
Feeds on bacteria
North/ South America, Asia
Via olfactory tract and cribiform plate. Rapid onset
What is treatment for amoebic meningoencephalitis?
Amphotericin B, with miconazole and rifampicin.
Miltefosine addition has shown some benefit
Mortality approximately 95%
Diagnosis of amoebic meningoencephalitis?
CSF microscopy
Brain biopsy
PCR/ serology in specialist centres
Viral meningitis is more common than bacterial, and often has milder disease.
Which viruses are responsible?
Up to 85% of cases no causative agent is identified
Enetroviruses - echoviruses, coxsackie A/B, poliviru
HSV
VSV
CMV
Paramyxovirus - mumps, nipah (pig farms Malaysia)
Rabies
Flavivirus - JE, WNV
HIV
Influenza H5N1 has been shown to cause encephalitis
Which neurological diseases can mimic encephalitis?
AI encephalitis, commonly:
VGKA receptor
NMDA receptor
HSV is most common cause of encephalitis.
Which patients groups get HSV1 or HSV2?
HSV1 - older patients. Reactivation in trigeminal ganglion, infection then passing to primary lobe of brain. Can also occur as primary infection
HSV2 - neonate. Acquire from mother due to shedding in genital tract
How to diagnose HSV encephalitis?
Herpetic skin/ mucosal lesions
CT/ MRI - temporal lobe enhancement
CSF HSV DNA PCR
EEG
What is mortality rate of HSV encephalitis?
What is treatment?
70% mortality if untreated
21 day course aciclovir
When do these viral encephalitis viruses cause diseases?
VZV
CMV
VZV - reactivation or new infection. Encephalitis can occur later
CMV - primary infection in utero, or reactivation when immunosuppressed e.g bone marrow transplant
What disease does enterovirus 71 cause?
Hand foot and mouth disease
Outbreaks have been associated with encephalitis in children <5, leaving permanent neurological damage
What is life cycle of Nipah virus, including hosts
SE Asia - Malaysia, India, Bangladesh
Fruit bat natural reservoir - virus in urine/ saliva
Pigs eat infected food
Aerosol transmission (unclear) to humans via close contact
Initially thought to be JE. Resulting in culling of 1 million infected pigs in region
Rabies kills 55 000 people each year. Occurs in 150 countries. It can infect any species of warm-blooded animals
Genus Lyssavirus
Species Rhabodviridae
What is structure of rabies virus?
Single stranded RNA virus
Bullet shaped
There are 7 genotypes if rhabdoviridae
What are they/ where are they found geographically?
1 - worldwide classic rabies virus
2, 3, 4 - African bat virus
5, 6 - European bat Lyssasviruses (EBLV)
What are hosts of rhabdoviridae?
Viruses excreted in saliva of infected dogs, foxes, jackals, wolves, skunks, raccoons, bats or transmission from humans
Virus can be in host saliva before symptoms present. If asymptomatic by day 15, then unlikely to have rabies.
Dogs are source of 99% of human infection.
Islands such as UK, Australia, Japan are free of rabies because of strict control on import of animals
What is incubation period of rabies?
How does it travel?
Typically 4-13 weeks, can be 6 months
Virus travels up motor or sensory neurones
Eventually reaches limbic system - causing behavioural change
Incubation period depends on where bite occurs e.g distal bite will take longer to spread
No antibody response as antigen remains within infected cells.
What are symptoms of rabies?
Pain at bite site Sore throat Headache Fever Difficulty swallowing water due to muscle spasms jaw (hydrophobia) Convulsions Paralysis
Once rabies has developed it is invariably fatal, leading to cardiac/ respiratory arrest
What are diagnostic tests for rabies?
Viral antigen by immunofluouresence
Viral RNA PCR skin biopsy
Brain biopsy
Intracytoplasmic inclusions called Negri bodies are seen in neurones
What are immediate treatment options of suspected rabies bite?
Prompt cleaning of wound
Cinical observation of animal - does it have rabies
Rabies immunoglobulin (RIG) provides passive immunisation. Administered IM around wound site
Active immunisation with killed rabies virus
Which flaviviruses are important causes of encephalitis?
All zoonoses
JE
WNV
SLE
Dengue/ YF are other examples of flaviviruses
What is geographical spread of JE?
Who is most commonly affected?
China/ India 70000 cases/year
Children - mortality 30%
Adults usually already been infected
What are hosts and transmission cycle of JE?
Inactivated and live attenuated vaccines exist
Pigs and wading birds - intermediate hosts
Culex mosquito
What is life cycle of West Nile virus?
Initially seen in Tunisia and Israel
Culex mosquito transmits to birds
Feeding mosquitoes obtain from infected birds, which then bite humans who are incidental hosts
Birds can have viraemia without death, or can have sudden mass death
Common in USA now. Reported in multiple Eastern European countries
How to diagnose WNV?
What is treatment and prevention of WNV?
Viral RNA PCR
IgM - serum/ CSF
Treatment - supportive
No vaccine
Mosquito control programmes
In inital HIV presentation, which organisms can present as encephalitis?
HIV itself can move into CNS, and cause mild mengitic illness
CMV
JC virus - PML
Cryptococcus
Toxoplasma
Viruses can cause myelopathy, inflammation of spinal cord. Symptoms can be symmetrical if it transverses the spinal cord.
Which viruses can be responsible for this?
Anterior horn cells affected causes pure motor symptoms, and results in acute flaccid paralysis. Examples include:
- polio
- coxsackie
- enterovirus 1
- WNV
Non-specific myelitis
- CMV
- EBV
- HSV
- VZV
- HTLV-1 - presents as tropical spastic paraparesis
- HIV
What is Guillain-Barre syndrome?
Inflammatory demyelinating condition of peripheral nervous system. Can rapidly lead to ascending muscle weakness. Usually little sensory loss.
May require mechanical ventilation
What is clinical history of patient with GBS?
2-4 weeks preceeding URTI, diarrhoeal disease, or other infection, prior to symptoms developing
What are causes of GBS?
Associated with variety of infections, including vaccination with non-infectious material e.g influenza vaccine
EBV CMV HIV WNV Zika
Campylobacter Jejuni - 1/3 of cases
Mycoplasma pneumoniae
Borrelia burgdorferi
What are treatments for GBS?
Supportive -
- ventilation
- IV immunoglobulin
- plasma exchange
What are protozoal causes of encephalitis?
African Trypanosomiasis Cysticercosis Hydatid Plasmodium Toxoplasma Toxocara
How does cerebral malaria occur?
Aseuxal stages of plasmodium (in humans) adhere to capillary walls, which affects BBB
How does toxocara infection causes encephalitis?
Toxocara cati - cat
Toxocara canis - dog
Usually infect children when eggs from cat/ dog faeces are infested. Eggs hatch in GI tract. Larvae migrate to various tissues including brain. Humans dead end hosts.
Granulomas form around larvae, which can cause encephalitis
What is treatment for neurotoxocariasis?
Steroids
Albendazole
What are bacterial causes of brain abscess?
Most brain abscesses related to underlying condition e.g surgery, trauma, chronic osteomyelitis, septic emboli.
Also seen in children with cyanotic congenital heart disease, as lungs fail to filter bacteria
Actinomyces Brucella Lyme disease Nocardia Syphilis TB
What are parasitic causes of brain abscess?/ chronic meningitis
Cysticercosis
Toxoplasma
What are fungal causes of brain abscess/ chronic meningitis?
Blastomycosis Candidiasis Cociddiomycosis Cryptococcus Histoplasmosis
Clostridium tentani/ botulinum release toxins which act on CNS, but do not actually invade CNS.
Tetanus spores widespread in soil, and originate from faeces of domestic animals.
How is Cl. tetani toxin carried to CNS
Spores enter a wound, and if necrotic tissue present, toxin tetanospasmin produced.
Carried up peripheral nerves, where it binds to neurones and blocks release of inhibitory mediators in spinal synapses, causing overactivity of motor neurones. Can also move along sympathetic nerve axons, leading to overactivity of sympathetic nervous system
Infection of umbilical stump can cause neonatal tetanus
What is incubation period of tetanus?
How is it diagnosed?
3-21 days
Often clinical diagnosis, and organisms often not isolated from wound. Only small number of organisms required to produce toxin
What are symptoms of tetanus?
Mortality 50%
Hyperreflexia Muscle rigidity Muscle spasms Trismus Dysphagia Neck stiffness
Tachycardia
Sweating
What is treatment of tetanus?
Clean wound
Penicillin
Tetanus toxoid vaccine booster - lasts for 10 years
If severe -
Anti-tetanus immunoglobulin
Cl botulinum spores widespread in soil, and contaminate vegetables, meat, fish. When foods are canned/ preserved without adequate sterilisation (often at home), contaminating spores can survive and germinate in anaerobic environment, leading to formation of toxin. Spores can even survive up to 5 hours after boiling.
IVDU can get botulism through infected drugs injection.
What is mechanism of action of toxin?
Absorbed from cut, into blood
Then acts on peripheral nerve synapses by blocking release of acetylcholine. It is type of food poisoning affecting motor and autonomic nervous systems
In infants, they can ingest by pacifiers covered in honey. Causing infant botulism
What is incubation period of botulism?
What are symptoms of botulism?
2hr-72hr
Descending weakness and paralysis including dysphagia, diplopia, vomiting, vertigo, respiratory muscle failure.
No GI symptoms or fever
Infants develop generalised weakness - floppy baby, but usually recover
How is botulism diagnosed?
Usually clinical diagnosis
Toxin can be found in suspected food
What is treatment for botulism?
Trivalent antitoxin - Type A/ B/ E toxin given promptly
Respiratory support
Which signs can be used to stretch the meninges, and demonstrate meningism?
Kernig’s sign - flex hip 90deg, try and straighten leg
Brudzinski’s sign - bend knees onto bed, flex neck. Will make neck pain worse
Each sign only has 5% rule out percentage
What are bacterial causes of meningitis in these groups of patients?
Neonates
GBS
E. Coli
Listeria
Outbreaks form gram neg rods such as Serratia, Citrobacter, Klebsiella in NICU
What are bacterial causes of meningitis in these groups of patients?
Infants/ teenagers/ adults
Strep pneumoniae
N meningitidis
Hib - if not immunised
M TB
What are bacterial causes of meningitis in these groups of patients?
Elderly
Pregnant
Strep pneumoniae
Listeria
Listeria
What are bacterial causes of meningitis in these groups of patients?
Immunocompromised
Complement deficiency increases risk infected encapsulated organisms:
Strep pneumoniae
N meningitidis
Hib
Listeria
Cryptococcus (not bacteria)
What are bacterial causes of meningitis in these groups of patients?
Post neurosurgery
S aureus Coagulase negative staph Corynebacteria Propionibacterium Pseudomonas
What are bacterial causes of meningitis in these groups of patients?
Post open trauma
S aureus
Pseudomonas
Gram negative rods
What are bacterial causes of meningitis in these groups of patients?
Post closed trauma, base of skull fracture, or associated with otitis media/ sinusitis
S pneumoniae
Other oral flora
Hib
Pseudomonas
What are contraindications to lumbar puncture?
papilloedema or other signs of raised intracranial pressure
suspicion of intracranial or cord mass
congenital neurological lesions in lumbrosacral region
signs suggesting raised intracranial pressure reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more)
relative bradycardia and hypertension
focal neurological signs
abnormal posture or posturing
unequal, dilated or poorly responsive pupils
papilloedema abnormal
‘doll’s eye’ movements “
shock
extensive or spreading purpura
after convulsions until stabilised
coagulation abnormalities
platelet count below 100 x 10^9/litre
receiving anticoagulant therapy
local superficial infection at the lumbar puncture site
Treatment for meningitis in following cases?
Adult
Pregnant
Post neurosurgery
Post open trauma
Adult - ceftriaxone
Pregnant - ceftriaxone + amoxicillin
Post neurosurgery - meropenem + vancomycin. Add intrathecal antibiotic if EVD in situ
Post open trauma - ceftriaxone + metronidazole + gentamicin
What is evidence of steroid use in meningitis?
Cochrane review showed reduced mortality in S pneumoniae only. Stop steroids if other organism is cause
Showed reduced deafness and neurologic deficit in all causes
Give 5 days dexamethasone 10mg QDS
What is duration of treatment for the following organisms?
N meningitidis
S pneumoniae
Listeria
GBS
E. coli
S. aureus
Haemophilus
N meningitidis - 5 days
S pneumoniae - 14 days
Listeria - 21 days
GBS - 21 days
E. coli - 21-28 days
S. aureus - 28 days
Haemophilus - 10 days
Can consider OPAT if had 5 days therapy, and clinically improved - Ceftriaxone 2g BD is example
What are causes of auto-immune encephalitis?
anti-NMDA receptor Ab
voltage-gated potassium channel Ab
What is ADEM?
Acute disseminated encephalomyelitis
Immune mediated inflammatory demyelinating condition, predominately affecting white matter of brain/ spinal cord.
Not necessarily directly due to infection, but is related to recent viral illness e.g measles, rubella, chickenpox, or following recent vaccination
Patient presents with diarrhoea, fever, mild photophobia. What is the cause?
Enterovirus - multiplies in GI tract
send CSF for viral PCR
Patient presents to GP with possible meningitis.
What treatment should be given in community?
Benzylpenicillin 1.2g IM
Ceftriaxone 2g IM
Cefotaxime 2g IM
If allergy penicillin/ cephalosporins - hold off antibiotics until arrival hospital.
Lumbar puncture in patients on LMWH.
What are the recommendations?
LMWH UFH Aspirin Clopidogrel DOAC
If on prophlyactic LMWH - do not perform until 12 hour after
If not on prophylactic LMWH - do not commence until 4h post-LP
If on treatment dose LMWH - do not perform until 24 hour after
If on UFH - can re-start 1 hour after LP
Aspirin - can proceed with LP
clopidogrel should be avoided 7 days before LP. But if benefits outweigh risks, can give platelet cover, and perform 8 hours after dose
DOAC - discuss with haematology. Dabigatran has reversal agent
What are platelet/ INR cut-offs for performing LP?
Platelets >50 - unless rapidly falling
INR below 1.5
Patient presents with possible meningoencephalitis. What investigations are required?
Including LP tests
Blood cultures
Pneumococcal/ meningococcal PCR
Throat/ rectal swab for enterovirus
Throat swab - neisseria
Procalcitonin - can help point towards bacterial rather than viral cause
HIV test
LP - opening pressure protein glucose - if above 2.6, unlikely to be bacterial cell count microscopy 16s PCR if bacterial considered Viral PCR
Viral PCR - HSV/ VZV/ Adenovirus/ Enterovirus/ Parechovirus
CSF results can be normal if immunocompromised
If first episode of meningitis, then does not need investigation for immunodeficiency at this point. If second episode - check immunology
What are isolation precautions for suspected meningitis?
Isolate patient with respiratory isolation until had 24 hours of antibiotics
Antibiotic chemoprophylaxis should be given to healthcare workers who have been in close contact with a patient with confirmed meningococcal disease ONLY when exposed to their respiratory secretions or droplets for example during intubation or as part of CPR when a mask was not worn
What are potential long term sequeale from meningitis?
Epilepsy
Hearing difficulties - hearing test
Psychiatric issues
Limb amputations
Headache
Neuropathic pain
What is treatment of viral meningitis? (not encephalitis)
Normally self-limiting illness - does not require anti-virals
Some people treat, but no evidence of benefit.
Recurrent HSV2 meningitis is sometimes called Mollaret’s meningitis, and some decide to put on prophylactic anti-virals.
What is treatment of suspected encephalitis?
Empirical
Viral PCR positive on initial LP
Viral PCR negative on initial LP
Aciclovir 10mg/kg TDS
Reduce dose if renal impairment
Treat 14 days - perform repeat LP, and can stop treatment on day 14 if CSF negative by PCR. If positive by PCR, continue for further 7 days
21 days treatment if immunocompromised
Viral PCR negative on initial LP -
- An alternative diagnosis has been made
- HSV PCR in the CSF is negative on two occasions 24-48 hours apart, and MRI is not characteristic for HSV Encephalitis
- HSV PCR in the CSF is negative once >72 hours after neurological symptom onset, with
unaltered consciousness, normal MRI (performed >72 hours after symptom onset), and a
CSF white cell count of less than 5/mm3
No evidence for corticosteroids
What is specific treatment for -
VZV encephalitis
Enterovirus encephalitis (includes Enterovirus/ parechovirus/ coxsackie)
VZV encephalitis - no specific treatment
Enterovirus encephalitis - no specific treatment is recommended for enterovirus encephalitis. If severe disease pleconaril (if available) or intravenous immunoglobulin may be worth considering
What is follow up for meningococcal meningitis?
Vaccination for MenB/ ACWY/ Hib/ PCV13
Offer vaccination to close contacts
Child with febrile conlvusions, considering encephalitis
What viruses need to be considered not in adult panel?
HHV 6/7
Tick borne encephalitis is flavivirus. Thetford forest has ticks with this, but no cases from there.
Cases across all of Europe
How is it transmitted?
Tick bite
Unpasteurised milk from goats/ sheep/ cows
What is treatment for TBE?
No treatment available
Vaccination can provide protection. Offer to those going to Europe doing outdoor leisure pursuits such as forestry working, camping, rambling and mountain biking, during tick season (spring to early autumn)
