Infections of the CNS Flashcards
A 3 year old boy is admitted to hospital with a 2 day history pf lethargy, irritability and poor feeding
On examination he is pyrexial and drowsy, there has 2-3 purplish-red lesions on the trunk and extremities which the parents say were not present when he was examined by their GP. There is no nickel stiffness but his right arm is painful with no history of trauma
What are you most worried about ?
- Meningococcal disease (see petechial/purpuric rash)
- May present with meningitis, sepsis or both
What are the features of infections in the CNS?
Infections of the CNS;
- Present in a range of (sometimes non-specific) ways
- Can progress quickly with high mortality or long-term sequelae
- Quick clinical thinking can improve outcomes
- Some can be prevented
What are the features of Purpura fulminans & gangrene ?
Purpura fulminans & gangrene
Mortality;
- 5-15% from meningococcal meningitis
- 40% + from meningococcal sepsis
Complications;
May affect 20+% of survivors
What are the potential complications of meningitis ?
- Seizures
- Hearing difficulties
- Other cranial nerve problems
- Focal paralysis
- Hydrocephalus
- Intellectual disability
- Ataxia
What are the complications of sepsis ?
- Limb amputations
- Arthritis and join pain
- Skin necrosis and scarring
- Organ dysfunction: liver, kidney, adrenal glands
What is meningitis ?
Meningitis - inflammation of the meninges
Typical features - Fever, headache, stiff neck
Bacteria most serious
What is Encephalitis ?
Encephalitis - inflammation of brain parenchyma
Viral is most dangerous in this (e.g herpes simplex)
What is Sepsis ?
Life threatening organ dysfunction caused by dysregulated host response to infection
Drop in BP, damage to kidneys
How do microbes invade the CNS ?
Blood-brain barrier (BBB) - Difficult to get across here!;
- Tightly packed endothelial cells line the blood vessels in the brain mechanically supported by thin basement membrane
- Breach by infectious agents cause encephalitis
Blood-cerebrospinal fluid (CSF) barrier;
- Similar barrier at arachnoid membrane and in ventricles
- Breach by infectious agents causes meningitis
Direct spread;
- Sinuses
- Ottis media (middle ear infection)
- Skull fracture (e.g car crash)
On rare occasions pathogens can traverse these barriers resulting in a typical inflammatory response associated with infection
How?
- Growing across & infecting cells comprising barrier
- Passive transfer in intracellular vacuoles
- Carriage across in infected white blood cells
(When a pathogen is even just near meninges maybe not even past barrier it being in close proximity can cause meningitis)
What are the causes of meningitis ?
Infection, Auto-immune disease, Malignancy
What are the most common causes of Meningitis ?
Infectious - bacterial most serious !
Bacterial;
- Neisseria meningitids
- Haemophilus influenzae
- Streptococcus pneumoniae
- Mycobacterium tuberculosis
Viruses;
Enteroviruses;
- Echovirus
- Coxsackie viruses A & B
- Poliovirus
Herpes viruses;
- Herpes Simplex 1 & 2
Paramyoxovirus;
- Complication of mumps
Fungi;
- Cryptococcus neoformans
Protozoa;
- Amoebae
- Naegleria
- Acanthamoeba
What are the main causative organisms of bacterial meningitis by each age group/risk factors?
Neonates;
- Eschericha coli
- Group B Streptococcus
- Listeria monocytogenes
< 5 year olds;
- Neisseria meningitidis *
- Haemophilus influnzae *
(can be picked up in birth canal)
Young adults;
- Neisseria meningitidis *
Older;
- Streptococcus pneumoniae *
- Listeria monocytogenes
Immunosuppressed;
Mycobacterium tuberculosis
Cryptococcus neoformans
- = key ones
What are the dangers with Neonatal meningitis ?
Early onset;
- Occurs < 7 days
- Infected by heavily colonised mother
- Premature rupture of membranes
- Preterm delivery
- 60% fatality rate
Late onset;
- occurs < 3 months
- Lack of maternal antibody
- Poor hygiene in nursery
- 20% fatality rate
Younger = more likely poor outcome
Hence why we swap birthing canal prior to birth to prevent bad infections and doc C-section in those cases
What its Neisseria meningtidis ?
Bacterial meningitis pathogen: Neisseria meningtidis
- Gram negative Intracellular diplococci
- Only infect humans
- Normal microbiota in nasopharynx
- Transmission by droplet spread (cough) or direct contact from carriers
- At least 12 serotypes stains - A, B, C, W135, Y
More common in African belt
Its vaccine preventable !
What are the features of Haemophilus influenzae ?
Haemophilus influenzae;
- Gram negativ coccobacilli
- Six capsular serotypes (a-f) known to cause disease
- Most virulent strain is H.influenzae type b (Hib)
Its Vaccine preventable !
What are the features of Streptococcus pneumoniae?
Streptococcus pneumoniae;
- Gram positive diplococci
- Normal microbiota in nasopharynx
- There are over 90 bacterial serotypes
- Common cause of meningitis in young children and adults with specific risk factors (e.g older, diabetic, alcohol excess, asplenic*)
- Pneumococci also causes pneumonia, otitis media and bloodstream infections
*Vaccinate splenic patients against capsulated organisms (N meningitidis, H influenzae b, S pneumoniae)
It is Vaccine preventable !
What are the key clinical features seen in meningitis and sepsis ?
Meningitis;
- Severe headache
- Stiff neck
- Photophobia
- Seizures
(In babies/small children);
- Tense or bulging soft spot on head (fontanelle)
- Refusing to feed
- Irritable when picked up, with a high pitched or moaning cry
- A stiff body with jerky movements, or else floppy and lifeless
(Don’t over-rely on things like ‘neck stiffness’ and classical ‘signs)
Sepsis;
- Limb/joint/muscle pain
- Cold hands and feet/shivering
- Pale or mottled skin
- Breathing fast/breathless
Both;
- Fever and or vomiting
- Rash
- Very sleepy/difficult to wake
- Confused/delirious
What are diagnostic tests we can use for testing infections of the CNS?
Blood;
- Biochemistry; U&E, CRP, lactate, glucose
- Haematology; FBC, clotting
- Microbiology; Blood culture, meningococcal & pneumococcal PCR, HIV test
CSF;
Biochemistry; Protein & Glucose
Microbiology;
- White cell count
- Gram stain & bacterial culture
- Meningococcal & pneumococcal PCR
- Viral PCR tests
- TB: microscopy, molecular tests & culture
- Cryptococcal: Indian ink, CrAg, fungal culture
How do you collect CSF?
Lumbar puncture; Level L3,4,5
Remember to;
- Measure opening pressure
- Take matched blood and CSF glucose samples
- Collect enough fluid (and some to spare!)
What findings would indicate the type of infection with a lumbar puncture?
Normal;
- Opening pressure: 12-20 cm (normal) CSF
- Appearance of CSF: Clear
- CSF WCC: Normal
- Predominant cell type: N/A
- Protein: Normal
- Glucose: Normal
- Plasma glucose ratio: Normal
Bacterial;
- Opening pressure: Raised
- Appearance of CSF: Turbid, cloudy, purulent
- CSF WCC: Raised
- Predominant cell type: Neutrophils
- Protein: Raised
- Glucose: Very low
- Plasma glucose ratio: Very low
Viral;
- Opening pressure: Normal/mildly raised
- Appearance of CSF: Clear
- CSF WCC: Raised
- Predominant cell type: Lymphocytes
- Protein: Mildly Raised
- Glucose: Normal/ slightly low
- Plasma glucose ratio: Normal/ slightly low
Tuberculous;
- Opening pressure: Raised
- Appearance of CSF: Clear or cloudy
- CSF WCC: Raised
- Predominant cell type: Lymphocytes
- Protein: Markedly Raised
- Glucose: Very low
- Plasma glucose ratio: Very low
Fungal;
- Opening pressure: Raised
- Appearance of CSF: Clear or cloudy
- CSF WCC: Raised
- Predominant cell type: Lymphocytes
- Protein: Raised
- Glucose: Low
- Plasma glucose ratio: Low
When should you delay or omit doing a lumbar puncture?
Not often but main reasons are;
- Risk of bleeding
- Focal neurology/papilledema suggesting a mass lesion in the brain
- Mass lesion
- Oedema
When do we need CNS imaging?
An important role of CT, in some patients is to exclude mass lesions and/or oedema which might make LP dangerous
In these patients a reduction of CSF pressure below the lesion following an LP could precipitate herniation of the brainstem or cerebellar tonsils
This may occur in patients with brain abscess, subdural empyema, tumour, or a necrotic swollen lobe in encephalitis
What is the treatment of bacterial meningitis ?
Use IV Ceftriaxone;
- Suspected meningococcal infection (+ Penicillin - pre-admission)
- N. meningitidis
- H. influenzae
- Strep. pneumoniae (+dexamethasone)
Use IV Cefotaxime;
- Suspected meningococcal infection (< 3 months old + amoxicillin)
- Group B streptococcus
- Gram negative bacilli
L. monocytogenes - IV Amoxicillin + Gentamicin
M. tuberculosis - Anti-tb antibiotics + Dexamethasone
If suspected use drug + a penicillin !
What vaccinations do we have against meningitis and other neurological infections?
Meningitis;
- Haemophilus influenzae b
- Pneumococcus
- Meningococcus A,B,C,W,Y
Other neurological infections;
- Polio
- Tetanus
What notification, prevention and control organisations work in preventing the transfer of Acute meningitis and meningococcal disease?
Reference Laboratories;
- Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL)
Public Health Action;
- Public Health will identify close contact and arrange antibiotics. Vaccination may also be required.
- If the patient is a child at school information letter and MRF info leaflets for all school parents are arranged
Public Awareness;
- The public should be aware of the key signs and symptoms and seek urgent medical advice if concerned
What is Viral Meningitis ?
- More common than bacterial meningitis (2-3 cases/100,000 per year)
- Identify by PCR of CSF
- No specific treatment
- Usually regarded as ‘benign’ & self-limiting
- Occasionally recurrent (HSV-2, Mollareet’s Meningitis) (Not very common but get it repeatedly)
- Long-term neuropsychiatric sequelae have been described - anxiety, depression, neurocongitive dysfunction
What are the features of Encephalitis ?
Most common cause: Herpes Simplex Virus-1
Symptoms and signs: altered cerebration - confusion, abnormal behaviour, seizures, fever
Investigations: similar to meningitis - typical findings on CSF, temporal lobe changes on MRI scan
Treatment: high dose IV aciclovir (best against herpes simplex)
Can present similarly to meningitis but the patient will appear more confused(where as meningitis would be headache and neck stiffness)
What are the features of Brain Abscesses?
Pre-disposing factors: otitis media, mastoiditis, sinusitis
Causes: often oral nasopharyngeal microbiota
- Aerobic (S.aureus, strep milleri)
- Anaerobic (Bacteroids sp, fusobacterium sp)
Pathophysiology: Diffuse inflammation -> focal lesion and Pia mater suppuration
Symptoms and signs; Headache, focal neurology, seizures
Investigations: CT/MRI scan +/- invasive sampling
Treatment: Antibiotics (often ceftriaxone + metronidazole)
What must you look for in CNS infections in immune-compromised patients?
Immune-compromised patients (e.g HIV, post transplant) may be at risk from a wider range of pathogens)
*There are other causes in high risk populations
