HNS09 Infection Of The CNS I Bacterial And Fungal Infections Flashcards
Syndromes from infection of CNS
- Meningitis (Ventriculitis: meningitis affecting ventricular lining)
- Subarachnoid space, Arachnoid mater, Pia mater - Encephalitis, Myelitis (mainly viral)
- Brain / spinal cord ***parenchyma - Abscess (Intracerebral / Intraspinal)
- Parameningeal infections (Epidural / Subdural abscess)
- Suppurative dural venous sinus thrombosis / Suppurative Intracranial Thrombophlebitis
- major venous sinus (cavernous, transverse, sagittal (superior / inferior))
Reasons for high morbidity and mortality of CNS infection
Sequelae:
- Neurons do NOT regenerate, cell death
—> permanent neurological dysfunction (e.g. deafness, mental retardation, epilepsy, paralysis) - Small amount of oedema / fluid collection within rigid skull (e.g. exudates, pus)
—> life threatening increase in intracranial pressure
—> fatal herniation of brain - Damaged meninges
—> failure of absorption of CSF
—> hydrocephalus
—> fatal herniation of brain
Increased in intracranial pressure
Normal rate of CSF circulation: 150ml every 8 hours
Head: rigid structure —> hard to put a few mL of fluids inside brain
- Production / absorption / obstruction of CSF
- Oedema / Pus collection in brain parenchyma
- Obstruction of flow of CSF
- Haematoma
***Clinical signs and symptoms of CNS infections
- Meningeal irritation
- headache (Trigeminal V1, C2)
- neck stiffness (C2-4)
- photophobia (irritation of basal meninges at diaphragma sellae)
- Kernig’s sign (resistance to knee extension when hip flexion)
- Brudzinki’s sign (reflex spasm of knee during neck flexion - Encephalopathic signs (parenchyma damage)
- alteration of conscious level
- generalised seizures (tonic / clonic phase) - Increased intracranial pressure
- headache
- vomiting
- Cushing’s reflex
- decreased HR (herniation of cerebellar tonsil across foramen magnum —> compress on medulla’s CVS centre)
- increased BP
- unilateral pupil dilatation (Uncus of temporal lobe herniates through tentorium —> compress on Oculomotor nerve) - Focal neurological signs
- loss of function: paralysis / sensory loss / focal epilepsy
- autonomic / endocrine dysfunction: labile BP/HR/rhythm, hypothalamic dysfunction, diabetes insipidus - Primary / metastatic foci of infection
- skin rashes (petechiae, purpura) (Neisseria meningitidis)
- arthritis
- pneumonia (pneumococcal meningitis)
- endocarditis
- sinusitis
- dental / facial infection - Systemic signs
- fever
- leukocytosis
Clinical picture
Meningitis: Meningeal irritation
Encephalitis: Alteration of conscious state (encephalopathic signs)
Brain abscess: Focal neurological signs +/- increased intracranial pressure
Viral infection: present as acute meningo-encephalitis
BUT ALL syndromes can produce these groups of clinical symptoms and signs
Bacterial meningitis cause
記: HNSS (Haemo, Neisser, Strep x2)
- Streptococcus suis
- Haemophilus influenzae
- Streptococcus pneumoniae (26% mortality)
- Neisseria meningitidis (aka Meningococcus)
- Enterobacteriaceae (>50% mortality)
- Group B Streptococcus (20% mortality) (i.e. Streptococcus agalactiae)
Viral meningitis causes
Cause of acute encephalitis
1. Enteroviruses
2. Herpes simplex type 1, 2
3. Varicella zoster virus
4. Mumps virus
5. Japanese encephalitis virus
6. HIV, Cytomegalovirus, Epstein-Barr virus (infectious mononucleosis)
Meningitis
Inflammation of meninges and surrounding brain/spinal cord tissues
Histopathology (can only perform post-mortem)
- Inflamed meninges
Clinical confirmation:
- Lumbar puncture: ↑ WBC in CSF
Clinical course and classification:
- Acute: 1-5 days after onset of symptoms
- Subacute / chronic: >= 1-4 weeks
Symptoms:
- High fever (rarely hypothermia)
- Severe and generalised headache
- Neck stiffness / nuchal rigidity
- Lethargy
- Normal cerebral function till late stage
Pathogenesis of pyogenic bacterial meningitis
- Asymptomatic ***colonisation of nasopharyngeal mucosa (by fimbriae/CD46)
- Bacterium transported across mucosa by ***phagosome —> overcome mucosal IgA (protease) —> enter blood stream
- Bacterial ***capsule effectively inhibits neutrophil phagocytosis and complement mediated bactericidal activity (WBC/complement/MBL)
- Sustained high grade **bacteraemia and other unknown factors (carriage in monocytes) —> opportunity to bacteria for attaching to **laminin receptors on brain microvascular endothelium
- Meningeal invasion —> breakdown of ***tight junctions between epithelial cells of ependyma / cross BBB by endocytosis
- Uncontrolled replication of bacteria in **subarachnoid space (defenceless ∵ low level of complement, Ab and WBC)
—> release of endotoxins / cell wall structures (LPS)
—> bind and activation of **Toll-like receptors (TLR) on endothelial cells and macrophages (cell wall activate TLR2, LPS activate TLR4)
—> ***Pro-inflammatory cascade activation: NF kappa B (transcription factor)
—> release IL-1, IL-6, TNF - Inflammatory damage
- Inflammation of subarachnoid space
- ↑ Permeability of vascular endothelium / BBB
- Inflammatory exudation
- Thrombosis - End result
- Venous cerebral edema (vicious cycle)
—> Arterial ischaemia + Cerebral infarction (septic thrombosis of vessels crossing inflamed subarachnoid space)
Common causes of acute pyogenic meningitis
0 - 8 weeks (through birth canal / intestinal tract):
- **E. coli (K1)
- **Enterobacteriaceae (Citrobacter, Salmonella)
- ***Streptococcus agalacteriae (group B type III) (in vagina)
- Listeria monocytogenes (milk products)
3 months - 18 years (encapsulated bacteria, through oropharynx: mastoid process / cribriform bone):
- **Haemophilus influenzae type B (vaccination available)
- **Neisseria meningitidis
- ***Streptococcus pneumoniae (vaccination available)
18 years - 50 years:
- Streptococcus pneumoniae
- Neisseria meningitidis
- ***Streptococcus suis
> 50 years:
- above 3 groups
- aerobic gram -ve bacilli (Klebsiella, Escherichia, Salmonella)
Immunosuppressed host:
- above 4 groups
- Listeria monocytogenes (early encephalopathy: seizures, focal neurologic deficits)
- Pseudomonas aeroginosa
Occupational exposure to pigs:
- Streptococcus suis (***deafness)
Exposure to contaminated fresh water:
- Nagleria fowleri / other free living amoeba (high mortality)
Ingestion of raw mollusk:
- Angiostrongylus cantonensis (parasite) (eosinophilia meningitis)
Head trauma, intrathecal infection and post-neurosurgery:
- Staphylococcus aureus
- Staphylococcus epidermidis
- Aerobic gram -ve bacilli
- Aspergillus spp / other mold
Post-shunting / intraventricular drains (skin / gut flora):
- Above 3 + Proprionibacterium acne
Disseminated strongyloidiasis:
- Mixed gut flora
Radiotherapy for nasopharyngeal cancer:
- Mixed upper airway flora and aerobic gram -ve bacilli
Normal CSF value
Protein: 0.15-0.45 g/L
Glucose: 2.8-3.9 mmol/L
Cell counts: 0-3 / mm^3
Organism: None
Appearance: Clear
***CSF findings in Bacterial, Viral, Tuberculosis/Fungal meningitis
- Total cell count
Bacterial: 1000-5000
Viral: 50-1000
Tuberculosis/Fungi: 50-500 - Differential WBC count (except for patients with neutropenia / steroid treatment / AIDs / very early stage of meningitis)
Bacterial: predominantly **neutrophils
Viral: predominantly **lymphocytes
Tuberculosis/Fungi: (initial neutrophil), then predominantly ***lymphocytes - Glucose
Bacterial: **Low
Viral: Normal
Tuberculosis/Fungi: **Low - Protein
Bacterial: High
Viral: Slightly high
Tuberculosis/Fungi: Very high - Gram stain
Bacterial: +ve
Viral: -ve
Tuberculosis/Fungi: -ve - Appearance
Bacterial: Turbid
Viral: Clear / slightly turbid
Tuberculosis/Fungi: Clear / slightly turbid
Diagnosis of acute bacterial meningitis
- CT scan to exclude space occupying lesion
- Blood cultures x 2
- If immunosupressed: past history of CNS disease, papilloedema, new onset of seizure, impaired consciousness / focal neurological signs
- Lumbar puncture (must be considered in suspected meningitis)
- CSF: ↑ protein, ↓ glucose, ↑ WBC, ↑ neutrophil
- **Gram smear: 60-90% +ve
- **Culture: 70-85% +ve (unless taken antibiotics prior)
- Antigen: Latex agglutination (for patients with prior antibiotic therapy)
- DNA: PCR for 16s rRNA gene / random high-throughput sequencing
- Blood, skin lesion, sputum culture
Management of acute bacterial meningitis
- Empirical, high dose, **IV antibiotics that cross BBB well
- e.g. **Penicillin G (Vancomycin) and ***Ceftriaxone
- given soon after 2 blood cultures (while waiting for lumbar puncture) - Adjunctive ***dexamethasone
- given just before / with first dose of antibiotic
- ↓ inflammatory complications and associated tissue damage (e.g. sensory neural deafness)
- recommended for children and adults with acute community acquired meningitis - Elevation of bed head by 30o + Anticonvulsants
- ↓ ICP - Chemoprophylaxis
- ***Rifampicin
- for contacts of patients with Neisseria meningitidis and Haemophilus influenzae type B - Active immunisation
- in areas of high attack rate / high risk groups (complement deficient patients / asplenic patients should in addition receive meningococcal vaccine)
- Protein conjugated capsular polysaccharide Haemophilus influenzae type B
- Pneumococcal vaccine
Subacute to chronic meningitis
- Onset of symptoms: >= 1-4 weeks
- Diagnosis often difficult as organisms ***walled off by adhesive and fibrotic basal meningitis (fibrotic granuloma) changes
- Large amount of CSF should be obtained by lumbar puncture (may need to repeat)
- Cisternal / Ventricular tapping indicated in case of intracranial hypertension / hydrocephalus
Common causes:
1. **Mycobacterium tuberculosis
2. **Cryptococcus neoformans
3. Treponema pallidum (Syphilis)
4. Borrelia burgdorferi (Lyme disease)
5. Nocardia (immunocompromised patients)
6. Dimorphic fungi, Candida
7. Acanthoamoeba, Angiostrongylus
8. Brucella
