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JC WCS > Neurology JC024: Fever And Confusion: Meningitis And Encephalitis, Suppurative Brain Infection > Flashcards

Neurology JC024: Fever And Confusion: Meningitis And Encephalitis, Suppurative Brain Infection Flashcards

1
Q

CNS infections

A
  1. Meningitis (Meninges)
  2. Encephalitis (Brain parenchyma)
  3. Myelitis (Spinal cord)
  4. Cerebral / Spinal cord abscess (Pus inside)
  5. Epidural / Subdural empyema (Pus outside)

Causative agents:
- Bacteria
- Virus
- Fungi
- Protozoa

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2
Q

Significance of CNS infections

A
  • Very common + important
  • High mortality + morbidity
  • Consider diagnosis + Start (empirical) treatment ASAP
  • ***Lumbar puncture if without CI
  • Quick septic workup
    —> blood culture before starting antimicrobial
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3
Q

Empirical treatment of CNS infections

A
  1. High dose parenteral antibiotics
    - Cefotaxime (3rd gen)
    - ***Ceftriaxone (3rd gen)
    - Meropenem
    - Penicillin
  2. ***IV Aciclovir
    - for Herpesviruses (e.g. VZV)
  3. Oral **Chloramphenicol, **Co-trimoxazole, ***Metronidazole
    - good CSF penetration
  4. ***Corticosteroid
    - controversial
    - useful in childhood meningitis / severe inflammation
  • Close liaison with clinical microbiologist, neurologist, neurosurgeon, paediatrician
  • Search for primary focus (of infection)
  • Regular monitoring (of clinical response)
  • Intrathecal seldom required now
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4
Q

Fever + Confusion: Approach

A
  1. Consider CNS infections
    - Meningitis
    - Encephalitis
    - Brain abscess
    - DDx:
    —> Systemic infection with **Toxic / Metabolic encephalopathy
    —> **    Connective tissue disease with multiple system involvement (including CNS)
  2. History:
    - Age
    - Onset, Duration of symptoms
    - Progression
    - Previous treatment (esp. antibiotics)
    - Travel
    - Systemic infection
    - Chronic illness
    - Immunisation
    - Immunological status
  3. S/S
    - **Fever
    - **    Higher mental functions (Encephalopathic signs: Altered consciousness, Epilepsy)
    - **Focal neurological signs (Paralysis, Hemiparesis)
    - **    ↑ ICP (Headache, Vomiting)
    - Neck stiffness
    - **Kernig’s sign
    - **    Brudzinski’s sign
    - CN palsy (Fibrotic entrapment of CN)
    - Septic thrombosis —> Infarct
  4. General P/E
  5. Investigations
    - Septic workup
    - CXR
    - **CBC with DC
    - **    ESR
    - PT, aPTT
    - **CRP
    - RG / FG (random glucose / fasting glucose)
    - LRFT
    - Blood gases
    - Toxicology screen
    - **    CT / MRI brain before LP
    - **Lumbar puncture —> CSF analysis
    - **    EEG (for suspected seizures)
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5
Q

Lumbar puncture

A
  • Left lateral position
  • Fetal position
  • Needle inserted at ***L4/5
  • Tip at ***Subarachnoid space

Can be Therapeutic:
- Analgesia
- CSF removal
- Chemotherapy (methotrexate, cytarabine, hydrocortisone)
- Baclofen (intrathecal)
- Contrast injection

Contraindications:
- Unequal pressures between Supra / Infratentorial compartments on CT (大腦小腦分界) —> ∵ may cause **Uncal herniation
- **Coagulopathies
- Local suppuration
- Local congenital lesions
- Spinal block
- ***Markedly raised ICP

Complications:
- **Headache
- **Brain herniation
- Dry tap
- ***Subdural haematoma
- Rupture of aneurysm —> SAH

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6
Q

CSF

A
  • produced at Choroid plexus + Ventricular lining
  • Production (***Pressure independent): 500 ml / day
  • Circulation: ***350 ml (Ventricular volume 150 ml)
  • Absorption (***Pressure dependent): across arachnoid villi by valve-like mechanism

Functions:
1. **Mechanical support
2. Protective water jacket
3. Regulating ionic composition
4. **Immunological isolation
5. ***Removal of metabolites
6. Protection from sudden pressure changes

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7
Q

CSF analysis

A
  1. ***Opening pressure (8-12 cm H2O)
  2. ***Microscopy (no. of cells)
  3. ***Protein
  4. ***Glucose (usually pair with Blood glucose)
  5. ***Gram smear
  6. Culture and Sensitivity
  7. AFB smear, culture
  8. Fungal smear, culture
  9. ***Indian ink
  10. ***Serological tests (Cryptococcal antigen, Viral Ab)
  11. ***PCR (HSV DNA, TB DNA)

Can be Diagnostic in:
- CNS infection
- Subarachnoid haemorrhage (SAH)
- Inflammatory disorders of CNS
- Demyelination
- Malignant disease of CNS
- CSF / Intracranial pressure

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8
Q

***CSF interpretation

A

Normal:
- Clear, Colourless, Odourless
- Opening pressure 8-12 cm H2O (Abnormal: <6, >20)
- Fluctuations with respiration
- WBC: 0-3 / uL
- Total protein: 0.15-0.45 g/L
- RBC: None
- Albumin: 0.08-0.25 g/L
- Glucose: 2.5-4 mmol/L (>=50% of Blood glucose)
- IgG: <15% of total CSF protein

Neutrophilic meningitis (Bacterial meningitis, Early TB meningitis, Early Mycotic meningitis)
- Turbid
- ↑ Opening pressure
- Marked pleocytosis (500-20,000 / mm^3) —> **Neutrophils predominant
- **↑ Protein (>0.45)
- **↓ Glucose (<50% of blood glucose)
- **Positive gram smear

Lymphocytic meningitis (**TB meningitis, **Fungal meningitis, Partially treated Pyogenic meningitis, **Malignant meningitis (Lymphoma, Leukaemia, Carcinomatosis))
- Clear / Slightly turbid
- ↑ ICP
- **Mild-Marked pleocytosis (10-500) —> **Lymphocyte predominant / Mixed
- **↑ Protein
- ***↓ Glucose
- Negative gram smear

Viral meningoencephalitis
- Aseptic / **Lymphocytic meningitis with **Normal glucose, ***Normal / ↑ Protein

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9
Q

***Meningitis

A

Inflammation of Leptomeninges

Causes:
- **Infection (bacterial, viral, fungal, protozoal)
- **Neoplastic infiltration
- Drugs irritation
- Contrast medium, blood irritation

Meningism: Symptoms of Meningeal irritation ***without actual inflammation

Source of infection:
- Local spread from nearby structures (sinuses, middle ear, mastoid, orbit, nasopharynx)
- Direct spread from skin via skull / meningeal defect (following head injury, neurosurgery)
- Haematogenous spread from distant foci (lung abscess, pneumonia, infective endocarditis, septicaemia, bacteraemia)

Common bacteria:
- **Neisseria meningitidis
- **Streptococcus pneumoniae
- **Streptococcus suis (occupational risk in butcher, handler of raw pork)
- **Mycobacterium TB
- **Haemophilus influenzae (type B)
- Less common: **Group B Streptococcus, E. coli, Staph aureus, Listeria monocytogenes

Common viruses:
- **Coxsackievirus A, B
- Poliovirus
- **Echoviruses
- ***Enteroviruses type 68-72 (faecal-oral route, young children, warm climates, poor hygiene)
- Less common viruses: Mumps, EBV, Lymphochorionic virus, Measles, Influenza, Herpes

Fungal:
- Cryptococcus (uncommon)

Protozoal organisms:
- Rare

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10
Q

Bacterial causes of Meningitis in different age group

A

Neonates:
Gram -ve organisms (∵ present in birth canal, pick up during childbirth)
- **E. coli
- **Group B Streptococcus
- ***Listeria monocytogenes

Infants:
- **Haemophilus influenzae
- Meningococcus (i.e. **Neisseria meningitidis)
- Pneumococcus (i.e. ***Streptococcus pneumoniae)
- Salmonella

Children, Young adults:
- **Meningococcus
—> **Petechial haemorrhages in skin
—> **DIC
—> **Septic shock
—> Adrenal haemorrhage
- ***Pneumococcus

Older adults:
- Pneumococcus

Elderly:
- Pneumococcus
- Gram -ve organisms
- Listeria monocytogenes

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11
Q

Diagnosis of Meningitis

A
  1. Clinical features
  2. LP + CSF findings

(3. CT / MRI
- ***Normal
- Contrast: ↑ meningeal enhancement)

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12
Q

Clinical features of Meningitis

A
  1. Non-specific
    - fever
    - chills
    - malaise
    - lethargy
    - **N+V
    - **    photophobia
  2. Meningeal irritation
    - neck rigidity (spasm of neck extensors)
    - **Kernig’s sign (spasm of leg hamstrings)
    - **    Brudzinski’s sign (involuntary hip / knee flexion upon neck flexion)
    - Bulging anterior fontanelle in infants (infants usually no neck stiffness)
  3. CT / MRI
    - ***Normal
    - Contrast: ↑ meningeal enhancement
  4. Neurological
    - Global
    —> poor concentration
    —> irritability
    —> drowsiness
    —> confusion
    —> coma
    —> ***epileptic seizures
  • Focal
    —> complications
    —> ***Sensorineural deafness (Streptococcus suis)
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13
Q

Complications of Meningitis

A
  1. Meningeal **adhesion
    - **    obstructive hydrocephalus
    - ↑ ICP
    - ***CN palsies
  2. Arteritis / ***Thrombophlebitis
    - cerebral infarction
  3. Intellectual impairment, Mental retardation, Cerebral palsy
    - in children
  4. ↑ Risk of ***Seizure and Epilepsy
  5. Local spread of infection
    - **cerebritis
    - **    cerebral abscess
    - subdural effusion / empyema
  6. Systemic
    - ***SIADH
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14
Q

Treatment of Meningitis

A

Empirical treatment for Bacterial meningitis
1. **3rd gen Cephalosporin + **Broad spectrum penicillin
- Cefotaxime
- Ceftriaxone
- Benzylpenicillin
- Amoxicillin / Ampicillin
—> all **IV for **7-10 days

  1. Vancomycin
    - controversial as 1st line
  • Modify regimen if needed when organism / sensitivity known
  • Response to treatment expected within a few days (***24-48 hours)

Neurosurgery for hydrocephalus:
- temporally CSF diversion
- obtain CSF for diagnosis
- permanent CSF diversion (Ventricular-peritoneal shunting)

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15
Q

Tuberculous meningitis

A

Other forms:
- ***Tuberculoma (conglomerates tubercles into a firm lump)
- Myelopathy
- Radiculopathy
- Arachnoiditis

Complications not uncommon
- ***Cerebral infarction

Treatment
- Prolonged course

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16
Q

Encephalitis

A

Inflammation of brain parenchyma

Causes:
- mostly ***Viral
- Usually with meningitis (myelitis less common)

Types:
1. ***Acute viral encephalitis
- HSV, VZV, JEV, Enterovirus

  1. ***Non-viral infectious meningoencephalitis
    - Mycoplasma, Legionella, Listeria monocytogenes
    - Toxoplasma, Plasmodium
  2. Post-infective encephalitis (Acute disseminated encephalomyelitis (ADEM)) —> inflammatory demyelinating disorder (immune-mediated)
    - Post-viral infection
    - Post-vaccination
  3. ***Chronic infective encephalitis
    - Prion disease
    - Progressive multifocal leukoencephalopathy (Papovavirus / Human polyomavirus 2 / JC virus)
    - Subacute sclerosing panencephalitis (Measles)
17
Q
  1. Acute viral encephalitis
A

Epidemic:
- ***Japanese B encephalitis
- Dengue fever
- Influenza

Sporadic:
- **HSV type 1
- **Enterovirus (Coxsackie virus, ECHO virus, Poliovirus)
- ***Herpesviruses (Cytomegalovirus, VZV, EBV)
- Mumps, Measles, Rubella
- Adenovirus
- Lymphochorionic virus
- Rabies virus
- HIV

18
Q
  1. Non-viral infectious meningoencephalitis
A

Bacteria:
- **Listeria monocytogenes
- **Legionella
- ***Mycoplasma pneumoniae
- Rickettsia (Typhus, Scrub typhus, Rocky mountain spotted fever)

Parasite:
- **Plasmodium falciparum (Malaria)
- **Toxoplasma gondii
- Trypanosomiasis
- Strongyloides stercoralis

19
Q
  1. Post-infective encephalitis
A

In form of ***Acute disseminated encephalomyelitis (ADEM)

Pathophysiology:
- ***Hypersensitivity reaction to myelin —> Immune-mediated

  1. Occur after common viral infections:
    - Measles, Mumps, Rubella
    - ***Chickenpox
    - Childhood exanthemata
  2. Following vaccinations:
    - Rabies
    - **Smallpox
    - **    Influenza
    - Pertussis
20
Q
  1. Chronic infective encephalitis
A
  • Slow virus: ***Prion disease (e.g. CJD)
  • ***Progressive multifocal leukoencephalopathy (Papovavirus) (now known as Human polyomavirus 2 / JC virus)
  • ***Subacute sclerosing panencephalitis (Measles)
21
Q

Clinical features of Encephalitis

A
  1. **Cerebritis
    - **    epileptic seizures
    - **myoclonus
    - chorea / athetosis
    - limb weakness
    - visual changes
    - **    memory impairment
    - **aphasia
    - agnosia
    - **    confusion
    - delirium
    - drowsiness
    - **stupor
    - **    coma
    - psychiatric manifestations
  2. Features of ***↑ ICP from cerebral edema
  3. Non-specific systemic symptoms
    - fever
    - ***viral syndrome
    - headache
    - nausea
    - general malaise
22
Q

DDx of Encephalitis

A
  1. ***Complicated bacterial meningitis + Cerebral edema / Cerebral venous thrombosis
  2. ***Toxic encephalopathy
    - due to Septicaemia / other febrile illnesses / overdose of drug, toxins
  3. ***Metabolic encephalopathy
    - due to hypoglycaemia, organ failure, electrolyte imbalance
23
Q

Diagnosis of Encephalitis

A
  1. CT / MRI of brain
    - CT usually normal
    - ***MRI may reveal abnormalities in grey / white matter (T2: Hyperintense signals, T1: Hypointense signals)
  2. LP + CSF analysis
  3. **EEG
    - **    diffuse slow waves + spike activities
    - but may be focal in Herpes encephalitis (e.g. periodic lateralising epileptiform discharges from one / both temporal lobes)

Others
4. Paired sera
- for viral titres

  1. Urine, faeces, throat swab for viral culture
  2. Brain biopsy (seldom done now)
24
Q

Treatment of encephalitis

A

Empirical treatment:
- **IV Aciclovir (effective for Herpesviruses only)
- 10 mg/kg
- Q8H
- **10-14 days
- Dose adjusted according to RFT

(May need Ceftriaxone to cover most bacteria, Ampicillin to cover ***Listeria monocytogenes)

25
Q

Herpes simplex encephalitis, Japanese B encephalitis, Nipah virus encephalitis

A

Herpes simplex encephalitis:
- HSV1
- **Predilection for **Temporal, Frontal lobes

Japanese B encephalitis:
- Mosquito-borne **flavivirus related to **St. Louis encephalitis virus
- **Subclinical infection common
- Endemic in Asia
- Vaccine available
- Mosquito control
- **Supportive treatment mainly

Nipah virus encephalitis:
- Paramyxovirus
- Outbreak amongst **pig farm and abattoir workers in **Malaysia
- Atypical pneumonia
- Serology for IgM Ab
- Multiple, discrete deep cortical / white matter lesions on MRI
- IV Ribavirin
- High mortality and disability

26
Q

Brain abscess

A

Source of infection:
1. Local extension of infection
- paranasal sinuses
- middle ear
- mastoids
- orbit
- cavernous sinus
- scalp

  1. Direct spread from skin
    - skull
    - meningeal defect
  2. Haematogenous
    - spread from distant focus
27
Q

Clinical features of Brain abscess

A
  1. ***↑ ICP
  2. Non-specific systemic upset due to infection
  3. ***Focal deficits depending on site of abscess (paralysis, hemiparesis)
  4. ***Epileptic seizures (up to 30%)
28
Q

Causative agents of Brain abscess

A

Usually ***mixed aerobic + anaerobic organisms (Polymicrobial)

Aerobic, Microaerophilic bacteria:
- Streptococcus milleri
- **Pneumococcus
- **Staphylococcus aureus
- ***Enterobacteriaecae
- Pseudomonas

Anaerobic bacteria:
- **Bacteroides (GI)
- **Fusobacterium (Oral)
- Peptostreptococcus
- Actinomyces
- ***Nocardia

Rare:
- Cryptococcus, Aspergillus, Amoeba, Toxoplasma, Angiostronglyloides cantonesis, Tenia solium (cysticercosis), Echinococcus (hydatid cyst)

29
Q

Diagnosis of Brain abscess

A

***Avoid LP

  1. CT brain (Plain + Contrast)
  2. MRI brain
    T2W
    - **Peri-lesional hypodense area —> **Edema
    - ***↑ H2O content inside abscess (appear hyperintense)

T1W + contrast
- **Hyperintense abscess wall (outlying uniform ring enhancement (bright))
- **Hypodense (dark) centre —> leukocyte and necrotic debris

  1. Microbiological work-up
    - blood culture
    - ***aspirated pus for smear, culture
  2. CXR, Echocardiogram, X-ray of paranasal sinus, Skull XR, ENT exam
    - look for underlying septic foci
  3. ***EEG
    - detect foci epileptic discharges
30
Q

Treatment of Brain abscess

A
  1. Empirical treatment:
    **Benzylpenicillin + **3rd gen Cephalosporin (Cefotaxime / Ceftriaxone) + Metronidazole
    - all IV
    - >=    6 weeks
    - clinical + radiological monitoring
    - need high dose ***Cloxacillin / Fusidic acid to cover Staphylococcus aureus (in abscesses complicating skull injury / neurosurgery)
  2. Neurosurgery
    - usually not required for small + multiple abscesses
    - ***drainage in abscess / empyema
    —> establish Diagnosis + Bacteriology
    —> ↓ mass effect
    - Stereotactic guided aspiration
    - USG guided aspiration
    - Craniotomy + Excision of abscess cavity
  3. Close monitoring
    - serial CT head
  4. ***Anti-epileptic medications
    - prophylaxis
31
Q

Chemoprophylaxis + Immunoprophylaxis of contacts

A

Meningococcal Meningitis
1. **Rifampicin 4 days (or Ceftriaxone IM once)
2. **Meningococcal vaccine

Haemophilus influenzae type B meningitis
1. **Rifampicin 4 days (or Ceftriaxone IM 2 days)
2. **Hib vaccine

32
Q

Immunocompromised hosts

A
  1. Asplenism (**Pneumococcal meningitis)
    - **    post-splenectomy
    - ***sickle cell anaemia
    - celiac disease
  2. Complement deficiency (**Meningococcal infection)
    - **    congenital complement deficiency
    - active SLE
  3. Neutropenia (**Bacterial, Fungal)
    - aplastic anaemia
    - **    chemotherapy
    - extensive irradiation of bone marrow
    —> organisms from skin, GI tract, respiratory tract
  4. Humoral immunodeficiency states (**Bacterial, Viral infections)
    - **    hypogammaglobulinaemia
    - **myeloma
    - **    chronic lymphocytic leukaemia
  5. Cell-mediated immunodeficiency (**Virus, Fungus, Parasite, Mycobacteria, Listeria infections, Reactivation of latent infections)
    - **    HIV AIDS
    - **lymphoproliferative disorders (e.g. Hodgkin’s disease)
    - **    Immunosuppression for various autoimmune diseases / ***Organ transplant

Consideration:
- New / **Reactivation of latent infection
- **Haematogenous spread usual
- ***Unusual infection / Unusual presentation of common infections
- Fever, headache, +/- meningism, altered mental state, focal neurological sign, meningism may be absent

Treatment:
- Empirical treatment of likely organisms in adequate dose

JC WCS (134 decks)

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