Neurology JC024: Fever And Confusion: Meningitis And Encephalitis, Suppurative Brain Infection Flashcards
CNS infections
- Meningitis (Meninges)
- Encephalitis (Brain parenchyma)
- Myelitis (Spinal cord)
- Cerebral / Spinal cord abscess (Pus inside)
- Epidural / Subdural empyema (Pus outside)
Causative agents:
- Bacteria
- Virus
- Fungi
- Protozoa
Significance of CNS infections
- 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
Empirical treatment of CNS infections
- High dose parenteral antibiotics
- Cefotaxime (3rd gen)
- ***Ceftriaxone (3rd gen)
- Meropenem
- Penicillin - ***IV Aciclovir
- for Herpesviruses (e.g. VZV) - Oral **Chloramphenicol, **Co-trimoxazole, ***Metronidazole
- good CSF penetration - ***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
Fever + Confusion: Approach
- Consider CNS infections
- Meningitis
- Encephalitis
- Brain abscess
- DDx:
—> Systemic infection with **Toxic / Metabolic encephalopathy
—> **Connective tissue disease with multiple system involvement (including CNS) - History:
- Age
- Onset, Duration of symptoms
- Progression
- Previous treatment (esp. antibiotics)
- Travel
- Systemic infection
- Chronic illness
- Immunisation
- Immunological status - 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 - General P/E
- 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)
Lumbar puncture
- 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
CSF
- 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
CSF analysis
- ***Opening pressure (8-12 cm H2O)
- ***Microscopy (no. of cells)
- ***Protein
- ***Glucose (usually pair with Blood glucose)
- ***Gram smear
- Culture and Sensitivity
- AFB smear, culture
- Fungal smear, culture
- ***Indian ink
- ***Serological tests (Cryptococcal antigen, Viral Ab)
- ***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
***CSF interpretation
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
***Meningitis
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
Bacterial causes of Meningitis in different age group
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
Diagnosis of Meningitis
- Clinical features
- LP + CSF findings
(3. CT / MRI
- ***Normal
- Contrast: ↑ meningeal enhancement)
Clinical features of Meningitis
- Non-specific
- fever
- chills
- malaise
- lethargy
- **N+V
- **photophobia - 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) - CT / MRI
- ***Normal
- Contrast: ↑ meningeal enhancement - Neurological
- Global
—> poor concentration
—> irritability
—> drowsiness
—> confusion
—> coma
—> ***epileptic seizures
- Focal
—> complications
—> ***Sensorineural deafness (Streptococcus suis)
Complications of Meningitis
- Meningeal **adhesion
- **obstructive hydrocephalus
- ↑ ICP
- ***CN palsies - Arteritis / ***Thrombophlebitis
- cerebral infarction - Intellectual impairment, Mental retardation, Cerebral palsy
- in children - ↑ Risk of ***Seizure and Epilepsy
- Local spread of infection
- **cerebritis
- **cerebral abscess
- subdural effusion / empyema - Systemic
- ***SIADH
Treatment of Meningitis
Empirical treatment for Bacterial meningitis
1. **3rd gen Cephalosporin + **Broad spectrum penicillin
- Cefotaxime
- Ceftriaxone
- Benzylpenicillin
- Amoxicillin / Ampicillin
—> all **IV for **7-10 days
- 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)
Tuberculous meningitis
Other forms:
- ***Tuberculoma (conglomerates tubercles into a firm lump)
- Myelopathy
- Radiculopathy
- Arachnoiditis
Complications not uncommon
- ***Cerebral infarction
Treatment
- Prolonged course
Encephalitis
Inflammation of brain parenchyma
Causes:
- mostly ***Viral
- Usually with meningitis (myelitis less common)
Types:
1. ***Acute viral encephalitis
- HSV, VZV, JEV, Enterovirus
- ***Non-viral infectious meningoencephalitis
- Mycoplasma, Legionella, Listeria monocytogenes
- Toxoplasma, Plasmodium -
Post-infective encephalitis (Acute disseminated encephalomyelitis (ADEM)) —> inflammatory demyelinating disorder (immune-mediated)
- Post-viral infection
- Post-vaccination - ***Chronic infective encephalitis
- Prion disease
- Progressive multifocal leukoencephalopathy (Papovavirus / Human polyomavirus 2 / JC virus)
- Subacute sclerosing panencephalitis (Measles)
- Acute viral encephalitis
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
- Non-viral infectious meningoencephalitis
Bacteria:
- **Listeria monocytogenes
- **Legionella
- ***Mycoplasma pneumoniae
- Rickettsia (Typhus, Scrub typhus, Rocky mountain spotted fever)
Parasite:
- **Plasmodium falciparum (Malaria)
- **Toxoplasma gondii
- Trypanosomiasis
- Strongyloides stercoralis
- Post-infective encephalitis
In form of ***Acute disseminated encephalomyelitis (ADEM)
Pathophysiology:
- ***Hypersensitivity reaction to myelin —> Immune-mediated
- Occur after common viral infections:
- Measles, Mumps, Rubella
- ***Chickenpox
- Childhood exanthemata - Following vaccinations:
- Rabies
- **Smallpox
- **Influenza
- Pertussis
- Chronic infective encephalitis
- Slow virus: ***Prion disease (e.g. CJD)
- ***Progressive multifocal leukoencephalopathy (Papovavirus) (now known as Human polyomavirus 2 / JC virus)
- ***Subacute sclerosing panencephalitis (Measles)
Clinical features of Encephalitis
-
**Cerebritis
- **epileptic seizures
- **myoclonus
- chorea / athetosis
- limb weakness
- visual changes
- **memory impairment
- **aphasia
- agnosia
- **confusion
- delirium
- drowsiness
- **stupor
- **coma
- psychiatric manifestations - Features of ***↑ ICP from cerebral edema
- Non-specific systemic symptoms
- fever
- ***viral syndrome
- headache
- nausea
- general malaise
DDx of Encephalitis
- ***Complicated bacterial meningitis + Cerebral edema / Cerebral venous thrombosis
- ***Toxic encephalopathy
- due to Septicaemia / other febrile illnesses / overdose of drug, toxins - ***Metabolic encephalopathy
- due to hypoglycaemia, organ failure, electrolyte imbalance
Diagnosis of Encephalitis
- CT / MRI of brain
- CT usually normal
- ***MRI may reveal abnormalities in grey / white matter (T2: Hyperintense signals, T1: Hypointense signals) - LP + CSF analysis
-
**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
- Urine, faeces, throat swab for viral culture
- Brain biopsy (seldom done now)
Treatment of encephalitis
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)
Herpes simplex encephalitis, Japanese B encephalitis, Nipah virus encephalitis
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
Brain abscess
Source of infection:
1. Local extension of infection
- paranasal sinuses
- middle ear
- mastoids
- orbit
- cavernous sinus
- scalp
- Direct spread from skin
- skull
- meningeal defect - Haematogenous
- spread from distant focus
Clinical features of Brain abscess
- ***↑ ICP
- Non-specific systemic upset due to infection
- ***Focal deficits depending on site of abscess (paralysis, hemiparesis)
- ***Epileptic seizures (up to 30%)
Causative agents of Brain abscess
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)
Diagnosis of Brain abscess
***Avoid LP
- CT brain (Plain + Contrast)
- 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
- Microbiological work-up
- blood culture
- ***aspirated pus for smear, culture - CXR, Echocardiogram, X-ray of paranasal sinus, Skull XR, ENT exam
- look for underlying septic foci - ***EEG
- detect foci epileptic discharges
Treatment of Brain abscess
- 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) - 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 - Close monitoring
- serial CT head - ***Anti-epileptic medications
- prophylaxis
Chemoprophylaxis + Immunoprophylaxis of contacts
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
Immunocompromised hosts
- Asplenism (**Pneumococcal meningitis)
- **post-splenectomy
- ***sickle cell anaemia
- celiac disease - Complement deficiency (**Meningococcal infection)
- **congenital complement deficiency
- active SLE - Neutropenia (**Bacterial, Fungal)
- aplastic anaemia
- **chemotherapy
- extensive irradiation of bone marrow
—> organisms from skin, GI tract, respiratory tract - Humoral immunodeficiency states (**Bacterial, Viral infections)
- **hypogammaglobulinaemia
- **myeloma
- **chronic lymphocytic leukaemia - 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
