Meningitis

Definitions
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges.

Epidemiology

Viral	Peaks in late summer to early fall: Enteroviruses and arthropod-borne viruses predominate in warm months. Mumps usually occurs in the winter and spring, often in epidemics. More common than bacterial meningitis Occurs in both outbreak and sporadic form
Bacterial	Predominant age: Neonates, infants, and elderly Male = Female 3–10/100,000 population

Aetiology

Viral	Enteroviruses, herpes simplex virus type 2 (and less commonly type 1), varicella zoster virus (known for causing chickenpox and shingles), mumps virus, HIV, and LCMV
Bacterial	Vary by age Risk and/or Predisposing Factor Bacterial Pathogen Age 0-4 weeks S agalactiae (group B streptococci) E coli K1 L monocytogenes Age 4-12 weeks S agalactiae E coli H influenzae S pneumoniae N meningitidis Age 3 months to 18 years N meningitidis S pneumoniae H influenzae Age 18-50 years S pneumoniae N meningitidis H influenzae Age older than 50 years S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
Aseptic	No evidence of bacterial infection. Usually due to viruses, but may be due partially treated to bacterial infection
Parasitic	Angiostrongylus cantonensis and Gnathostoma spinigerum.Tuberculosis, syphilis, cryptococcosis,
Non-infectious	Spread of cancer to the meninges (malignant meningitis) Certain drugs (mainly non-steroidal anti-inflammatory drugs,antibiotics and intravenous immunoglobulins). sarcoidosis(which is then called neurosarcoidosis), connective tissue disorders such as SLE vasculitis - Behçet's disease. Epidermoid cysts and dermoid cysts migraine (very rare) *Mollaret's meningitis is a syndrome of recurring episodes of aseptic meningitis; it is now thought to be caused byherpes simplex virus type 2.

Pathophysiology
Infection causes inflammation of the pia-arachnoid and its fluid and the fluid of the ventricles.
Bacteria can reach the meninges via bloodstream or direct contact/nasal cavity/skin.
Immune cells (astrocytes and microglia) response  by releasing cytokines
The BBB becomes more permeable leading to vasogenic cerebral oedema
WBC enter the CSF causing onflammation leading to interstitial oedema
Blood vessels wall also become inflamed causing cytotoxic oedema.
The three forms of oedema cause raised ICP
It is harder for blood to enter the brain causing apoptosis of brain cells

Presentation

Early signs	Headache, leg pains, cold hands and feet, abnormal skin colour
Later signs	Meningism: neck stiffness, photophobia Kernig’s sign (pain+resistance on passive knee extension with hip fully flexed) Brudzinski’s sign: an involuntary flexion of the hip and knee when the neck is passively flexed Conscious level↓, coma Seizures (~20%) + focal CNS signs (~20%) Petechial rash (non-blanching; may only be 1 or 2 spots, or none) Signs of galloping sepsis; slow capillary refill; DIC; BP ↓. To and pulse: ↑ or normal
Other symptoms in babies	tense or bulging fontanelle (soft spot); blotchy skin, getting paler or turning blue; refusing to feed; be irritable when picked up, with a high pitched or moaning cry; a stiff body with jerky movements or else floppy and lifeless. Tumble test- If a glass tumbler is pressed firmly against a septicaemic rash, the rash will not fade. It will remain visible through the glass.
Symptoms of septicaemia	(This form of the illness often starts with non-specific flu-like symptoms): Rash; fever/vomiting; cold hands and feet/shivering; limb/joint/muscle pain; abdominal pain (sometimes with diarrhoea); ↓ capillary refill time, pale or mottled skin; rapid or unusual breathing, drowsy and less responsive/vacant.

Ddx
Malaria
encephalitis
septicaemia
subarachnoid bleed
dengue
tetanus

Investigation

Brain CT	Perform CT if lumbar puncture is contraindicated (in Pt with risk of herniation): newly onset seizure impaired consciousness (GSC <9) focal signs papillodema trauma middle ear pathology major coagulopathy sign of space-occupying lesions immunocompromised If CT is required or LP proves difficult - start treatment first
Lumbar Puncture	Measure the opening pressure and send the fluid for cell count (and differential count), chemistry (ie, CSF glucose and protein), and microbiology (ie, Gram stain and cultures) CSF Viral/aseptic Pyogenic Tuberculous Cryptococcal opening pressure (mm CSF) Normal (90-200) 200-300 180-300 180-300 Appearance Normal-Clear Turbid Fibrin web Predominant cell lymphocytes Polymorph lymphocytes lymphocytes WBC count per µL 10-300 100-5000 100-500 10-200 Glucose (mg/dL) Normal (50-75) ↓(<40) ↓(<40) ↓(<40) Protein (mg/L) Normal (15-40) ↑(>100) ↑(>100) 50-200 Microbiology Viral isolation, PCR Bacteria in smear &culture Acid-fast bacilulus stain, culture, PCR India ink, cryptococcal antigen, culture
Lab	U&E, FBC, LFT, glucose, coagulation screen.
CXR	may reveal silent area of pneumonitis or abscess.
Sinus/skull radiographs	may reveal cranial osteomyelitis, paranasal sinusitis, or skull fracture but rarely indicated.

Management

Pre-hospital	IV/IM Benzylpenicilin 1.2g immediately
On admission	ABC, high flow O2, IVI + fluid resus, ask a nurse to draw up cefotaxime 2g Do septicaemia or meningitic features predominate?
If septicaemia predominates	Do not attempt LP. Give antibiotic (eg. cefotaxime 2g iv) Get help from critical team
If meningitis predominates	Dexamethaxone 4-10mg/6h iv Do LP if no  ↑ ICP or shock. Antibiotic post LP (eg. cefotaxime 2g iv) or pre-LP if >1/2h delay
Empiric Antibiotic of choice:	Predisposing Feature Antibiotic(s) Age 0-4 weeks Ampicillin plus cefotaxime or an aminoglycoside Age 1-3 months Ampicillin plus cefotaxime plus vancomycin* Age 3 months to 50 years Ceftriaxone or cefotaxime plus vancomycin* Older than 50 years Ampicillin plus ceftriaxone or cefotaxime plus vancomycin* Impaired cellular immunity Ampicillin plus ceftazidime plus vancomycin* Neurosurgery, head trauma, or CSF shunt Vancomycin plus ceftazidime
Then, if shock	Take to ICU fluid bolus of 20 ml/kg sodium chloride 0.9% over 5–10 minutes. If persist give second bolus or human albumin 4.5% solution, If persist give third bolus pre-emptive intubation (call anaesthetist) Inotropes/vassopressor Activated protein C2 Aim for systoloc BP >80 and urine flow >30mL/h
Monitor	Monitor for changes in the patient's consciousness and the development of new neurologic signs, subtle seizures, and to treat severe agitation effectively. Respiratory isolation for 24 hours. Cefotaxime 2-4g/8h iv (eg for 10d), ↓ dose in renal failure. Maintain fluid.
Follow up	Deafness assessment for cochlear implants reviewed by a paediatrician with the results of their hearing test 4–6 weeks after discharge Review orthopaedic complications (damage to bones and joints) skin complications (including scarring from necrosis) psychosocial problems neurological and developmental problems renal failure Vaccination HIB, S pneumoniae, N menigitidis Prophylaxis to household contact: Rifampicin (600mg/12h PO for 2d, Children >1y 10mg/kg/12h, <1y 5mg/kg/12h), or ciprofloxacin (500mg PO, 1 dose child 5-12y:250mg stat)

Complications
Neurologic compilication in 30% of survivors following an episode of bacterial meningitis. Closely monitor for the development of these complications.

• Cranial nerve palsies and the effects of impaired cerebral blood flow, such as cerebral infarction, are caused by increased ICP.
• Other early complications include the development of venous sinus thrombosis, obstruction of CSF flow, or the formation of subdural empyema and brain abscess.

The long-term neurologic sequelae can be grouped into 3 categories as follows:

• Hearing impairment
• Obstructive hydrocephalus
• Brain parenchymal damage: This is the most important feared complication of bacterial meningitis. It could lead to sensory and motor deficits, cerebral palsy, learning disabilities, mental retardation, cortical blindness, and seizures.

Prognosis
Patients with viral meningitis usually have a good prognosis.
worse for patients at the extremes of age (ie, <2 y, >60 y) and those with significant comorbidities and underlying immunodeficiency.
A seizure during an episode of meningitis also is a risk factor for mortality or neurologic sequelae.
The presence of low-level pleocytosis (<20 cells) in patients with bacterial meningitis suggests a poorer outcome.
Meningitis caused by S pneumoniae, L monocytogenes, and gram-negative bacilli has a higher case-fatality rate compared to meningitis caused by other bacterial agents.
The prognosis of meningitis caused by opportunistic pathogens also depends on the underlying immune function of the host. Many of the survivors require lifelong suppressive therapy (eg, long-term fluconazole for suppression in patients with HIV-associated cryptococcal meningitis).