Meningitis

by Alja Parežnik

Introduction

Meningitis is an inflammation of the membranes of the brain and spinal cord. It can be related to infectious and noninfectious causes. The infection agent is usually bacteria or virus, and occasionally fungus. Additionally; physical injury, autoimmune disorders, cancer or certain drugs can cause meningitis .

Pathogenesis

Bacteria can breach the blood-brain barrier (BBB) to infect the meninges by direct spread, or contiguous infection (from a source such as the sinuses or middle ear), trauma, neurosurgery, or indwelling medical devices. Nasopharyngeal colonization from infected droplets of respiratory secretions or distant localized infection (lungs, urine) with subsequent bloodstream invasion, are other sources of infection.

Pathogens causing meningitis can be spread in different ways:

  • during birth from mother to her baby,
  • through stool (enteroviruses),
  • through coughing and sneezing,
  • through kissing, sexual contact or contact with infected blood,
  • from eating a specific food (Listeria monocytogenes),
  • from rodents and insects (leptospirosis by mice, hamsters, rats and West Nile virus through mosquito bites).

Etiology

The severity of illness and the treatment differ depending on the cause.

Bacterial meningitis is a life-threatening neurological and infectious emergency. It can lead to death within hours. Bacterial meningitis can lead to long-term problems, like hearing loss, vision loss, problems with memory and concentration, epilepsy, coordination, movement and balance problems, learning difficulties and behavioral problems. In community-acquired meningitis, S. pneumoniae is the most common pathogen since routine immunization of infants with H. influenzae type B began in 1992. Table 1 presents the most common bacteria and their specification. M. tuberculosis, S.aureus, Borrelia burgdorferi and gram negative bacilli are among the rare causes.

Main common bacterial pathogens in meningitis and their specifications

Neisseria meningitidisStreptococcus pneumoniaeHaemophilus influenzeListeria monocytogenes
Age Children, adults (living in crowded spaces)Children, adultsAdults, not vaccinated childrenolder, newborns, pregnant women, immunocompromised
Vaccineyesyesyes
Associated diseasesSore throatEar infection, sinusitis, pneumoniaSinusitis
CharacteristicsPetechial rash, muscle pain and weakness Rash,
Neurological changes (seizures, focal)		Rash
Original by author

 

Viral meningitis is much more common than bacterial. It tends to be less severe and usually recovers completely without specific therapy. Most common viral pathogens causing meningitis are;

  • Enteroviruses (Coxsackie, echoviruses)
  • Arboviruses (KME, West Nile),
  • Herpes viruses (HSV-1,2, VZV, EBV, CMV)
  • Others (mumps, HIV, parvovirus, rotavirus, etc)

Fungal meningitis is rare form and generally occurs only in immunocompromised people.

Case Presentation

A 55-year-old previously healthy woman presented with fever, headache, vomiting, and photophobia for three days. One week earlier, she started to complain about a sore throat and pain in the right ear. Neurological examination revealed diminished consciousness and neck rigidity. Lumbar puncture was performed and in CSF found >10.000 leukocytes/mm3. Direct examination of CSF showed Gram-positive cocci in chains and culture yielded S. pyogenes. The patient had treated with Ceftriaxone (4 gr/day).

Critical Bedside Actions and General Approach

Stabilization of an unstable patient is the priority. Check the airway and breathing (respiratory rate, saturation) and give oxygen if needed. Check circulation (pulse, capillary refill time, urine output, blood pressure) and give fluids or medications if needed. Then, check disability (Glasgow coma scale or AVPU (alert, voice, pain, unresponsive), focal neurological signs, seizures, papilledema, glucose).

Differential Diagnoses

  • Encephalitis,
  • meningitis,
  • septicemia,
  • brain abscess,
  • subdural empyema,
  • subarachnoid bleeding,
  • tetanus,
  • malaria,
  • cancer of meninges,
  • vasculitis of CNS.

History and Physical Examination Hints

The classic triad with fever, neck stiffness and altered mental status is present in only 44% of cases. However, the absence of all of the triad almost eliminates the possibility of meningitis. More than 95% of patients have two out of four criteria: a headache, fever, neck stiffness and altered mental status. Some patients may show dislike of bright lights, rash, sleepy or difficulty to wake, or seizure. Babies may present with refusing to feed, irritable, high pitched or moaning cry, stiff body with jerking movements.

Some people are at the highest risk for developing meningitis. Risky age groups are children under age 5, teenagers from 16-25 years and adults over the age of 55. Certain medical conditions, such as damaged or absent spleen, chronic disease or immune system disorders increase the risk. Traveling to areas where meningitis is common is another risk factor.

Search for meningismus sign using one or more of the following tests. In jolt accentuation test, the patient rotates his head horizontally at a frequency of two to three rotations per second. The test is positive if there is the exacerbation of an existing headache. The absence of jolt accentuation has a specificity of 97% for ruling out meningitis. Kernig’s sign is the inability to straighten the leg when the hip is flexed to 90 degrees. Brudzinski’s sign is positive when forced flexion of the neck elicits a reflex flexion of the hips. Both Kernig and Brudzinski have reported low sensitivity (5%) but high specificity (95%). Most common meningeal symptoms and their sensitivity are presented below.

  • Fever >38 °C: 75-85%
  • Stiff neck: 70-83%
  • Altered mental status: 69%
  • Headache: 87%
  • Vomiting 35%
  • Focal neurological exam: 23-33%
  • Seizures 15-30%
  • Kernig’s sign 9%
  • Brudzinski’ sign 1%
  • Jolt accentuation of headache 100%

Abnormal neurologic exam, photophobia, and lethargy are among the other related signs. Petechial rash, muscle aches, and weakness are characteristic for meningococcal meningitis.

Tests for confirming physical meningeal signs:

A) Kernig’s sign is an failure to straighten the leg when the hip is flexed to 90 degrees because of the stiffness of the hamstrings.

 

B) Brudzinski’s sign is neck stiffness causes a patient’s hips and knees to flex when the neck is flexed.

In sum, ask about typical clinical signs: fever, headache, photophobia, stiff neck, vomiting, and neurological changes. Previous diseases, associated diseases, family history, vaccination, allergy, social status, medications and traveling to other countries are also important. Pay attention to age, immunocompromised state, living in dorms, traveling to states with common meningitis infection, contacts with infected people.

In the physical exam, we look for the meningeal signs with different tests (jolt accentuation of headache, Kerning’s sign, Brudzinski’s sign) and neurological changes (AVPU, GCS).

Emergency Diagnostic Tests and Interpretation

Routine blood work is often obtained but frequently unrevealing. Blood cultures should be drawn in all patients.

The gold standard of confirming meningitis is an analysis of cerebral-spinal fluid (CSF) obtained by lumbar puncture (LP). It should be obtained in all patients with suspected meningitis unless contraindicated. The first results are gram stain and latex agglutination tests. The culture of CSF later confirms the diagnosis. The combination of all three mentioned tests is proved to be more productive than any of the single test alone. Specific findings (white and red blood cell counts, glucose and protein levels) in CSF helps us to differentiate between the types of meningitis.

It is essential to perform LP as soon as possible. In some cases, LP is delayed due to imaging, limited resources, signs of severe sepsis or rapidly evolving rash, severe respiratory or cardiac compromise and significant bleeding risk. It is prudent to give empiric antibiotic therapy first. In pneumococcal meningitis, an approximate window to perform an LP after antibiotic administration is 4-10 hours. In meningococcal infections, it is only 1 hour.

Computer tomography (CT) has to be performed before lumbar puncture (LP) in order to exclude increased intracranial pressure (ICP) or alternate mass lesion when the patient has any of these criteria: immunocompromised state, history of CNS disease, new-onset seizure, papilledema, abnormal level of consciousness (GCS<12) or focal neurologic deficit. CSF analysis is important, table below shows the main charactheristics of CSF in different types of meningitis.

Common CSF findings in different types of meningitis

INDEXNormalBacterialViralFungal
WBC (white blood cells)<5>1000<1000<1000
Differential (neutrophils)<15%>80%<15%<15%
CSF glucose (mg/dL)45-65reducednormalreduces
CSF protein (mg/dL)20-45>25050-250>250
Opening pressure (cmH20)<20Normal to high, typically 15-30Normal to highNormal to high
Gram stain+
PCR+
Quattromani EN, Aldeen AZ. Focus on: emergent evaluation and management of bacterial meningitis. American college of emergency physicians news. 2008 May[updated 2014]. https://www.acep.org/Clinical---Practice-Management/Focus-On--Emergent-Evaluation-and-Management-of-Bacterial-Meningitis/. Accessed April 18, 2016.

 

Emergency Treatment Options

Initial stabilization: Obtain venous access, give oxygen and fluids and resuscitate if necessary.

Medications: Antibiotics are the cornerstone of treatment of bacterial meningitis. Administer empiric antibiotic therapy as soon as possible, before LP.

Empirical antibiotic therapy options;

  • Ceftriaxon/Ceftazidime 4g IV daily immediately (child 100mg/kg up to 4g)
  • + Vancomycin 12,5mg/kg up to 500mg IV 6 hours if S.pneumonie or S.aureus is suspected, recent travel, risk of resistance
  • + Ampicillin 2,4g IV 4hours if immunosuppressed, if Listeria monocytogenes (adults >50years) is suspected (child 60mg/kg to 2,4g)
  • Penicillin/Cephalosporin anaphylaxis: Chloramphenicol 25mg/kg IV

Below list has recommendations for therapy after pathogen identification by positive Gram stain. Multiple studies have shown an association between time of antibiotic administration and poor outcome, is greater above 4-6 hours.

  • S. pneumonie = Ceftriaxon + Vancomycin
  • N. meningitidis = Ceftriaxone
  • Listeria monocytogenes = Ampicillin or penicillin G
  • S. agalacticae = Ampicillin or penicillin G
  • H. influenzae = Cefriaxone

While controversial, adjunctive steroids are recommended in all suspected cases of bacterial meningitis especially with Streptococcus pneumoniae meningitis and should be given before or with the first dose of antibiotic. Give Dexamethasone, 0,15 mg/kg (max. 10 mg) IV every 6 hours for 4 days in adults and 0,4 mg/kg IV every 12 hours for 2 days for children. There is no evidence of mortality benefits but prevention of hearing loss and long-term neurologic squeals.

As we are treating meningitis in the emergency department, it is reasonable to give a dose of dexamethasone with the first round of antibiotics for the agent is unknown.

Primary treatment of viral meningoencephalitis is symptomatic. In meningitis caused by HSV-1 or 2, or severe EBV and VZV Acyclovir is added in therapy. Seriously ill patients should receive Acyclovir IV 15-30 mg/kg per day in 3 divided doses, which can be followed by an oral dose, 800 mg, five times daily for the total course of 7-14 days. Patients who are less ill can be treated with oral drug alone.

Prevention and prophylaxis

Patients hospitalized with suspected N. meningitidis infection or meningitis of uncertain etiology require droplet precautions for the first 24 hours of treatment or until N. meningitidis can be ruled out.

Those who came in close contacts with an infected person, especially with N. meningitidis or H. influenzae, give Rifampin (600mg/12h oral for 2 days; children >1year 10 mg/kg/12h, <1year 5 mg/kg/12h) or Ciprofloxacin (500mg oral, 1 dose 250mg for child 5-12 years). In pregnancy give a single dose of Ceftriaxone 250mg IM or ciprofloxacin 500 mg oral.

Procedures

If there is suspicion of bacterial meningitis, the emergency physician should perform tasks in the following order: blood cultures, steroids, antibiotics, CT and LP

Pediatric, Geriatric and Pregnant Patients

An atypical presentation is common in elderly (>65 years) as lethargy, the absence of fever and minimal signs of meningismus. Older adults and people with additional medical conditions may only present with a slight headache and fever or general weakness.

Neonates, infants and young children usually show poor feeding, irritability, and fever. In babies, a fever, irritability, decreased appetite, rash, vomiting, and a shrill cry may point to meningitis. Other signs include stiff body and bulging soft spots on the head that aren’t caused by crying. Babies with meningitis may cry when handled.

Young children with meningitis may have flu-like symptoms, cough or respiratory distress. In children, history of respiratory tract infection is common, and they are also more likely than adults to experience a seizure. When a child is looking sick and has a fever, has bacterial meningitis until proven otherwise.

Laboratory findings in blood and CSF can be normal in extreme ages.

Disposition Decisions

Admission criteria: If there is clinical suspicion of meningitis, patients should be admitted for further workup and treatment.

ICU Referral: Patients with signs of shock or septicemia must be admitted to Intensive unit care (ICU). These signs include capillary refill time more than 4 seconds, unusual skin colour or rapidly progressive rash, systolic hypotension <90mmHg, pulse rate <40 or >140/min, respiratory rate <8 or >30/min, acidosis pH < 7,3 or base excess more negative than -5, white blood count < 4×109/L, lactate > 4mmol/L, GCS < 12 or a drop of 2 points, moribund state, altered mental state/decreased conscious level, poor urine output, poor response to initial fluid resuscitation.

References and Further Reading

  • Roos KL, Tyler KL. Meningitis, encephalitis, brain abscess, and empyema. In: Longo DL et al. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 2012; 18, vol.2: 3410-3434.
  • Tunkel AR, Van de Beek D, Scheld WM. Acute meningitis. In: Bennett JE, Dolin R, Blaser MJ, et al. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Philadelphia: Elsevier Churchill Livingstone; 2015; 8: chap 89
  • Quattromani EN, Aldeen AZ. Focus on: emergent evaluation and management of bacterial meningitis. American college of emergency physicians news. 2008 May[updated 2014]. https://www.acep.org/Clinical—Practice-Management/Focus-On–Emergent-Evaluation-and-Management-of-Bacterial-Meningitis/. Accessed April 18, 2016.
  • Bamberger DM.Diagnosis, initial management and prevention of meningitis. Am Fam Physician. 2010 Dec 15; 82(12):1492-1498. http://www.aafp.org/afp/2010/1215/p1491.html. Accessed April 25, 2016.
  • http://meningococcal-septicaemia.com/wp-content/uploads/2013/12/meningitissymptoms.png
  • http://images.slideplayer.com/19/5881836/slides/slide_35.jpg
  • Swartz MN, Nath A. Meningitis: bacterial, viral, and other. In: Goldman L, Schafer AI, et al. Goldman’s Cecil Medicine. Philadelphia: Elsevier Saunders; 2012; 24: chap 420.
  • Newman D. Clinical assessment of meningitis in adults. Ann Emerg Med. 2004;44:71-3.
  • Van de Beek L, De Gans J, Spanjaard L et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004 Oct 28;351(18):1849-59.
  • Mohammadi SF, Patil AB, Nadagir SD, et al. Diagnostic value of latex agglutination test in diagnosis of acute bacterial meningitis. An Indian Acad Neurol. 2013 Oct-Dec; 16(4):645-649. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841619/. Accessed April 25, 2016.
  • Clark T, Duffell E, Stuart J et al. Lumbar puncture in the management of adults with suspected bacterial meningitis: a survey of practice. J Infection. 2006; 52: 315-19.
  • Hasbun R, Abrahams J et al. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. NEJM. 2001; 345: 1727-1733.
  • Therapeutic Guidelines Ltd. Therapeutic Guidelines. Antibiotic; Version 13, 2006.
  • Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2013; 6:CD004405.
  • Chauduri A, Martin PM, Kennedy PGE, et al. EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on Acute Bacterial Meningitis in Older Children and Adults. European J Neurol. 2008;15:649-659.
  • Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1267-84.
  • Verani JR, et al. Prevention of perinatal group B streptococcal disease: Revised guidelines from CDC, 2010. MMWR, 59(RR-10): 1-36. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm?s_cid=rr5910a1_w. Accessed April 19, 2016.

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