You have a new patient!
A 21-year-old male presented to a clinic. He is a refugee and has been here with a high-grade fever and a severe headache for the past three days. The patient had been working as a laborer in construction sites in the area for the past six months. At triage, his vital signs are as follows: temperature of 39.1°C (102.5°F), blood pressure of 110/70 mmHg, heart rate of 110 beats per minute, and respiratory rate of 22 breaths per minute.
Further examination reveals that the patient is quite photophobic. You note that he prefers to sit still, and when you examine him further, you feel that his neck is quite uncomfortable when flexed, and there is discomfort with flexed hips and passive knee extension. The patient was accompanied by a co-worker who reported that this morning, the patient was vomiting and had been confused. The patient had no history of recent travel or vaccination.
What do you need to know?
Importance
Meningitis is an important infectious disease with severe consequences if not promptly recognized and treated. Meningitis is caused by inflammation of the meninges, the membranes covering the brain and spinal cord. It can be caused by a bacterial, viral, fungal, or parasitic infection. Moreover, meningitis can be triggered by physical injury, autoimmune disorders, cancer, or certain drugs that can cause meningitis. Generally, when discussing meningitis, we are primarily concerned with infectious etiologies. In addition to the high mortality associated with meningitis, survivors may suffer from long-term sequelae, such as hearing loss, cognitive impairment, and neurologic deficits [1]. Infants, children, and immunocompromised patients are at a higher risk of developing meningitis, and outbreaks can occur in crowded living conditions, with classic examples including crowded urban areas (including slums), university dormitories, and military barracks [2]. Prompt recognition and treatment with appropriate antibiotics or antivirals are critical for improving outcomes in patients with meningitis [3].
Epidemiology
Meningitis is a significant global health problem, particularly in low- and middle-income countries. According to the World Health Organization (WHO), there are an estimated 1.2 million cases of bacterial meningitis each year, resulting in 250,000 deaths [4]. According to the Global Burden of Disease study, meningitis is responsible for an estimated 21.9 million disability-adjusted life years (DALYs) globally [5]. The burden of meningitis is particularly high in sub-Saharan Africa, where large-scale epidemics of meningococcal meningitis occur. In these regions, outbreaks are often associated with overcrowding, malnutrition, and poor sanitation, and can cause high rates of mortality and long-term disability. While vaccination has helped to reduce the burden of meningitis in many parts of the world, there is still a need for continued surveillance and control measures, particularly in high-risk populations.
Pathophysiology
Bacteria (and viruses and chemicals) can cross the blood-brain barrier to infect or inflame the meninges by spreading from the bloodstream. Pathogens can also spread from contiguous infection (from a source such as the sinuses or middle ear), trauma, neurosurgery, or indwelling medical devices [6]. Nasopharyngeal colonization from infected droplets of respiratory secretions or distant localized infection (lungs, urine) with subsequent bloodstream invasion are other sources of infection [6].
Once the pathogen reaches the meninges, it triggers an immune response, releasing pro-inflammatory cytokines, which attract immune cells to the site of infection. This immune response leads to the characteristic symptoms of meningitis, including fever, headache, neck stiffness, and altered mental status. In severe cases, the inflammation can lead to increased intracranial pressure, cerebral edema, and brain herniation, which is life-threatening and frequently fatal [6].
Bacterial meningitis poses an emergent risk to the neurological system; progression can result in rapid fatality. Furthermore, bacterial meningitis has the potential to cause long-term complications, including hearing and vision impairment, memory and concentration issues, epilepsy, coordination and balance difficulties, learning challenges, and behavioral disorders [6]. In community-acquired meningitis, S. pneumoniae has become the most common pathogen since routine immunization of infants against H. influenzae type B [7]. It’s important to note that the most common causes of meningitis can vary depending on the patient’s age, geography, and immune status [8]. Table 1 summarizes most common pathogens of meningitis.
Table 1: Common Infectious Causes of Meningitis [7-14].
Pathogen | Common Etiologies |
Bacteria | Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, Listeria monocytogenes |
Viruses | Enteroviruses (e.g. Coxsackie virus, Echovirus), Herpes simplex virus, Varicella-zoster virus, Mumps virus |
Fungi | Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis |
Parasites | Naegleria fowleri, Acanthamoeba species |
Medical History
Key features in the medical history of meningitis include the onset and duration of symptoms, recent travel or exposure to infectious agents, immunization status, underlying medical conditions, and medication use. It is important to obtain a detailed history of present illness, including the timing and progression of symptoms such as fever, headache, neck stiffness, altered mental status, and rash. Patients may also report symptoms such as nausea, vomiting, photophobia, and seizures. Recent travel or exposure to individuals with known or suspected meningitis can help identify potential infectious agents. Immunization status, particularly regarding vaccines against meningococcal and pneumococcal infections, is also important to determine. Patients with chronic medical conditions or who are taking immunosuppressive medications may be at increased risk for certain pathogens or complications.
Physical Examination
The physical exam findings in a patient with meningitis include vital signs, general appearance, and specific neurological findings. Vital signs such as fever, tachycardia, and hypotension are common. Patients may appear acutely ill, with a lethargic or altered mental status. They may exhibit signs of meningeal irritation, such as photophobia, neck stiffness, and a positive Kernig or Brudzinski sign. 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 [6]. Both Kernig and Brudzinski have reported low sensitivity (5%) but high specificity (95%) [6]. Neurological findings such as altered level of consciousness, focal neurologic deficits, and seizures may also occur or be present. Skin findings such as a petechial or purpuric rash may present in meningococcal meningitis patients. In infants, bulging fontanelles and poor feeding are concerning. Jolt accentuation testing can provide additional value: the patient horizontally rotates the head at two to three rotations per second [15]. The worsening of an existing headache indicates a positive result, though the sensitivity of jolt accentuation for diagnosing meningitis varies widely, with estimates ranging from 40-96% [15].
Table 2: Common signs/symptoms of meningitis, with sensitivity [8-10]
Sign / Symptom | Sensitivity |
Neck stiffness | 30-100 |
Headache | 70-100 |
Photophobia | 50-90 |
Nausea/vomiting | 50-90 |
Altered mental status | 50-80 |
Jolt accentuation | 40-90 |
Fever | 70-80 |
Seizures | 10-30 |
Focal neurological deficits | <10 |
Alternative & Differential Diagnoses
- Encephalitis: inflammation and swelling of the brain parenchyma; encephalitis tends to cause more neurological symptoms such as confusion, seizures, and changes in behavior or personality.
- Chemical meningitis (e.g., due to contrast agents, medications, or illicit drugs): The patient should have a history of exposure to a triggering agent, such as a medication or contrast dye.
- Carcinomatous meningitis (e.g., metastatic cancer cells in cerebrospinal fluid); history or imaging with evidence of metastatic disease.
- Aseptic meningitis (e.g., due to autoimmune disorders, sarcoidosis, or drug reactions) symptoms are usually milder. They may include fever, headache, and neck stiffness, often including other symptoms such as rash or joint pain.
- Cerebral vasculitis is inflammation and damage to the blood vessels that supply the brain. It may have a more insidious onset and a chronic or recurrent course.
- Traumatic meningitis (e.g., due to head injury or neurosurgical procedures)
- Brain abscess or subdural empyema; likely to include more focal neurological symptoms/deficits such as weakness or paralysis, seizures, or speech and vision problems.
- Subarachnoid bleeding is commonly associated with sudden, severe headaches, nausea, vomiting, and, at times, syncope.
- Tetanus is commonly associated with other symptoms such as jaw stiffness, diffuse muscle rigidity/spasm, difficulty swallowing, and respiratory distress.
- Malaria, particularly cerebral malaria, is typically found in areas with high transmission rates of malaria, and cerebral malaria typically has a more gradual onset. It can progress over several days to weeks.
Acing Diagnostic Testing
Acute diagnostic testing is crucial in managing meningitis as it allows for early detection and appropriate treatment. The accepted gold standard for diagnosing meningitis is cerebrospinal fluid (CSF) analysis, obtained through a lumbar puncture [6,16]. CSF analysis includes cell count, protein and glucose levels, culture, and gram stain [16]. Elevated CSF white blood cell count and protein levels are common findings in meningitis, while glucose levels are often decreased. CSF culture and gram stain are essential to identify the causative organism, guide antimicrobial therapy, and can be used to monitor response to treatment.
In addition to CSF analysis, imaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI) may also be obtained to evaluate for complications of meningitis, such as hydrocephalus, cerebral edema, or abscess formation. However, these imaging studies are typically not used for the initial diagnosis of meningitis. CT is a strong consideration to be performed before lumbar puncture (LP) to exclude increased intracranial pressure (ICP) or mass lesion when CT is available and a patient has any of these criteria: immunocompromised state, history of CNS disease, new-onset seizure, papilledema, severe decreased consciousness (GCS<12) or focal neurologic deficit [6].
Blood cultures may also be obtained to help identify the causative organism and determine appropriate antimicrobial therapy. In particular, meningococcemia can rapidly lead to shock and multiorgan failure. Other laboratory tests, such as complete blood count (CBC), chemistry panel, and coagulation studies, are also routinely obtained to evaluate potential complications or comorbidities.
Rapid diagnostic tests, such as polymerase chain reaction (PCR) or antigen tests, may also be available in some settings. These tests can help quickly identify some causes of meningitis, such as bacterial or viral meningitis. They can provide near real-time speciation of the causative organism and help tailor appropriate treatment.
Table 3: CSF Testing Characteristics [9-11, 17-19]
Test | Normal Results | Bacterial Meningitis Results | Viral Meningitis Results | Fungal Meningitis Results |
Appearance | Clear, colorless | Cloudy or turbid | Clear to slightly cloudy | Cloudy or turbid |
WBC count | <5 cells/microliter | Elevated | Elevated, often lymphocytic | Elevated, often lymphocytic |
Glucose | 40-70 mg/dL | Decreased | Normal or slightly decreased | Decreased |
Protein | 15-45 mg/dL | Elevated | Normal to slightly elevated | Elevated |
Gram stain | No organisms | Gram-positive or gram-negative organisms | Negative for bacteria, positive for virus | Negative for bacteria and virus |
Culture | Negative | Positive for bacterial growth | Negative for bacteria, positive for virus | Positive for fungal growth |
Risk Stratification
Several features in the history, physical examination, and testing can indicate a worse outcome in a patient with meningitis. Some of these include advanced age, altered mental status, presence of seizures, hypotension, tachycardia, high cerebrospinal fluid (CSF) protein and low glucose levels, high white blood cell count in CSF, and delayed initiation of appropriate antimicrobial therapy.
Various risk stratification tools have been developed for meningitis, such as the Glasgow Meningococcal Septicemia Prognostic Score (GMSPS), which is used to predict mortality in meningococcal disease. This tool includes variables such as age, Glasgow Coma Scale score, presence of meningismus, and presence of shock. This tool is most helpful in identifying the most sick cases, which are likely to be evident based on the clinical history and exam. Although this score exists, it is not routinely used in clinical practice. Another tool is the Bacterial Meningitis Score (BMS), which helps clinicians differentiate bacterial from aseptic meningitis based on the presence of certain clinical and laboratory features. The BMS includes age, cerebrospinal fluid protein level, cerebrospinal fluid neutrophil count, and peripheral blood absolute neutrophil count.
Management
In patients with whom you have concerns about meningitis, stabilization of an unstable patient is the priority. Assess the airway and breathing, including monitoring the respiratory rate and saturation levels. Administer supplemental oxygen if necessary. Evaluate circulation by checking the pulse, capillary refill time, and blood pressure. Provide fluids or administer medications as required. Next, the neurological function can be evaluated using tools like the Glasgow Coma Scale or AVPU (Alert, Verbal, Painful, Unresponsive) scale. Additionally, glucose levels and the presence of focal neurological signs, seizures, and papilledema should be assessed.
Empiric antibiotics should be started as soon as possible, even before the results of CSF culture and sensitivity are available, in order to reduce the risk of mortality and morbidity. In addition, supportive measures such as fluid and electrolyte management, seizure prophylaxis, and management of increased intracranial pressure are essential in managing meningitis. Patients with severe disease or complications may require ICU admission. Close follow-up with repeat CSF analysis and neuroimaging may be necessary to monitor response to treatment and identify potential complications.
Empiric treatment for bacterial meningitis typically involves using third-generation cephalosporins, such as ceftriaxone or cefotaxime, with or without vancomycin to cover for potential penicillin-resistant strains of Streptococcus pneumoniae. In infants under 1 month of age and patients over 50 years, ampicillin is often added to cover for Listeria monocytogenes [2]. Dexamethasone, a corticosteroid, is also given prior to or at the time of antibiotic initiation in adults and children with suspected or confirmed bacterial meningitis to reduce the risk of neurologic sequelae. The administration of corticosteroids has been shown to significantly reduce hearing loss and neurological complications in patients with meningitis.
However, using corticosteroids has not significantly impacted overall mortality rates [20]. The management of viral meningitis is mainly supportive. Antiviral treatment may be considered for specific viral pathogens, such as acyclovir for herpes simplex virus (HSV) or ganciclovir for cytomegalovirus (CMV). However, empiric antiviral treatment is not recommended in most cases of viral meningitis. The use of corticosteroids, such as dexamethasone, is controversial in viral meningitis and is not generally recommended [20].
Pre-exposure prophylaxis, though intrapartum prophylaxis of group B streptococcus in pregnant women, has significantly reduced the risk of early-onset group B strep meningitis [21]. Post-exposure prophylaxis is also an important consideration in contacts of patients diagnosed with meningitis; close contacts are defined as individuals who have had prolonged close contact with the index case, such as household contacts, healthcare workers, or individuals who shared a room or had direct contact with respiratory or oral secretions. Antibiotic prophylaxis is typically recommended within 24-48 hours of identification of the index case and may include rifampin, ciprofloxacin, or ceftriaxone, depending on the age and health status of the contact. In addition to antibiotics, vaccination with the meningococcal conjugate vaccine may be recommended for close contacts, particularly those at increased risk.
The recommended antibiotic prophylaxis is usually a single dose of intramuscular ceftriaxone (250 mg for adults and children weighing > 45 kg and 125 mg for children weighing < 45 kg). Alternatively, oral antibiotics such as rifampin, ciprofloxacin, or azithromycin can be used as alternatives. For exposure to Streptococcus pneumoniae, oral amoxicillin is recommended for prophylaxis, and for exposure to Haemophilus influenzae type b (Hib), rifampin or ceftriaxone is recommended.
Special Patient Groups
Elderly individuals, particularly those over 65, may present with atypical meningitis characterized by lethargy, minimal signs of meningismus, and the absence of fever. Conversely, younger individuals such as neonates, infants, and children often present with symptoms such as poor feeding, irritability, fever, and in babies, a shrill cry, decreased appetite, rash, and vomiting. In young children, the presentation of meningitis can mimic flu-like symptoms, including cough or respiratory distress, and it is not uncommon for them to have a history of respiratory tract infection. Seizures are also more frequently observed in this age group with meningitis. When evaluating a febrile child who appears unwell, it is crucial to consider bacterial meningitis as a potential diagnosis until ruled out. It is worth noting that blood and cerebrospinal fluid results may appear normal, especially in extremely young or old age groups.
When To Admit This Patient
Patients with suspected meningitis should be admitted to the hospital from the emergency department, as this is a potentially life-threatening condition that requires urgent evaluation and treatment. Admission should be considered for patients with a high likelihood of meningitis based on clinical presentation and laboratory findings. Patients with severe symptoms such as altered mental status, seizures, or signs of sepsis are particularly high-risk and should be admitted promptly. Patients with risk factors such as immunocompromised status, recent head trauma, or history of neurosurgical procedures should also be admitted.
Patients with meningitis who present with severe symptoms or complications such as altered mental status, seizures, respiratory distress, or signs of sepsis should be considered for admission to the intensive care unit (ICU). In addition, patients with bacterial meningitis or other severe forms of meningitis, such as fungal or tuberculous meningitis, and those immunocompromised should also be admitted to the ICU for close monitoring and aggressive treatment. Patients with a high risk of developing cerebral edema or increased intracranial pressure, such as those with hydrocephalus or brain abscess, may also require ICU admission. Close monitoring of vital signs, neurologic status, and laboratory parameters, such as blood glucose and electrolytes, is likely best done in an ICU.
Revisiting Your Patient
Let’s go back to the clinical presentation of your 21-year-old male refugee. He has fever, tachycardia, vomiting and confusion, and meningitis was suspected. You performed a lumbar puncture, and the cerebrospinal fluid analysis showed a white cell count of 1500 cells/µL with predominant neutrophils, protein level of 150 mg/dL, and glucose level of 30 mg/dL. The patient was started on treatment with intravenous ceftriaxone and vancomycin and admitted to the hospital. The patient was diagnosed with bacterial meningitis and was continued on intravenous antibiotics for a total of 14 days.
The patient responded well to the treatment and was discharged after completing the course of antibiotics. Appropriate public health notification was made, and the patient was scheduled for post-discharge follow-up care and vaccination.
Author
J. Austin Lee, MD MPH DTMH
Austin Lee, MD MPH DTMH, is a practicing emergency medicine doctor in the United States. He currently works with Indiana University Health, across several hospital sites. Dr. Lee obtained an MPH at the George Washington University before going to medical school at Indiana University. He completed his emergency medicine residency at the University of Virginia, and then worked at Brown University where he was a part of the Global Emergency Medicine fellowship. Austin has worked on a number of international emergency medicine projects, and is actively engaged in supporting the development of emergency medicine in Kenya.
Listen to the chapter
References
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Reviewed and Edited By
Arif Alper Cevik, MD, FEMAT, FIFEM
Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.
