Meningitis and encephalitis are neurologic emergencies that require rapid recognition and treatment. Prompt diagnosis and administration of antimicrobials, alongside adjuvant steroids in select cases, are crucial for treatment and improvement in outcomes. Severe complications of meningitis and encephalitis may include seizures, hyponatremia, elevated intracranial pressure (ICP), cerebral edema and herniation, vasculitis and cerebral ischemia. Critical care management focuses on appropriate antimicrobials, seizure control, ICP monitoring and optimization, and, if severe, neurosurgical intervention for cerebrospinal fluid diversion or decompression.
Key points
-
•
Meningitis and encephalitis are uncommonly encountered infections that are associated with significant morbidity and mortality.
-
•
Though the classic triad of fever, meningismus, and headache may be present, clinical features may vary by pathogen and may be associated with unique risk factors that could facilitate empirical antimicrobial administration.
-
•
In addition to antibiotics, steroids, and anti-seizure medications, management of elevated intracranial pressure (ICP) and hydrocephalus may necessitate a stepwise approach that could culminate in the need for decompressive surgical craniotomy.
-
•
In patients with elevated ICP, cerebrospinal fluid diversion via intracranial devices, lumbar drains, or serial lumbar punctures has demonstrated improved clinical outcomes and decreased morbidity.
Abbreviations
| ABC | airway, breathing, and circulatory support |
| ASM | anti-seizure medication |
| CMV | cytomegalovirus |
| CSF | cerebrospinal fluid |
| CT | computed tomography |
| EEG | electroencephalography |
| FLAIR | fluid-attenuated inversion recovery |
| GCS | Glasgow Coma Scale |
| HIV | Human Immunodeficiency Virus |
| HOB | head of bed |
| HSV | Herpes Simplex virus |
| ID | Infectious Diseases |
| IDSA | Infectious Diseases Society of America |
| LD | lumbar drains |
| LP | lumbar puncture |
| MRI | magnetic resonance imaging |
| NCS | Neurocritical Care Society |
| TB | tuberculosis |
| TBM | tuberculous meningitis |
| VZV | Varicella Zoster virus |
Introduction
Meningitis and encephalitis are uncommon causes of infections that can lead to critical illness and represent 2.9% of all cases in the ICU. Meningitis is an inflammation of the membranes that surround the brain and spinal cord, called the meninges, while encephalitis is an inflammation of the brain itself. Despite the low prevalence, CNS infections cause high rates of long-term neurological sequelae and, mortality. Mortality rates for bacterial meningitis vary from 10% in high-income countries to 58% in low-income countries with up to 25% with residual focal neurologic deficits. Encephalitis mortality rates are similarly elevated at 5.6% to 39.3% with survivors suffering profound neurologic deficits like memory, attention, and vision impairments. When treating meningitis and encephalitis, prompt recognition, identification of the pathogen and management are crucial in decreasing the risk of neurologic injury and death. In this article, we will review clinical presentations and evidence-based management strategies for meningitis and encephalitis.
Clinical presentations and risk factors
The hallmark features of meningitis and encephalitis include altered mental status, fever, headache, and meningismus. In bacterial meningitis, these symptoms may present in isolation or in combination with one another. Several studies have reported at least two of these symptoms being present in at least 72% to 95% of patients, with only 44% having the classic triad of fever, headache, and meningismus. , Seizures as a presenting symptom is more common in encephalitis. , Other non-specific symptoms may be lethargy, photophobia, nausea, vomiting, and rash. In some cases, unique clinical features alongside close identification of risk factors may aid in diagnosis and management. Table 1 highlights pathogen-specific risk factors and unique clinical features.
Table 1
Summary of risk factors and unique clinical features of common pathogens
Data from refs. ,,,,,,,,,,,,,,,,,,
| Pathogen | Risk Factors | Clinical Features |
|---|---|---|
| Neisseria meningitidis | Complement pathway deficiencies, asplenia, chronic disease, large group gatherings, Human Immunodeficiency Virus infection, exposure to the African meningitis belt, and active or passive smoking |
Petechial rash → larger purpuric rash (42%–70%) → necrosis/purpura fulminans (25%)
DIC, coma, adrenal hemorrhage, death , |
| Streptococcus pneumoniae | Immunocompromised states, HIV, splenectomy, DM, alcoholism |
Cerebrovascular complications—arterial stroke (30%), venous sinus thrombosis (9%), intracranial hemorrhage (9%)
High risk of long-term neurological sequela, such as hearing loss (up to 50% of cases) Death even with appropriate clinical management (20%) |
| Listeria Monocytogenes |
Consumption of contaminated soft cheeses, processed meats, livestock, raw produce, foods with a long shelf-half life
Chronic kidney or liver disease, pregnancy, age over 50 |
Rhombencephalitis
Asymmetric cranial nerve palsies, cerebellar signs, hemiparesis, hemisensory loss |
| Mycobacterium Tuberculosis |
Young age (especially < 5), HIV, immunosuppression
,,
Farmers, miliary TB, malnutrition |
|
| Herpes simplex virus | Extremes of age, immunocompromise, HIV | Temporal lobe hemorrhages, hyponatremia, focal EEG changes |
| Varicella zoster virus | Older age, HIV, hematologic malignancies, glucocorticoids, chronic obstructive pulmonary disorder, DM, solid cancer, stroke, congestive heart failure | Confusion, nausea, headache, gait disturbance, personality changes |
| Cryptococcus neoformans | Immunocompromised state, HIV, chronic steroid use, chronic kidney, liver, lung disease, malignancy, transplants, iatrogenic , |
Subacute to chronic onset
Headache, intracranial hypertension, altered mental status, photophobia, seizures , |
| Coccidioides spp. | Filipino and African American descent, DM, and third trimester pregnancies, less commonly immunocompromise | Intracranial hypertension, altered sensorium, neuropsychiatric symptoms |
| Candida spp. |
Infants
Neurosurgical procedures, most commonly ventriculoperitoneal shunts, lumbar cistern peritoneal shunts, external ventricular drains, and ventriculostomies , |
Neonates: systemic symptoms
Post-surgical: meningeal signs and altered mental status |
| Histoplasma spp. | Immunocompromise | Subacute to chronic onset of meningeal symptoms |
| Naeglaria fowleri | Exposure to warm freshwater, nasal irrigation with contaminated water | Rapidly progressive meningitis, high mortality |
|
Balamuthia
spp.
Acanthamoeba spp. |
Immunocompromise, diabetes, pregnancy, and liver disease | Subacute onset of meningeal symptoms |
| Toxoplasma gondii | Malignancy, HIV, immunosuppressive agents, pregnancy, primary ingestion of undercooked meat , |
Subacute onset of focal neurologic deficits, seizures, and altered mental status
Signs and symptoms of elevated intracranial pressure |
The most common causes of bacterial meningitis include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenza type b, Group B Streptococcus (GBS), Escherichia coli , Salmonella sp., Klebsiella, sp. Staphylococcus aureus, Listeria monocytogenes , and Mycobacterium tuberculosis. On the other hand, viruses—including Herpes Simplex virus (HSV), Varicella Zoster virus (VZV), enteroviruses, and arborviruses—are the most common cause of infectious encephalitis, ranging from 1.4 to 13.8 cases per 100,000 persons per year worldwide. , Risk factors for viral encephalitides are poorly understood but extremes of age and an immunocompromised state have been frequently reported. HSV encephalitis may present with temporal lobe hemorrhages, focal changes on electroencephalography (EEG), and hyponatremia. ,
Severe manifestations of fungal infections include meningitis and one of the most common fungal etiologies being Cryptococcus neoformans. Of one million cases of cryptococcus globally, the incidence of cryptococcus meningitis has been reported at 223,000. Other less common causes of fungal meningitis include Coccidioides sp ., Candida sp ., and Histoplasma capsulatum .
Finally, extremely rare causes of meningitis and encephalitis include protozoan parasites and typically follow a subacute onset of meningeal symptoms. These organisms include Naeglaeria fowleri, Acanthamoeba sp. , Balamuthia sp., and Toxoplasma gondii and are also included in Table 1 .
Tuberculosis (TB) is one of the most prevalent diseases in the world, affecting 10 million people a year. , Of these, 2% to 5% may develop tuberculous meningitis (TBM). Risk factors include young age, Human Immunodeficiency Virus (HIV) infection, a previous history of miliary TB, malnutrition, and other causes of immunosuppression. ,,, Though symptoms of TBM may be variable and non-specific, three phases have been described. The prodromal phase begins with the subacute onset of cough, fever, malaise, weight loss, and the gradual onset of headache. Within a few weeks, the meningitic phase emerges, with symptoms characterized by meningismus, headache, cranial nerve palsies, and confusion. Unfortunately, by this stage, a rapid deterioration into the third paralytic phase of TBM occurs, which is defined by coma, seizure, hemiplegia, and death. , Atypical presentations may include progressive dementia and personality changes. ,
Diagnostic workup
Diagnosing meningitis and encephalitis promptly is imperative for instituting targeted treatments. The first step is obtaining a detailed history for symptoms and identification of pathogen-specific risk factors. Additionally, key physical examination findings include meningismus, focal neurologic deficits, papilledema, rashes, and altered sensorium. In cases with high clinical suspicion, empiric treatment for meningitis/encephalitis must be instututed with broad spectrum antimicrobials with or without steroids depending upon the clinical suspicion for bacterial, viral versus fungal or tuberculous meningits.
Laboratory Workup
Serum and cerebrospinal fluid (CSF) testing, highlighted in Table 2 , should be sent promptly as part of the workup but should not delay initiation of empirical antibiotics. A lumbar puncture (LP), which is the gold standard for diagnosis, should also be pursued as soon as possible. Table 3 summarizes normal and abnormal CSF profiles by pathogen. ,,,,,,,, These values are not absolute and may vary among patients, especially in partially treated infections. Of note, if done in the early acute phase of meningitis or encephalitis, an LP may yield negative results. If the suspicion remains high, it is important to repeat the LP. For HSV encephalitis, false negatives are not uncommon when an LP is performed within 72 hours of illness. In a retrospective multicenter center study of critically ill patients admitted for possible encephalitis, 4% of patients tested negative within 4 days of symptom onset, leading to delayed treatment. The Infectious Diseases Society of America (IDSA) therefore recommends re-testing CSF within 3 to 7 days and continuation of antibiotics during this time. Additionally, broadening the workup is sometimes required to identify the causative agent. Of note, limitations do exist with multiplex PCR panels. Firstly, they include the most common pathogens for meningitis and encephalitis; and, individualized evaluation of a patient’s risk factors should warrant a more expanded workup for pathogens not included in the multiplex panel. Secondly, in a meta-analysis, multiplex panels were found to have moderate sensitivities but excellent specificities for both bacteria and viruses. As such, these panels are excellent for ruling in pathogens but are not as effective for ruling out pathogens. More specifically, for bacteria, the sensitivity and specificity were 89.5% and 97.4%, respectively. For viruses, the sensitivity and specificity were at least 75.5% and 99%, respectively. , Moreover, for specific pathogens, such as Listeria monocytogenes, Hemophilus influenzae, and Escherichia coli, the validity of the multiplex PCR panel was suboptimal. Additionally, in another meta-analysis of 113 studies by Tansarli and colleagues, HSV-1 and 2, enterovirus, and Cryptococcus spp. had the highest proportions of false negatives when sending multiplex PCR panels. In clinical practice, if multiplex panels return negative but the suspicion for certain bacterial, viral, and fungal meningitides and encephalitides persist, de-escalation of antimicrobials should occur only after dedicated PCR testing of the specific pathogen.
Table 2
Laboratory diagnosis of meningitis and encephalitis
Data from Ref.
|
|
Table 3
Cerebrospinal fluid profiles in meningitis and encephalitis
Data from refs. ,,,,,,,,
| Normal | Bacterial | Viral | Fungal | TB | Parasitic | |
|---|---|---|---|---|---|---|
| Color | Clear | Cloudy, purulent | Clear | Clear | Clear | Clear |
| Opening Pressure (cm H2O) | 6–25 | Elevated | Normal | Variable | Variable | Variable |
| WBC Count (cells/μL) and Differential |
0–5
Rare PMNs |
Elevated (typically > 1000)
PMN predominance |
Normal to mildly elevated (typically < 150)
Lymphocytic predominance |
Elevated (typically 100–500)
Lymphocytic predominance |
Elevated (typically 100–500)
Lymphocytic predominance |
Elevated
May have eosinophilia |
| Protein (mg/dL) | 15–45 | Elevated | Normal to mildly elevated | Elevated | Elevated | Elevated |
| Glucose (mg/dL) |
45–80
60%–80% of serum glucose |
Reduced | Normal | Significantly reduced | Significantly reduced | Low normal-normal |
Head Imaging
Prior to an LP, head imaging should be pursued to rule out mass lesions or other causes of elevated ICP that could place a patient at risk for herniation. A computed tomographic (CT) scan is generally adequate for this screening.
The IDSA recommends pursuing head imaging if a patient meets any of the following:
-
•
Immunocompromised state
-
•
History of CNS disease
-
•
New-onset seizure
-
•
Papilledema
-
•
Altered mental status
-
•
New focal neurologic deficit.
-
Despite these guidelines, one observational study demonstrated over-utilization of head imaging, citing the use in 65% of patients who did not meet criteria.
MRI may also be a helpful diagnostic tool. In patients with meningoencephalitis, almost 50% of patients will have MRI findings of abnormal meningeal enhancement on post-contrast T1 sequences and hyperintensity on fluid-attenuated inversion recovery (FLAIR) sequences. , A common misconception is delaying an LP to obtain an MRI so as to avoid iatrogenic meningeal enhancement. Studies have shown that unexplained meningeal enhancement after LP is very rare and not more common than in cases with no prior LP. If an LP is performed before MRI and meningeal enhancement is found, it should only be attributed to the LP after all other causes have been ruled out. Key MRI findings of common pathogens, summarized by Perillo and colleagues, are highlighted in Table 4 and Fig. 1 . ,,
Table 4
MRI findings in meningitis and encephalitis by pathogen
Adapted from Perillo T, Capasso R, Pinto A. Neuroimaging of the Most Common Meningitis and Encephalitis of Adults: A Narrative Review. Diagnostics 2024;14(11):1064. https://doi.org/10.3390/diagnostics14111064 ; with permission. Data from refs. ,,
| Mycobacterium tuberculosis | Leptomeningeal Enhancement, Hydrocephalus, Vasculitis, Tuberculomas |
| Cryptococcus neoformans | Leptomeningeal enhancement, Pseudocysts, Cryptococcomas |
|
Candida albicans
A. fumigatus |
Abscesses, Vascular lesions |
| HSV-1 | T2 and FLAIR hyperintensities in the medial temporal lobes, sometimes associated with hemorrhagic foci |
| VZV | Leptomeningeal enhancement, Cerebellitis |
| CMV | Periventricular white matter T2 FLAIR hyperintensities |
| WNV | T2 and FLAIR hyperintensities in basal ganglia, thalamus, midbrain |
| Enterovirus | Rhombencephalitis |
| Listeria monocytogenes | Subcortical abscesses, Cranial nerve enhancement |
| Borrelia burgdorferi | Single or multiple small non-enhancing subcortical or periventricular white matter hyperintensities, most often supratentorial |
| Toxoplasma gondii | Multiple concentric and eccentric enhancing lesions, primarily in the basal ganglia, thalami, cortico-medullary junction |
Neuroradiology findings of meningitis and encephalitis caused by various pathogens. ( A – B ) T2 FLAIR hyperintensities of the L medial temporal lobe and the bilateral insula in HSV encephalitis. ( C – D ) Multifocal luminal irregularity and stenosis of the right middle cerebral artery and its branches in a patient with CMV meningoencephalitis. ( E – F ) Left medial temporal lobe and insular enhancement in a patient with Candida auris meningitis. ( G – H ) Multifocal ring-enhancing lesions in the cerebellum and brainstem in a patient with Listeria monocytogenes meningitis. ( I ) Leptomeningeal enhancement in a patient with Streptococcus pneumoniae meningitis. ( J ) Pachymeningeal enhancement in the same patient with S pneumoniae meningitis. CMV, cytomegalovirus; HSV, Herpes Simplex virus.
Seizures are a common complication of encephalitis and, less frequently, meningitis. Clinical and electrographic seizures, the latter may be difficult to detect on bedside assessment, lead to worse outcomes both during hospitalization and long-term for affected patients. In a retrospective cohort study by Carrera and colleagues on patients with CNS infection and persistent altered mental status, 33% of patients with CNS infection had electrographic seizures, most without any clinical correlate. Of note, 86% of these patients had evidence of a clinical seizure prior to EEG monitoring. The utilization of EEG monitoring is thus important for prevention of secondary neurologic injury. EEG monitoring should also be pursued in patients with prior evidence of a clinical seizure or persistently poor mental status.
Related posts:
Recognition and Management of Infectious Biothreats and Emerging Pathogens
Optimal Approach to Source Control in Intensive Care Unit Patients
The Global Intensive Care Unit
Recognizing and Managing Hemophagocytic Lymphohistiocytosis in Adults in the Intensive Care Unit
Antibiotic Considerations in the Critically Ill
Lower Respiratory Tract Infections
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
