CONTENTS
- Rapid Reference: Obtundation with suspected CNS infection 🚀
- Clinical manifestations
- Labs
- Imaging
- Management
- Related topics
- Podcast
- Questions & discussion
- Pitfalls
diagnostic approach ✅
blood tests 📖
- Fingerstick glucose STAT.
- Electrolytes, complete blood count with differential, coagulation studies.
- Blood cultures x2.
- HIV screen as appropriate.
head CT scan
- CT is indicated prior to LP in patients with substantially altered mental status.
- Addition of CT angiography (CTA) and venography (CTV) should be considered in patients with focal neurologic abnormality or stupor/coma (e.g., bacterial meningitis may cause arterial or venous occlusion).
lumbar puncture
- Hold DVT prophylaxis to facilitate lumbar puncture.
- Lumbar Puncture:
- Measure opening pressure & LP labs.
- Target MAP > [60 + 0.7(Opening Pressure in cm)]
MRI?
- MRI may be considered if the diagnosis remains elusive despite the above tests.
- Diagnoses that may be clarified by MRI include:
- Patterns of parenchymal involvement may suggest various types of infectious or autoimmune encephalitis.
- Septic emboli.
- Noninfectious differential diagnoses (e.g., ischemic stroke, PRES).
therapeutic approach ✅
initial empiric therapy prior to LP 📖
- 2 grams ceftriaxone IV.
- 10 mg dexamethasone IV.
- 10 mg/kg acyclovir IV.
- (Subsequently adjust antibiotics based on LP results.)
fever prevention
- Scheduled acetaminophen (1,000 mg PO q6hr for most patients).
- External cooling, if needed to achieve normothermia.
seizure control 📖
- If concern for seizures, obtain EEG.
definitions
- Meningitis is inflammation of the subarachnoid space, the fluid bathing the brain (between the arachnoid and the pia mater; figure above). Most common causes are bacterial or viral.
- Encephalitis is inflammation of the brain tissue itself. Most common causes are viral or autoimmune.
- Meningoencephalitis involves inflammation of the subarachnoid space and also brain parenchyma.
#1/3: suspicion for meningitis
frequency of symptoms in patients with bacterial meningitis (27062097)
- Headache ~80%
- Neck stiffness ~80%
- Nuchal rigidity is resistance to passive flexion. Stiffness to flexion-extension reflects meningeal irritation, whereas stiffness to rotation does not. (LaHue 2021)
- Fever (>38C): ~80%
- Nausea/vomiting ~70%
- Often present, but under recognized as a symptom of CNS infection.(Louis 2021)
- Altered mental status ~60%
- Coma in ~15%
- Focal neurologic deficits ~30%
symptom combinations in meningitis
- The classic triad of meningitis is fever, nuchal rigidity, and altered mental status.
- All three features are only seen in about 40% of patients.(27062097) If encountered this combination is highly suggestive, but it has a low sensitivity.
- Nearly all patients with meningitis (~99%) will have at least one of these three features. However, only one feature is quite nonspecific.(8416268)
- 95% of patients with bacterial meningitis will have at least two of the following four cardinal symptoms: fever, nuchal rigidity, altered mental status, and headache.(34798976)
- When in doubt, it's generally better to err on the side of getting a lumbar puncture (especially among intubated patients who can't be closely observed for deterioration).
#2/3: suspicion for encephalitis
encephalitis is tricker to diagnose than meningitis
- Patients with encephalitis usually lack nuchal rigidity.
- Encephalitis tends to present with more prominent focal neurologic findings and/or seizures. These features may not immediately lead to a suspicion for infection.
- Among critically ill patients, meningitis and encephalitis can be indistinguishable. For example, patients are often obtunded and thus unable to participate in a detailed neurologic examination.
diagnostic criteria for encephalitis
- The following criteria shouldn't mandate clinical management of an individual patient, but they may help us conceptualize the approach to a patient who might have encephalitis.
- (1) Altered mental status lasting >24 hours, without an alternative cause identified.
- (2) At least two of the following:
- Documented fever >38C within the last 72 hours before or after presentation.
- New focal neurological signs.
- CSF pleocytosis.
- New neuroimaging findings suggestive of encephalitis.
- Seizure activity not related to a pre-existing seizure disorder.
- Abnormal findings on EEG that are consistent with encephalitis.(35738892)
#3/3: patients admitted to the hospital for awhile
- Fever and altered mental status are extremely common among patients admitted to the hospital.
- It is uncommon for a patient admitted with an unrelated problem to suddenly develop meningitis while in the hospital.
- In general, a lower index of suspicion is appropriate for patients who have been admitted to the hospital for a few days, unless they have a disease process that could cause meningitis (e.g., bacterial endocarditis, pneumococcal bacteremia, status post neurosurgery).
neurologic complications of bacterial meningitis include
- Acute ischemic stroke may occur in ~25% of patients.(27105658)
- Evaluate for the possibility of underlying endocarditis.
- CVT (cerebral venous thrombosis), including cortical vein thrombosis.
- ICH (intracerebral hemorrhage).
- Purulent infection: Cerebritis, brain abscess, or subdural empyema.
- Seizures, including ongoing epilepsy (these may correlate with other complications, such as ischemic stroke or subdural empyema).
- Hydrocephalus:
- Usually communicating hydrocephalus, due to impaired CSF reabsorption.
- Noncommunicating hydrocephalus may occur due to a space-occupying lesion or diffuse brain edema.(27105658)
- Ventriculitis.
- Cranial nerve palsies (especially hearing loss).
investigation for complications
- MRI with MRV (MR venography) is generally advisable for critically ill patients with meningitis.
- EEG, if there is concern regarding seizures.
CT findings in meningitis
- Noncontrast CT is usually normal.
- Occasionally, findings due to meningitis may be seen:
- Complications or associated pathology may occasionally be seen, for example:
- A primary focus of infection which invaded the meninges (e.g., otitis media, sinusitis, mastoiditis).
- Complications of meningitis (e.g., abscess formation, subarachnoid hemorrhage, hydrocephalus).
MRI findings in meningitis
- MRI is not typically used to diagnose meningitis due to the time delay. However, MRI may be useful in some clinical circumstances, for example:
- Comatose patient with low index of suspicion for infection is undergoing an MRI to evaluate for other pathologies.
- Lumbar puncture isn't possible due to technical difficulty or coagulopathy.
- Unfortunately, half of contrast-enhanced MRIs may be normal in meningitis – so a normal MRI cannot exclude meningitis.(33896533)
- Meningitis may generate purulent exudates in the basal cisterns and superficial sulci, with the following appearance:
- FLAIR hyperintensity (unlike normal CSF, it's not dark). This gives the CSF a “dirty” appearance on FLAIR.(31485117) This isn't specific for meningitis, as other causes of this phenomenon include subarachnoid hemorrhage, leptomeningeal carcinomatosis, use of 100% inhaled oxygen, slow flow in pial vessels due to proximal vascular occlusion/stenosis, or retained contrast in renal failure patients.(31964490)
- Diffusion restriction may be caused by purulent exudates, which is more specific for infection (figure below).
- (On T1, purulent exudates may be isointense with brain parenchyma.)
- Leptomeningeal contrast enhancement can improve the sensitivity for meningitis.📖(24977138)
- Basal meningitis (abnormalities centered on the basal cisterns, prepontine cisterns, and sylvian fissures) suggests unusual etiologies (e.g., tuberculosis, fungal meningitis, or sarcoidosis).(31731899)
encephalitis: organisms that tend to affect various components of the brain
- Temporal lobes: See limbic encephalitis: 📖
- Brainstem encephalitis: 📖.
- Deep gray matter: 📖
- Cerebellum: 📖
Empiric antibiotic selection should generally focus on the most common agents. In the United States, these are as follows:(28187808)
most common causes of bacterial meningitis
- Streptococcus pneumoniae (3,000-6,000 cases/yr).
- Neisseria meningitidis (500-700 cases/yr).
- Group B streptococcus (GBS) (~500 cases/yr).
- Haemophilus influenzae.
- Listeria monocytogenes (~250 cases/yr).
- Listeria only accounts for 2% of all patients with encephalitis/meningitis. However this may not be generalizable to other countries, for example Listeria accounts for 16% of meningitis cases among patients >65 years old in France.(31402154)
most common causes of encephalitis
- West nile virus (1,000-2,500 cases/yr). However, incidence may vary substantially depending on season and geography.
- Herpes simplex virus (~1,250 cases/yr). This is the most common sporadic cause of viral encephalitis.
- Varicella-zoster virus (~800 cases/yr).
- Autoimmune encephalitis (unclear, but likely similar to Herpes simplex).
- 💡 Autoimmune encephalitis is common, and should also be routinely considered.
basics of this regimen
- This regimen is for patients with suspected meningitis/encephalitis, prior to obtaining CSF results.
- If you're seriously suspecting meningitis, initiate therapy without delay. In particular, treatment should not be delayed until CT and LP can be performed, as these may take quite a while.
- Realistically, most of the patients treated with this regimen won't have meningitis or encephalitis at all.
components of the regimen (“2-10-10”)
- 2 grams ceftriaxone IV (or, alternatively, 2 grams of meropenem if patient has history of allergy to advanced generation cephalosporins).
- 10 mg dexamethasone 10 mg IV (or 60 mg IV methylprednisolone if that's all you have). Steroid should ideally be given simultaneously/before antibiotics, but it's still recommended up to four hours after the first dose of antibiotic per European guidelines, or up to twelve hours after antibiotic initiation per British and French guidelines.(27062097, 26845731, 31402154)
- 10 mg/kg acyclovir IV.
rationale for this regimen
- Many practitioners will also add vancomycin and ampicillin here. However, immediate administration of vancomycin and ampicillin is arguably unnecessary:
- The only reason to use vancomycin is for highly drug-resistant pneumococcus, whereas the only reason to use ampicillin is for listeria. Both of these pathogens are rare when we consider all patients with encephalitis/meningitis (~2% or less; see table above).
- Among patients with possible CNS infection, most of these patients won't actually end up having any CNS infection at all. At most, perhaps ~20% of such patients have a CNS infection.
- Multiplying 20% by 2% indicates that the likelihood that a patient with possible CNS infection has listeria or highly drug-resistant pneumococcus is <0.5%. This rate is so low that it arguably doesn't require empiric coverage.
- Patients will get a lumbar puncture within a few hours, so antibiotics can be broadened subsequently if the results suggest bacterial infection.
- ⚠️ The most common mistake made at this juncture is failing to include empiric dexamethasone.
basics of this regimen
- This regimen is for patients who have CSF results which indicate a bacterial meningitis.
- More on the bacterial pattern of CSF results here. This CSF pattern can also be caused by rupture of a brain abscess into the CSF, which would require a different antibiotic regimen – so adequate neuroimaging remains important.
components of the regimen:
- (1) Dexamethasone 10 mg IV q6hr for four days. Dexamethasone is supported best in meningitis due to Streptococcus pneumoniae or Haemophilus influenzae.(31402154) However, dexamethasone may be continued in all patients with bacterial meningitis, except those with Listeria monocytogenes.(34303412, 31402154)
- (2) Ceftriaxone 2 grams IV q12hr.
- If the patient has a history of allergy to advanced generation cephalosporins, may use meropenem 2g IV q8hr.
- (3) Listeria coverage in patients >50-55 years old, pregnancy, or immunocompromise (e.g., diabetes, immunosuppressive medications, cirrhosis, alcoholism, malignancy, pregnancy). More on risk factors for Listeria here: 📖
- The usual coverage for listeria is ampicillin 2 grams IV q4hours. However, ampicillin isn't required for patients on meropenem (which covers Listeria).
- Further discussion of the epidemiology of listeria: 📖
- (4) Coverage for cephalosporin-resistant pneumococcus:
- This is generally provided, although it may not be needed if there is a low local incidence of cephalosporin-resistant pneumococcus.(27828810)
- Either vancomycin or rifampin may be used for this, in conjunction with ceftriaxone.(27062097) For patients at risk of acute kidney injury, rifampin might be safer (600 mg q12hr). Rifampin may also offer some anti-inflammatory effects and superior meningeal penetration.(26306393)
basics of this regimen
- This regimen is for patients who have CSF results consistent with a viral pattern. 📖
- The differential diagnosis may include herpesviruses, listeria, and tick-borne encephalitides (depending on the patient's exposures and degree of immunocompromise).
components of the regimen:
- (1) Acyclovir 10 mg/kg q8hr is the cornerstone of this regimen (pending the return of HSV and VZV PCR results)(algorithm below).
- (2) Consider doxycycline 100 mg twice daily if rocky mountain spotted fever or tick-borne encephalitis is possible.
- (3) Listeria can mimic a viral pattern, so listeria coverage might be considered in patients at risk for this (e.g., older or immunocompromised patients). If the CSF lactate level is normal, then listeria doesn't need to be covered.
Streptococcus pneumoniae
- Penicillin-sensitive (MIC <0.06-0.1 ug/mL)(27062097)
- Standard therapy: Penicillin or ampicillin.
- Alternative: Ceftriaxone.
- Penicillin-resistant, but cephalosporin susceptible (MIC <1-2 ug/mL)(27062097)
- Standard therapy: Ceftriaxone.
- Alternative therapy: Cefepime, meropenem.
- Cephalosporin-resistant (MIC ≧1-2 ug/mL)(27062097, 31021955)
- Standard therapy: Ceftriaxone + vancomycin; ceftriaxone + rifampin.
- Alternative therapy: Linezolid.
- Duration of treatment: 10-14 days (27062097)
Neisseria meningitidis
- Penicillin susceptible (MIC <0.064-0.1 ug/mL)(27062097; 31402154)
- Standard therapy: Penicillin or ampicillin.
- Alternative therapy: Ceftriaxone.
- Penicillin resistant (MIC ≧0.1 ug/mL)(27062097)
- Standard treatment: Ceftriaxone.
- Alternative therapy: Cefepime, meropenem, ciprofloxacin.
- Duration of treatment: 7 days (27062097)
Listeria monocytogenes
- Standard therapy: Ampicillin or Penicillin.
- Alternative therapy: Trimethoprim-sulfamethoxazole, meropenem, linezolid.
- Duration of therapy: At least 21 days. Patients with rhomboencephalitis may require longer courses of therapy.
Haemophilus influenzae
- Beta-lactamase negative, ampicillin sensitive:
- Standard treatment: Ampicillin.
- Alternative therapy: Ceftriaxone, cefepime.
- Beta-lactamase negative, ampicillin resistant:
- Standard treatment: Ceftriaxone.
- Alternative therapy: Ciprofloxacin.
- Beta-lactamase positive:
- Standard treatment: Ceftriaxone.
- Alternative therapy: Cefepime, ciprofloxacin.
- Duration of treatment: 7-10 days.
Staphylococcus aureus
- Methicillin-sensitive Staph. aureus (MSSA)(27062097)
- Standard treatment: Nafcillin.
- Alternative therapy: Vancomycin, linezolid.
- Methicillin-resistant Staph. aureus (MRSA)(27062097)
- Standard therapy: Vancomycin +/- rifampin.
- Alternative therapy: Linezolid, trimethoprim-sulfamethoxazole (if sensitive).
- Vancomycin resistant Staph. aureus (MIC >2 ug/mL)(27062097)
- Standard therapy: Linezolid +/- rifampin.
- Alternative therapy: Daptomycin.
- Duration of treatment: At least 14 days.
Streptococcus agalactiae (Group B strep.)
- Standard therapy: Ampicillin or Penicillin.
- Alternative therapy: Ceftriaxone.
More on meningeal penetration in the antibiotics chapter here.
- Patients who are truly obtunded/comatose due to CSF infection will usually require CT scan, lumbar puncture, and MRI. Intubation is often required to facilitate performing MRI safely.
- Patients may have elevated ICP, so there should be meticulous attention to:
- Avoiding hypercapnia.
- Avoiding hypoxemia.
- Avoiding hypotension (ideally keep MAP >75 mm; more on this below).
- However, excessive deviation from your usual intubation practice may also cause errors. High-quality rapid sequence intubation by an experienced operator with attention to blood pressure is generally a reasonable approach.
- Immediately following intubation, titrate end tidal CO2 to 30mm. An ABG may then be obtained, targeting normocapnia (pCO2 35-45 mm).
- More discussion on intubating the neurocritically ill patient here.
- There is no direct evidence for this in meningitis/encephalitis, but fever is generally harmful for neurocritically ill patients.
- Scheduled acetaminophen (usually 1 gram Q6hr) is a good first step, but this is often ineffective.
- Physical cooling (e.g., arctic sun or ice packs) may be needed as well.
- Seizures are common in severe meningitis and especially encephalitis. Seizure will make a bad situation much, much worse.
- If there is concern for non-convulsive status epilepticus, this should be excluded with continuous EEG. This includes patients with depressed mental status without a clear structural explanation.(33896533)
- In the absence of clear evidence, seizure prophylaxis may be reasonable, especially among substantially altered patients who cannot be continuously monitored with EEG (e.g., 500 mg levetiracetam PO/IV Q12 hours). Seizure prophylaxis may be more beneficial in encephalitis than in meningitis.
pathophysiology
- Elevated intracranial pressure is commonly seen in severe meningitis. The most common cause is simply reduced CSF reabsorption, due to inflammation of the meninges. Alternative or additional causes include arterial infarctions (causing focal tissue edema) or cerebral venous thrombosis (which may cause focal tissue edema, as well as impaired CSF reabsorption).
- Among patients with encephalitis, elevated intracranial pressure may result from diffuse swelling of parenchymal tissue.
adjust MAP target to obtain adequate cerebral perfusion pressure (CPP)
- Cerebral perfusion pressure (CPP) = MAP – ICP
- A reasonable target CPP may be >60 mm (ideal target unknown, sources vary between 60-70 mm).
- For patients with unknown ICP, targeting a generous MAP (e.g. >75 mm) may be reasonable.
- Once the ICP is known, MAP target can be adjusted accordingly:
- Target MAP > [60 mm + 0.7(lumbar puncture opening pressure measured in cm water)]
- Either norepinephrine or phenylephrine are reasonable to maintain MAP above target.
consider therapeutic drainage of CSF for patients with meningitis
- Patients with meningitis may benefit from therapeutic removal of CSF if they have the following:
- (a) Significantly elevated ICP (e.g., opening pressure >27 cm water).
- (b) Abnormal mental status.
- (c) No underlying structural brain abnormality (e.g. normal head CT).
- CSF drainage may serve to reduce the ICP and also drain off infected material (“source control”).
- Two ways of achieving CSF drainage:
- (a) Lumbar drain placement by neurosurgery.
- (b) Serial lumbar puncture (e.g., Q12 hr) with measurement of opening pressure, removal of ~20 ml, and measurement of closing pressure.
- This is a well known complication of cryptococcal meningitis. This strategy is more controversial for bacterial meningitis, with evidence discussed further here.(29088943)
potential reasons for treatment failure may include:
- Failure of infection control:
- Inadequate antibiotics or antibiotic resistance.
- Anatomic focus of infection that requires drainage (e.g., abscess, mastoiditis).
- Neurological complication:
- Cerebral venous sinus thrombosis.
- Vasculitis, vasospasm, ischemic stroke, intracerebral hemorrhage.
- Hydrocephalus.
- Hyponatremia precipitating edema and/or metabolic encephalopathy.
- Subdural effusion or empyema, brain abscess, ventriculitis.
- Seizure.
- Hypothalamic-pituitary dysfunction.(31306182)
evaluations to consider may include:
- Definitive imaging (e.g., MRI/MRV) if not recently obtained. Vascular imaging may additionally be considered to evaluate for vasospasm or venous sinus thrombosis.
- EEG (continuous EEG is the most sensitive for detection of non-convulsive seizures, but if unavailable serial routine EEGs could be used).
- Repeat lumbar puncture (primarily used in meningitis; see below).
repeat lumbar puncture in meningitis (31402154)
- Objectives:
- (1) The primary objective is to ensure that the CSF has been sterilized (this should occur within <24 hours of adequate antibiotic therapy). Other signs of an adequate response to therapy includes a rising glucose level and falling lactate level.
- (2) A secondary objective is to evaluate for communicating hydrocephalus.
- (3) If possible, drug levels within the CSF may be measured. However, this is generally not feasible.
- Potential indications for repeat lumbar puncture:
- (1) Organism with a high risk of treatment failure, most notably Streptococcus pneumoniae with cephalosporin resistance. Repeat lumbar puncture may also be considered for other unusual bacteria (e.g., MRSA).
- (2) Failure to clinically improve after 2-3 days of therapy.
Chronic meningitis is defined as persistent clinical and laboratory evidence of meningeal inflammation lasting for over a month.(28634505) Although this often won't lead to ICU admission, patients may develop complications requiring critical care (e.g., vasculitic infarctions or seizures).
A primary question is whether the patient is immunocompromised. Among immunocompetent patients, there is a relatively restricted differential diagnosis for chronic meningitis.
causes of chronic meningitis among immunocompetent patients (28634505)
- Bacteria and mycobacteria:
- Tuberculosis.
- Syphilis.
- Lyme.
- (Rarely: Brucellosis.)
- Fungi:
- Cryptococcus neoformans or Cryptococcus gattii (most common).
- Coccidioidomycosis.
- Histoplasmosis.
- Blastomycosis.
- (Rarely: Sporotrichosis.)
- Other infections:
- Neurocystiercersosis.
- HIV (other viral infections don't generally cause chronic meningitis.)
- Leptomeningeal metastasis.
- Inflammatory conditions:
- Sarcoidosis.
- Vasculitis (primary CNS angiitis, systemic vasculitis.)
- (Rarely: Behcet disease, Vogt-Koyanagi-Harada syndrome.)
Follow us on iTunes
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Failure to give steroid along with antibiotic. Steroid is recommended by both US and European guidelines, based on prospective RCTs proving reduction in long-term neurologic disability.
- Under-utilization of ultrasound-guided lumbar puncture for morbidly obese patients (if you're sending patients for IR-guided lumbar puncture, consider ultrasound).
- Delaying steroid/antibiotic therapy (e.g., for lumbar puncture).
- Failing to check VZV PCR (this is seen occasionally, so if you're going to get HSV PCR it's worth getting VZV also).(23566589)
- Keep in mind that antibiotics often require higher doses to penetrate the meninges (“meningeal dose”). Thus, simply because the patient is on an antibiotic doesn't mean that meningitis is necessarily covered adequately.
- Recognize that a patient with meningitis/encephalitis and obtundation is critically ill, and should usually receive care in an ICU.
Acknowledgement: Thanks to Dr. Richard Choi (@rkchoi) for thoughtful comments on this chapter.
Guide to emoji hyperlinks
- = Link to online calculator.
- = Link to Medscape monograph about a drug.
- = Link to IBCC section about a drug.
- = Link to IBCC section covering that topic.
- = Link to FOAMed site with related information.
- = Link to supplemental media.
References
- 23566589 Becerra JC, Sieber R, Martinetti G, Costa ST, Meylan P, Bernasconi E. Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study. Int J Infect Dis. 2013 Jul;17(7):e529-34. doi: 10.1016/j.ijid.2013.01.031 [PubMed]
- 24977138 Vaswani AK, Nizamani WM, Ali M, Aneel G, Shahani BK, Hussain S. Diagnostic Accuracy of Contrast-Enhanced FLAIR Magnetic Resonance Imaging in Diagnosis of Meningitis Correlated with CSF Analysis. ISRN Radiol. 2014 Mar 20;2014:578986. doi: 10.1155/2014/578986 [PubMed]
- 26046515 Fink KR, Benjert JL. Imaging of Nontraumatic Neuroradiology Emergencies. Radiol Clin North Am. 2015 Jul;53(4):871-90, x. doi: 10.1016/j.rcl.2015.02.004 [PubMed]
- 26065933 Shih RY, Koeller KK. Bacterial, Fungal, and Parasitic Infections of the Central Nervous System: Radiologic-Pathologic Correlation and Historical Perspectives. Radiographics. 2015 Jul-Aug;35(4):1141-69. doi: 10.1148/rg.2015140317 [PubMed]
- 26306393 Bretonnière C, Jozwiak M, Girault C, Beuret P, Trouillet JL, Anguel N, Caillon J, Potel G, Villers D, Boutoille D, Guitton C. Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study. Crit Care. 2015 Aug 26;19(1):303. doi: 10.1186/s13054-015-1021-7 [PubMed]
- 27021774 Piquet AL, Cho TA. The Clinical Approach to Encephalitis. Curr Neurol Neurosci Rep. 2016 May;16(5):45. doi: 10.1007/s11910-016-0650-9. [PubMed]
- 27062097 van de Beek D, Cabellos C, Dzupova O, Esposito S, Klein M, Kloek AT, Leib SL, Mourvillier B, Ostergaard C, Pagliano P, Pfister HW, Read RC, Sipahi OR, Brouwer MC; ESCMID Study Group for Infections of the Brain (ESGIB). ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect. 2016 May;22 Suppl 3:S37-62. doi: 10.1016/j.cmi.2016.01.007 [PubMed]
- 27105658 Lucas MJ, Brouwer MC, van de Beek D. Neurological sequelae of bacterial meningitis. J Infect. 2016 Jul;73(1):18-27. doi: 10.1016/j.jinf.2016.04.009 [PubMed]
- 27828810 Costerus JM, Brouwer MC, Bijlsma MW, van de Beek D. Community-acquired bacterial meningitis. Curr Opin Infect Dis. 2017 Feb;30(1):135-141. doi: 10.1097/QCO.0000000000000335 [PubMed]
- 2810603 Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis. An analysis of the predictive value of initial observations. JAMA. 1989 Nov 17;262(19):2700-7 [PubMed]
- 28187808 Halperin JJ. Diagnosis and management of acute encephalitis. Handb Clin Neurol. 2017;140:337-347. doi: 10.1016/B978-0-444-63600-3.00018-0 [PubMed]
- 28634505 Snider S, Bhattacharyya S. A 57-Year-Old Man With Headache, Numbness, and Weakness. Neurohospitalist. 2017 Jul;7(3):141-144. doi: 10.1177/1941874417692276 [PubMed]
- 29088943 Tariq A, Aguilar-Salinas P, Hanel RA, Naval N, Chmayssani M. The role of ICP monitoring in meningitis. Neurosurg Focus. 2017 Nov;43(5):E7. doi: 10.3171/2017.8.FOCUS17419 [PubMed]
- 30366550 Venkatesan A, Murphy OC. Viral Encephalitis. Neurol Clin. 2018 Nov;36(4):705-724. doi: 10.1016/j.ncl.2018.07.001 [PubMed]
- 30366556 Figueiredo AHA, Brouwer MC, van de Beek D. Acute Community-Acquired Bacterial Meningitis. Neurol Clin. 2018 Nov;36(4):809-820. doi: 10.1016/j.ncl.2018.06.007 [PubMed]
- 30921087 Stahl JP, Mailles A. Herpes simplex virus encephalitis update. Curr Opin Infect Dis. 2019 Jun;32(3):239-243. doi: 10.1097/QCO.0000000000000554 [PubMed]
- 31021955 Hasbun R. Update and advances in community acquired bacterial meningitis. Curr Opin Infect Dis. 2019 Jun;32(3):233-238. doi: 10.1097/QCO.0000000000000543 [PubMed]
- 31306182 Robinson CP, Busl KM. Meningitis and encephalitis management in the ICU. Curr Opin Crit Care. 2019 Oct;25(5):423-429. doi: 10.1097/MCC.0000000000000640 [PubMed]
- 31402154 Hoen B, Varon E, de Debroucker T, Fantin B, Grimprel E, Wolff M, Duval X; expert and reviewing group. Management of acute community-acquired bacterial meningitis (excluding newborns). Long version with arguments. Med Mal Infect. 2019 Sep;49(6):405-441. doi: 10.1016/j.medmal.2019.03.009 [PubMed]
- 31485117 Patra A, Janu A, Sahu A. MR Imaging in Neurocritical Care. Indian J Crit Care Med. 2019 Jun;23(Suppl 2):S104-S114. doi: 10.5005/jp-journals-10071-23186. [PubMed]
- Torbey, M. T. (2019). Neurocritical Care (2nd ed.). Cambridge University Press.
- 31731899 Gadde JA, Weinberg BD, Mullins ME. Neuroimaging of Patients in the Intensive Care Unit: Pearls and Pitfalls. Radiol Clin North Am. 2020 Jan;58(1):167-185. doi: 10.1016/j.rcl.2019.08.003 [PubMed]
- 31964490 Nguyen I, Urbanczyk K, Mtui E, Li S. Intracranial CNS Infections: A Literature Review and Radiology Case Studies. Semin Ultrasound CT MR. 2020 Feb;41(1):106-120. doi: 10.1053/j.sult.2019.09.003 [PubMed]
- 32778604 Kapadia RK, Tyler KL, Pastula DM. Encephalitis in adults caused by herpes simplex virus. CMAJ. 2020 Aug 10;192(32):E919. doi: 10.1503/cmaj.191636 [PubMed]
- 33223083 Aksamit AJ Jr. Treatment of Viral Encephalitis. Neurol Clin. 2021 Feb;39(1):197-207. doi: 10.1016/j.ncl.2020.09.011 [PubMed]
- 33767093 Wall EC, Chan JM, Gil E, Heyderman RS. Acute bacterial meningitis. Curr Opin Neurol. 2021 Jun 1;34(3):386-395. doi: 10.1097/WCO.0000000000000934 [PubMed]
- 33896533 McEntire CRS, Anand P, Cervantes-Arslanian AM. Neuroinfectious Disease Emergencies. Neurol Clin. 2021 May;39(2):565-588. doi: 10.1016/j.ncl.2021.02.003 [PubMed]
- 34303412 van de Beek D, Brouwer MC, Koedel U, Wall EC. Community-acquired bacterial meningitis. Lancet. 2021 Jul 22:S0140-6736(21)00883-7. doi: 10.1016/S0140-6736(21)00883-7 [PubMed]
- 34623095 Aksamit AJ Jr, Berkowitz AL. Meningitis. Continuum (Minneap Minn). 2021 Aug 1;27(4):836-854. doi: 10.1212/CON.0000000000001016 [PubMed]
- LaHue S.C. and Levin M. (2021). Emergency Neurology (What Do I Do Now) (2nd ed.). Oxford University Press.
- Louis ED, Mayer SA, Noble JM. (2021). Merritt’s Neurology (Fourteenth). LWW.
- 34798976 Bystritsky RJ, Chow FC. Infectious Meningitis and Encephalitis. Neurol Clin. 2022 Feb;40(1):77-91. doi: 10.1016/j.ncl.2021.08.006 [PubMed]
- 35665717 Bhimraj A, Hasbun R. Diagnostic approach and update on encephalitis. Curr Opin Infect Dis. 2022 Jun 1;35(3):231-237. doi: 10.1097/QCO.0000000000000832 [PubMed]
- 35738892 Alam AM, Easton A, Nicholson TR, Irani SR, Davies NW, Solomon T, Michael BD. Encephalitis: diagnosis, management and recent advances in the field of encephalitides. Postgrad Med J. 2022 Jun 23:postgradmedj-2022-141812. doi: 10.1136/postgradmedj-2022-141812 [PubMed]