Encephalitis implies inflammation of the brain parenchyma. It is manifest clinically by neurologic dysfunction. Encephalitis may occur during or after a viral infection. (See 'Encephalitis' above.)
●Encephalitis occurs predominantly among children, the elderly, immunocompromised hosts, and individuals who are exposed to arthropod vectors (table 5). (See 'Epidemiology' above.)
●In many cases of encephalitis, the etiology remains unknown despite extensive evaluation. Viruses are the most commonly diagnosed cause of encephalitis. Other infectious causes include bacteria, fungi, and parasites (table 3). (See 'Etiology' above.)
●The list of potential infectious pathogens may be narrowed according to clinical clues (table 2), location (or travel history) (table 4), and exposure to arthropod vectors (table 5). (See 'Viral pathogens' above and "Acute viral encephalitis in children and adolescents: Clinical manifestations and diagnosis".)
Initial evaluation and management of suspected encephalitis in children older than one month of age
| History |
| Symptoms: Altered mental status; decreased level of consciousness; lethargy; personality change; fever; seizure; ataxia |
| Travel |
| Exposure (animals, insects, freshwater swimming, toxins) |
| Immunizations |
| Immune status |
| Physical findings |
| Vital signs and general examination |
| Neurologic examination, particularly for focal findings and GCS |
| Laboratory studies |
| Screening laboratories: CBC; glucose; electrolytes; BUN; creatinine; ammonia; blood pH; blood cultures; LFTs; urinalysis; urine drug screen; save a sample of acute serum |
| Lumbar puncture: perform emergently, often after neuroimaging if a focal lesion is suspected; obtain opening pressure when clinically feasible; send CSF for cell count/differential, glucose, protein, bacterial culture, HSV PCR, enterovirus PCR; save a sample of CSF |
| Other laboratory tests to consider: influenza testing during influenza season; tests for toxic metabolic encephalopathy and inborn errors of metabolism (see text); antibody studies for NMDAR and VGKC (see text) |
| Ancillary studies |
| Neuroimaging: MRI preferred, but CT if MRI not promptly available, impractical, or cannot be performed |
| EEG: as soon as is feasible (for evidence of encephalitis or nonconvulsive seizure) |
| Treatment |
| Stabilization |
| Support airway, breathing and circulation: |
| Endotracheal intubation for GCS ≤8 or compromised airway |
| Fluid resuscitation with normal saline (20 mL/kg, initial bolus) for signs of shock |
| Obtain rapid glucose; treat if hypoglycemic with 2.5 mL/kg of 10 percent dextrose solution |
| Treat seizures with lorazepam (0.1 mg/kg intravenously) or equivalent benzodiazepine |
| Empiric therapy (initial dose)* |
| Treat for influenza, as indicated, during influenza season with oseltamivir (0 to 3 months: 12 mg orally; 4 to 5 months: 17 mg orally; 6 to 11 months: 24 mg orally; ≥12 months and ≤15 kg: 30 mg orally; 15 to 23 kg: 45 mg orally; 23 to 40 kg: 60 mg orally; >40 kg and/or >12 years old: 75 mg orally) |
| Administer acyclovir¶ (>28 days to <3 months: 20 mg/kg intravenously; ≥3 months to <12 years: 10 to 15 mg/kg intravenously; ≥12 years: 10 mg/kg intravenously) to all patients without a specific diagnosis other than HSV |
| Treat for bacterial meningitis as indicated (eg, vancomycin [15 mg/kg intravenously] plus either ceftriaxone [50 mg/kg intravenously] or cefotaxime [100 mg/kg intravenously])Δ |
| Treat for rickettsial infection (eg, Rocky Mountain spotted fever, Q fever) or ehrlichiosis in children at risk (doxycycline [2.2 mg/kg intravenously or orally])◊ |
GCS: Glasgow coma scale; CBC: complete blood count; BUN: blood urea nitrogen; LFT: liver function tests; CSF: cerebrospinal fluid; HSV: herpes simplex virus; PCR: polymerase chain reaction; NMDAR: anti-N-methyl-D-aspartate receptor; VGKC: voltage-gated potassium channel; MRI: magnetic resonance imaging; CT: computed tomography; EEG: electroencephalography.
* The medication doses listed in the section on "Empiric therapy" are initial doses. Please refer to the text for information about ongoing dosing and care.
¶ Presumptive treatment for herpes simplex virus.
Δ For patients in whom bacterial meningitis cannot be excluded.
◊ Exposure to ticks in endemic regions; exposure to cats, sheep, goats; blood smear characteristic of ehrlichiosis.
* The medication doses listed in the section on "Empiric therapy" are initial doses. Please refer to the text for information about ongoing dosing and care.
¶ Presumptive treatment for herpes simplex virus.
Δ For patients in whom bacterial meningitis cannot be excluded.
◊ Exposure to ticks in endemic regions; exposure to cats, sheep, goats; blood smear characteristic of ehrlichiosis.
Graphic 51779 Version 13.0
Clinical clues to viral infections of the central nervous system in children
| Etiology | Frequency of meningitis versus encephalitis* | Potential clinical clues | |
| Meningitis | Encephalitis | ||
| Enteroviruses | |||
| Coxsackie A and B viruses | Common | Rare | Herpangina, hand-foot-mouth disease, conjunctivitis, pharyngitis, pleurodynia, myopericarditis, rash |
| Echoviruses | Common | Rare | Rash |
| Polioviruses | Common | Rare | Flaccid paralysis |
| Arthropod-borne viruses (arboviruses) | |||
| West Nile virus | Infrequent | Common | Rash; mosquito exposure |
| St. Louis encephalitis virus | Common | Common | Mosquito exposure |
| La Crosse (California) encephalitis virus | Common | Common | Mosquito exposure |
| Eastern equine encephalitis virus | Rare | Common | Mosquito exposure |
| Western equine encephalitis virus | Common | Common | Mosquito exposure |
| Powassan virus | Uncommon | Common | Tick exposure |
| Herpesviruses | |||
| Herpes simplex type 1 | Rare | Common | Oral lesions |
| Herpes simplex type 2 | Common | Rare | Genital lesions, sacral radiculopathy (urinary retention, constipation, paresthesia, weakness) |
| Cytomegalovirus | Infrequent | Common | Immunocompromised host |
| Varicella zoster virus | Common | Infrequent | Vesicular rash; shingles |
| Epstein-Barr virus | Infrequent | Common | |
| Other viruses | |||
| Human immunodeficiency virus | Common | Common | Intravenous drug use, risky sexual behavior |
| Rabies virus | Rare | Common | Animal exposure; prodrome of nonspecific symptoms (fever, headache, malaise, myalgia, cough, sore throat, nausea, vomiting) |
| Lymphocytic choriomeningitis virus | Common | Infrequent | Rodent pets or contact with rodent droppings or urine |
| Influenza virus | Rare | Common | Classic influenza symptoms: fever, cough, vomiting, headache, diarrhea |
| Mumps virus | Common | Infrequent | Painful parotitis; occurs in unvaccinated or incompletely vaccinated individuals |
| Measles virus | Common | Rare | Conjunctivitis, coryza, cough; occurs in unvaccinated or incompletely vaccinated individuals |
* The terms common, infrequent, and rare refer to the propensity of a viral CNS infection to result in either meningitis or encephalitis and not to how commonly a specific virus causes CNS infection.
Graphic 56505 Version 4.0
Possible infectious etiologies of meningoencephalitis
|
|
Pathogens depicted in red may require specific antimicrobial therapy. Pathogens depicted in bold text are the most commonly isolated.
Courtesy of Hordur Hardarson, MD.
Graphic 62512 Version 8.0
Travel history and possible etiologic agent(s) of viral encephalitis
| Travel | Possible infectious agent(s) |
| Africa | Rabies virus, West Nile virus, Plasmodium falciparum, Dengue virus, Trypanosoma brucei gambiense, T. brucei rhodesiense |
| Australia | Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus |
| Central America | Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Dengue virus, Rickettsia rickettsii, P. falciparum, Taenia solium |
| Europe | West Nile virus, tick-borne encephalitis virus, Borrelia burgdorferi, Anaplasma phagocytophilum |
| India, Nepal | Rabies virus, Japanese encephalitis virus, P. falciparum, Dengue virus |
| Middle East | West Nile virus, P. falciparum |
| Russia | Tick-borne encephalitis virus |
| South America | Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Dengue virus, R. rickettsii,Bartonella bacilliformis (Andes mountain), P. falciparum, Taenia solium |
| Southeast Asia, China, Pacific Rim | Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnathostoma species, Taenia solium, Dengue virus |
Modified with permission from: Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303. Copyright © 2008 University of Chicago Press.
Graphic 73833 Version 4.0
Important viral zoonoses that cause encephalitis
| Family/virus | Vector | Vertebrate host | Ecology | Geographic distribution | Epidemics |
| Togaviridae | |||||
| Eastern equine encephalitis | Mosquitoes | Birds | R | Americas | Yes |
| Western equine encephalitis | Mosquitoes | Birds, rabbits | R | Americas | Yes |
| Venezuelan equine encephalitis | Mosquitoes | Rodents | R | Americas | Yes |
| Flaviviridae | |||||
| Dengue | Mosquitoes | Humans | R, S, U | Americas, Africa, Asia | |
| Japanese encephalitis | Mosquitoes | Birds | R, S | Asia | Yes |
| Murray Valley encephalitis | Mosquitoes | Birds | R | Australia | Yes |
| St. Louis encephalitis | Mosquitoes | Birds | R, S, U | Americas | Yes |
| West Nile encephalitis | Mosquitoes | Birds | R, S, U | Asia, Africa, North America, | Yes |
| Powassan | Ticks | R, S | Europe, Northern United States, Canada | No | |
| Tick-borne encephalitis | Ticks | Rodents | R | Europe, Asia | No |
| Bunyaviridae | |||||
| La Crosse encephalitis | Mosquitoes | Rodents | R, S | North America | No |
| California encephalitis | Mosquitoes | Rodents | R | North America, Europe, Asia | Yes |
| Reoviridae | |||||
| Colorado tick fever | Ticks | Rodents, small mammals | R | Western United States, Canada | No |
R: rural; S: suburban; U: urban.
Graphic 77283 Version 3.0
Acute viral encephalitis in children and adolescents: Clinical manifestations and diagnosis
Encephalitis causes neurologic dysfunction and has a broad range of presenting symptoms and signs. The clinical manifestations vary depending upon which portions of the central nervous system (CNS) are affected, the etiologic agent, and various host factors (eg, age, immune status). (See 'Presentation' above.)
●In neonates and young infants, encephalitis can present with fever, seizure, poor feeding, irritability, or lethargy; decreased perfusion may occur in infants with encephalitis and concomitant disseminated viral infection. Fever is a variable finding. (See 'Neonates and young infants' above.)
●In older children and adolescents, encephalitis can present with fever, psychiatric symptoms, emotional lability, movement disorder, ataxia, seizures, stupor, lethargy, coma, or localized neurologic changes. (See 'Children and adolescents' above.)
●The differential diagnosis of encephalitis is broad (table 3). It may be narrowed through history, examination, laboratory, and radiologic evaluation. Autoimmune encephalitis is an increasingly identified noninfectious etiology. (See 'Differential diagnosis' above.)
●The evaluation of the child with suspected encephalitis begins with assessment of the airway, breathing, and circulation. The first priorities are stabilization of cardiorespiratory status and management of seizures (table 1). (See "Initial assessment and stabilization of children with respiratory or circulatory compromise" and "Management of convulsive status epilepticus in children", section on 'Initial treatment'.)
●After the child is stabilized, the evaluation includes:
•History and examination (table 6 and table 7 and table 8) (see 'History' above and 'Examination' above)
•Neuroimaging (magnetic resonance imaging [MRI] is preferred, but because it is generally not available in the acute setting, many children undergo computed tomography before lumbar puncture [LP] to exclude contraindications, and MRI after LP) (see 'Neuroimaging' above)
•Electroencephalography (EEG) (see 'Electroencephalogram' above)
●The goals of the evaluation are to define the clinical syndrome (eg, acute encephalitis, postinfectious encephalitis, autoimmune encephalitis, meningitis, toxic or metabolic encephalopathy, etc) and to identify a specific etiology (table 2 and table 3). It is particularly important to consider etiologies that require specific therapy. (See 'Overview' above.)
●Clinical diagnosis of encephalitis requires evidence of neurologic dysfunction (encephalopathy) and CNS inflammation (eg, cerebrospinal fluid [CSF] pleocytosis, findings consistent with encephalitis on neuroimaging or EEG). Other causes of altered brain function must be excluded (table 3). (See 'Diagnostic criteria' above.)
●The causative viral pathogen may be identified through testing of the CSF (eg, polymerase chain reaction, IgM antibodies) and/or testing of anatomic sites other than the CNS (eg, stool culture, serology). (See 'Etiologic diagnosis' above and 'Laboratory evaluation' above.)
Conditions that mimic viral encephalitis (all of these conditions require specific therapy)
| Condition | Potential clues |
| Bacterial infections | |
| Bacterial meningitis | Meningeal signs; CSF pleocytosis with predominance of polymorphonuclear cells |
| CNS tuberculosis | Residing in, travel to, or exposure to contact from endemic areas (Asia, Africa, Latin America, Eastern Europe); contact with an adult with tuberculosis; lacunar infarction; hydrocephalus; low CSF glucose and elevated CSF protein |
| Parameningeal infection | |
| Listeriosis | Age <1 month; immune compromise; rhomboencephalitis (ataxia, cranial nerve deficits, nystagmus) |
| Cat scratch disease | Cat bite/scratch; regional lymphadenopathy; neuroretinitis |
| Parasitic infections | |
| Amoebiasis | Immune compromise; swimming in lakes/brackish water; travel to an endemic area; change in taste or smell |
| Cerebral malaria | Travel to endemic area without prophylaxis |
| Toxoplasmosis | Immune compromise; extrapyramidal symptoms and signs |
| Cysticercosis | Travel to endemic area; seizures, hydrocephalus; ingestion of undercooked pork |
| Echinococcus (tapeworm) | Hydatid cysts |
| Trichinosis | Gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea); ingestion of bear meat or other potentially contaminated foods |
| Fungal infections | |
| Histoplasmosis | Residing in or travel to endemic area (eastern and central US and Canada) |
| Blastomycosis | Residing in or travel to endemic area (in the US, southeastern, central, and states bordering the Great Lakes) |
| Cryptococcus | Immune compromise; exposure to bird droppings |
| Coccidiomycosis | Residing in or travel to endemic areas, such as the southwestern United States |
| Candidiasis | Immune compromise |
| Rickettsial infection | |
| Rocky Mountain spotted fever | Tick exposure in endemic region; maculopapular/petechial rash; intractable seizures |
| Murine typhus | Flea exposure |
| Q fever | Exposure to cats, sheep, goats (particularly placental tissue, parturient fluids, newborn animals) |
| Ehrlichiosis | Tick exposure, rash, leukopenia, thrombocytopenia |
| Other central nervous system conditions | |
| Head trauma | History of trauma (may be absent in child abuse) |
| Hypertensive encephalopathy | Hypertension; exclusion of other causes |
| Intracranial hemorrhage | Neuroimaging; intracranial hemorrhage may be an indication for lumbar puncture |
| Intracranial thrombosis | Neuroimaging |
| Idiopathic intracranial hypertension (pseudotumor cerebri) | Visual obscurations, diplopia, cranial nerve palsy; papilledema; increased opening pressure during lumbar puncture |
| Status epilepticus (especially nonconvulsive seizures) | Electroencephalogram |
| Systemic lupus erythematosus | Arthritis, nephritis, dermatitis, leukopenia |
| Polyarteritis nodosa | Fever, weight loss, dermatitis, eosinophilia |
| Acute disseminated encephalomyelitis (ADEM, postinfectious encephalitis) | History of recent infection or immunization; multifocal neurologic signs and symptoms; neuroimaging |
| Tumor | Neuroimaging; increased opening pressure during lumbar puncture (however, lumbar puncture usually is not performed if a tumor is suspected) |
| Acute confusional migraine | History of migraine headaches; exclusion of other causes |
| Anti-N-methyl-D-asparate receptor encephalitis* | No identifiable infectious etiology; encephalitis with psychiatric manifestations |
| Metabolic disorders | |
| Hypoglycemia | Serum glucose |
| Uremic encephalopathy | Elevation of blood urea nitrogen, creatinine |
| Hepatic encephalopathy | Elevation of serum aminotransferases; increased opening pressure during lumbar puncture |
| Toxins | |
| Acute toxic ingestion | Toxicology screening; pupillary changes |
| Lead poisoning | History of lead exposure or pica; elevated blood lead level (confirmatory) |
| Reye syndrome | History of aspirin use; recent viral infection; increased opening pressure during lumbar puncture |
| Inborn errors of metabolism (eg, organic acidemia, urea cycle disorder, mitochondrial disorders, mitochondrial fatty acid oxidation disorders, etc) | Abnormal laboratory findings (eg, hypoglycemia, hyperammonemia, acidosis) |
CNS: central nervous system; CSF: cerebrospinal fluid.
* Associated with certain tumors (eg, ovarian teratoma).
* Associated with certain tumors (eg, ovarian teratoma).
Courtesy of Hordur Hardarson, MD.
Graphic 68501 Version 6.0
Typical cerebrospinal fluid findings in central nervous system infections*
| Glucose (mg/dL) | Protein (mg/dL) | Total white blood cell count (cells/microL) | |||||
| <10¶ | 10 to 40Δ | 100 to 500◊ | 50 to 300§ | >1000 | 100 to 1000 | 5 to 100 | |
| More common | Bacterial meningitis | Bacterial meningitis | Bacterial meningitis |
Viral meningitis
Nervous system Lyme disease (neuroborreliosis)
Neurosyphilis
TB meningitis¥ | Bacterial meningitis |
Bacterial or viral meningitis
TB meningitis |
Early bacterial meningitis
Viral meningitis
Neurosyphilis
TB meningitis |
| Less common |
TB meningitis
Fungal meningitis |
Neurosyphilis
Some viral infections (such as mumps and LCMV) | Some cases of mumps and LCMV | Encephalitis | Encephalitis | ||
TB: tuberculosis; LCMV: lymphocytic choriomeningitis virus.
* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so wide that the absence of one or more of these findings is of little value. Refer to the UpToDate topic reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous meningitis; concentrations >500 mg/dL are an indication of blood-brain barrier disruption or increased intracerebral production of immunoglobulins, and extremely high concentrations, in the range of 2 to 6 g/dL, may be found in association with subarachnoid block.
* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so wide that the absence of one or more of these findings is of little value. Refer to the UpToDate topic reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous meningitis; concentrations >500 mg/dL are an indication of blood-brain barrier disruption or increased intracerebral production of immunoglobulins, and extremely high concentrations, in the range of 2 to 6 g/dL, may be found in association with subarachnoid block.
Graphic 76324 Version 9.0
Poisoning syndromes (toxidromes)
| Toxidrome | Mental status | Pupils | Vital signs | Other manifestations | Examples of toxic agents |
| Sympathomimetic | Hyperalert, agitation, hallucinations, paranoia | Mydriasis | Hyperthermia, tachycardia, hypertension, widened pulse pressure, tachypnea, hyperpnea | Diaphoresis, tremors, hyperreflexia, seizures | Cocaine, amphetamines, cathinones, ephedrine, pseudoephedrine, phenylpropanolamine, theophylline, caffeine |
| Anticholinergic | Hypervigilance, agitation, hallucinations, delirium with mumbling speech, coma | Mydriasis | Hyperthermia, tachycardia, hypertension, tachypnea | Dry flushed skin, dry mucous membranes, decreased bowel sounds, urinary retention, myoclonus, choreoathetosis, picking behavior, seizures (rare) | Antihistamines, tricyclic antidepressants, cyclobenzaprine, orphenadrine, antiparkinson agents, antispasmodics, phenothiazines, atropine, scopolamine, belladonna alkaloids (eg, Jimson Weed) |
| Hallucinogenic | Hallucinations, perceptual distortions, depersonalization, synesthesia, agitation | Mydriasis (usually) | Hyperthermia, tachycardia, hypertension, tachypnea | Nystagmus | Phencyclidine, LSD, mescaline, psilocybin, designer amphetamines (eg, MDMA ["Ecstasy"], MDEA) |
| Opioid | CNS depression, coma | Miosis | Hypothermia, bradycardia, hypotension, apnea, bradypnea | Hyporeflexia, pulmonary edema, needle marks | Opioids (eg, heroin, morphine, methadone, oxycodone, hydromorphone), diphenoxylate |
| Sedative-hypnotic | CNS depression, confusion, stupor, coma | Variable | Hypothermia, bradycardia, hypotension, apnea, bradypnea | Hyporeflexia | Benzodiazepines, barbiturates, carisoprodol, meprobamate, glutethimide, alcohols, zolpidem |
| Cholinergic | Confusion, coma | Miosis | Bradycardia, hypertension orhypotension, tachypnea or bradypnea | Salivation, urinary and fecal incontinence, diarrhea, emesis, diaphoresis, lacrimation, GI cramps, bronchoconstriction, muscle fasciculations and weakness, seizures | Organophosphate and carbamate insecticides, nerve agents, nicotine, pilocarpine, physostigmine, edrophonium, bethanechol, urecholine |
| Serotonin syndrome | Confusion, agitation, coma | Mydriasis | Hyperthermia, tachycardia, hypertension, tachypnea | Tremor, myoclonus, hyperreflexia, clonus, diaphoresis, flushing, trismus, rigidity, diarrhea | MAOIs alone or with: SSRIs, meperidine, dextromethorphan, TCAs, L-tryptophan |
LSD: lysergic acid diethylamide; CNS: central nervous system; GI: gastrointestinal; MAOI: monoamine oxidase inhibitor; SSRI: serotonin reuptake inhibitor; TCA: tricyclic antidepressant.
Graphic 71268 Version 13.0
Epidemiologic and historic clues to the etiology of encephalitis in children
| Epidemiologic clues | Potential etiologies |
| Age (0 to 28 days) |
Infectious: CMV, HSV-2 or HSV-1, rubella virus
Noninfectious: Inborn error of metabolism (eg, organic acidemia, urea cycle disorder) |
| Season: | |
| Summer | Enterovirus, free living amebae |
| Late summer/fall | Arbovirus |
| Winter | Postinfectious encephalitis in countries with low rates of MMR immunization |
| Infection in horses, birds | Arbovirus, Hendra virus |
| Blood transfusion or transplant recipient | CMV, EBV, HIV, rabies, tick-borne encephalitis, WNV |
| Immunodeficiency | CMV, enterovirus, HHV6, HSV, VZV, WNV |
| Historical clues | |
| Rash | |
| Vesicular | HSV, VZV, enterovirus (hand, foot, and mouth disease), herpes B virus |
| Hand, foot, mouth | Enterovirus |
| Erythematous macules and papules with cephalocaudad spread | Measles |
| Maculopapular | WNV |
| Maculopapular/petechial begins on ankles and wrists | Rocky Mountain spotted fever |
| Exposures | |
| Mosquitoes | Arbovirus |
| Ticks | Borrelia burgdorferi, Powassan virus, Rickettsia rickettsii, tick-borne encephalitis |
| Animal bite/exposure (dog, bat, cat, birds, livestock, others) | Rabies, arboviruses, cat scratch disease, Q fever |
| Blood transfusion or transplant recipient | CMV, EBV, HIV, rabies, tick-borne encephalitis, WNV |
| Recent infectious illness | ADEM |
| Recreational activity | |
| Swimming | Enteroviruses, free-living amebae |
| Spelunking | Rabies |
| Sexual activity | HIV, Treponema pallidum |
| Travel | |
| Immunization | |
| Lack of immunization for specific agent | Japanese encephalitis, measles, mumps, rubella, VZV, polio |
| Recent immunization | ADEM |
CMV: cytomegalovirus; HSV: herpes simplex virus; MMR: measles, mumps, rubella; EBV: Epstein-Barr virus; HIV: human immunodeficiency virus; WNV: West Nile virus; HHV6: human herpesvirus 6; VZV: varicella zoster virus; ADEM: acute disseminated encephalomyelitis.
Data from:
- Willoughby RE, Long SS. Encephalitis, meningoencephalitis, acute disseminated encephalomyelitis, and acute necrotizing encephalopathy. In: Principles and Practice of Pediatric Infectious Diseases, 2nd ed, Long SS, Pickering LK, Prober CG (Eds), Churchill Livingstone, New York 2008. p.310.
- Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303.
- Bronstein DE, Shields WD, Glaser CA. Encephalitis and meningoencephalitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.492.
Graphic 57122 Version 8.0
Travel history and possible etiologic agent(s) of viral encephalitis
| Travel | Possible infectious agent(s) |
| Africa | Rabies virus, West Nile virus, Plasmodium falciparum, Dengue virus, Trypanosoma brucei gambiense, T. brucei rhodesiense |
| Australia | Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus |
| Central America | Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Dengue virus, Rickettsia rickettsii, P. falciparum, Taenia solium |
| Europe | West Nile virus, tick-borne encephalitis virus, Borrelia burgdorferi, Anaplasma phagocytophilum |
| India, Nepal | Rabies virus, Japanese encephalitis virus, P. falciparum, Dengue virus |
| Middle East | West Nile virus, P. falciparum |
| Russia | Tick-borne encephalitis virus |
| South America | Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Dengue virus, R. rickettsii,Bartonella bacilliformis (Andes mountain), P. falciparum, Taenia solium |
| Southeast Asia, China, Pacific Rim | Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnathostoma species, Taenia solium, Dengue virus |
Modified with permission from: Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303. Copyright © 2008 University of Chicago Press.
Graphic 73833 Version 4.0
Clinical findings and possible etiologic agent(s) in encephalitis
| Clinical presentation | Possible infectious agent(s) |
| General findings | |
| Hepatitis | Herpes simplex virus (infant only), enterovirus (in infants), Coxiella burnetii; any severe hepatitis can cause encephalopathy |
| Lymphadenopathy | HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other bartonella species,Mycobacterium tuberculosis, Toxoplasma gondii, Trypansoma brucei gambiense |
| Parotitis | Mumps virus |
| Rash | Herpes simplex virus, varicella zoster virus, herpes B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii,Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum |
| Respiratory tract findings | Venezuelan equine encephalitis virus, Nipha virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum |
| Retinitis | Cytomegalovirus, T. gondii, West Nile virus, B. henselae, T. pallidum |
| Urinary symptoms (dysuria, urgency, incontinence) | St. Louis encephalitis virus (during prodrome) |
| Neurologic findings | |
| Cerebellar ataxia | Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense |
| Cranial nerve abnormalities | Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans,Coccidioides species, H. capsulatum |
| Dementia | HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles, T. pallidum, T. whipplei |
| Myorhythmia | T. whipplei (oculomasticatory) |
| Parkinsonism (bradykinesia, masked facies, cogwheel rigidity, postural instability) | Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense |
| Poliomyelitis-like flaccid paralysis | Japanese encephalitis virus, West Nile virus, tick-borne encephalitis virus, enteroviruses (enterovirus 71, coxsackieviruses), poliovirus |
| Rhomboencephalitis | Enterovirus 71, herpes simplex virus, West Nile virus, L. monocytogenes |
Modified with permission from: Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303. Copyright © 2008 University of Chicago Press.
Graphic 71744 Version 5.0
Glasgow Coma Scale and Pediatric Glasgow Coma Scale
| Sign | Glasgow Coma Scale[1] | Pediatric Glasgow Coma Scale[2] | Score |
| Eye opening | Spontaneous | Spontaneous | 4 |
| To command | To sound | 3 | |
| To pain | To pain | 2 | |
| None | None | 1 | |
| Verbal response | Oriented | Age-appropriate vocalization, smile, or orientation to sound, interacts (coos, babbles), follows objects | 5 |
| Confused, disoriented | Cries, irritable | 4 | |
| Inappropriate words | Cries to pain | 3 | |
| Incomprehensible sounds | Moans to pain | 2 | |
| None | None | 1 | |
| Motor response | Obeys commands | Spontaneous movements (obeys verbal command) | 6 |
| Localizes pain | Withdraws to touch (localizes pain) | 5 | |
| Withdraws | Withdraws to pain | 4 | |
| Abnormal flexion to pain | Abnormal flexion to pain (decorticate posture) | 3 | |
| Abnormal extension to pain | Abnormal extension to pain (decerebrate posture) | 2 | |
| None | None | 1 | |
| Best total score | 15 | ||
The Glasgow Coma Scale (GCS) is scored between 3 and 15, 3 being the worst, and 15 the best. It is composed of three parameters: best eye response (E), best verbal response (V), and best motor response (M). The components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS of 9. A score of 13 or higher correlates with mild brain injury; a score of 9 to 12 correlates with moderate injury; and a score of 8 or less represents severe brain injury. The pediatric Glasgow coma scale (PGCS) was validated in children two years of age or younger.
Data from:
- Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2:81.
- Holmes JF, Palchak MJ, MacFarlane T, Kuppermann N. Performance of the pediatric Glasgow coma scale in children with blunt head trauma. Acad Emerg Med 2005; 12:814.
Graphic 59662 Version 11.0
Neonatal herpes simplex virus scalp vesicles
Scalp lesions of neonate with skin, eye, and mouth neonatal herpes simplex virus (HSV) infection associated with fetal scalp monitor. Gram-stained smear and bacterial cultures were negative, and the lesions did not respond to topical and systemic antibiotics. Viral cultures grew HSV type 2, and the lesions responded to intravenous acyclovir.
Courtesy of Jane Troendle-Atkins, MD, and Gail J Demmler-Harrison, MD, Texas Children's Hospital.
Graphic 56041 Version 2.0
Neck vesicles in neonate with herpes simplex virus infection
The early, untreated skin lesions associated with neonatal herpes simplex virus (HSV) infection are characteristically clear vesicles on an erythematous base, often touching or "kissing," or coalesced in groups of vesicles. Culture of the clear fluid aspirated or swabbed from the vesicles will readily grow HSV in 24 to 48 hours, and slides made from cells scraped from the base of the lesion will show HSV viral antigens by direct immunofluorescence assay (DFA).
Courtesy of Gail J Demmler-Harrison, MD, Texas Children's Hospital.
Graphic 75059 Version 2.0
Eye vesicles in neonate with herpes simplex virus infection
Neonate with herpes simplex virus (HSV) infection of the eye, showing characteristic coalescing vesicles on an erythematous base on eyelid and surrounding skin. Ophthalmologic evaluation of the eye should also be performed to determine if keratitis or keratoconjunctivitis is present.
Courtesy of Jenny Ravenscroft, MD, and Gail J Demmler-Harrison, MD, Department of Pediatrics, Texas Children's Hospital.
Graphic 78598 Version 2.0
West Nile virus fever and rash
Four patients with West Nile virus fever and erythematous, maculopapular rashes on the back (top left), flank (top right), posterior thigh (bottom left), and back (bottom right).
Reproduced with permission from: Ferguson DD, Gershman K, LeBailly A, Petersen LR. Characteristics of the rash associated with West Nile Virus fever. Clin Infect Dis 2005; 41:1204. Copyright © 2005 University of Chicago Press.
Graphic 54623 Version 2.0
Hand-foot-and-mouth disease - lip and hand
(A) Oral lesion: note the oval shape and rim of erythema.
(B) Oval intact vesicles are noted on the palm.
(B) Oval intact vesicles are noted on the palm.
Reproduced with permission from: Goodheart HP. Goodheart's Photoguide of Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins, Philadelphia 2003. Copyright © 2003 Lippincott Williams & Wilkins.
Graphic 52800 Version 6.0
Hand-foot-and-mouth disease
Small ulcers are present on the oral mucosa.
Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.
Graphic 58566 Version 5.0
Hand-foot-and-mouth disease
Multiple small ulcers are present on the tongue.
Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.
Graphic 71314 Version 4.0
Hand-foot-and-mouth disease
Multiple vesicular lesions on an erythematous base are present on the foot.
Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.
Graphic 53423 Version 5.0
Rocky mountain spotted fever rash
Child with Rocky Mountain spotted fever has the rash that is characteristic but typically does not appear until several days after fever onset.
From: Fatal Cases of Rocky Mountain Spotted Fever in Family Clusters --- Three States, 2003. MMWR Morb Mortal Wkly Rep 2004; 53(19):407.http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5319a1.htm.
Graphic 58061 Version 4.0
Suggested initial laboratory evaluation for children and adolescents with encephalitis
| For nonimmunocompromised patients |
| Blood |
| Complete blood count with differential count and platelets |
| Blood culture |
| Serum electrolytes, glucose, ammonia, blood urea nitrogen, creatinine; blood pH |
| Serum aminotransferases (alanine aminotransferase, aspartate aminotransferase) |
| Coagulation studies |
| Serology for EBV, HIV, and Mycoplasma pneumoniae (IgM and IgG) |
| Anti-NMDAR and anti-VGKC antibodies if clinically indicated |
| Acute serum sample (to hold for subsequent serologic testing if necessary) |
| CSF |
| Opening pressure (when feasible) |
| Cell count, differential, protein, glucose, Gram stain, acid fast stain |
| Bacterial culture; M. tuberculosis culture (if clinically indicated) |
| PCR: HSV, enterovirus (PCR for other Herpesviridae, WNV, influenza, and other pathogens, as indicated by history and epidemiology) |
| CSF sample (to hold for subsequent testing) |
| Respiratory samples |
| Respiratory panel (PCR) (influenza, adenovirus, human metapneumovirus, and respiratory syncytial virus) |
| Viral culture of respiratory secretions and nasopharynx |
| Throat swab for HSV, enterovirus, M. pneumoniae |
| Stool (or rectal swab) |
| Viral culture of stool |
| Enterovirus PCR |
| Urine |
| Urinalysis |
| Urine toxicology screen |
| Skin lesions (if present) |
| Biopsy for DFA and PCR for R. rickettsia |
| Culture and/or DFA of skin lesions for HSV, VZV, and enteroviruses |
| For immunocompromised patients |
| Above tests, plus: |
| Blood: Serum cryptococcal antigen, Toxoplasma gondii IgG |
| CSF: Cryptococcal antigen, Histoplasma antigen; PCR for CMV, CJ, HHV6, WNV |
| Urine: Histoplasma antigen |
EBV: Epstein-Barr virus; HIV: human immunodeficiency virus; NMDAR: N-methyl-D-aspartate receptor; VGKC: voltage-gated potassium channel; CSF: cerebrospinal fluid; PCR: polymerase chain reaction; HSV: herpes simplex virus; WNV: West Nile virus; DFA: direct fluorescent antibody; VZV: varicella zoster virus; CMV: cytomegalovirus; CJ: Creutzfeldt-Jakob disease; HHV6: human herpesvirus 6.
Data from:
- Willoughby RE, Long SS. Encephalitis, meningoencephalitis, acute disseminated encephalomyelitis, and acute necrotizing encephalopathy. In: Principles and Practice of Pediatric Infectious Diseases, 2nd ed, Long SS, Pickering LK, Prober CG (Eds), Churchill Livingstone, New York 2008. p.310.
- Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303.
- Bronstein DE, Shields WD, Glaser CA. Encephalitis and meningoencephalitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.492.
Graphic 63632 Version 6.0
Causes of intracranial hypertension
| Traumatic brain injury/intracranial hemorrhage |
| Subdural, epidural, or intraparenchymal hemorrhage |
| Ruptured aneurysm |
| Diffuse axonal injury |
| Arteriovenous malformation or other vascular anomalies |
| Central nervous system infections (eg, encephalitis, meningitis, abscess) |
| Ischemic stroke |
| Neoplasm |
| Vasculitis |
| Hydrocephalus |
| Idiopathic intracranial hypertension (pseudotumor cerebri) |
| Idiopathic |
Graphic 69683 Version 5.0
Herpes virus encephalitis magnetic resonance imaging
T2-weighted MR image shows the entire left temporal lobe to be swollen and to show abnormal hyperintensity of cortex and white matter from edema (open arrow). In addition, notice similar but less extensive changes on the right (small arrow).
MR: magnetic resonance.
Reproduced with permission from: Wolters Kluwer. Copyright ©2008.
Graphic 80797 Version 3.0
Brain and spine MRI of a 7 year old boy with acute disseminated encephalomyelitis (ADEM)
Axial T2-weighted magnetic resonance imaging (MRI) of the brain show relatively symmetric high signal intensity in the deep gray matter, including bilateral thalami (panel A). There is also high T2 signal within the left aspect of the pons (panel B). Sagittal T2-weighted MRI of the cervical spine demonstrates expansion/swelling and high signal intensity within the spinal cord (panel C), and corresponding axial T2-weighted MRI reveal that the high signal is mostly posterior (panel D). One month later, T2-weighted axial images demonstrate resolution of the findings in the deep gray matter (panel E) and pons (panel F).
Courtesy of Eric D Schwartz, MD.
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Computed tomography: Intracranial calcifications in congenital cytomegalovirus infection
Intracranial computed tomography of an infant born with congenital cytomegalovirus disease and central nervous system involvement. Scan shows classic linear periventricular calcifications and cortical atrophy. The infant had microcephaly at birth and developmental disabilities and major motor impairment at eight years of age.
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Acute viral encephalitis in children and adolescents: Treatment and prevention
Provision of empiric antimicrobial therapy and supportive care are the cornerstones of therapy for viral encephalitis in children and adolescents (table 2). (See 'Overview of treatment' above.)
●We recommend prompt initiation of empiric acyclovir for children with encephalitis (Grade 1A). (See 'Empiric acyclovir' above and "Herpes simplex virus type 1 encephalitis" and "Neonatal herpes simplex virus infection: Management and prevention", section on 'Acyclovir therapy'.)
●Empiric treatment for bacterial meningitis (vancomycin PLUS a third-generation cephalosporin [ceftriaxone or cefotaxime]) also may be warranted if bacterial meningitis cannot be excluded. (See 'Bacterial meningitis' above and "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)
●Empiric treatment for rickettsiae and ehrlichiosis (doxycycline) should be provided if there is epidemiologic or clinical information to support these infections. (See 'Rickettsial infection' above and 'Ehrlichiosis' above.)
●Children with severe encephalitis should be cared for in an intensive care unit with cardiorespiratory monitoring and careful attention to fluid and electrolyte status. Potential complications include status epilepticus, cerebral edema, fluid and electrolyte disturbance, cardiorespiratory failure, gastrointestinal bleeding, and disseminated intravascular coagulation. (See 'Supportive care' above.)
●Strategies to prevent encephalitis include hand hygiene, cesarean delivery in women with active herpes simplex virus (HSV) lesions, immunization, and insect control and avoidance measures. (See 'Primary prevention'above.)
●Patients who are hospitalized with encephalitis should be placed on airborne, droplet, and contact precautions at the time of admission, pending identification of a pathogen. (See 'Infection control' above.)
Conditions that mimic viral encephalitis (all of these conditions require specific therapy)
| Condition | Potential clues |
| Bacterial infections | |
| Bacterial meningitis | Meningeal signs; CSF pleocytosis with predominance of polymorphonuclear cells |
| CNS tuberculosis | Residing in, travel to, or exposure to contact from endemic areas (Asia, Africa, Latin America, Eastern Europe); contact with an adult with tuberculosis; lacunar infarction; hydrocephalus; low CSF glucose and elevated CSF protein |
| Parameningeal infection | |
| Listeriosis | Age <1 month; immune compromise; rhomboencephalitis (ataxia, cranial nerve deficits, nystagmus) |
| Cat scratch disease | Cat bite/scratch; regional lymphadenopathy; neuroretinitis |
| Parasitic infections | |
| Amoebiasis | Immune compromise; swimming in lakes/brackish water; travel to an endemic area; change in taste or smell |
| Cerebral malaria | Travel to endemic area without prophylaxis |
| Toxoplasmosis | Immune compromise; extrapyramidal symptoms and signs |
| Cysticercosis | Travel to endemic area; seizures, hydrocephalus; ingestion of undercooked pork |
| Echinococcus (tapeworm) | Hydatid cysts |
| Trichinosis | Gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea); ingestion of bear meat or other potentially contaminated foods |
| Fungal infections | |
| Histoplasmosis | Residing in or travel to endemic area (eastern and central US and Canada) |
| Blastomycosis | Residing in or travel to endemic area (in the US, southeastern, central, and states bordering the Great Lakes) |
| Cryptococcus | Immune compromise; exposure to bird droppings |
| Coccidiomycosis | Residing in or travel to endemic areas, such as the southwestern United States |
| Candidiasis | Immune compromise |
| Rickettsial infection | |
| Rocky Mountain spotted fever | Tick exposure in endemic region; maculopapular/petechial rash; intractable seizures |
| Murine typhus | Flea exposure |
| Q fever | Exposure to cats, sheep, goats (particularly placental tissue, parturient fluids, newborn animals) |
| Ehrlichiosis | Tick exposure, rash, leukopenia, thrombocytopenia |
| Other central nervous system conditions | |
| Head trauma | History of trauma (may be absent in child abuse) |
| Hypertensive encephalopathy | Hypertension; exclusion of other causes |
| Intracranial hemorrhage | Neuroimaging; intracranial hemorrhage may be an indication for lumbar puncture |
| Intracranial thrombosis | Neuroimaging |
| Idiopathic intracranial hypertension (pseudotumor cerebri) | Visual obscurations, diplopia, cranial nerve palsy; papilledema; increased opening pressure during lumbar puncture |
| Status epilepticus (especially nonconvulsive seizures) | Electroencephalogram |
| Systemic lupus erythematosus | Arthritis, nephritis, dermatitis, leukopenia |
| Polyarteritis nodosa | Fever, weight loss, dermatitis, eosinophilia |
| Acute disseminated encephalomyelitis (ADEM, postinfectious encephalitis) | History of recent infection or immunization; multifocal neurologic signs and symptoms; neuroimaging |
| Tumor | Neuroimaging; increased opening pressure during lumbar puncture (however, lumbar puncture usually is not performed if a tumor is suspected) |
| Acute confusional migraine | History of migraine headaches; exclusion of other causes |
| Anti-N-methyl-D-asparate receptor encephalitis* | No identifiable infectious etiology; encephalitis with psychiatric manifestations |
| Metabolic disorders | |
| Hypoglycemia | Serum glucose |
| Uremic encephalopathy | Elevation of blood urea nitrogen, creatinine |
| Hepatic encephalopathy | Elevation of serum aminotransferases; increased opening pressure during lumbar puncture |
| Toxins | |
| Acute toxic ingestion | Toxicology screening; pupillary changes |
| Lead poisoning | History of lead exposure or pica; elevated blood lead level (confirmatory) |
| Reye syndrome | History of aspirin use; recent viral infection; increased opening pressure during lumbar puncture |
| Inborn errors of metabolism (eg, organic acidemia, urea cycle disorder, mitochondrial disorders, mitochondrial fatty acid oxidation disorders, etc) | Abnormal laboratory findings (eg, hypoglycemia, hyperammonemia, acidosis) |
CNS: central nervous system; CSF: cerebrospinal fluid.
* Associated with certain tumors (eg, ovarian teratoma).
* Associated with certain tumors (eg, ovarian teratoma).
Courtesy of Hordur Hardarson, MD.
Graphic 68501 Version 6.0
Initial evaluation and management of suspected encephalitis in children older than one month of age
| History |
| Symptoms: Altered mental status; decreased level of consciousness; lethargy; personality change; fever; seizure; ataxia |
| Travel |
| Exposure (animals, insects, freshwater swimming, toxins) |
| Immunizations |
| Immune status |
| Physical findings |
| Vital signs and general examination |
| Neurologic examination, particularly for focal findings and GCS |
| Laboratory studies |
| Screening laboratories: CBC; glucose; electrolytes; BUN; creatinine; ammonia; blood pH; blood cultures; LFTs; urinalysis; urine drug screen; save a sample of acute serum |
| Lumbar puncture: perform emergently, often after neuroimaging if a focal lesion is suspected; obtain opening pressure when clinically feasible; send CSF for cell count/differential, glucose, protein, bacterial culture, HSV PCR, enterovirus PCR; save a sample of CSF |
| Other laboratory tests to consider: influenza testing during influenza season; tests for toxic metabolic encephalopathy and inborn errors of metabolism (see text); antibody studies for NMDAR and VGKC (see text) |
| Ancillary studies |
| Neuroimaging: MRI preferred, but CT if MRI not promptly available, impractical, or cannot be performed |
| EEG: as soon as is feasible (for evidence of encephalitis or nonconvulsive seizure) |
| Treatment |
| Stabilization |
| Support airway, breathing and circulation: |
| Endotracheal intubation for GCS ≤8 or compromised airway |
| Fluid resuscitation with normal saline (20 mL/kg, initial bolus) for signs of shock |
| Obtain rapid glucose; treat if hypoglycemic with 2.5 mL/kg of 10 percent dextrose solution |
| Treat seizures with lorazepam (0.1 mg/kg intravenously) or equivalent benzodiazepine |
| Empiric therapy (initial dose)* |
| Treat for influenza, as indicated, during influenza season with oseltamivir (0 to 3 months: 12 mg orally; 4 to 5 months: 17 mg orally; 6 to 11 months: 24 mg orally; ≥12 months and ≤15 kg: 30 mg orally; 15 to 23 kg: 45 mg orally; 23 to 40 kg: 60 mg orally; >40 kg and/or >12 years old: 75 mg orally) |
| Administer acyclovir¶ (>28 days to <3 months: 20 mg/kg intravenously; ≥3 months to <12 years: 10 to 15 mg/kg intravenously; ≥12 years: 10 mg/kg intravenously) to all patients without a specific diagnosis other than HSV |
| Treat for bacterial meningitis as indicated (eg, vancomycin [15 mg/kg intravenously] plus either ceftriaxone [50 mg/kg intravenously] or cefotaxime [100 mg/kg intravenously])Δ |
| Treat for rickettsial infection (eg, Rocky Mountain spotted fever, Q fever) or ehrlichiosis in children at risk (doxycycline [2.2 mg/kg intravenously or orally])◊ |
GCS: Glasgow coma scale; CBC: complete blood count; BUN: blood urea nitrogen; LFT: liver function tests; CSF: cerebrospinal fluid; HSV: herpes simplex virus; PCR: polymerase chain reaction; NMDAR: anti-N-methyl-D-aspartate receptor; VGKC: voltage-gated potassium channel; MRI: magnetic resonance imaging; CT: computed tomography; EEG: electroencephalography.
* The medication doses listed in the section on "Empiric therapy" are initial doses. Please refer to the text for information about ongoing dosing and care.
¶ Presumptive treatment for herpes simplex virus.
Δ For patients in whom bacterial meningitis cannot be excluded.
◊ Exposure to ticks in endemic regions; exposure to cats, sheep, goats; blood smear characteristic of ehrlichiosis.
* The medication doses listed in the section on "Empiric therapy" are initial doses. Please refer to the text for information about ongoing dosing and care.
¶ Presumptive treatment for herpes simplex virus.
Δ For patients in whom bacterial meningitis cannot be excluded.
◊ Exposure to ticks in endemic regions; exposure to cats, sheep, goats; blood smear characteristic of ehrlichiosis.
Graphic 51779 Version 13.0
Possible infectious etiologies of meningoencephalitis
|
|
Pathogens depicted in red may require specific antimicrobial therapy. Pathogens depicted in bold text are the most commonly isolated.
Courtesy of Hordur Hardarson, MD.
Graphic 62512 Version 8.0
Typical cerebrospinal fluid findings in central nervous system infections*
| Glucose (mg/dL) | Protein (mg/dL) | Total white blood cell count (cells/microL) | |||||
| <10¶ | 10 to 40Δ | 100 to 500◊ | 50 to 300§ | >1000 | 100 to 1000 | 5 to 100 | |
| More common | Bacterial meningitis | Bacterial meningitis | Bacterial meningitis |
Viral meningitis
Nervous system Lyme disease (neuroborreliosis)
Neurosyphilis
TB meningitis¥ | Bacterial meningitis |
Bacterial or viral meningitis
TB meningitis |
Early bacterial meningitis
Viral meningitis
Neurosyphilis
TB meningitis |
| Less common |
TB meningitis
Fungal meningitis |
Neurosyphilis
Some viral infections (such as mumps and LCMV) | Some cases of mumps and LCMV | Encephalitis | Encephalitis | ||
TB: tuberculosis; LCMV: lymphocytic choriomeningitis virus.
* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so wide that the absence of one or more of these findings is of little value. Refer to the UpToDate topic reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous meningitis; concentrations >500 mg/dL are an indication of blood-brain barrier disruption or increased intracerebral production of immunoglobulins, and extremely high concentrations, in the range of 2 to 6 g/dL, may be found in association with subarachnoid block.
* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so wide that the absence of one or more of these findings is of little value. Refer to the UpToDate topic reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous meningitis; concentrations >500 mg/dL are an indication of blood-brain barrier disruption or increased intracerebral production of immunoglobulins, and extremely high concentrations, in the range of 2 to 6 g/dL, may be found in association with subarachnoid block.
Graphic 76324 Version 9.0
Rocky Mountain spotted fever. Number of reported cases, by county - United States, 2010
Although RMSF cases have been reported throughout most of the contiguous United States, five states (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri) account for over 60 percent of RMSF cases. The primary tick that transmits R. rickettsii in these states is the American dog tick (Dermacentor variabilis Dermacentor andersoni).
Reproduced from: Rocky Mountain Spotted Fever (RMSF): Statistics and Epidemiology. Centers for Disease Control and Prevention.http://www.cdc.gov/rmsf/stats/ (Access on September 13, 2013).
Graphic 68225 Version 2.0
Rocky mountain spotted fever rash
Child with Rocky Mountain spotted fever has the rash that is characteristic but typically does not appear until several days after fever onset.
From: Fatal Cases of Rocky Mountain Spotted Fever in Family Clusters --- Three States, 2003. MMWR Morb Mortal Wkly Rep 2004; 53(19):407.http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5319a1.htm.
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Approximate distribution of vector tick species for human monocytotropic ehrlichiosis and human granulocytotropic anaplasmosis
Champman AS, Bakken JS, Folk SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain Spotted Fever, Ehrlichioses, and Anaplasmosis -- United States: A practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep 2006; 55(RR-4):1.
Graphic 56962 Version 2.0
Wright-Giemsa stain morula
Wright-Giemsa stain of a buffy coat specimen revealed the presence of a morula, or cluster of intracellular coccobacilli, inside of a polymorphonuclear leukocyte (arrow).
Reproduced with permission from: Donato, AA, Chaudhary, A. Photo Quiz: A 78-Year-Old Man with the "Summer Flu" and Cytopenias. Clin Infect Dis 2009; 48:1433. Copyright ©2009 University of Chicago Press.
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Morulae of anaplasmosis in circulating neutrophils
A 51-year-old man with no significant past medical history presented with a five-day history of fever, malaise, and diffuse myalgias with no recollection of a tick bite. He was found to have thrombocytopenia, elevated transaminase levels, and renal insufficiency. Examination of the peripheral smear suggested the diagnosis of anaplasmosis. He was started on a course of doxycycline with eventual complete resolution of symptoms.
The peripheral smear (1000x, "feather edge") shows morulae of anaplasmosis in the patient's granulocytes. Photomicrographs B and C were taken from the extreme feather edge, and show exploded neutrophils containing well-delineated morulae.
The peripheral smear (1000x, "feather edge") shows morulae of anaplasmosis in the patient's granulocytes. Photomicrographs B and C were taken from the extreme feather edge, and show exploded neutrophils containing well-delineated morulae.
Peripheral smear and patient information kindly provided by Dr. Eddy J Chen and Dr. German Pihan, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Boston, MA.
Graphic 60471 Version 3.0
Suggested initial therapy for agents that cause encephalitis
| Agent | Specific therapy |
| ADEM | Corticosteroids |
| Bacteria | |
| Listeria monocytogenes | Ampicillin plus gentamicin; trimethoprim-sulfamethoxazole |
| Tropheryma whipplei | Ceftiaxone, followed by either trimethoprim-sulfamethoxazole or cefixime |
| Fungi | |
| Coccidioides | Fluconazole, itraconazole, voriconazole, amphotericin B |
| Cryptococcus neoformans | Amphotericin B plus flucytosine |
| Histoplasma capsulatum | Liposomal amphotericin B |
| Helminths | |
| Baylisascaris procyonis | Albendazole plus diethylcarbamazine |
| Gnathostoma | Albendazole or ivermectin |
| Taenia solium (cycticercosis) | Albendazole and corticosteroids |
| Mycobacteria | |
| Mycobacterium tuberculosis | 4 drug regimen; consider addition of corticosteroid |
| Protozoa | |
| Acanthamoeba | Trimethoprim-sulfamethoxazole plus rifampin plus ketoconazole |
| Balamuthia mandrillaris | Pentamidine plus macrolide and fluconazole and sulfadiazine and flucytosine and phenothiazine |
| Naegleria fowleri | Amphotericin B and rifampin |
| Plasmodium falciparum | Quinine, quinidine or artemether |
| Toxoplasma gondii | Pyrimethamine plus sulfadiazine or clindamycin |
| Trypanosoma brucei gambiense | Eflornithine |
| Trypanosoma brucei rhodesiense | Melarsoprol |
| Rickettsioses and ehrlichioses | |
| Anaplasma phagocytophilum | Doxycycline |
| Ehrlichia chafeensis | Doxycycline |
| Rickettsia rickettsii | Doxycycline |
| Spirochetes | |
| Borrelia burgdorferi | Ceftriaxone, cefotaxime |
| Treponema pallidum | Penicillin G |
| Viruses | |
| Cytomegalovirus | Ganciclovir plus foscarnet |
| Epstein-Barr | No specific treatment |
| Herpes B virus | Valgancyclovir |
| Herpes simplex | Acyclovir |
| Human herpesvirus 6 | Gancyclovir or foscarnet |
| Human immunodeficiency virus | Antiretroviral therapy |
| JC virus | Reversal of immunosuppression if possible |
| Measles | Ribavirin |
| Nipah | Ribavirin |
| St. Louis encephalitis | Interferon-2 alpha |
| Varicella-zoster | Acyclovir |
| West Nile | No specific treatment |
ADEM: acute disseminated encephalomyelitis.
Adapted from: Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303-27.
Graphic 69990 Version 6.0
Epidemiologic and historic clues to the etiology of encephalitis in children
| Epidemiologic clues | Potential etiologies |
| Age (0 to 28 days) |
Infectious: CMV, HSV-2 or HSV-1, rubella virus
Noninfectious: Inborn error of metabolism (eg, organic acidemia, urea cycle disorder) |
| Season: | |
| Summer | Enterovirus, free living amebae |
| Late summer/fall | Arbovirus |
| Winter | Postinfectious encephalitis in countries with low rates of MMR immunization |
| Infection in horses, birds | Arbovirus, Hendra virus |
| Blood transfusion or transplant recipient | CMV, EBV, HIV, rabies, tick-borne encephalitis, WNV |
| Immunodeficiency | CMV, enterovirus, HHV6, HSV, VZV, WNV |
| Historical clues | |
| Rash | |
| Vesicular | HSV, VZV, enterovirus (hand, foot, and mouth disease), herpes B virus |
| Hand, foot, mouth | Enterovirus |
| Erythematous macules and papules with cephalocaudad spread | Measles |
| Maculopapular | WNV |
| Maculopapular/petechial begins on ankles and wrists | Rocky Mountain spotted fever |
| Exposures | |
| Mosquitoes | Arbovirus |
| Ticks | Borrelia burgdorferi, Powassan virus, Rickettsia rickettsii, tick-borne encephalitis |
| Animal bite/exposure (dog, bat, cat, birds, livestock, others) | Rabies, arboviruses, cat scratch disease, Q fever |
| Blood transfusion or transplant recipient | CMV, EBV, HIV, rabies, tick-borne encephalitis, WNV |
| Recent infectious illness | ADEM |
| Recreational activity | |
| Swimming | Enteroviruses, free-living amebae |
| Spelunking | Rabies |
| Sexual activity | HIV, Treponema pallidum |
| Travel | |
| Immunization | |
| Lack of immunization for specific agent | Japanese encephalitis, measles, mumps, rubella, VZV, polio |
| Recent immunization | ADEM |
CMV: cytomegalovirus; HSV: herpes simplex virus; MMR: measles, mumps, rubella; EBV: Epstein-Barr virus; HIV: human immunodeficiency virus; WNV: West Nile virus; HHV6: human herpesvirus 6; VZV: varicella zoster virus; ADEM: acute disseminated encephalomyelitis.
Data from:
- Willoughby RE, Long SS. Encephalitis, meningoencephalitis, acute disseminated encephalomyelitis, and acute necrotizing encephalopathy. In: Principles and Practice of Pediatric Infectious Diseases, 2nd ed, Long SS, Pickering LK, Prober CG (Eds), Churchill Livingstone, New York 2008. p.310.
- Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303.
- Bronstein DE, Shields WD, Glaser CA. Encephalitis and meningoencephalitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.492.
Graphic 57122 Version 8.0
Travel history and possible etiologic agent(s) of viral encephalitis
| Travel | Possible infectious agent(s) |
| Africa | Rabies virus, West Nile virus, Plasmodium falciparum, Dengue virus, Trypanosoma brucei gambiense, T. brucei rhodesiense |
| Australia | Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus |
| Central America | Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Dengue virus, Rickettsia rickettsii, P. falciparum, Taenia solium |
| Europe | West Nile virus, tick-borne encephalitis virus, Borrelia burgdorferi, Anaplasma phagocytophilum |
| India, Nepal | Rabies virus, Japanese encephalitis virus, P. falciparum, Dengue virus |
| Middle East | West Nile virus, P. falciparum |
| Russia | Tick-borne encephalitis virus |
| South America | Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Dengue virus, R. rickettsii,Bartonella bacilliformis (Andes mountain), P. falciparum, Taenia solium |
| Southeast Asia, China, Pacific Rim | Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnathostoma species, Taenia solium, Dengue virus |
Modified with permission from: Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303. Copyright © 2008 University of Chicago Press.
Graphic 73833 Version 4.0
Clinical findings and possible etiologic agent(s) in encephalitis
| Clinical presentation | Possible infectious agent(s) |
| General findings | |
| Hepatitis | Herpes simplex virus (infant only), enterovirus (in infants), Coxiella burnetii; any severe hepatitis can cause encephalopathy |
| Lymphadenopathy | HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other bartonella species,Mycobacterium tuberculosis, Toxoplasma gondii, Trypansoma brucei gambiense |
| Parotitis | Mumps virus |
| Rash | Herpes simplex virus, varicella zoster virus, herpes B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii,Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum |
| Respiratory tract findings | Venezuelan equine encephalitis virus, Nipha virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum |
| Retinitis | Cytomegalovirus, T. gondii, West Nile virus, B. henselae, T. pallidum |
| Urinary symptoms (dysuria, urgency, incontinence) | St. Louis encephalitis virus (during prodrome) |
| Neurologic findings | |
| Cerebellar ataxia | Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense |
| Cranial nerve abnormalities | Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans,Coccidioides species, H. capsulatum |
| Dementia | HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles, T. pallidum, T. whipplei |
| Myorhythmia | T. whipplei (oculomasticatory) |
| Parkinsonism (bradykinesia, masked facies, cogwheel rigidity, postural instability) | Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense |
| Poliomyelitis-like flaccid paralysis | Japanese encephalitis virus, West Nile virus, tick-borne encephalitis virus, enteroviruses (enterovirus 71, coxsackieviruses), poliovirus |
| Rhomboencephalitis | Enterovirus 71, herpes simplex virus, West Nile virus, L. monocytogenes |
Modified with permission from: Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303. Copyright © 2008 University of Chicago Press.
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System of isolation precautions for infection control
| Type of precaution | Selected patients | Major specifications |
| Standard | All patients |
Handwashing before and after every patient contact*
Gloves, gowns, eye protection as required
Safe disposal or cleaning of instruments and linen
Cough etiquette: Patients and visitors should cover their nose or mouth when coughing, promptly dispose used tissues, and practice hand hygiene after contact with respiratory secretions.
|
| Contact |
Colonization of any bodily site with multidrug-resistant bacteria (MRSA, VRE, drug-resistant gram-negative organisms)
Enteric infections (Clostridium difficile, Escherichia coli O157:H7, viral infections [RSV, HSV, enterovirus, parainfluenza])
Scabies
Impetigo
Noncontained abcesses or decubitus ulcers (especially forStaphylococcus aureus and group A Streptococcus)
|
In addition to standard precautions:
Wash hands with soap and water before and after leaving the patient's room
Private room preferred; cohorting allowed if necessary
Gloves required upon entering room. Change gloves after contact with contaminated secretions.
Gown required if clothing may come into contact with the patient or environmental surfaces or if the patient has diarrhea
Minimize risk of environmental contamination during patient transport (eg, patient can be placed in a gown)
Noncritical items should be dedicated to use for a single patient if possible
|
| Droplet |
Known or suspected:
Neisseria meningitidis
Haemophilus influenzae type B
Mycoplasma pneumoniae
Bordetella pertussis
Diphtheria
Pneumonic plague
Influenza
Rubella
Mumps
Adenovirus
Parvovirus B19
RSV
|
In addition to standard precautions:
Private room preferred; cohorting allowed if necessary
Wear a mask when within three feet of the patient
Mask the patient during transport
Cough etiquette: Patients and visitors should cover their nose or mouth when coughing, promptly dispose used tissues and practice hand hygiene after contact with respiratory secretions.
|
| Airborne |
Known or suspected:
Tuberculosis
Varicella
Measles
Smallpox
SARS
|
In addition to standard precautions:
Place the patient in an AIIR (a monitored negative pressure room with at least 6 to 12 air exchanges per hour).
Room exhaust must be appropriately discharged outdoors or passed through a HEPA filter before recirculation within the hospital.
A certified respirator must be worn when entering the room of a patient with diagnosed or suspected tuberculosis. Susceptible individuals should not enter the room of patients with confirmed or suspected measles or chickenpox.
Transport of the patient should be minimized; the patient should be masked if transport within the hospital is unavoidable.
Cough etiquette: Patients and visitors should cover their nose or mouth when coughing, promptly dispose used tissues and practice hand hygiene after contact with respiratory secretions.
|
This system of isolation precautions is recommended by the United States Healthcare Infection Control Practices Advisory Committee.
MRSA: methicillin-resistant S. aureus; VRE: vancomycin-resistant enterococci; RSV: respiratory syncytial virus; HSV: herpes simplex virus; SARS: severe acute respiratory syndrome; AIIR: airborne infection isolation room; HEPA: high-efficiency particulate aerator.
* Alcohol-based hand disinfectant is an acceptable alternative to soap and water in all situations EXCEPT in the setting of C. difficile, for which soap and water should be used.
* Alcohol-based hand disinfectant is an acceptable alternative to soap and water in all situations EXCEPT in the setting of C. difficile, for which soap and water should be used.
Modified from Garner JS. Infect Control Hosp Epidemiol 1996; 17:53.
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