Sandbox encephalitis2

# Overview
Acyclovir (1020 mg/kg IV q8h) should be administered to all patients with suspected encephalitis as early as possible to reduce the risk of neurologic sequelae.  Doxycycline should be added to empirical regimen if epidemiological or clinical clues suggest rickettsial or ehrlichial infection.  Despite the wide range of viruses that cause encephalitis, specific antiviral agent is generally limited to infections caused by the herpesviridae and human immunodeficiency virus (HIV).  Treatment for other viral encephalitis is largely supportive.

# Medical Therapy

## General Considerations
- Reliably tested specific antiviral agents are available only for a few viral agents (e.g. acyclovir or ganciclovir for herpes simplex virus and varicella-zoster encephalitis). Administer the first dose of acyclovir as soon as possible (in the emergency department itself). Acyclovir can be initiated with or without antibiotics or steroids.The advantages of an early antiviral drug administration are:
Decreases disease duration
Decreases development of latency
Decreases development of complications
Decreases recurrence
Decreases transmission from infected person
- Decreases disease duration
- Decreases development of latency
- Decreases development of complications
- Decreases recurrence
- Decreases transmission from infected person
- Treatment for Toxoplasma gondii and cytomegalovirus encephalitis are available but are used with limited success
- Treatment is usually symptomatic. In patients who are very sick, supportive treatment, such as mechanical ventilation, is equally important.
- Systemic complications like hypotension, shock, hypoxemia, electrolyte imbalances (hyponatremia, SIADH should be treated promptly.
- Neuroimaging with MRI or CT scan should be done before lumbar puncture especially if raised intracranial pressure is suspected.
- Lab tests like blood samples should be taken before initiation of therapy.
- Bed rest, plenty of fluids and anti-inflammatory drugs to relieve headache and fever should be used.

## Treatment for Increased Intracranial Pressure

### General
- Elevation of head end of the bed
- Hyperventilation may be used to decrease intra-cranial pressure on emergency basis
- Constant monitoring of neurological status
- Avoid increase in intra cranial pressure i.e. control of straining and coughing
- Antipyretics and analgesic for fever and pain.
- Monitoring and preventing seizures and hypotension.

### Drug Therapy
- Furosemide 20 mg iv and mannitol 1 gm/kg intravenously for diuresis (blood pressure and CVP should be monitored while administrating these drugs)
- Dexamethasone 10mg intravenously 6 hourly to decrease cerebral edema.

# Antimicrobial Regimen  Empiric Therapy
Adapted from The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America:
- Adults with suspected encephalitis
Acyclovir 10 mg/kg IV q8h
- Acyclovir 10 mg/kg IV q8h
- Children with suspected encephalitis
Acyclovir 10 mg/kg IV q8h
- Acyclovir 10 mg/kg IV q8h
- Neonates with suspected encephalitis
Acyclovir 20 mg/kg IV q8h
- Acyclovir 20 mg/kg IV q8h

# Antimicrobial Regimen  Pathogen-Based Therapy
Adapted from The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America:

## Viruses
- Adenovirus
Epidemiological or clinical features:
Children or immunocompromised patients
Associated with pneumonia
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Children or immunocompromised patients
- Associated with pneumonia
- Recommended therapy:
- Supportive care
- B virus
Epidemiological or clinical features:
Transmitted by bites or scratches from macaques
Vesicular eruption at site of bite or scratch, followed by neurologic symptoms in 37 days
Transverse myelitis
Recommended therapy:
Wound decontamination
Acyclovir OR valacyclovir OR ganciclovir for established disease
Prophylactic valacyclovir after bite or scratch
- Epidemiological or clinical features:
- Transmitted by bites or scratches from macaques
- Vesicular eruption at site of bite or scratch, followed by neurologic symptoms in 37 days
- Transverse myelitis
- Recommended therapy:
- Wound decontamination
- Acyclovir OR valacyclovir OR ganciclovir for established disease
- Prophylactic valacyclovir after bite or scratch
- CMV
Epidemiological or clinical features:
Immunocompromised hosts (particularly those with AIDS)
Retinitis, pneumonitis, adrenalitis, myelitis, polyradiculopathy
Recommended therapy:
Ganciclovir AND
Foscarnet
- Epidemiological or clinical features:
- Immunocompromised hosts (particularly those with AIDS)
- Retinitis, pneumonitis, adrenalitis, myelitis, polyradiculopathy
- Recommended therapy:
- Ganciclovir AND
- Foscarnet
- Eastern equine encephalitis virus
Epidemiological or clinical features:
North America (especially Atlantic and Gulf states)
Mainly affects children and elderly persons
Abrupt onset with fulminant course
Seizures, headache, or altered consciousness
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- North America (especially Atlantic and Gulf states)
- Mainly affects children and elderly persons
- Abrupt onset with fulminant course
- Seizures, headache, or altered consciousness
- Recommended therapy:
- Supportive care
- EBV
Epidemiological or clinical features:
Exposure to saliva from those with asymptomatic shedding
Seizures, coma, personality changes, cerebellar ataxia, cranial nerve palsies
Transverse myelitis
Recommended therapy:
Supportive care
May consider corticosteroids
- Epidemiological or clinical features:
- Exposure to saliva from those with asymptomatic shedding
- Seizures, coma, personality changes, cerebellar ataxia, cranial nerve palsies
- Transverse myelitis
- Recommended therapy:
- Supportive care
- May consider corticosteroids
- Hendra virus
Epidemiological or clinical features:
Australia
Transmitted through excretions from infected horses
Fever, drowsiness, seizures, and coma accompanying severe flulike illness
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Australia
- Transmitted through excretions from infected horses
- Fever, drowsiness, seizures, and coma accompanying severe flulike illness
- Recommended therapy:
- Supportive care
- HHV-6
Epidemiological or clinical features:
Immunocompromised hosts (particularly in transplant recipients)
Recent exantham ; seizures
Delirium  occurs more commonly than seizures
Recommended therapy:
Ganciclovir OR foscarnet
- Epidemiological or clinical features:
- Immunocompromised hosts (particularly in transplant recipients)
- Recent exantham ; seizures
- Delirium  occurs more commonly than seizures
- Recommended therapy:
- Ganciclovir OR foscarnet
- HIV
Epidemiological or clinical features:
Acute encephalopathy with seroconversion
Most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation)
Recommended therapy:
HAART
- Epidemiological or clinical features:
- Acute encephalopathy with seroconversion
- Most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation)
- Recommended therapy:
- HAART
- HSV
Epidemiological or clinical features:
Most common causes of identified sporadic encephalitis worldwide
Fever, hemicranial headache, language and behavioral abnormalities, memory impairment, seizures, or SIADH
Recommended therapy:
Acyclovir
- Epidemiological or clinical features:
- Most common causes of identified sporadic encephalitis worldwide
- Fever, hemicranial headache, language and behavioral abnormalities, memory impairment, seizures, or SIADH
- Recommended therapy:
- Acyclovir
- Influenza virus
Epidemiological or clinical features:
Often affects children
Prior or concomitant respiratory tract symptoms
Associated with bilateral thalamic necrosis (also called acute necrotizing encephalopathy)
Recommended therapy:
Oseltamivir
- Epidemiological or clinical features:
- Often affects children
- Prior or concomitant respiratory tract symptoms
- Associated with bilateral thalamic necrosis (also called acute necrotizing encephalopathy)
- Recommended therapy:
- Oseltamivir
- Japanese encephalitis virus
Epidemiological or clinical features:
Japan, China, Korea, Taiwan, Southeast Asia, India, Nepal, northern Australia
Mainly children
Seizures, parkinsonian features, poliomyelitis-like flaccid paralysis
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Japan, China, Korea, Taiwan, Southeast Asia, India, Nepal, northern Australia
- Mainly children
- Seizures, parkinsonian features, poliomyelitis-like flaccid paralysis
- Recommended therapy:
- Supportive care
- JC virus
Epidemiological or clinical features:
Cell-mediated immunodeficiencies or immunomodulating therapy (natalizumab, rituximab)
Cognitive dysfunction
Limb weakness, gait disturbance, or coordination difficulties, visual field cuts
Recommended therapy:
Reversal of immunosuppression
Administer HAART in AIDS patients
- Epidemiological or clinical features:
- Cell-mediated immunodeficiencies or immunomodulating therapy (natalizumab, rituximab)
- Cognitive dysfunction
- Limb weakness, gait disturbance, or coordination difficulties, visual field cuts
- Recommended therapy:
- Reversal of immunosuppression
- Administer HAART in AIDS patients
- La Crosse virus
Epidemiological or clinical features:
Midwestern and eastern United States
School-aged children
Fulminant onset, with seizures, paralysis, focal weakness
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Midwestern and eastern United States
- School-aged children
- Fulminant onset, with seizures, paralysis, focal weakness
- Recommended therapy:
- Supportive care
- Measles virus
Epidemiological or clinical features:
Unvaccinated children and adults
Decline of consciousness, seizures, or focal neurologic signs
Recommended therapy:
Ribavirin for life-threatening disease
Intrathecal ribavirin for SSPE
- Epidemiological or clinical features:
- Unvaccinated children and adults
- Decline of consciousness, seizures, or focal neurologic signs
- Recommended therapy:
- Ribavirin for life-threatening disease
- Intrathecal ribavirin for SSPE
- Mumps virus
Epidemiological or clinical features:
Unvaccinated individuals
Previous parotitis
Headaches, vomiting, seizures, altered consciousness, sensorineural hearing loss
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Unvaccinated individuals
- Previous parotitis
- Headaches, vomiting, seizures, altered consciousness, sensorineural hearing loss
- Recommended therapy:
- Supportive care
- Murray Valley encephalitis virus
Epidemiological or clinical features:
Australia, New Guinea
Aboriginal children
Rapid disease progression in infants
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Australia, New Guinea
- Aboriginal children
- Rapid disease progression in infants
- Recommended therapy:
- Supportive care
- Nipah virus
Epidemiological or clinical features:
South Asia
Close exposure to infected pigs or bats
Fever, headache, altered mental status, dizziness, and vomiting
Headaches, vomiting, seizures, altered consciousness, sensorineural hearing loss
Myoclonus, dystonia, areflexia, and hypotonia; pneumonitis
Recommended therapy:
Supportive care
May consider ribavirin
- Epidemiological or clinical features:
- South Asia
- Close exposure to infected pigs or bats
- Fever, headache, altered mental status, dizziness, and vomiting
- Headaches, vomiting, seizures, altered consciousness, sensorineural hearing loss
- Myoclonus, dystonia, areflexia, and hypotonia; pneumonitis
- Recommended therapy:
- Supportive care
- May consider ribavirin
- Nonpolio enteroviruses
Epidemiological or clinical features:
Late summer and early fall
Aseptic meningitis occurs more commonly than encephalitis
Enterovirus 71 causes rhombencephalitis (myoclonus, tremors, ataxia, and cranial nerve defects)
Recommended therapy:
Supportive care
Intraventricular gamma-globulin for severe disease
- Epidemiological or clinical features:
- Late summer and early fall
- Aseptic meningitis occurs more commonly than encephalitis
- Enterovirus 71 causes rhombencephalitis (myoclonus, tremors, ataxia, and cranial nerve defects)
- Recommended therapy:
- Supportive care
- Intraventricular gamma-globulin for severe disease
- Poliovirus
Epidemiological or clinical features:
Unvaccinated infants in Africa and Asia
Disturbances in consciousness, seizures, or flaccid paralysis
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Unvaccinated infants in Africa and Asia
- Disturbances in consciousness, seizures, or flaccid paralysis
- Recommended therapy:
- Supportive care
- Powassan virus
Epidemiological or clinical features:
New England states, Canada, Asia
Focal neurologic deficits in > 50% of patients
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- New England states, Canada, Asia
- Focal neurologic deficits in > 50% of patients
- Recommended therapy:
- Supportive care
- Rabies virus
Epidemiological or clinical features:
Transmitted by the bite of an infected animal
Furious form: agitation, hydrophobia, bizarre behavior, and delirium progressing to disorientation, stupor, and coma
Paralytic form: ascending paralysis and later cerebral involvement
Most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation)
Recommended therapy:
Supportive care
Postexposure prophylaxis with immunoglobulin and vaccine
- Epidemiological or clinical features:
- Transmitted by the bite of an infected animal
- Furious form: agitation, hydrophobia, bizarre behavior, and delirium progressing to disorientation, stupor, and coma
- Paralytic form: ascending paralysis and later cerebral involvement
- Most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation)
- Recommended therapy:
- Supportive care
- Postexposure prophylaxis with immunoglobulin and vaccine
- Rubella virus
Epidemiological or clinical features:
Unvaccinated adults
Rash followed within 16 days by headache, dizziness, behavioral abnormalities, seizures
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Unvaccinated adults
- Rash followed within 16 days by headache, dizziness, behavioral abnormalities, seizures
- Recommended therapy:
- Supportive care
- St. Louis encephalitis virus
Epidemiological or clinical features:
North America (endemic in western United States, with periodic outbreaks in eastern United States), Central and South America
Urinary symptoms (dysuria, urgency, and incontinence) followed by tremors, seizures, headache, nausea, vomiting, stupor, or paresis
Recommended therapy:
Supportive care
May consider IFN alpha 2b
- Epidemiological or clinical features:
- North America (endemic in western United States, with periodic outbreaks in eastern United States), Central and South America
- Urinary symptoms (dysuria, urgency, and incontinence) followed by tremors, seizures, headache, nausea, vomiting, stupor, or paresis
- Recommended therapy:
- Supportive care
- May consider IFN alpha 2b
- Tickborne encephalitis virus
Epidemiological or clinical features:
Eastern Russia, central Europe, Far East
Unpasteurized milk consumption
Acute progression; poliomyelitis-like paralysis
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Eastern Russia, central Europe, Far East
- Unpasteurized milk consumption
- Acute progression; poliomyelitis-like paralysis
- Recommended therapy:
- Supportive care
- Vaccinia
Epidemiological or clinical features:
Abrupt onset of encephalopathy
Focal neurologic deficits 230 days after vaccination
Disturbances in consciousness, seizures, or flaccid paralysis
Recommended therapy:
Supportive care
May consider corticosteroids
- Epidemiological or clinical features:
- Abrupt onset of encephalopathy
- Focal neurologic deficits 230 days after vaccination
- Disturbances in consciousness, seizures, or flaccid paralysis
- Recommended therapy:
- Supportive care
- May consider corticosteroids
- Venezuelan equine encephalitis virus
Epidemiological or clinical features:
Florida and southwestern United States, Central and South America
Prominent myalgias; headache; pharyngitis
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Florida and southwestern United States, Central and South America
- Prominent myalgias; headache; pharyngitis
- Recommended therapy:
- Supportive care
- VZV
Epidemiological or clinical features:
Recrudescent disease occurs in immunocompromised hosts
Cerebellar involvement in children
Delirium occurs more commonly than seizures
Herpes zoster ophthalmicus
Recommended therapy:
Acyclovir OR ganciclovir
May consider corticosteroids
- Epidemiological or clinical features:
- Recrudescent disease occurs in immunocompromised hosts
- Cerebellar involvement in children
- Delirium occurs more commonly than seizures
- Herpes zoster ophthalmicus
- Recommended therapy:
- Acyclovir OR ganciclovir
- May consider corticosteroids
- West Nile virus
Epidemiological or clinical features:
North and Central America, Africa, parts of Asia, Middle East, and southern Europe
Older patients (age > 50 years) and immunocompromised hosts
Abrupt onset of fever, headache, neck stiffness, and vomiting
Tremors, myoclonus, parkinsonism, and poliomyelitis-like flaccid paralysis
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- North and Central America, Africa, parts of Asia, Middle East, and southern Europe
- Older patients (age > 50 years) and immunocompromised hosts
- Abrupt onset of fever, headache, neck stiffness, and vomiting
- Tremors, myoclonus, parkinsonism, and poliomyelitis-like flaccid paralysis
- Recommended therapy:
- Supportive care
- Western equine encephalitis virus
Epidemiological or clinical features:
North America (west of the Mississippi), Central and South America
Headache, altered consciousness, seizures
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- North America (west of the Mississippi), Central and South America
- Headache, altered consciousness, seizures
- Recommended therapy:
- Supportive care

## Bacteria
- Anaplasma phagocytophilum (human granulocytotrophic ehrlichiosis)
Epidemiological or clinical features:
Europe and mid-Atlantic and northern United States
Abrupt onset of fever, headache, and myalgias followed by  altered mental status
Recommended therapy:
Doxycycline
- Epidemiological or clinical features:
- Europe and mid-Atlantic and northern United States
- Abrupt onset of fever, headache, and myalgias followed by  altered mental status
- Recommended therapy:
- Doxycycline
- Bartonella bacilliformis (Oroya fever)
Epidemiological or clinical features:
Middle altitudes of Andes mountains
Acute onset of severe headache
Seizures, hallucinations, delirium, or altered mental status
Profound hemolytic anemia
Recommended therapy:
Chloramphenicol OR Ciprofloxacin OR Doxycycline OR Ampicillin OR TMP-SMZ
- Epidemiological or clinical features:
- Middle altitudes of Andes mountains
- Acute onset of severe headache
- Seizures, hallucinations, delirium, or altered mental status
- Profound hemolytic anemia
- Recommended therapy:
- Chloramphenicol OR Ciprofloxacin OR Doxycycline OR Ampicillin OR TMP-SMZ
- Bartonella henselae (Cat scratch disease)
Epidemiological or clinical features:
Bites or scratches from cats or other animals
Regional lymphadenopathy, seizures, neuroretinitis
Recommended therapy:
Doxycycline OR Azithromycin with or without Rifampin
- Epidemiological or clinical features:
- Bites or scratches from cats or other animals
- Regional lymphadenopathy, seizures, neuroretinitis
- Recommended therapy:
- Doxycycline OR Azithromycin with or without Rifampin
- Borrelia burgdorferi (Lyme disease)
Epidemiological or clinical features:
North America, Europe, and Asia
Neurologic symptoms may develop shortly after erythema migrans or with arthritis
Facial nerve palsy, particularly bilateral, meningitis, or radiculitis
Recommended therapy:
Ceftriaxone OR Cefotaxime OR Penicillin G
- Epidemiological or clinical features:
- North America, Europe, and Asia
- Neurologic symptoms may develop shortly after erythema migrans or with arthritis
- Facial nerve palsy, particularly bilateral, meningitis, or radiculitis
- Recommended therapy:
- Ceftriaxone OR Cefotaxime OR Penicillin G
- Coxiella burnetii (Q fever)
Epidemiological or clinical features:
Contact with cats, sheep, goats (particularly placental tissues)
Seizures and coma
Recommended therapy:
Doxycycline AND
Fluoroquinolone AND
Rifampin
- Epidemiological or clinical features:
- Contact with cats, sheep, goats (particularly placental tissues)
- Seizures and coma
- Recommended therapy:
- Doxycycline AND
- Fluoroquinolone AND
- Rifampin
- Ehrlichia chaffeensis (human monocytotrophic ehrlichiosis)
Epidemiological or clinical features:
South central, southeastern, mid-Atlantic, and coastal states of the United States
Confusion, photophobia, stupor, or hallucinations
Recommended therapy:
Doxycycline
- Epidemiological or clinical features:
- South central, southeastern, mid-Atlantic, and coastal states of the United States
- Confusion, photophobia, stupor, or hallucinations
- Recommended therapy:
- Doxycycline
- Listeria monocytogenes
Epidemiological or clinical features:
Neonates 50 years of age
Pregnancy, alcohol abuse, and defects in cell-mediated immunity
Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)
Recommended therapy:
Ampicillin OR TMP-SMZ AND
Gentamicin
- Epidemiological or clinical features:
- Neonates 50 years of age
- Pregnancy, alcohol abuse, and defects in cell-mediated immunity
- Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)
- Recommended therapy:
- Ampicillin OR TMP-SMZ AND
- Gentamicin
- Mycobacterium tuberculosis
Epidemiological or clinical features:
Most commonly presents with basilar meningitis followed by lacunar infarctions and hydrocephalus
Dementia, ophthalmoplegia, myoclonus, cerebellar ataxia, or psychiatric signs
Oculomasticatory myorhythmia
Recommended therapy:
Isoniazid AND
Rifampin AND
Pyrazinamide AND
Ethambutol
Add dexamethasone in patients with meningitis
- Epidemiological or clinical features:
- Most commonly presents with basilar meningitis followed by lacunar infarctions and hydrocephalus
- Dementia, ophthalmoplegia, myoclonus, cerebellar ataxia, or psychiatric signs
- Oculomasticatory myorhythmia
- Recommended therapy:
- Isoniazid AND
- Rifampin AND
- Pyrazinamide AND
- Ethambutol
- Add dexamethasone in patients with meningitis
- Mycoplasma pneumoniae
Epidemiological or clinical features:
More common in children
Previous upper or lower respiratory tract disease
Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)
Recommended therapy:
Azithromycin OR Fluoroquinolone OR Doxycycline
- Epidemiological or clinical features:
- More common in children
- Previous upper or lower respiratory tract disease
- Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)
- Recommended therapy:
- Azithromycin OR Fluoroquinolone OR Doxycycline
- Rickettsia rickettsii (Rocky Mountain spotted fever)
Epidemiological or clinical features:
North, Central, and South America
Maculopapular, petechial rash on wrists and ankles beginning 35 days after onset of illness with rapid spread to palms and soles
Altered mental status or intractable seizures
Recommended therapy:
Doxycycline OR Chloramphenicol (for pregnant patients)
- Epidemiological or clinical features:
- North, Central, and South America
- Maculopapular, petechial rash on wrists and ankles beginning 35 days after onset of illness with rapid spread to palms and soles
- Altered mental status or intractable seizures
- Recommended therapy:
- Doxycycline OR Chloramphenicol (for pregnant patients)
- Treponema pallidum (syphilis)
Epidemiological or clinical features:
Transmitted through sexual contact
General paresis, rapidly progressive dementia
Psychiatric features
Recommended therapy:
Penicillin G OR Ceftriaxone
- Epidemiological or clinical features:
- Transmitted through sexual contact
- General paresis, rapidly progressive dementia
- Psychiatric features
- Recommended therapy:
- Penicillin G OR Ceftriaxone
- Tropheryma whipplei (Whipple's disease)
Epidemiological or clinical features:
Most commonly presents with progressive subacute encephalopathy
Dementia, ophthalmoplegia, myoclonus, cerebellar ataxia, or psychiatric signs
Oculomasticatory myorhythmia
Recommended therapy:
Ceftriaxone for 24 weeks, followed by TMP-SMZ OR Cefixime for 12 years
- Epidemiological or clinical features:
- Most commonly presents with progressive subacute encephalopathy
- Dementia, ophthalmoplegia, myoclonus, cerebellar ataxia, or psychiatric signs
- Oculomasticatory myorhythmia
- Recommended therapy:
- Ceftriaxone for 24 weeks, followed by TMP-SMZ OR Cefixime for 12 years

## Fungi
- Coccidioides
Epidemiological or clinical features:
Semi-arid regions of the southwestern United States, Mexico, and South America
Disorientation, lethargy, confusion, or memory loss
Recommended therapy:
Fluconazole OR Itraconazole OR Voriconazole OR Amphotericin B
- Epidemiological or clinical features:
- Semi-arid regions of the southwestern United States, Mexico, and South America
- Disorientation, lethargy, confusion, or memory loss
- Recommended therapy:
- Fluconazole OR Itraconazole OR Voriconazole OR Amphotericin B
- Cryptococcus neoformans
Epidemiological or clinical features:
Often occurs in immunocompromised hosts
Disorientation, lethargy, confusion, or memory loss
Recommended therapy:
Amphotericin B PLUS Flucytosine x 2 weeks, then Fluconazole x 8 weeks
Amphotericin B PLUS Flucytosine x 610 weeks
Consider V-P shunt in patients with persistent IICP
- Epidemiological or clinical features:
- Often occurs in immunocompromised hosts
- Disorientation, lethargy, confusion, or memory loss
- Recommended therapy:
- Amphotericin B PLUS Flucytosine x 2 weeks, then Fluconazole x 8 weeks
- Amphotericin B PLUS Flucytosine x 610 weeks
- Consider V-P shunt in patients with persistent IICP
- Histoplasma capsulatum
Epidemiological or clinical features:
Endemic in Ohio and Mississippi River valleys in the United States
More common in immunocompromised hosts
Recommended therapy:
Amphotericin B lipid complex x 46 weeks, then Itraconazole x 1 year until resolution of CSF abnormalities
- Epidemiological or clinical features:
- Endemic in Ohio and Mississippi River valleys in the United States
- More common in immunocompromised hosts
- Recommended therapy:
- Amphotericin B lipid complex x 46 weeks, then Itraconazole x 1 year until resolution of CSF abnormalities

## Protozoa
- Acanthamoeba
Epidemiological or clinical features:
Chronic alcoholism or immunocompromised hosts
Commonly present with altered mental status and/or focal neurologic deficits
Seizures, hemiparesis, and fever
Preferred regimen:
TMP-SMZ AND
Rifampin AND
Ketoconazole
Alternative regimen:
Fluconazole AND
Sulfadiazine AND
Pyrimethamine
- Epidemiological or clinical features:
- Chronic alcoholism or immunocompromised hosts
- Commonly present with altered mental status and/or focal neurologic deficits
- Seizures, hemiparesis, and fever
- Preferred regimen:
- TMP-SMZ AND
- Rifampin AND
- Ketoconazole
- Alternative regimen:
- Fluconazole AND
- Sulfadiazine AND
- Pyrimethamine
- Balamuthia mandrillaris
Epidemiological or clinical features:
Both immunocompetent or immunocompromised hosts
Fever, headache, vomiting, ataxia, hemiparesis, or cranial nerve palsies
Seizures, hemiparesis, and fever
Recommended therapy:
Azithromycin OR Clarithromycin AND
Pentamidine AND
Flucytosine AND
Fluconazole AND
Sulfadiazine AND
Thioridazine OR Trifluoperazine
- Epidemiological or clinical features:
- Both immunocompetent or immunocompromised hosts
- Fever, headache, vomiting, ataxia, hemiparesis, or cranial nerve palsies
- Seizures, hemiparesis, and fever
- Recommended therapy:
- Azithromycin OR Clarithromycin AND
- Pentamidine AND
- Flucytosine AND
- Fluconazole AND
- Sulfadiazine AND
- Thioridazine OR Trifluoperazine
- Naegleria fowleri
Epidemiological or clinical features:
Swimming in lakes and brackish water
Change in taste or smell 25 days after swimming
Meningismus, papilledema, nystagmus, cranial nerve palsies, and ataxia
Acute progression to coma and death
Recommended therapy:
Amphotericin B AND
Rifampin AND
Azithromycin OR Sulfisoxazole OR Miconazole
- Epidemiological or clinical features:
- Swimming in lakes and brackish water
- Change in taste or smell 25 days after swimming
- Meningismus, papilledema, nystagmus, cranial nerve palsies, and ataxia
- Acute progression to coma and death
- Recommended therapy:
- Amphotericin B AND
- Rifampin AND
- Azithromycin OR Sulfisoxazole OR Miconazole
- Plasmodium falciparum
Epidemiological or clinical features:
Travel to tropical and subtropical areas of endemicity
Impaired consciousness, seizures, focal neurologic deficits, and/or psychosis
Preferred regimen:
Quinine OR Quinidine OR Artesunate
Alternative regimen:
Atovaquone proguanil
Exchange transfusion with > 10% parasitemia or cerebral malaria
- Epidemiological or clinical features:
- Travel to tropical and subtropical areas of endemicity
- Impaired consciousness, seizures, focal neurologic deficits, and/or psychosis
- Preferred regimen:
- Quinine OR Quinidine OR Artesunate
- Alternative regimen:
- Atovaquone proguanil
- Exchange transfusion with > 10% parasitemia or cerebral malaria
- Toxoplasma gondii
Epidemiological or clinical features:
Reactivation in immunocompromised hosts
Intrauterine infection may lead to severe necrotizing encephalitis
Extrapyramidal signs, seizures, hemiparesis, or cranial nerve palsies
Preferred regimen:
Pyrimethamine AND
Sulfadiazine OR Clindamycin
Alternative regimen:
TMP-SMZ
- Epidemiological or clinical features:
- Reactivation in immunocompromised hosts
- Intrauterine infection may lead to severe necrotizing encephalitis
- Extrapyramidal signs, seizures, hemiparesis, or cranial nerve palsies
- Preferred regimen:
- Pyrimethamine AND
- Sulfadiazine OR Clindamycin
- Alternative regimen:
- TMP-SMZ
- Trypanosoma brucei gambiense (West African trypanosomiasis)
Epidemiological or clinical features:
Chronic disease with late CNS sequelae developing in months to years
Irritabililty, personality changes, inability to concentrate, sleep disturbances, severe headache, ataxia, or extrapyramidal signs
Recommended therapy:
Eflornithine OR Melarsoprol
- Epidemiological or clinical features:
- Chronic disease with late CNS sequelae developing in months to years
- Irritabililty, personality changes, inability to concentrate, sleep disturbances, severe headache, ataxia, or extrapyramidal signs
- Recommended therapy:
- Eflornithine OR Melarsoprol
- Trypanosoma brucei rhodesiense (East African trypanosomiasis)
Epidemiological or clinical features:
Acute disease with early CNS disease
Sleep disturbances, refractory headaches leading to death within weeks to months
Recommended therapy:
Melarsoprol
- Epidemiological or clinical features:
- Acute disease with early CNS disease
- Sleep disturbances, refractory headaches leading to death within weeks to months
- Recommended therapy:
- Melarsoprol

## Helminths
- Baylisascaris procyonis
Epidemiological or clinical features:
Children with raccoon exposure or playing in or eating dirt contaminated with raccoon feces
CNS dysfunction, neurologic deficits, coma, death
Recommended therapy:
Albendazole AND
Diethylcarbamazine AND
Corticosteroids
- Epidemiological or clinical features:
- Children with raccoon exposure or playing in or eating dirt contaminated with raccoon feces
- CNS dysfunction, neurologic deficits, coma, death
- Recommended therapy:
- Albendazole AND
- Diethylcarbamazine AND
- Corticosteroids
- Gnathostoma
Epidemiological or clinical features:
Southeast Asia (particularly Thailand and Japan) and Latin America
Ingestion of undercooked fish, frogs, snakes, or fowl
Headache, radicular pain, paralysis, and urinary incontinence
Recommended therapy:
Albendazole OR Ivermectin
- Epidemiological or clinical features:
- Southeast Asia (particularly Thailand and Japan) and Latin America
- Ingestion of undercooked fish, frogs, snakes, or fowl
- Headache, radicular pain, paralysis, and urinary incontinence
- Recommended therapy:
- Albendazole OR Ivermectin
- Taenia solium (cysticercosis)
Epidemiological or clinical features:
Mexico, Central America, South America, Southeast Asia
Ingestion of undercooked fish, frogs, snakes, or fowl
Seizures, hydrocephalus, chronic meningitis
Recommended therapy:
Corticosteroids AND
Albendazole OR Praziquantel
- Epidemiological or clinical features:
- Mexico, Central America, South America, Southeast Asia
- Ingestion of undercooked fish, frogs, snakes, or fowl
- Seizures, hydrocephalus, chronic meningitis
- Recommended therapy:
- Corticosteroids AND
- Albendazole OR Praziquantel

## Prion
- Human transmissible spongiform encephalopathy
Epidemiological or clinical features:
Sporadic CJD: dementia and ataxia followed by myoclonic jerks or other movement disorders, rapidly progressive dementia, and ultimately death
Variant CJD: early psychiatric and sensory abnormalities, followed by cerebellar ataxia and rapidly progressive dementia
Recommended therapy:
Supportive care
- Epidemiological or clinical features:
- Sporadic CJD: dementia and ataxia followed by myoclonic jerks or other movement disorders, rapidly progressive dementia, and ultimately death
- Variant CJD: early psychiatric and sensory abnormalities, followed by cerebellar ataxia and rapidly progressive dementia
- Recommended therapy:
- Supportive care

# Encephalitis Drug Summary

## Acyclovir
- It is effective for HSV1, HSV2 and varicella zoster.
- It is selectively taken up by the body cells infected with HSV and varicella zoster
- Prompt treatment with acyclovir is useful in decreasing complications, latency and communicability
- Side effects may include nausea, vomiting, diarrhea, loss of appetite, and muscle or joint pain. Rarely, serious adverse effects may include renal and liver functions abnormalities or suppression of bone marrow activity.

## Foscarnet
- It is effective against HSV 1, HSV 2 and CMV
- It is useful in patients who have developed resistance or are non-responders against acyclovir for e.g. HIV positive patients
- Drug dosage depends on the renal function of the patient as Foscarnet is excreted through kidneys.

## Dexamethasone
- It is used in post-infectious and disseminated encephalitis.
- It may be used as an adjunct with the antiviral agents

## Furosemide
- It is used to in encephalitis associated with increased intracranial pressure. The mechanism of action is;
It decreases the production of CSF by inhibiting carbonic anhydrase enzymes.
Decreases cerebral sodium uptake
Inhibits cellular membrane chloride pumps.
- It decreases the production of CSF by inhibiting carbonic anhydrase enzymes.
- Decreases cerebral sodium uptake
- Inhibits cellular membrane chloride pumps.
- The dose should be individualized for patients.

## Mannitol
- Used only on short term basis.
- The doses should be individualized based on renal function.

## Lorazepam
- It is used for treatment of seizures associated with encephalitis.