ENCEPHALITIS

What is it?
-

an inflammation of the brain parenchyma

- presents as diffuse and/or focal neuropsychological dysfunction

What is it?
- most

commonly a viral infection with parenchymal damage varying from mild to profound.

Pathophysiology
Portals of entry : VIRUSES
Transmission :
- HUMANS (mostly) - TICKS & MOSQUITOES arboviruses - other animals rabies virus - Immunocompromised host VZV, CMV, etc.

Pathway
virus replicates outside the CNS
gains entry either by hematogenous spread or by traveling along neural (rabies, HSV, VZV) and olfactory (HSV) pathways

cross the blood-brain barrier & enters neural cells

Resulting in:
-

disruption in cell functioning perivascular congestion hemorrhage inflammatory response diffusely affecting gray matter disproportionately to white matter.

Focal pathology is the result of neuron cell membrane receptors found only in specific portions of the brain and accounts for regional tropism found with some viruses.

(eg. HSV has a predilection for the inferior and medial temporal lobes.)

Focal Pathology
-

is the result of neuron cell membrane receptors found only in specific portions of the brain and accounts for regional tropism found with some viruses. (eg. HSV has a predilection for the inferior and medial temporal lobes)

Diagnosis
-

Most histologic features are nonspecific

For Rabies :
brain

biopsies Presence of Negri bodies in the hippocampus and cerebellum HSV Cowdry type A inclusions with hemorrhagic necrosis in the temporal and orbitofrontal lobes.

Mortality / Morbidity
related
-

to host factors

preexisting CNS injury virulence of infecting organism

Poor outcomes can be anticipated in infants younger than 1 year and adults older than 55 years.

Mortality / Morbidity

Untreated HSE has a mortality rate of 50-75%

- virtually 100% of survivors have long term motor and mental disabilities.

Treated HSE correlates strongly with severity of illness at the time of medical intervention - morbidity is usually quoted at approximately 20%.

Risk Factors

Individuals at the extremes of age are at highest risk, particularly for HSE.

Risk Factors
-

Neonatal HSE is a manifestation of disseminated infection (type 1 or 2).

Older infants, children, and adults succumb to localized CNS infection (almost exclusively type 1) according to a bimodal pattern of 5-30 years and older than 50 years

Clinical Picture
-History

Physical

History
-

Clinical presentation : Acuity & severity correlates with prognosis History of animal bite for which antirabies treatment may not have been obtained

History
-

The general viral prodrome is several days long

-

consists of :
- fever

- Headache - nausea and vomiting - Lethargy - myalgias

History
-

Classic presentation : encephalopathy with diffuse or

focal neurologic symptoms including :
-

Behavioural & personality changes Decreased level of consciousness Stiff neck, photophobia & lethargy Generalized & local seizures Acute confusion or amnestic states Flaccid paralysis

History
-

Less common symptoms:

Headache Complaints of meningismus

History
Neonatal HSV infection symptoms :
[(1-45 days) may occur in any combination] - Skin, eye & mouth lesions (early

presentation) - Encephalitis Change in level of alertness, irritability, seizures, poor feeling - Evidence of widespread, disseminated disease, such as rash or shock

History

HSE in older children & adults :

- Unrelated

to history of oral lesions in infants

- Acute

onset of severe symptoms of encephalitis

Physical
Look

for supporting evidence of viral infection.

- Signs of encephalitis may be diffuse or focal (80% of patients with HSE present with focal findings) as follows:
Altered

mental status and/or personality changes (most common)

Physical
Focal

findings, such as hemiparesis, focal seizures, and autonomic dysfunction

Movement
Ataxia Cranial

disorders

nerve defects

Physical
Dysphagia

(Rabies may account for foaming at the mouth and hydrophobia.) Meningismus (less common and less pronounced than in meningitis) Unilateral sensorimotor dysfunction

Physical
- HSV infection in the neonate (aged 145 d) : Herpetic skin lesions over the presenting surface from birth or with breaks in the skin, such as those resulting from fetal scalp monitors Keratoconjunctivitis

Physical
Oropharyngeal

involvement, particularly buccal mucosa and tongue Encephalitis symptoms, such as seizures, irritability, change in level of attentiveness, bulging fontanels Additional signs of disseminated HSV, such as shock, jaundice, and hepatomegaly

Physical
-

Toxoplasma encephalopathy :
[In immunosuppressed patients] 75% present with a focal neuropathology about one half with encephalopathic changes.

Differential Diagnosis
Acute CNS events, such as hemorrhagic stroke Acute confusional states secondary to drugs, toxins, psychosis Amoeba (Naegleria, Acanthamoeba)

Head

trauma CNS syphilis Ehrlichiosis Intracranial hemorrhage Intracranial tumor Trauma

Investigations (Lab Studies)

Complete blood count (CBC) with differential: Findings are usually within the reference range. Serum electrolytes: These are usually within the reference range. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs in 25% of patients with St Louis encephalitis.)

Investigations (Lab Studies)

Serum glucose level: Use this level as a baseline for determining normal CSF glucose values. The result may be low if glycogen stores are depleted or high in infected patients with diabetes mellitus. BUN/creatinine and liver function tests (LFTs): Assess organ function and the need to adjust the antibiotic dose.

Investigations (Lab Studies)

Platelet test and a coagulation profile: These are indicated in patients with chronic alcohol use, liver disease, or if disseminated intravascular coagulation (DIC) is suspected. The patient may require platelets or fresh-frozen plasma (FFP) before lumbar puncture (LP). Urinary electrolyte test: Perform this assessment if SIADH is suspected. Urine and/or serum toxicology screening: Perform 1 or both of these tests, if indicated.

Investigations (Lab Studies)

Other laboratory tests

CSF polymerase chain reaction (PCR): A PCR for DNA HSV is 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs. HSV cultures: These are used to test lesions (also Tzanck smear), CSF (rarely positive), and blood. Viral serology: Complement fixation antibodies are useful in identifying arbovirus. Cross-reactivity exists among one subgroup of arboviruses, the flaviviruses, and with antibodies raised in persons inoculated with the yellow fever vaccine.

Investigations (Lab Studies)

Viral

serology: Complement fixation antibodies are useful in identifying arbovirus. Heterophile antibody and cold agglutinins for EBV: These tests may be helpful. Serologic tests for toxoplasmosis: can be helpful in light of an abnormal CT scan, particularly in the case of single lesions.

Investigations (Imaging Studies)

Perform

head CT, with and without contrast agent, in virtually all patients with encephalitis before LP to search for evidence of elevated intracerebral pressure (ICP), obstructive hydrocephalus, or mass effect. It is helpful also in differential diagnosis. MRI is more likely to show abnormalities earlier in disease course than head CT.

Investigations (Imaging Studies)

In

HSE, an MRI may show several foci of increased T2 signal intensity in medial temporal lobes and inferior frontal gray matter. Head CT may show petechial hemorrhage in the same areas. EEE and tick-borne encephalitis may show similar increased signal intensity in the basal ganglia and thalami.

Investigations (Imaging Studies)

In

toxoplasmosis, contrastenhanced head CT typically reveals several nodular or ring-enhancing lesions. Because lesions may be missed without contrast, MRI should be performed in patients for whom use of contrast material is contraindicated.

Investigations (Other Tests)

Electroencephalography
In

HSE, characteristic paroxysmal lateral epileptiform discharges (PLEDs) often are observed, even before neuroradiographic changes. Eventually, PLEDs are positive in 80% of cases. The presence of PLEDs is not pathognomonic for HSE.

Investigations (Other Tests)

CSF

analysis is essential.

General

patterns in bacterial and fungal (cryptococcal) meningitis found during the measurement of CSF pressure and CSF analysis may support a diagnosis The most important diagnostic test in the ED to rule out bacterial meningitis is wellperformed Gram staining and, if available, polymerase chain reaction of the CSF in patients with suspected HSV encephalitis.

Treatment
Prehospital Care: Evaluate and treat for shock or hypotension. Administer a crystalloid infusion until the patient is euvolemic. Consider airway protection in patients with an altered mental status.

Treatment
Prehospital Care: Consider seizure precautions. Treat seizures according to usual protocol (ie, lorazepam 0.1 mg/kg given intravenously [IV]). Stabilize alert patients with normal vital signs by administering oxygen, securing IV access, and providing rapid transport to the ED.

Treatment
Emergency Department Care: With the important
exceptions of HSE and varicella-zoster encephalitis, the viral encephalitides are not treatable beyond supportive care. Treatments for T gondii and CMV encephalitis are available but generally not initiated in the ED.

The goal of treatment for acutely ill patients is administration of the first dose or doses acyclovir with or without antibiotics or steroids as quickly as possible.
The

standard for acute bacterial meningitis is the initiation of treatment within 30 minutes of arrival. Consider instituting an ED triage protocol to identify patients at risk for HSE.

Treatment
a) The goal of treatment for acutely ill patients is administration of the first dose or doses acyclovir with or without antibiotics or steroids as quickly as possible.
The

standard for acute bacterial meningitis is the initiation of treatment within 30 minutes of arrival. Consider instituting an ED triage protocol to identify patients at risk for HSE.

Treatment
b) Collect laboratory samples and blood cultures before the start of IV therapy. Even in uncomplicated cases of encephalitis, most authorities recommend a neuroimaging study (eg, contrastenhanced head CT scan) before LP.

Treatment
c) Signs of hydrocephalus and increased ICP
General

measures: Manage fever and pain, control straining and coughing, and avoid seizures and systemic hypotension. In otherwise stable patients, elevating the head and monitoring neurologic status usually are sufficient.

Treatment
When

more aggressive maneuvers are indicated, some authorities favor the early use of diuresis (eg, furosemide 20 mg IV, mannitol 1 g/kg IV) provided circulatory volume is protected. Dexamethasone 10 mg IV q6h helps in managing edema surrounding space-occupying lesions. Hyperventilation (PaCO2 30 mm Hg) may cause a disproportional decrease in cerebral blood flow (CBF), but it is used to control increasing ICP on an emergency basis.

Treatment
Intraventricular

ICP monitoring is controversial because some authorities believe dangerous focal edema with a pressure gradient between the temporal lobe and the subtentorial space usually is not detected by the monitor, leading to a false sense of security. In fact, monitor placement may potentially aggravate a pressure gradient.

Treatment
d) Look for and treat systemic complications, particularly in HSE, JE, such as hypotension or shock, hypoxemia, hyponatremia (SIADH), and exacerbation of chronic diseases.

Treatment
e) Empiric adult emergency treatment for HSV meningoencephalitis and VZV encephalitis is acyclovir 10 mg/kg (infuse over 1 h) q8h for 14-21 days. Give acyclovir 10-15 mg/kg IV q8h for neonatal HSV; for HSV encephalitis in the pediatric population, give acyclovir 10 mg/kg IV q8h.

Treatment
f) In HIV-positive patients, consider foscarnet, given increased incidence of acyclovir-resistant HSV and HZV.

Drugs
Antivirals

Foscarnet)

(Acyclovir,

Corticosteroids

(Dexamethasone)

Complications
Seizures Syndrome

of inappropriate secretion of antidiuretic hormone Increased ICP Coma

HERPES SIMPLEX ENCEPHALITIS

What is it?
-

In infants, children, and adults, HSE is usually localized to the temporal and frontal lobes and is caused by herpes simplex virus type 1 (HSV-1). In neonates, however, brain involvement is more often diffuse, and the usual cause is herpes simplex virus type 2 (HSV-2), which is acquired at the time of delivery.

What is it?
-

HSE must be distinguished from herpes simplex meningitis, which is more commonly caused by HSV-2 than by HSV1, and which often occurs in association with a concurrent herpetic genital infection. Like other forms of viral meningitis, herpes simplex meningitis usually has a benign course

Pathophysiology
Pathogenesis : Poorly understood
-

Brain infection is thought to occur primarily by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve. Factors that precipitate HSE are unknown. Immunocompromise is not an independent risk factor.

Mortality / Morbidity
Mortality

70% Treated patients: - Mortality : 19% - more than 50% of survivors are left with
moderate or severe neurologic deficits.
Female-to-Male

in untreated patients :

ratio = 1:1

Mortality / Morbidity

Age: HSE has a bimodal distribution by age, with 1 peak occurring in those younger than 20 years and 1 occurring in those older than 50 years.
- HSE in younger patients is thought to represent primary infection - in older individuals is believed to be a reactivation of a latent infection.

Clinical Picture
-History

Physical

History
-

no pathognomonic clinical findings reliably distinguish HSE from other neurologic disorders with similar presentations (eg, non-HSV encephalitis, brain abscess, tumor).
[ Confirmation of the diagnosis depends on the identification of HSV in the CSF by means of a polymerase chain reaction (PCR) or on the identification of HSV in brain tissue by means of brain biopsy ]

History
-

Typical symptoms include:

fever - Headache - Vomiting - memory loss - Seizures - focal weakness - Psychiatric symptoms
-

Physical
Most

frequent findings are fever and mental status abnormalities is uncommon

Meningismus

Physical
Typical findings include :
Alteration Seizures
Focal

of consciousness Fever Dysphasia Ataxia

findings Generalized findings

Hemiparesis Cranial

nerve

defects Visual field loss Papilledema

Investigations (Lab Studies)

Serologic analysis
Serologic evaluation of blood or CSF may be useful for retrospective diagnosis, but it has no role in the acute diagnosis and treatment of patients. Strategies based on increases in antibody levels and on the ratio of antibody levels in serum and CSF have not proven to be clinically useful.

Investigations (Lab Studies)

CSF analysis
Patients with HSE typically have mononuclear pleocytosis of 10-500 WBCs/mL (average, 100 WBCs/mL). Because of the hemorrhagic nature of the underlying pathologic process, the patient's RBC count may be elevated (10-500 RBCs/mL). Protein levels are elevated to the range 60-700 mg/dL (average, 100 mg/dL).

Investigations (Lab Studies)

Glucose values may be normal or mildly decreased (30-40 mg/dL). In about 5-10% of patients, especially children, initial CSF results may be normal. However, on serial examinations, the cell counts and protein values almost always increase. Viral cultures of CSF are rarely positive and should not be relied on to confirm the diagnosis.

Investigations (Lab Studies)

Polymerase chain reaction

PCR analysis of CSF for the detection of HSV DNA has virtually replaced brain biopsy as the criterion standard for diagnosis. PCR is highly sensitive (94-98%) and specific (98-100%). Results become positive within 24 hours of the onset of symptoms and remain positive for 5-7 days after the start of antiviral therapy.

Investigations (Lab Studies)

False-negative findings may occur early in the course of the disease when viral DNA levels are low (within 72 h of the onset of symptoms) or when blood is present in the CSF, as hemoglobin inhibits PCR. The viral load in the CSF, as measured with PCR, is well correlated with the clinical course, and the persistence of viral DNA at the end of antiviral therapy is associated with a poor outcome.

Investigations (Imaging Studies)

Magnetic
MRI

resonance imaging

of the brain is the preferred imaging study. MRI shows pathologic changes, which are usually bilateral, in the medial temporal and inferior frontal areas.

Investigations (Imaging Studies)

Findings

of localized temporal abnormalities are highly suggestive of HSE, but confirmation of the diagnosis depends on the identification of HSV by means of PCR or brain biopsy. Imaging modalities such as MRI can noninvasively establish many of the potential alternative diagnoses of HSE.

Investigations (Imaging Studies)

Computed
Head

tomography

CT may show changes in the temporal and/or frontal lobe, but CT is less sensitive than MRI. Approximately one third of patients with HSE have normal CT findings on presentation.

Investigations (Other Tests)

Electroencephalography
EEG

shows focal abnormalities, such as spike and slow- or periodic sharp-wave patterns over the involved temporal lobes. EEG is 84% sensitive to abnormal patterns in HSE but lacks specificity (32%). Changes may be apparent earlier on EEG than on MRI

Investigations (Procedures)
Brain
The

biopsy

results of brain biopsy can establish alternative diagnoses, both treatable (eg, brain tumor) and nontreatable (eg, nonHSV viral encephalitis). Studies have demonstrated that PCR testing of CSF is as accurate as brain biopsy in confirming the diagnosis of HSE.
Lumbar

puncture

Treatment
Emergency Department Care: A high index of suspicion is required to make the diagnosis. No pathognomonic clinical findings are associated with HSE. The diagnosis of HSE should be considered in any patient with a progressively deteriorating level of consciousness, fever, abnormal CSF findings, and focal neurologic abnormalities in the absence of any other causes.

Treatment
Proceed with expeditious evaluation after the diagnosis is considered. Empiric treatment of patients with suspected HSE is recommended pending confirmation of the diagnosis because acyclovir, the drug of choice, is relatively nontoxic and because the prognosis for untreated HSE is poor. Rapid initiation of acyclovir therapy is crucial to reduce mortality and morbidity risks.

Drugs

Antivirals (Acyclovir)

Complications
Seizures (prophylaxis with anticonvulsants) Cerebral edema (sometimes treated with steroids, however, use of steroids in HSE is controversial)
Other

standard therapy is by using Mannitol and Barbiturates

Complications

Patients with HSE are subject to the same complications as those of all seriously ill and immobilized patients with depressed levels of consciousness (eg, aspiration pneumonia, deep venous thromboses, decubiti).

Encephalitis Lethargica

Clinical Picture
high

fever

delayed

Headache double

physical & mental response

lethargy

vision

Acute Cases
Coma abnormal muscular

eye movements upper body weakness

pains tremors neck rigidity psychosis

Treatment

Symptomatic Treatment

Tick-Borne Encephalitis

What is it?
- Lyme disease is a systemic infection caused by the spirochete Borrelia burgdorferi. - The bacterium is inoculated into the skin by a tick bite. - The tick is almost always of the genus Ixodes.

Clinical Picture
-History

Physical

History
Systemic manifestations
Fever

is generally low grade. Fatigue is common. Myalgias and arthralgias occur early. Frank arthritis (ie, joint swelling, redness, pain) usually is a later manifestation but can occur in the early disseminated phase.

History
Flulike

illness (undifferentiated febrile illness) may occur. The season of onset, epidemiologic likelihood of a tick bite, paucity of respiratory and GI symptoms, and prompt response to antiborrelial therapy are diagnostic clues.

History
Cutaneous symptoms
The

classic rash, erythema multiforme (EM), is present in about 75% of patients. Because it is neither pruritic nor painful, some patients may have the rash but not notice it. EM can occur in the same patient more than once. About 20% of patients with Lyme disease have multiple lesions (from hematogenous dissemination).

History
Neurologic symptoms
Headache

can occur in early infection as a nonspecific finding and can herald CNS penetration and lymphocytic meningitis. The headache of Lyme disease typically is described as waxing and waning, and the severity varies from mild to severe, even in patients with frank meningitis.

History
Patients notice facial weakness, which is similar to a typical Bell palsy and which can be the presenting symptom of Lyme disease. About 25% of patients with borrelial facial palsy have bilateral involvement, which may be sequential and is a point of differential diagnostic significance. Other than Lyme disease and Guillain-Barr syndrome, bilateral seventh nerve palsy is rare.

History
Radicular

pain can occur and present as acute disk disease. Late Lyme disease can cause paresthesias or pain due to peripheral neuropathy and personality, cognitive, and sleep disturbances from chronic encephalopathy.

Nausea and vomiting

History
Cardiovascular involvement
occurs in fewer than 10% of patients with untreated Lyme disease and is more common in male patients than in female patients. Palpitations, lightheadedness, and syncope may be a manifestation of varying degrees of heart block, including complete heart block, which occurs in 50% of patients with cardiac involvement. Lyme disease is an important reversible cause of heart block.

History
Chest

pain and dyspnea can occur in the setting of Lyme pericarditis, myocarditis, and myopericarditis. Tamponade is possible.

History
Migratory pains in and around the joints and muscles
Migratory pain may occur from myositis, tendonitis, and bursitis. These symptoms classically wax and wane over hours or days. Later, arthritis occurs generally with swelling, redness, and pain in one or a few large joints, typically the knees. Synovitis occasionally occurs in the earlydisseminated phase of Lyme disease.

History
Red, itchy eyes from conjunctivitis
Red,

itchy eyes are the most common ocular symptom. Blurred vision and eye pain can occur from keratitis and iritis. Unilateral blindness from panophthalmitis is also possible.

Physical Examination
Dermatologic findings
Classic

EM is an erythematous papule or macule that occurs at the site of the tick bite (1-33 d later; average, 7-10 d). Often, a central punctum is found at the site. The size varies enormously (as large as 70 cm; average, 16 cm) and depends on disease duration

Physical Examination
EM

usually is flat, round, or oval and monocyclic. Generally, neither itching nor pain is present. The rash enlarges a few centimeters per day and fades, even if untreated, after a few weeks. The rash can be triangular or linear and is sometimes fleeting in duration. Rash location is another important diagnostic clue

Physical Examination
Neurologic signs
Neck stiffness can occur early, with or without frank meningitis. Facial nerve palsy is a lower motor neuron lesion that causes facial weakness of both the lower face and forehead. It can be bilateral. As in idiopathic Bell palsy, sometimes a polycranial neuropathy exists with any nerve involved. Nearly every cranial nerve has been reported to be involved, although this is uncommon.

Physical Examination
Weakness

and abnormal sensation can occur because of meningoradiculitis. Diminished reflexes can occur with this syndrome. CSF frequently reflects pleocytosis. Neuropsychiatric testing and minimental status testing may uncover cognitive, memory, and personality changes that occur in late Lyme encephalopathy.

Physical Examination
Peripheral

axonal neuropathy can lead to patchy, generally distal abnormalities in sensation. Sensory findings are more pronounced than motor findings.

Physical Examination
Cardiovascular findings In patients with complete heart block, Canon A waves may be observed in the neck. A slow or irregular pulse may be palpated. A cardiac rub, S3 and/or S4, may be auscultated in patients with myocarditis or pericarditis.

Physical Examination
Signs

of tamponade very rarely can occur. In patients with chronic cardiac involvement with congestive heart failure, typical signs of congestive heart failure may be present.

Physical Examination
Musculoskeletal findings
Muscle tenderness can result from myositis; tenderness of tendons and periarticular structures may be present. Frank arthritis can occur after weeks, months, or years and may lead to erythema, edema, synovial effusion, and tenderness of the affected joints. Usually, this is a monoarthritis or oligoarthritis involving large joints, especially the knee. Swelling often is disproportional to the tenderness.

Physical Examination
Ocular signs
Conjunctival

erythema and injection or retinal hemorrhages and exudates may be present. On slit lamp examination, signs of keratitis and cells in the anterior chamber from iritis may be seen. In children, papilledema may be present in a pseudotumor cerebrilike syndrome.

Investigation

Serologic testing for Lyme disease is complex. Rational ordering and interpretation of these test results requires some understanding of the basic underlying principles and performance characteristics of the test. Patients may remain seropositive for long periods; therefore, serologic test results cannot be used as a proof or test of cure.

Investigation

Also, if a patient with past Lyme disease who remains seropositive comes in with new symptoms, care should be taken to not necessarily ascribe these new symptoms to Lyme disease. Lumbar puncture ought to be performed if Lyme meningitis is in the differential diagnosis.

Treatment
Oral antibiotics (eg, amoxicillin, doxycycline, cefuroxime axetil, erythromycin, azithromycin, amoxicillinclavulanate) intravenous ceftriaxone may be administered for coexistent neurologic disease. Arthritis may be treated with oral antibiotics for 30-60 days