Encephalitis Atman Shah

Encephalitis Definition Inflammation of the brain’s meninges which also can include the parenchyma and/or spinal cord or nerve roots.

Encephalitis In the United States ~20,000 reported cases of encephalitis. Herpes virus encephalitis is MC in the US. Japanese virus encephalitis is the most common viral encephalitis outside the United States.

Encephalitis Untreated Herpes encephalitis has a mortality rate of 50-75% Affects males and female equally. Individuals at the extremes of age are at highest risk, particularly for herpes simplex encephalitis.

Etiology MC causes in immunocompetent adults is HSV-1, VZV and enteroviruses. Epidemics of encephalitis are caused by Arboviruses

Etiology Arboviruses Alphaviruses: Eastern & Western equine encephalitis virus Flaviviruses: St. Louis enceph. Virus, WNV Bunyaviruses: California enceph. Virus serotypes

Etiology Causes in immunocompromised (from organ transplantation, AIDS) include HSV-1 Varicella-zoster virus (VZV) Epstein-Barr virus (EBV) cytomegalovirus (CMV) human herpesvirus-6 (HHV-6) Enteroviruses

Clinical Presentation Any degree of altered consciousness, ranging from mild lethargy to deep coma. Personality changes, hallucinations, agitations and other behavior disorders. Focal or generalization seizures may occur. Neurological disturbances

Clinical Presentation (cont.) MC focal findings include: (depending on location of inflammation) aphasia & ataxia hemiparesis, DTR++, Babinski reflex +ve, myoclonic jerks & other movement disorders tremors and cranial nerve deficits.

Clinical Presentation (cont.) Hypothalamic-Pituitary axis (HPA) may be involved resulting in Temperature dysregulation SIADH

Pathophysiology (1) Primary infection with HSV-1 usually occurs in the oropharyngeal mucosa and is typically asymptomatic. Symptomatic disease is characterized by fever, pain, and an inability to swallow caused by lesions on the buccal and the gingival mucosa. The duration of illness is 2 to 3 weeks.

Pathophysiology (2) After primary infection, HSV-1 is spread by retrograde transport via a division of the trigeminal nerve The virus then establishes latency in the trigeminal ganglion. Reactivation of latent ganglionic infection with replication of virus leads to viral encephalitis

Pathophysiology (3) HSV-1 encephalitis may also be the result of primary infection from either intranasal inoculation of virus with direct invasion of the olfactory bulb and tract leading to  infection in the temporal cortex and limbic system structures.

HSV-1 encephalitis showing extensive destruction of inferior frontal and anterior temporal lobes. (seizures, personality change, and neurologic deficits)

Histopathology Necrotizing inflammatory process characterizes the acute herpes encephalitis Perivascular inflammatory infiltrates are usually present, and Cowdry type A intranuclear viral inclusion bodies may be found in both neurons and glia.

Necrotizing inflammatory process characterizes the acute herpes encephalitis

Differential Diagnosis Brain Abscess Epidural and Subdural Infections Neoplasms Meningitis Stroke (Hemorrhagic or Ischemic)

Diagnosis Cerebrospinal fluid analysis: CSF analysis typically reveals a mononuclear pleocytosis (5-500 cells/mm) with mildly elevated protein and normal or mildly reduced glucose Because of the hemorrhagic nature of the process within the brain parenchyma, the red blood cell (RBC) count is usually elevated.

Diagnosis Polymerase chain reaction: PCR analysis of CSF is sensitive and specific for the diagnosis of HSE, even in patients already taking antiviral therapy. (has replaced brain biopsy as the criterion standard for establishing the diagnosis) Results are usually available within 24 hours of receipt of the CSF specimen.

Diagnosis Imaging Studies: Magnetic resonance imaging MRI of the brain is the preferred imaging study. The MRI shows pathologic changes, which are usually bilateral, in the medial temporal and inferior frontal areas. Findings of localized temporal abnormalities are highly suggestive of HSE, but confirmation of the diagnosis depends on identification of HSV by means of PCR or brain biopsy.

Treatment The DOC for HSE is acyclovir, an antiviral agent that selectively inhibits viral replication. Intravenous acyclovir (10 mg/kg every 8 hours for 2-3 weeks) is standard Acyclovir has relatively few serious adverse effects. The drug is excreted by the kidney, and the dose should be reduced in patients with renal dysfunction. Acyclovir is considered to be appropriate for serious infections during pregnancy.

Case Presentation 65 year old man who presented with a seizure after a three day h/o abdominal pain, odd smells, and low grade fever. Six weeks previously he had numbness and tingling of the right arm, face and leg which resolved.CT scan performed at that time was normal. On admission, the temperature was 104 degrees F.

Case Presentation (cont.) Spinal fluid contained 113 WBCs 40 RBCs protein 97 glucose 80 Unit (mg/dl)

Case Presentation (cont.) He was treated with acyclovir, and multiple blood and CSF cultures were negative. On examination: The patient was awake and alert with good attention. His language was fluent and spontaneous, though he perseverated and confabulated. Comprehension of simple verbal commands and word repetition were normal. Memory was intact to three of three objects at three minutes.

Case Presentation (cont.) Magnetic resonance imaging was performed 5 days after onset of his current symptoms.

In this set of images, there is a region of very bright signal on MR in the medial temporal lobe at left (patient's right).

Case Presentation (cont.) Treatment Outcome: The patient improved dramatically after a three week course of acylovir. (Intravenous acyclovir (10 mg/kg every 8 hours for 3 weeks) Impaired renal function developed, presumed due to acyclovir.