Herpes simplex encephalitis

Alternate names

Herpetic encephalitis; Herpes simplex meningo-encephalitis; Herpes simplex neuroinvasion; HSV encephalitis; Herpes simplex virus encephalitis; HSE; HSVE

Definition

Herpes simplex encephalitis is a rare neurological condition that is characterized by inflammation of the brain (encephalitis). People affected by this condition may experience a headache and fever for up to 5 days, followed by personality and behavioral changes; seizures; hallucinations; and altered levels of consciousness. Without early diagnosis and treatment, severe brain damage or even death may occur.

Cause

• Herpes simplex encephalitis is caused by a virus called the herpes simplex virus.
• Most cases are associated with herpes simplex virus type I (the cause of cold sores or fever blisters), although rare cases can be caused by herpes simplex virus type II (genital herpes).
• Changes (mutations) in genes such as TLR3 and TRAF3 have been observed suggesting there may be a genetic component in some cases.
• About 90% of cases of herpes encephalitis are caused by herpes simplex virus-1 (HSV-1), the same virus that causes cold sores.
• 57% of American adults are infected with HSV-1.
• which is spread through droplets, casual contact and sometimes sexual contact, though most infected people never have cold sores.
• The rest of cases are due to HSV-2, which is typically spread through sexual contact and is the cause of genital herpes.

Pathophysiology

• HSV-1 is 1 of 8 human herpes viruses (HHV), including HSV-2, varicella zoster virus (VZV; HHV-3), Epstein–Barr virus (HHV-4), cytomegalovirus (HHV-5), HHV-6, HHV-7, and HHV-8.
• The herpesviruses are large, double-stranded DNA viruses that are well-adapted to human infection as they establish lifelong infection, rarely cause death of the host, and are readily spread between individuals.
• HSV initially gains access to host tissues through mucous membranes or damaged skin.
• After primary infection of the mucosal or skin epithelium, the virus infects sensory neurons via interactions with cell-surface glycosaminoglycans such as heparan sulfate , and cell adhesion molecules such as nectin-1 , and travels to the neuronal cell body in the dorsal root ganglion via fast retrograde axonal transport .
• The mechanisms by which HSV gains access to the central nervous system (CNS) in humans are unclear, and this remains an area of debate.
• The most likely routes include retrograde transport through the olfactory or trigeminal nerves , via hematogenous dissemination.

Epidemiology

• HSV-1 infection is common, with seropositivity among older adults estimated to be 60–90 % worldwide.
• The incidence of HSVE worldwide is estimated to be between 2 and 4 cases/1,000,000, and the incidence in the USA.

Signs and symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• CSF lymphocytic pleiocytosis
• EEG abnormality

30%-79% of people have these symptoms

• Fatigue(Tired)
• Fever
• Headache(Headaches)
• Hyponatremia(Low blood sodium levels)
• Increased CSF protein
• Leukocytosis(Elevated white blood count)
• Loss of consciousness(Passing out)
• Nausea and vomiting
• Neurological speech impairment(Speech disorder)
• Neutrophilia(Increased blood neutrophil counts)
• Nuchal rigidity
• Respiratory failure requiring assisted ventilation

5%-29% of people have these symptoms

• Alcoholism
• Cerebral edema(Swelling of brain)
• Chills
• Coma
• Elevated C-reactive protein level
• Excessive daytime somnolence(More than typical sleepiness during day)
• Focal aware seizure
• Focal impaired awareness seizure
• Functional motor deficit
• Hyperreflexia(Increased reflexes)
• Hypoglycorrhachia(Low glucose levels in cerebral spinal fluid)
• Immunodeficiency(Decreased immune function)
• Status epilepticus(Repeated seizures without recovery between them).

Diagnosis

• Brain CT scan (with/without contrast). Complete prior to lumbar puncture to exclude significantly increased ICP, obstructive hydrocephalus, mass effect.
• Brain MRI—Increased T2 signal intensity in frontotemporal region → viral (HSV) encephalitis.

Treatment

• Herpesviral encephalitis can be treated with high-dose intravenous acyclovir, which should be infused 10 mg/kg(adult) over 1 hour to avoid kidney failure.
• Without treatment, HSE results in rapid death in approximately 70% of cases; survivors suffer severe neurological damage.
• When treated, HSE is still fatal in one-third of cases, and causes serious long-term neurological damage in over half of survivors.
• Twenty percent of treated patients recover with minor damage.
• Only a small population of untreated survivors (2.5%) regain completely normal brain function.
• Many amnesic cases in the scientific literature have etiologies involving HSE.
• Earlier treatment (within 48 hours of symptom onset) improves the chances of a good recovery.
• Rarely, treated individuals can have relapse of infection weeks to months later.
• There is evidence that aberrant inflammation triggered by herpes simplex can result in granulomatous inflammation in the brain, which responds to steroids.

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Capsaicin (Brand name: Qutenza) Management of neuropathic pain associated with postherpetic neuralgia