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Herpes Simplex Encephalitis - Etiology, Signs and Symptoms, and Treatment.

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Herpes simplex encephalitis is a rare neurological disorder where brain inflammation is seen. More information is given in the article.

Medically reviewed by

Dr. Abhishek Juneja

Published At September 11, 2023
Reviewed AtMarch 26, 2024

Introduction:

Encephalitis is described as a serious condition impacting the brain that needs prompt treatment to lower the risk of lasting complications or death. Herpes viruses are stated as large double-stranded DNA (deoxyribonucleic acid) viruses. Eight types of herpes viruses affect humans. Herpes simplex virus is one of them. Herpes simplex encephalitis (HSE) is a neurological disorder that is rarely seen and is characterized by inflammation of the brain, also known as encephalitis. Common symptoms include headaches, drowsiness, fevers, hyperactivity, or general weakness. The disorder can show some symptoms identical to those associated with meningitis, such as altered reflexes, stiff neck, confusion, or speech abnormalities. Skin lesions are not found in association with herpes simplex encephalitis normally. Herpes simplex encephalitis is caused by a virus called herpes simplex virus (HSV).

What Is Herpes Simplex Encephalitis?

Herpes simplex encephalitis happens because of the herpes simplex virus. Herpes simplex virus has two varieties such as herpes simplex virus type-1 (HSV-1) and herpes simplex virus type-2 (HSV-2). Herpes simplex encephalitis is a subacute or acute illness associated with global or focal cerebral dysfunction provoked by herpes simplex viruses belonging to either type 1 (HSV-1) or type 2 (HSV-2). The vast majority of herpes simplex encephalitis is caused by HSV-1, with HSV-2 comprising less than 12 percent of cases. HSV-1 causes encephalitis in children after the neonatal period and also in adults, and it is the most common etiology for sporadic non-seasonal encephalitis seen all around the world. Brain infection is thought to happen by means of direct neuronal transmission of the virus from a site peripheral to the brain via olfactory or trigeminal nerve and indirect immune-mediated processes inducing neuroinflammation. The exact pathogenesis is imprecise, and the factors responsible for the herpes simplex virus are unknown.

What Is the Etiology of Herpes Simplex Encephalitis?

HSV-1 and HSV-2 are constituents of the human herpesvirus family (HHV), which also contains a varicella-zoster virus (VZV; HHV-3), Epstein-Barr virus (HHV4), cytomegalovirus (HHV-5), (human herpesvirus) HHV-6, (human betaherpesvirus) HHV-7, and HHV-8 (Kaposi sarcoma-associated herpesvirus). All human herpes viruses excluding HHV-8, are known to be encephalitides causing, though herpes simplex viruses, especially HSV-1, cause the majority of herpes encephalitis. The brain gets affected via local spread from a peripheral site or possible viremia. There are presumably three routes by which the HSV-1 is thought to enter the brain from the initial peripheral site of infection. The first route is from the primary oro-pharyngeal infection to the brain through trigeminal or olfactory nerves. The second route involves the identical neuronal pathways from the reactivation of a peripheral initial infection. The last mechanism is purely due to the reactivation of the dormant in-situ HSV -1 in the brain. Viremia is well-documented in immunocompromised and neonates patients. Encephalitis in most children is caused by primary infection. Neonatal encephalitis can be either due to primary infection or secondary infection due to viremia and multisystem involvement. In neonates, primary infection is always almost acquired due to perinatal exposure during labor or after delivery.

What Is the Pathophysiology of Herpes Simplex Encephalitis?

The invasiveness and virulence depend on viral as well as host immune factors. HSV-1 encephalitis is not common among the immunosuppressed, which explains that much of the HSV-1 infections are supposed to be immune-mediated. The specific mechanism of neuronal destruction is not known. It could be either due to direct injury caused by the virus or an immune-mediated cell injury. HSV-1 can cause apoptosis of the cells involved affecting programmed cell death. A retrospective study on imaging found involvement of the temporal lobe in 60 percent of patients, with involvement of the pure temporal lobe in 20 percent, pure extratemporal involvement in 15 percent, and normal imaging in 25 percent of the patients. Studies prior to the acyclovir era have documented a rapidly evolving viral infection within the limbic system spreading to both sides of the brain with resultant inflammation and necrosis of the involved areas within three weeks. Hemorrhagic and lytic areas are often noted in the medial part of the temporal lobes and the inferior part of the frontal lobes. There is no evidence of increased incidence of herpes simplex encephalitis (HSE) in immunocompromised hosts, although the mortality and morbidity are quite high. More diffuse involvement with the predominance of extratemporal lobe areas is often noted in such patients.

What Are the Signs and Symptoms of Herpes Simplex Encephalitis?

Patients with herpes simplex encephalitis may have an onset of fever, malaise, nausea, and headache followed by subacute or acute onset of encephalopathy, whose symptoms include lethargy, confusion, and delirium. Yet, no pathognomonic clinical findings reliably differentiate herpes simplex encephalitis from other neurologic disorders with similar presentations.

The following are the symptoms:

  • Headache.

  • Vomiting.

  • Psychiatric illnesses.

  • Focal weakness.

  • Memory loss.

  • Fever.

The initial presentation can be mild or atypical in immunocompromised patients.

What Are the Differential Diagnosis of Herpes Simplex Encephalitis?

Differential diagnoses should enlist conditions that could mimic encephalopathy or encephalitis. These include the following.

  • Primary or secondary central nervous system infections are caused by bacteria, consisting of mycobacteria or atypical organisms or viruses or prions or fungi or parasites.

  • Non-infectious causes for encephalitis (for example, autoimmune or paraneoplastic encephalitis, acute disseminated encephalomyelitis).

  • Hypoxemic and septic encephalopathies.

  • Metabolic causes include hepatic or uremic encephalopathies, mitochondrial encephalopathies, Wernicke encephalopathy, hypoglycemia, hyponatremia or hypernatremia, hypercalcemia, or hypocalcemia.

  • Drugs or toxins, including alcohol and heavy metals, cerebrovascular accidents, primary or secondary brain tumors, seizure disorders, neurosyphilis, vasculitis, systemic lupus erythematosus (SLE), Behcet disease, and trauma.

  • Arboviral infections, such as West Nile and St Louis encephalitides, Eastern & Western equine encephalitis, and California and Japanese encephalitides.

  • Miscellaneous causes like mumps, dengue, enterovirus, adenovirus, lymphocytic choriomeningitis, subacute sclerosing panencephalitis due to hypermutated measles virus & progressive multifocal leukoencephalopathy caused by John Cunningham (JC) virus.

What Is the Treatment of Herpes Simplex Encephalitis?

The strategy of emergency management includes an assessment of the airway, breathing, and circulation and taking appropriate measures consequently. A lumbar puncture has to be pursued in suspected cases if the brain imaging does not present evidence of intracranial hypertension or a space-occupying lesion. Intravenous (IV) acyclovir needs to be started in all adults with confirmed or suspected cases of herpes simplex encephalitis at the dose of 10 mg per Kg body weight every eight hours for about 18 to 22 days. Children up to 11 years and also neonates are treated with higher doses (15 to 20 mg per kg body weight). Ideal body weight is used for dose calculation in patients suffering from obesity. An extensive retrospective study showed a delay in initiating acyclovir for more than 48 hours as one of the factors associated with poor outcomes. In severe cases, steps should be taken accordingly, suitable at that time.

What Is the Prognosis of Herpes Simplex Encephalitis?

In adults, herpes simplex encephalitis is associated with significant morbidity and mortality. Morbidity and mortality are significant in neonates and children, whether treated or untreated. Significant long-term morbidity, including behavioral and cognitive abnormalities, anterograde amnesia, and features of Klüver Busy Syndrome, are well documented. Even though the standard mental status examination is within normal limits, many suffer from dysnomia and difficulty with new learning, especially via visual and verbal media. Untreated herpes simplex encephalitis is progressive and often fatal in seven to 14 days. Patients who are comatose at diagnosis have a poor prognosis regardless of their age. In non-comatose patients, the prognosis is age-related, with better outcomes occurring in patients younger than 32 years.

Conclusion:

The physician should stress that the initial outbreak of lesions can occur at any time after infection, possibly even years later. No available strategies presently prevent herpes simplex encephalitis in older children or adults. The person-to-person spread has not been represented. Prophylactic treatment of intimate contacts and isolation precautions are not suggested. Neonatal transmission can be managed by conducting a cesarian delivery of the baby in women with active herpes labialis during pregnancy and or avoiding contact with persons with an active infection in the neonatal period.

Dr. Abhishek Juneja
Dr. Abhishek Juneja

Neurology

Tags:

herpes simplex virusherpes simplex encephalitis
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