Herpes simplex encephalitis

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Herpes simplex encephalitis
Other namesHerpes encephalitis,
Herpesviral encephalitis
Hsv encephalitis.jpg
Coronal T2-weighted MR image shows high signal in the temporal lobes including hippocampal formations and parahippogampal gyrae, insulae, and right inferior frontal gyrus. A brain biopsy was performed and the histology was consistent with encephalitis. PCR was repeated on the biopsy specimen and was positive for HSV
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Herpes simplex encephalitis (HSE), or simply herpes encephalitis, is encephalitis due to herpes simplex virus. It is estimated to affect at least 1 in 500,000 individuals per year, [1] and some studies suggest an incidence rate of 5.9 cases per 100,000 live births. [2]

Contents

About 90% of cases of herpes encephalitis are caused by herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. According to a 2006 estimate, 57% of American adults were infected with HSV-1, [3] 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.

Two-thirds of HSE cases occur in individuals already seropositive for HSV-1, few of whom (only 10%) have history of recurrent orofacial herpes, while about one third of cases results from an initial infection by HSV-1, predominantly occurring in individuals under the age of 18. [1] Approximately half of individuals who develop HSE are over 50 years of age. [4]

The most common cause for encephalitis in children and adults is HSV-1. However, encephalitis found in newborns and immunocompromised individuals is mainly caused by HSV-2. [5]

Signs and symptoms

Most individuals with HSE show a decrease in their level of consciousness and an altered mental state presenting as confusion, and changes in personality. Increased numbers of white blood cells can be found in patient's cerebrospinal fluid, without the presence of pathogenic bacteria and fungi. Patients typically have a fever [1] and may have seizures. The electrical activity of the brain changes as the disease progresses, first showing abnormalities in one temporal lobe of the brain, which spread to the other temporal lobe 7–10 days later. [1] Imaging by CT or MRI shows characteristic changes in the temporal lobes (see Figure). After the first symptoms appear, patients might lose their sense of smell. This can also be accompanied by the inability to read, write, or speak coherently, and understand verbal speech. [6]

Definite diagnosis requires testing of the cerebrospinal fluid (CSF) by a lumbar puncture (spinal tap) for presence of the virus. The testing takes several days to perform, and patients with suspected Herpes encephalitis should be treated with acyclovir immediately while waiting for test results. Atypical stroke-like presentation of HSV encephalitis has been described as well and the clinicians should be aware that HSV encephalitis can mimic a stroke. [7]

Associated conditions

Herpesviral encephalitis can serve as a trigger of anti-NMDA receptor encephalitis. [8] About 30% of HSE patients develop this secondary immunologic reaction, [9] which is associated with impaired neurocognitive recovery. [10]

Epidemiology

The annual incidence of herpesviral encephalitis is from 2 to 4 cases per 1 million population. [11]

Pathophysiology

HSE is thought to be caused by the transmission of virus from a peripheral site on the face following HSV-1 reactivation, along a nerve axon, to the brain. [1] The virus lies dormant in the ganglion of the trigeminal cranial nerve, but the reason for reactivation, and its pathway to gain access to the brain, remains unclear, though changes in the immune system caused by stress clearly play a role in animal models of the disease. The olfactory nerve may also be involved in HSE, [12] which may explain its predilection for the temporal lobes of the brain, as the olfactory nerve sends branches there. In horses, a single-nucleotide polymorphism is sufficient to allow the virus to cause neurological disease; [13] but no similar mechanism has been found in humans.

Diagnosis

Brain CT scan (with/without contrast). Complete prior to lumbar puncture to exclude significantly increased ICP, obstructive hydrocephalus, mass effect [14]

Brain MRI—Increased T2 signal intensity in frontotemporal region → viral (HSV) encephalitis [15]

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. [1] 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. [4] 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. [16] While the herpes virus can be spread, encephalitis itself is not infectious. Other viruses can cause similar symptoms of encephalitis, though usually milder (Herpesvirus 6, varicella zoster virus, Epstein-Barr, cytomegalovirus, coxsackievirus, etc.). [17] [11]

Related Research Articles

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Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

<span class="mw-page-title-main">Viral meningitis</span> Medical condition

Viral meningitis, also known as aseptic meningitis, is a type of meningitis due to a viral infection. It results in inflammation of the meninges. Symptoms commonly include headache, fever, sensitivity to light and neck stiffness.

<span class="mw-page-title-main">Varicella zoster virus</span> Herpes virus that causes chickenpox and shingles

Varicella zoster virus (VZV), also known as human herpesvirus 3 or Human alphaherpesvirus 3 (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles in adults but rarely in children. As a late complication of VZV infection, Ramsay Hunt syndrome type 2 may develop in rare cases. VZV infections are species-specific to humans. The virus can survive in external environments for a few hours.

<span class="mw-page-title-main">Shingles</span> Viral disease caused by the varicella zoster virus

Shingles, also known as herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Other common symptoms are fever, headache, and tiredness. The rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.

<span class="mw-page-title-main">Aseptic meningitis</span> Inflammation of the meninges not due to common bacterial infection

Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycobacteria, spirochetes, fungi, medications, and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what the actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause.

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<span class="mw-page-title-main">Viral encephalitis</span> Medical condition

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<span class="mw-page-title-main">Meningoencephalitis</span> Medical condition

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<span class="mw-page-title-main">Herpes simplex virus</span> Species of virus

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<span class="mw-page-title-main">Genital herpes</span> Infection by herpes simplex viruses of the genitals

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<span class="mw-page-title-main">Foix–Chavany–Marie syndrome</span> Medical condition

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<span class="mw-page-title-main">Limbic encephalitis</span> Inflammation involving the limbic system in the brain

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<span class="mw-page-title-main">Mollaret's meningitis</span> Medical condition

Mollaret's meningitis is a recurrent or chronic inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Since Mollaret's meningitis is a recurrent, benign (non-cancerous), aseptic meningitis, it is also referred to as benign recurrent lymphocytic meningitis. It was named for Pierre Mollaret, the French neurologist who first described it in 1944.

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<span class="mw-page-title-main">Herpes</span> Viral disease caused by herpes simplex viruses

Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herpes, though other forms also exist.

<span class="mw-page-title-main">Herpes meningitis</span> Medical condition

Herpes meningitis is inflammation of the meninges, the protective tissues surrounding the spinal cord and brain, due to infection from viruses of the Herpesviridae family - the most common amongst adults is HSV-2. Symptoms are self-limiting over 2 weeks with severe headache, nausea, vomiting, neck-stiffness, and photophobia. Herpes meningitis can cause Mollaret's meningitis, a form of recurrent meningitis. Lumbar puncture with cerebrospinal fluid results demonstrating aseptic meningitis pattern is necessary for diagnosis and polymerase chain reaction is used to detect viral presence. Although symptoms are self-limiting, treatment with antiviral medication may be recommended to prevent progression to Herpes Meningoencephalitis.

<span class="mw-page-title-main">Lymphocytic pleocytosis</span> Increase in lymphocytes within cerebrospinal fluid

Lymphocytic pleocytosis is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid (CSF). It is usually considered to be a sign of infection or inflammation within the nervous system, and is encountered in a number of neurological diseases, such as pseudomigraine, Susac's syndrome, and encephalitis. While lymphocytes make up roughly a quarter of all white blood cells (WBC) in the body, they are generally rare in the CSF. Under normal conditions, there are usually less than 5 white blood cells per μL of CSF. In a pleocytic setting, the number of lymphocytes can jump to more than 1,000 cells per μL. Increases in lymphocyte count are often accompanied by an increase in cerebrospinal protein concentrations in addition to pleocytosis of other types of white blood cells.

References

  1. 1 2 3 4 5 6 Whitley RJ (September 2006). "Herpes simplex encephalitis: adolescents and adults". Antiviral Research. 71 (2–3): 141–148. doi:10.1016/j.antiviral.2006.04.002. PMID   16675036.
  2. ↑ Kropp RY, Wong T, Cormier L, Ringrose A, Burton S, Embree JE, Steben M (June 2006). "Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study". Pediatrics. 117 (6): 1955–1962. doi:10.1542/peds.2005-1778. PMID   16740836. S2CID   9632498.
  3. ↑ Xu F, Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ, et al. (August 2006). "Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States". JAMA. 296 (8): 964–973. doi: 10.1001/jama.296.8.964 . PMID   16926356.
  4. 1 2 Whitley RJ, Gnann JW (February 2002). "Viral encephalitis: familiar infections and emerging pathogens". Lancet. 359 (9305): 507–513. doi:10.1016/S0140-6736(02)07681-X. PMID   11853816. S2CID   5980017.
  5. ↑ Ak, Ajith Kumar; Mendez, Magda D. (2023), "Herpes Simplex Encephalitis", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32491575 , retrieved 2023-10-02
  6. ↑ "Encephalitis, Herpes Simplex - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2023-10-02.
  7. ↑ Gupta, Harsh; Malhotra, Samira; Batra, Amit (2019-04-15). "An Unusual Stroke-Like Presentation of HSV Encephalitis". The Journal of the Arkansas Medical Society. 115– via ResearchGate.
  8. ↑ Dalmau J, Armangué T, Planagumà J, Radosevic M, Mannara F, Leypoldt F, et al. (November 2019). "An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models". The Lancet. Neurology. 18 (11): 1045–1057. doi:10.1016/S1474-4422(19)30244-3. PMID   31326280. S2CID   197464804.
  9. ↑ Prüss H, Finke C, Höltje M, Hofmann J, Klingbeil C, Probst C, et al. (December 2012). "N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis". Annals of Neurology. 72 (6): 902–911. doi:10.1002/ana.23689. PMC   3725636 . PMID   23280840.
  10. ↑ Westman G, Studahl M, Ahlm C, Eriksson BM, Persson B, Rönnelid J, et al. (November 2016). "N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis". Clinical Microbiology and Infection. 22 (11): 934–940. doi: 10.1016/j.cmi.2016.07.028 . PMID   27497810.
  11. 1 2 Ajith Kumar AK, Mendez MD (14 March 2022). "Herpes Simplex Encephalitis". StatPearls. PMID   32491575.
  12. ↑ Dinn JJ (November 1980). "Transolfactory spread of virus in herpes simplex encephalitis". British Medical Journal. 281 (6252): 1392. doi:10.1136/bmj.281.6252.1392. PMC   1715042 . PMID   7437807.
  13. ↑ Van de Walle GR, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N (July 2009). "A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease". The Journal of Infectious Diseases. 200 (1): 20–25. doi: 10.1086/599316 . PMID   19456260.
  14. ↑ "Herpes Meningoencephalitis". Johns Hopkins Medicine. 19 November 2019. Retrieved 13 July 2021.
  15. ↑ "Encephalitis". The Lecturio Medical Concept Library. Retrieved 13 July 2021.
  16. ↑ Varatharaj A, Nicoll JA, Pelosi E, Pinto AA (April 2017). "Corticosteroid-responsive focal granulomatous herpes simplex type-1 encephalitis in adults". Practical Neurology. 17 (2): 140–144. doi:10.1136/practneurol-2016-001474. PMID   28153849. S2CID   12859405.
  17. ↑ "Encephalitis". Mayo Foundation for Medical Education and Research (MFMER). Retrieved 13 July 2021.
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