herpes simplex encephalitis

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 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. 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.{{Cite web |title=Encephalitis, Herpes Simplex - Symptoms, Causes, Treatment {{!}} NORD |url=https://rarediseases.org/rare-diseases/encephalitis-herpes-simplex/ |access-date=2023-10-02 |website=rarediseases.org |language=en-US}}

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.{{cite journal |url=https://www.researchgate.net/publication/332427377 |last1=Gupta |first1=Harsh |last2=Malhotra |first2=Samira |last3=Batra |first3=Amit |date=2019-04-15 |title=An Unusual Stroke-Like Presentation of HSV Encephalitis |volume=115 |journal=The Journal of the Arkansas Medical Society |via=ResearchGate}}

Herpesviral encephalitis can serve as a trigger of anti-NMDA receptor encephalitis.{{cite journal | vauthors = Dalmau J, Armangué T, Planagumà J, Radosevic M, Mannara F, Leypoldt F, Geis C, Lancaster E, Titulaer MJ, Rosenfeld MR, Graus F | display-authors = 6 | title = An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models | journal = The Lancet. Neurology | volume = 18 | issue = 11 | pages = 1045–1057 | date = November 2019 | pmid = 31326280 | doi = 10.1016/S1474-4422(19)30244-3 | s2cid = 197464804 }} About 30% of HSE patients develop this secondary immunologic reaction,{{cite journal | vauthors = Prüss H, Finke C, Höltje M, Hofmann J, Klingbeil C, Probst C, Borowski K, Ahnert-Hilger G, Harms L, Schwab JM, Ploner CJ, Komorowski L, Stoecker W, Dalmau J, Wandinger KP | display-authors = 6 | title = N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis | journal = Annals of Neurology | volume = 72 | issue = 6 | pages = 902–911 | date = December 2012 | pmid = 23280840 | pmc = 3725636 | doi = 10.1002/ana.23689 }} which is associated with impaired neurocognitive recovery.{{cite journal | vauthors = Westman G, Studahl M, Ahlm C, Eriksson BM, Persson B, Rönnelid J, Schliamser S, Aurelius E | display-authors = 6 | title = N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis | language = English | journal = Clinical Microbiology and Infection | volume = 22 | issue = 11 | pages = 934–940 | date = November 2016 | pmid = 27497810 | doi = 10.1016/j.cmi.2016.07.028 | doi-access = free }}

The annual incidence of herpesviral encephalitis is from 2 to 4 cases per 1 million population.{{cite journal | vauthors = Ajith Kumar AK, Mendez MD | title = Herpes Simplex Encephalitis | journal = StatPearls | volume = | issue = | date = 14 March 2022 | pmid = 32491575 | doi = }}

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. 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,{{cite journal | vauthors = Dinn JJ | title = Transolfactory spread of virus in herpes simplex encephalitis | journal = British Medical Journal | volume = 281 | issue = 6252 | pages = 1392 | date = November 1980 | pmid = 7437807 | pmc = 1715042 | doi = 10.1136/bmj.281.6252.1392 }} 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;{{cite journal | vauthors = Van de Walle GR, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N | title = A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease | journal = The Journal of Infectious Diseases | volume = 200 | issue = 1 | pages = 20–25 | date = July 2009 | pmid = 19456260 | doi = 10.1086/599316 | doi-access = free }} but no similar mechanism has been found in humans.

Brain CT scan (with/without contrast). Complete prior to lumbar puncture to exclude significantly increased ICP, obstructive hydrocephalus, mass effect{{cite web |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/herpes-hsv1-and-hsv2/herpes-meningoencephalitis| title=Herpes Meningoencephalitis|website=Johns Hopkins Medicine | date=19 November 2019|access-date= 13 July 2021}}

Brain MRI—Increased T2 signal intensity in frontotemporal region → viral (HSV) encephalitis{{cite web |url=https://www.lecturio.com/concepts/encephalitis/| title=Encephalitis|website=The Lecturio Medical Concept Library |access-date= 13 July 2021}}

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.{{cite journal | vauthors = Varatharaj A, Nicoll JA, Pelosi E, Pinto AA | title = Corticosteroid-responsive focal granulomatous herpes simplex type-1 encephalitis in adults | journal = Practical Neurology | volume = 17 | issue = 2 | pages = 140–144 | date = April 2017 | pmid = 28153849 | doi = 10.1136/practneurol-2016-001474 | s2cid = 12859405 | url = https://eprints.soton.ac.uk/413486/1/Varatharaj_et_al_2017.doc }} 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.).{{cite web |url=https://www.mayoclinic.org/diseases-conditions/encephalitis/symptoms-causes/syc-20356136| title=Encephalitis|website= Mayo Foundation for Medical Education and Research (MFMER) |access-date= 13 July 2021}}

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• {{cite journal | vauthors = Kumar M, Hill JM, Clement C, Varnell ED, Thompson HW, Kaufman HE | title = A double-blind placebo-controlled study to evaluate valacyclovir alone and with aspirin for asymptomatic HSV-1 DNA shedding in human tears and saliva | journal = Investigative Ophthalmology & Visual Science | volume = 50 | issue = 12 | pages = 5601–5608 | date = December 2009 | pmid = 19608530 | pmc = 2895993 | doi = 10.1167/iovs.09-3729 }}
• {{cite journal | vauthors = Kaufman HE, Azcuy AM, Varnell ED, Sloop GD, Thompson HW, Hill JM | title = HSV-1 DNA in tears and saliva of normal adults | journal = Investigative Ophthalmology & Visual Science | volume = 46 | issue = 1 | pages = 241–247 | date = January 2005 | pmid = 15623779 | pmc = 1200985 | doi = 10.1167/iovs.04-0614 }}
• {{cite journal | vauthors = Hill JM, Zhao Y, Clement C, Neumann DM, Lukiw WJ | title = HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling | journal = NeuroReport | volume = 20 | issue = 16 | pages = 1500–1505 | date = October 2009 | pmid = 19801956 | pmc = 2872932 | doi = 10.1097/WNR.0b013e3283329c05 }}

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{{Medical resources

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| ICD10 = {{ICD10|B|00|4|b|00}}

| ICD9 = {{ICD9|054.3}}

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| eMedicineTopic = 1165183

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{{Viral diseases}}

{{CNS diseases of the nervous system}}

Category:Viral encephalitis

Category:Pediatrics

Category:Herpes simplex virus–associated diseases