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Posted: March 25th, 2020
Herpes Simplex Virus Encephalitis
Abstract
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Herpes simplex virus encephalitis is an infectious type of encephalitis primarily caused by herpes simplex virus I and II. Herpes simplex virus is the leading cause of encephalitis, raising its relapse rate by 5%. Even though both herpes simplex virus I and II can cause encephalitis, it is HSV-I that primarily causes inflammation and capable of invasion of ganglia, latency, and recurrence. In the case of newborn named Mercedes Mondego, was exposed to herpes simplex virus, soon after developed herpes simplex virus encephalitis. With an early diagnosis of Mercedes, she was able to be treated with Acyclovir. Unfortunately, the virus remained latent for three years only to reoccur again. Mercedes was able to be treated with acyclovir again, but was left with partial paralysis in her right part of her face and arm. The hospital was able to quickly diagnose and start Mercedes treatment and other patients alike with several types of tests including PCR, MRI, EEG, and CT scan.
Herpes simplex virus (HSV) was first to be documented by Hippocrates who used the term herpes to describe cranial herpetic infection. Herpes simplex virus is the most common cause of viral encephalitis, having an increase in reported relapse cases by five percent. Both herpes simplex virus (HSV) I and II can lead to herpes simplex virus encephalitis (HSE) by accessing and colonizing both the brain and nervous system. With the colonization of both the brain and nervous system HSV can cause latency and recurrence. The initial contact of the infection may be asymptomatic, but the virus is able to reactivate later in life depending on stress level and age. Herpes simplex virus encephalitis affects both adults and adolescents, but it is primarily a condition associated with small children and neonates with predisposition to the virus. Children contacting the virus is a serious but manageable condition depending on when a diagnosis is made and how early treatment can begin ( Dwibedi, 2016). In the case of Mercedes Mondego, she was diagnosed herpes simplex virus encephalitis, after treating herpes simplex virus encephalitis was forced to face this virus again at a young age.
Mercedes Mondego was born a healthy baby, growing to normal weight and length, reach all monthly milestones set by the doctor. Six months after birth, Mercedes experienced a spiked fever of 39.7℃, vomiting and experienced seizures, which was cured with diazepam. Admission into the emergency room, Mercedes underwent several tests, starting with an analysis of the cerebrospinal fluid (CSF). Initially, viral meningoencephalitis was suspected because of an increase in white blood cells {94% of which were lymphocytes} and protein concentration {55 mg/dL; normal 20-50 mg/dL}. Retesting the CSF resulted in a positive test for HSV-1 antigen; positive polymerase chain reaction (PCR) confirmed the HSV-1 infection. Other lab tests were used to help evaluate Mercedes condition, one being an electroencephalographic (EEG) and the other being a magnetic resonance imaging (MRI),showing spike-waves in the left temporal lobe and hyperintensity of the signal in the same lobe (Geha & Notarangelo, 2012).
Treatment began with intravenous acyclovir for three weeks, improving Mercedes condition dramatically. Antibodies to HSV-1 were detected after being treated. For three years Mercedes was able to live a normal life without any new major health complication, living her life as her fellow peers. Four months after her birthday Mercedes displayed, signs that of recurrence herpes simplex encephalitis, having a spiked fever, series of seizures, paralysis, and photophobia. Laboratory scientist tested her cerebral spinal fluid for increased proteins, white blood cells, and bacterial growth; 180 cells/µL, with 97% lymphocytes; 62 mg/µL protein. Along with a positive PCR test for HSV-1, an MRI unfortunately revealed Mercedes left parietal lobe contained new lesions. As before, Mercedes was treated with acyclovir and progressive clinical improvement. To evaluate all possibilities of what the cause(s) of relapsing herpes were simplex encephalitis (HSE), a genetic test was done. The acyclovir proved to be successful, showing zero episodes of the viral infection at the age of five, but it is noted that Mercedes still has partial paralysis in her right part of her face and arm (Geha & Notarangelo, 2012).
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Herpes simplex encephalitis (HSE) is the leading neurological disorder characterized by inflammation in the brain in the world. Each year the amount of reported cases rises, with the U.S reporting about 2,000 cases each year; HSE accounting for 10% of all reported cases. (Encephalitis, 2009) Affecting both females and males equally in the US, the virus acute form being the most prominent. Age is a factor when the viral infection causes HSE, according to a survey done in 2005-2010, roughly 60-90% of all cases were between the ages of 14-49. Despite the age gap for those who primarily reported to have HSE, there is a bimodal distribution with the peak of reported cases with the age group being three years or younger (Bradshaw & Venkatesean, 2016)
Herpes simplex virus (HSV) also known as human herpes virus are an enlarged double-stranded DNA virus. This virus is well adapted, establishing lifelong infection. Herpes simplex virus (HSV) I and II are the leading cause of infection, with both capable of causing HSE. HSV-I us the leading cause of HSE, accounting for the majority of all reported cases of HSE by invading through mucous membrane or damaged skin. The virus replicates at exposed sites further spreading the virus in the surrounding area (Alsweed, Alsuhibani, Casaanova & Al-Hajjar, 2018). After the initial exposure to the virus, it infects sensory neurons via interactions with cell-surface glycosaminoglycans followed by retrograde transport of viral DNA toward the dorsal root ganglia. Pathogenesis of the HSV is heavily dependent upon the strength of the host’s immune system and the unclear ability on which HSV is able to invade the brain (Bradshaw & Venkatesean, 2016). HSV-I has the ability to remain latent till a colonized ganglion is to be stimulated, allowing the recurrence of the virus to spread to either lobe of the brain.
Early recognition of HSE is key to its treatment, early symptoms that are associated with HSE develop over a series of days, but can be abrupt without warning. Symptoms supportive of HSE include fever, seizures, focal neurological signs, headaches, drowsiness, weakness, and disorientation. HSE may manifest more severe symptoms causing speech abnormalities, higher fever, diminished communication skills, aphasia, psychotic episodes and neurological defects (Encephalitis, 2009). In a series of cases, some cases are more prevalent in hospital admissions: abnormal behavior (23 %), loss of consciousness (13 %), seizures (32 %), and confusion or disorientation (13 %) (Bradshaw & Venkatesean, 2016). Though the symptoms are important to identifying HSE in its earliest stage, the viral infection can be falsely diagnosed as meningitis and neurosyphilis because of their characterization of inflammation around the spinal cord and brain (Encephalitis, 2009). Laboratory testing is the only way to assure proper diagnosis and treatment.
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The rapid onset of HSE presents a dilemma for the caring physician for diagnosing HSE. Early stages of HSE are the most critical, being that earliest diagnosis ensures the most effective treatment. Symptoms can general and similar to other infection, hence the importance of laboratory test. A key diagnostic procedure that is done to diagnose HSE is a lumbar puncture (LP) to drain cerebral spinal fluid that allows a polymerase chain reaction (PCR) test to be analyzed. PCR test are highly specific and sensitive for the virus’s DNA, with a 98% specify and sensitivity to the virus’s DNA. Time is a variable that can affect the results of a PCR test, a study has shown that sooner the test is ran the higher the chance of confirming the patient’s viral infection. A study reported higher positivity the sooner the specimen was collected and ran, showing 100% PCR positivity reported when collected within 10 days and 30% positivity for those collected between 11-20 days. Also an electroencephalogram (EEG) can be used by attaching electrodes to a patients scalp recording their brain’s electrical activity. Certain abnormal patterns may indicate a diagnosis of encephalitis. Another test that can be useful to properly making a clinical assessment is a computed tomography (CT or CAT) scan or a magnetic resonance imaging (MRI) can provide clear imaging of the brain, allowing the clinician to see if there is swelling or lesions around the brain. Though a CT and MRI scan can be very useful, 10% of those with normal MRI scans were PCR-positive patients ( Dwibedi, 2016) . With the use of each laboratory test, proper treatment can begin.
Early diagnosis is crucial for treatment to begin, valacyclovir, famciclovir, ganciclovir, and a helicase/ primase inhibitor can be used to treat HSE. Though there are other option to cure HSE, they are less potent, acyclovir is the leading antiviral to treat HSE. The recommended dosage of Acyclovir is 45 mg/kg per day for children and 60 mg/kg per day for neonates (Alsweed, Alsuhibani, Casaanova & Al-Hajjar, 2018). Treatment for herpes simplex virus encephalitis (HSE) is a delicate process, even more delicate for those who under the age of five with recurrence HSE. It is difficult to asses the outcome of children being treated with Acyclovir, therefore a follow up should be done. Adverse effects have been reported for those between the age of 3-40 months of age, resulting in children with permanent disabilities to death. Though there are those who are unfortunate when being treated with acyclovir, is has been able to lower the mortality and morbidity rate by more than 14% . Acyclovir therapy should be halted when CSF HSV PCR are negative, normal MRI results, normal EEG, and a low cell count in the CSF (Dwibedi, 2016) .
Herpes simplex virus encephalitis is a life-threatening condition caused by HSV-I and HSV-II. HSE is associated with a high mortality and morbidity rate. With herpes simplex virus having the ability to establish latency in its host, cases have reported to the reactivation of encephalitis. As early diagnosis of HSE is challenging, the use of PCR and MRI test has allowed clinicians to administer Acyclovir as quick as possible.
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