Herpetic encephalitis

The probability of infection with Herpes simplex viruses (herpes simplex) is very high. It is believed that the vast majority of the adult population of the planet is seropositive against labial herpes. The insidiousness of this intracellular parasite lies in the fact that it is able to remain in a latent state for a long time, and under conditions favorable for its development, affect the central nervous system. 

Encephalitis is an inflammation of the brain parenchyma with neurological dysfunction that can be caused by infectious, post-infectious, and non-infectious causes. [1]Infection accounts for approximately 50% of the cases identified and is the most common etiological category of encephalitis. [2]

Herpetic encephalitis is a rather rare and severe disease, most of the cases of which are caused precisely by the virus of the first type. In the absence of timely diagnosis and a course of antiviral therapy, the disease is accompanied by high mortality and a large number of severe neurological complications associated with local involvement in the process of the limbic system of the brain.

The word herpes is translated as “creeping” or “creeping”, and is a reference to herpetic skin lesions. Goodpasture [3] et al have demonstrated that material from herpetic lips and genital lesions caused encephalitis when they entered the cicatricial cornea or skin of rabbits. In the 1920s, the Matthewson Commission was among the first reports that HSV caused encephalitis in humans. The first pediatric report on HSVE was published in 1941. [4]The first adult case, a 25-year-old man with a headache, fever, aphasia, and dilated left pupil, was reported in 1944. [5]A post-mortem examination revealed numerous petechiae and ecchymoses with a perivascular lymphocytic cuff in the left temporal lobe, midbrain and lower back. Intranuclear inclusions were identified and the virus was isolated from the patient's brain. Since the advent of these early reports, significant progress has been made in the field of pathobiology, diagnosis and treatment of HSVE.

Epidemiology

From two to four out of a million people get sick with herpetic encephalitis in the world every year. Among all encephalitis of various origins, herpetic cases are about 15%, this figure varies from year to year in a slightly larger or smaller direction.

In 60-90% of cases, HSV-1 herpes virus is detected in patients. [6] Most experts do not note the connection of the incidence with the season of the year, but some indicated that in the spring, herpetic encephalitis is more common.

A person can be ill of any gender and age, however, about a third of cases occur in children and adolescents (up to 20 years), and half - in patients who have overcome half a century of age.

Although encephalitis is rare in infected people, HSV-1 is invariably the single most common cause of sporadic encephalitis worldwide. [7],  [8] The incidence of HSV in the world, estimated at 2 to 4 cases / 1 million,  [9] while in the US the incidence is similar. There is a bimodal distribution with peak incidence in children (up to 3 years old) and again in adults over the age of 50 years, but most cases occur in people over 50 years old, regardless of gender. [10], [11]

Causes of the herpetic encephalitis

Most experts are inclined to believe that the development of this disease occurs as a result of the activation of herpes viruses that latently exist, integrating into the DNA chains of cells of the nervous tissue.

In the form of an inflammatory process in the cortex, subcortex, white matter of the brain, primary infection with HSV-1 or 2 can occur and be the only manifestation of infection. Such cases are characteristic of the first meeting with herpes virus in childhood and adolescence.

Diffuse herpes simplex virus damage, when visceral organs and skin are involved, can often spread to the central nervous system with the development of encephalitis.

In the vast majority of patients with herpetic inflammation of the brain substance, the herpes simplex virus of the first type (HSV-1) is detected, namely the one that appears with itchy vesicles on the lips, much less often - the second (HSV-2), the so-called genital. In cases of chronic sluggish encephalitis, HSV-3 (Zoster’s herpes, causing chickenpox / shingles), HSV-4 (Epstein-Barr virus, causing Filatov’s disease or infectious mononucleosis), cytomegalovirus HSV-5, human herpesviruses HSV-6 and HSV 7, which are "noticed" in the development of chronic fatigue syndrome. Sometimes in one patient cells of different tissues are affected by viruses of different strains (mixed form). So, theoretically, the defeat of all these species can lead to herpetic encephalitis.

A complication in the form of inflammation of the brain is sometimes caused by the so-called herpetic sore throat. Strictly speaking, this disease has nothing to do with the herpes virus. Therefore, the encephalitis that arose against its background is viral, but not herpetic. The causative agent is the Coxsackie virus - this is enterovirus. It is related to herpes by their viral nature - the ability to parasitize inside cells, including the brain. The same applies to a disease such as herpetic stomatitis. In fact, the so-called herpetic sore throat (stomatitis) is one and the same disease, just with angina, the pharyngeal mucosa is more affected, vesicle formations (vesicles) resembling herpes are poured on it. With stomatitis, the mucous membrane of the oral cavity is affected more. Modern medicine refers to this pathology as enteroviral vesicular pharyngitis or stomatitis, depending on the prevailing rash zone and the discomfort associated with them. These diseases, basically, end quite safely, complete recovery, however, in rare cases, complications in the form of viral encephalitis may develop, the symptoms of which are identical to herpetic.

Herpes viruses that infect human skin cells or mucous membranes of the orolabial zone, integrate into them, begin to multiply and migrate through the body through the hematogenous and lymphogenous pathways, reaching the nerve cells. After the suppression of the active stage, which develops after infection, the viruses integrate into their genetic apparatus and remain in the “sleeping” state of the nerve cells, do not multiply and do not show themselves in most carriers. In studies of post-mortem oligonucleotide probing of herpes simplex virus DNA, the brain substance of the majority of the dead was found in neurons, the cause of death of which was absolutely not connected with infection with this microorganism. It was found that the introduction of the herpes virus into cells, in particular, nerve tissues, is not always accompanied by its multiplication and death of the host cell. Usually, it inhibits alien replication, and the microorganism goes into a state of incubation.

But under the influence of some triggering factors, the herpes virus is activated, and the latent course of the infection passes into an acute or subacute process, and the substance of the brain will not necessarily be affected.

Risk factors

The risk factors that trigger the reactivation process are not precisely established. It is assumed that this can be local injuries in the face, stress, hypothermia or overheating, immunosuppression, hormonal fluctuations, frequent vaccinations and careless behavior after them. It matters age, the most at risk of getting herpetic encephalitis are infants and the elderly.

Pathogenesis

The pathogenesis of herpetic encephalitis is not uniform. It is assumed that for the first infected, the herpes simplex virus of the first type (childhood and adolescence) enters the cells of the brain substance from the epithelium of the mucous membrane of the nasopharynx. Having overcome the tissue barrier, in a neurogenic way (along the neurites of the olfactory neurons), the microorganism migrates to the olfactory bulb and, under conditions favorable for its development, causes inflammation of the brain substance.

The mechanisms by which HSV gains access to the central nervous system (CNS) in humans are unclear, and this remains a matter of debate. The most likely routes include retrograde transport through the olfactory or trigeminal nerves  [12],  [13] or through hematogenous dissemination. Viral tropism of the orbitofrontal and mesotemporal lobes in most cases opposes hematogenous dissemination. Experimental animal data confirm transmission to the central nervous system via one or both of the trigeminal nerve and olfactory pathways and suggest that virions can spread to the contralateral temporal lobe through the anterior commissure. [14]

Unlike other cranial nerves with sensory functions, the olfactory nerve pathways do not pass through the thalamus, but connect directly to the frontal and mesotemporal lobes (including the limbic system). There is some evidence to support the spread of smell in the central nervous system in humans, but accurate data are scarce. [15], The  [16] trigeminal nerve innervates meninges and can spread along the orbitofrontal and mesiotemporal lobes. [17] However, since the sensory nuclei of the trigeminal nerve are located in the brain stem, one would expect that the relatively rare brain stem encephalitis associated with HSVE would be more common if, in most cases, this was the main pathway to the central nervous system. [18], [19]

Whether HSVE is a reactivation of a latent virus or caused by a primary infection is also in dispute; both can happen. Presumptive pathogenic mechanisms include reactivation of latent HSV in the trigeminal ganglia, followed by the spread of infection to the temporal and frontal lobes, primary CNS infection, or possibly reactivation of the latent virus in the brain parenchyma itself. [20],  [21] At least half the HSVE virus strain responsible for encephalitis, different from the strain causing herpetic skin lesions in the same patient, an observation which suggests the possibility of primary CNS infections. [22]

Infection with HSV causes a strong response from the innate immune system until adaptive immunity can help eliminate an active infection. At the beginning of the immune response to HSV, pattern recognition receptors called Toll-like receptors (TLRs) located on the cells of the innate immune system recognize and bind to pathogen-associated molecular patterns. [23] This triggers TLR dimerization, which subsequently activates signaling pathways that initiate the production of pro-inflammatory cytokines, such as interferons (IFN), tumor necrosis factor, and various interleukins. [24] IFNs contribute to the host's resistance to viral proliferation by activating the Jak-Stat signaling pathway  [25] and by triggering the production of both RNAse enzymes that destroy cellular RNA (both the host and the virus), and double-stranded RNA-dependent protein kinase, which stops cell translation. [26] Deficiencies in the immune response to HSV (for example, TLR-3 pathway defects, including TLR3 itself, UNC93B1, TIR-domain-containing adapter-inducing IFN-β, factor-3 associated with the tumor necrosis factor receptor, TANK-binding kinase 1 or regulatory factor IFN-3) leave the host susceptible to HSVE. [27], [28]

The inflammatory cascade triggers adaptive immunity, which can lead to necrosis and apoptosis of infected cells. Although the host's immune response is crucial for possible viral control, an inflammatory response, especially the recruitment of activated white blood cells, can contribute to tissue destruction and subsequent neurological consequences. [29], [30]

After the initial infection, the virus establishes a latent state for the life of the host and remains at rest if it is not activated. [31] To establish and maintain a delay, a number of complex processes must be balanced. These include silencing the viral genes of the lytic phase, the abolition of host cell defense mechanisms (e.g. Apoptosis) and evading host immunity, including both the innate and acquired immune responses (e.g., suppressing the expression of the main histocompatibility complex)  [32],  [33] HSV-specific CD8 + T cells settle in the trigeminal ganglia and help maintain the virus in a latent state. [34] During reactivation, the expression of viral genes occurs in a temporarily organized manner, as was recently considered. [35] After reactivation, the virus can infect neighboring neurons and move into tissues innervated by the infected ganglia of the dorsal root, causing a relapse of the disease and releasing infectious viral particles that can be transmitted to others.

In early infancy, the HSV-2 virus is more often detected. The main part of infections falls on the advancement of the child through the birth canal of the mother, if she currently has an acute stage of the disease (there are rashes on the genitals). The probability of infection at the time of birth is highest, therefore, women with acute form of genital herpes are usually recommended to give birth using Cesarean section.

Much less often, herpetic encephalitis in newborns can be the result of intrauterine infection, and also - it can be caused by contact with a sick parent or a representative of the hospital staff after birth, but such cases are much smaller.

Adult patients with this neuroinfection usually had herpetic eruptions in the past or, according to the test results, turned out to be seropositive to herpes simplex viruses. Encephalitis could develop upon reinfection with another strain of the virus - in this case, a strain of herpes virus is found on the mucous membrane of the oral cavity or pharynx (nose) that is different from that which affected the substance of the brain. Different strains are found in about a quarter of patients with herpetic encephalitis.

Three quarters of the remaining cases have orolabial virus strains identical to those found in brain tissue. In this case, two scenarios are expected. The first option considers the hypothesis that the virus is latent in the nodes of the trigeminal nerve or sympathetic chains, and when reactivated by the neurogenic pathway (along the nerves that innervate the middle cranial fossa), it reaches the brain tissue. The second option assumes that the virus, upon infection, has already reached the neurons of the brain and was there in a state of latency, where, under favorable conditions, its reactivation occurred.

Herpes virus replication occurs intracellularly, with the formation of intranuclear inclusions, affecting neurons, auxiliary cells (glia) and destroying interneuronal connections.

How is herpetic encephalitis transmitted?

Close contact with the patient is not dangerous in the sense of direct infection with herpetic encephalitis. Only the virus itself is transmitted. More often this occurs when in direct contact with an infected person in the acute stage, when he has orolabial, genital, skin rashes. No wonder herpes is also called "the disease of kisses." The liquid secret from the accumulation of vesicles on the patient's lips is simply oversaturated with viruses, its saliva and nasal discharge are also seeded with pathogens. The infection affects damaged skin (with microcracks, scratches) when droplets of saliva seeded with microorganisms or rhinobronchial secretions get on coughing and sneezing of the patient, emotional conversation, in direct contact, for example, with a kiss. In young children, the virus can penetrate even through intact skin. It can be infected by the alternate use of one towel, dishes, lipstick and other similar actions.

You can get a cell parasite of the first and second type during oral-genital sex with an infected partner. And if the vesicles on the lips are clearly visible, then it is often problematic to determine the active phase of HSV-2 (sexual), since in most infected people, exacerbations can occur in an erased form, and the patient himself may simply not be aware of this.

In the latent stage, you can also get infected. Usually this occurs with frequent direct contact of the mucous membranes or in the presence of injuries and microdamages on the contact surfaces of the body of a healthy person.

Genital herpes is transmitted from the mother infected during pregnancy to the baby through the vertical (in utero) and contact way during childbirth.

Symptoms of the herpetic encephalitis

The first signs of the disease are non-specific and resemble the manifestation of many acute infectious diseases. In the early stage, there is a high (39 ℃ and above) temperature, worsening headache in the forehead and temples, weakness, drowsiness, and lack of appetite. Nausea and vomiting, in about half of patients, join the symptoms of general intoxication in the first hours of the disease. Quite quickly, in the early stage, on the second or third day, neurological symptoms begin to appear, indicating the possibility of herpetic encephalitis.

The patient begins to behave inappropriately, and behavioral disorders progress. Confusion occurs, the patient loses the spatial-temporal orientation, sometimes ceases to recognize loved ones, forgets words, events. Hallucinations are observed - auditory, visual, olfactory, tactile, focal and even generalized epileptiform seizures, indicating damage to the limbic part of the brain. Behavioral disorders can be pronounced, in some patients a state of delirium is observed - they are hyper-excitable, aggressive, uncontrollable. In some cases (when the virus infects the mediabasal areas of the temporal lobes), ocular seizures are observed - the patient makes automatic chewing, sucking, and swallowing movements.

Herpetic encephalitis in young children is often accompanied by myoclonic seizures.

Contact with a patient already at an early stage presents certain difficulties associated with a slowdown in mental reactions, memory lapses, confusion and stupor of consciousness.

The early stage of herpetic encephalitis usually lasts several days, sometimes up to a week, but can proceed with lightning speed and in a few hours go to the stage of the height of the disease, which is characterized by impaired consciousness up to the development of stupor and coma. In a state of sopor, the patient’s consciousness is absent, he does not respond to turning to himself, but motor reactions to pain, light, and auditory stimuli persist. [36], [37]

In a series of 106 cases of HSVE, the main reasons for appearing in the hospital were convulsions (32%), abnormal behavior (23%), loss of consciousness (13%) and confusion or disorientation (13%). [38]

Symptoms that indicate the development of a coma in a patient are respiratory rhythm disturbances, with intermittent stops (apnea), motor disorders on both sides, symptoms of decortication (disabling the functions of the cerebral cortex) and decerebration (disabling the anterior brain). These posotonic reactions are extremely unfavorable signs.

Pose, indicating the onset of decortication rigidity - the upper limbs are bent, and the lower ones are unbent. Decerebral posture - the patient’s body is pulled into a string, all limbs are unbent, the extensor muscles are tense, and the limbs are straightened. The level of damage to the brain stem is determined by the degree of impaired consciousness and dysfunction of the facial and bulbar nerves.

In the absence of adequate treatment, cerebral edema develops, displacing the location of its trunk in relation to other structures. The wedge of the temporal portions of the brain into the tentorial opening is characteristic, which is accompanied by a triad of symptoms: loss of consciousness, different sizes of the pupils of the eyes (anisocoria); weakening of one half of the body. Other focal lesions of the brain and cranial nerves are also observed.

The stage of reverse development of herpetic encephalitis occurs towards the end of the month from the onset of the disease and its duration can be calculated in months. About a fifth of patients recover completely, the rest have a lifelong neurological deficit of varying severity. It can be local psychomotor disorders, or it can be a vegetative state.

Herpetic encephalitis in newborns is most difficult to tolerate premature and weakened babies. They often have a disease in fulminant necrotic form or respiratory failure, leading to a coma, quickly develops. There are usually no rashes, but there are almost always cramps, paresis, as a result of which the swallowing reflex is disturbed, and the child can not eat.

In full-term infants, a milder course is usually observed. The condition worsens gradually - hyperthermia, the child is weak and capricious, there is no appetite. Later, neurological symptoms - convulsions, myoclonus, paresis may join.

Chronic progressive herpetic encephalitis in newborns manifests itself in symptoms in the first or second week of life. The baby's temperature rises, it becomes lethargic and tearful, characteristic vesicular vesicles appear on the head and body, and later epileptiform symptomatology joins. Without treatment, the baby may fall into a coma and die.

Herpetic encephalitis in adults and older children also proceeds with varying degrees of severity. The classic acute course of the disease caused by the virus of the first and second type is described above. Subacute is distinguished by relatively less pronounced symptoms of intoxication and neurological deficiency. It does not reach a coma, but hyperthermia, headache, photophobia, nausea, febrile seizures, drowsiness, cognitive impairment, forgetfulness, and confusion are necessary.

In addition, there are more “softer” variants of the course of the disease. Chronic sluggish herpetic encephalitis is a progressive viral lesion of the brain, which is more often affected by people over 50 years old. Symptomatology differs from an acute course by a gradual increase. A person notices constant increased fatigue, progressive weakness. He may periodically, for example, in the evening, the temperature rises to subfebrile values, and a constant subfebrile condition can be observed. Against the background of increased nervous and physical stress, stress, after suffering colds and flu, as a rule, an aggravation of a sluggish process is observed. The asthenization of the body increases and ultimately leads to a decrease in intellectual potential, loss of working capacity and dementia.

One of the forms of sluggish herpetic encephalitis is chronic fatigue syndrome, the trigger for the development of which is usually a transferred disease with flu-like symptoms. After this, the patient can not recover for a long period of time (more than six months). He feels constant weakness, he is tired of the usual daily activities, which he had not noticed before the illness. All the time I want to lie down, performance is at zero, attention is scattered, memory fails, and so on. The cause of this condition is currently considered a neuroviral infection, and the most probable etiofactors are herpes viruses and not only simple, but also HSV-3 - HSV-7.

Types of herpetic encephalitis are classified according to different criteria. According to the severity of symptoms (form of course), the disease is divided into acute, subacute and chronic relapsing.

According to the degree of damage to the substance of the brain, a focal and diffuse inflammatory process is distinguished.

The localization of lesions is reflected in the following classification:

• inflammation of the predominantly gray matter of the brain - polyoencephalitis;
• predominantly white - leukoencephalitis;

Generalized process, covering all tissues - panencephalitis.

Complications and consequences

Herpetic encephalitis is a potentially treatable disease, but timely treatment is of great importance. With its absence or late onset, the disease often causes the death of the patient or severe neuropsychiatric complications. The most severe consequence of herpetic encephalitis is akinetic mutism or a progressive vegetative state. The patient completely loses the ability to intellectual activity, does not speak and does not move, only the cycle of sleep and wakefulness is fully restored. In addition, the function of respiration and blood circulation is preserved. All other vital processes are abnormal: the patient is not able to eat, drink, monitor the hygiene of his body, does not control the emptying of the intestines and bladder. This condition is irreversible and is the result of large-scale damage to brain tissue. It develops in patients after exiting a prolonged coma.

In many patients who survived the severe course of herpetic encephalitis, persistent neuropsychic disorders of varying severity remain for life: hemiparesis, hemiplegia, visual and hearing impairment (often on the one hand), epileptiform seizures. [39]

Diagnostics of the herpetic encephalitis

The first suggestion of such a diagnosis is the presence of neurological disorders - inappropriate behavior, convulsive seizures, confusion, arising from symptoms such as high fever and severe headache.

If the possibility of herpetic encephalitis is assumed, then analyzes are urgently ordered (cerebrospinal fluid microscopy and its polymerase chain reaction to detect fragments of the herpes virus genotype), as well as instrumental studies, the most informative of which is nuclear magnetic resonance imaging. If this is not possible, computed tomography and electroencephalography are done,  [40] which may be useful for evaluating the effectiveness of anticonvulsants. True, the insidiousness of the disease lies in the fact that in the early stages of development, diagnostic criteria may not go beyond the norm. Then the studies are repeated during the first week.

The polymerase-chain reaction of cerebrospinal fluid yields results with high accuracy and allows you to replace such a traumatic study as a biopsy of a brain substance. The revealed DNA fragments of the herpes virus indicate a herpetic etiology of encephalitis, and the positive result of the study remains for a week after the start of antiviral therapy.

Microscopy of the cerebrospinal substance reveals lymphocytosis, the presence of red blood cells (with hemorrhagic form), an increased level of proteins, low or normal glucose.

The main imaging method is nuclear MRI. It is used for emergency reasons. In addition, it allows you to clarify whether the patient can do a lumbar puncture for analysis. Herpetic encephalitis on MRI shows amplification of signals in the temporal lobes or islet region of the cerebral cortex, on the surface of the orbital frontal gyrus, which are characterized by one-sided or two-sided lesions with lack of symmetry. These results are devoid of specificity, but coupled with clinical symptoms and laboratory test data, in most cases an accurate diagnosis can be made. [41]

Early diagnosis does not always confirm the diagnosis: in 10% of patients, CSF microscopy and MRI data, and in 5% of patients, PCR results are false negative. [42] Nevertheless, in most patients, at least some research confirms the diagnosis, and subsequent visualizations reveal obvious and progressive changes - the presence of edema and hemorrhage, diffuse spread of lesions.

Differential diagnosis

First of all, it is necessary to identify the origin of the pathogen, since the main treatment is aimed at neutralizing it: viral encephalitis requires massive antiviral therapy, bacterial - the appointment of antibiotics, parasitic - the corresponding antiparasitic drugs, etc. In this sense, the results of analyzes, especially PCR, play a decisive role. [43], [44]

Herpetic encephalitis must be distinguished from multiple sclerosis, neoplasm, abscess, cerebrovascular accident, for example, with a stroke in the basin of the middle cerebral artery, the basal nuclei are usually damaged (as can be seen on MRI), and with herpetic encephalitis they are not affected, myelitis - inflammation spinal cord, especially since disseminated neuroinfection often spreads to areas of the spinal cord (herpetic encephalomyelitis).

HSV-2 virus more often than HSV-1 causes an inflammatory process in the soft membranes of the brain (herpetic meningitis), although it is rarely the same localization. Inflammation quickly spreads to the brain substance - neurons and glial cells, and herpetic meningoencephalitis develops. If the origin of the pathogen is established, then the treatment principle is similar (antiviral therapy). But the lesion area is larger, respectively, complications and consequences can be more serious. Differentiates according to the results of instrumental studies.

Treatment of the herpetic encephalitis

Patients with suspected acute damage to the brain by the herpes simplex virus must be hospitalized, moreover, in the intensive care unit or intensive care unit. [45] This is due to the high likelihood of developing coma, respiratory failure, disorders of the act of swallowing and other disorders of vital functions, which cannot be maintained at home.

At the initial stage, it is recommended to administer Curantil antithrombotic agent three times a day in a single dose of 25-50 mg. This is done to prevent ischemic cerebrovascular accident.

The main one is etiotropic treatment aimed at reducing the activity of the herpes virus (it is not currently possible to completely destroy it). The drug of choice is Acyclovir and its synonyms, especially effective against HSV-1 and HSV-2 herpes viruses. Timely antiviral therapy can significantly increase the patient's chances of a favorable outcome of the disease and minimal complications.

Acyclovir is a drug focused on the so-called molecular targets, a purine analogue of guanine, a component of nucleic acids. A similar structure allows acyclovir to penetrate the cell of the virus and, interacting with its enzymes, turn into acyclovir triphosphate, which, integrating into the chain of viral DNA, interrupts the process of reproduction of the pathogenic microorganism. And most importantly - Acyclovir does not significantly affect the gene apparatus of human cells and helps mobilize immunity.

Patients with severe forms of herpetic encephalopathy with the development of coma are prescribed acyclovir in a single dose of 10-15 mg per kilogram of the patient's weight three times a day intravenously. Usually it is dripped, since it is necessary to inject the drug into the vein very slowly. The course of treatment is from one to two weeks. The advantage of acyclovir in HSVE was established by 2 iconic clinical trials conducted in the mid-1980s. Whitley et al. [46]. In modern guidelines, it is recommended to use acyclovir intravenously for 14–21 days in cases of HSV. [47]

With a milder course of the disease, if the patient can swallow the medicine on his own, a tablet form of the drug can be prescribed.

Acyclovir is also available in tablets. The dose is prescribed by the doctor depending on the condition and age of the patient, since encephalitis is treated with high doses of the drug. In patients with severe renal failure, the dose is adjusted. Take pills for medicinal purposes up to five times a day.

If possible, the oral form is sometimes preferred Valaciclovir. This is a more modern drug, the advantage of which is that it acts prolonged and can not be taken as often as its predecessor. In the body, the active substance is broken down into acyclovir, followed by the main, antiherpetic effect, and valine - aliphatic acid, a natural ingredient in proteins. With herpetic encephalitis, the ability of this substance to protect and regenerate the myelin sheath of nerve fibers is valuable. Valine increases the energy potential of the muscles of the body muscles, improves coordination of movements, stimulates cell synthesis and promotes tissue renewal.

These antiviral drugs are contraindicated in people with hypersensitivity to acyclovir. According to vital indications, they are prescribed to pregnant women, since the teratogenicity of the drug has not been identified, however, complete safety has not yet been proven. Valacyclovir is not prescribed for children. Side effects from taking expressed headache, nausea, impaired hematopoiesis and excretory function of the kidneys.

Recent studies have found that the anti-influenza drug Arbidol is also active against the second type of herpes simplex virus. In addition to virologic ability, it also stimulates the synthesis of interferon, humoral and cellular immunity.

Other immunomodulators can be prescribed, for example, Laferobion, which is a human interferon or Levamisole. The dosage and duration of administration of drugs to stimulate the immune system is prescribed by the doctor. Usually they are used for a short time from three to five days. They can also cause allergic reactions and are not desirable for people with chronic diseases of the heart, blood vessels, liver and kidneys.

To reduce inflammation and prevent brain edema, glucocorticosteroids (Prednisolone, Medrol, Dexamethasone) are prescribed. [48] Their usefulness in encephalitis is not recognized by all experts, since corticosteroids have both a strong anti-inflammatory and immunomodulating effect, which theoretically can contribute to the replication of the virus, it is not surprising that there are different opinions regarding their use in HSVE  [49],  [50] and the number of side effects is frightening, therefore, they pulse therapy short course. When taking them, in no case should you violate the dosage and dosage regimen. A non-randomized retrospective study of 45 patients with HSV showed that the addition of corticosteroids to acyclovir may be associated with improved results,  [51] which leads to larger clinical trials.

B vitamins are prescribed to improve the functioning of the central nervous system, maintain normal metabolism in the substance of the brain, and restore myelin sheaths of nerve fibers. Thiamine, pyridoxine, cyancobalamin (B1, B6, B12) are most significant for the functioning of the nervous system. Thiamine normalizes the conduction of nerve impulses, pyridoxine strengthens the myelin sheath of nerve fibers and the production of neurotransmitters. Cyanocobalamin supplements all of the above effects, in addition, it stimulates the conduction of nerve impulses in the distal nervous system. This group of vitamins contributes to the normalization of blood formation, which is important for such a serious illness and serious drug therapy.

They can be taken in tablets (Neurorubin, Neurobion) or pricked - each separately, alternating with each other. This option is considered preferred.

Ascorbic acid is also administered, the daily dose of which should be at least 1.5 g.

If the patient is in a state of psychomotor agitation, he may be prescribed antipsychotics, with epileptiform seizures - anticonvulsants, nootropics, antihypertensive drugs are also used.

Symptomatic treatment aimed at stabilizing the work of all organs and systems is carried out by dehydration therapy (diuretics), with severe degrees of damage - detoxification. They support the vital functions of the body - respiratory, if necessary, carry out artificial ventilation of the lungs; normalize the water-electrolyte balance, rheological properties and composition of the blood, and others.

Deoxyribonucleosis can be prescribed, with secondary bacterial infection - a course of antibacterial therapy. [52]

Almost any drug can cause an allergic reaction in a patient, therefore desensitizing drugs (Diphenhydramine, Suprastin, Claritin) are necessarily included in the treatment regimen.

During the recovery period, the patient may also need medical support and physiotherapeutic treatment.

Herpetic encephalitis is too serious a disease; it is not advisable to count on alternative treatment in this case. The outcome of the disease directly depends on the speed of initiation of antiviral therapy. In the past, mortality ranged from 70 to 100% before the discovery of antiherpetic drugs. So, hoping for a herbal treatment, you can only miss the time and chance for recovery. However, alternative medicine recipes may come in handy during the recovery period. Medicinal herbs can stop a headache, reduce anxiety, reduce anxiety. For this, motherwort, valerian, mint, peony are suitable. St. John's wort is known as a natural antidepressant, and echinacea as an immunomodulator. However, it is better to apply herbal treatment under the supervision of a qualified phytotherapist.

In the recovery period, homeopathy can also be useful, in its arsenal there are many tools for detoxification, normalization of the nervous system, strengthening immunity, but in the period of acute herpetic encephalitis it is better to contact the infectious disease specialist as soon as possible.

Surgical treatment of herpetic encephalitis is not used, but with the development of complications in the form of focal pharmacoresistant epilepsy, brain surgery may be recommended to eliminate the focus of the pathology. Such operations are carried out according to individual strict indications.

Prevention

The main goal of preventive tactics is to avoid infection with herpes. This can be compared to trying to protect against respiratory viral infections. First of all, good immunity can help, for which you need to lead a healthy lifestyle: eat well and variably, combine physical activity with relaxation, increase your stress resistance, since no one can completely avoid stress in the modern world, abandon the habits that bring harm health. Practice shows that herpesvirus is very common, however, some people show resistance to infection, and in this they should only thank their own immune system.

Nevertheless, if you see a person with obvious symptoms of labial herpes, do not hug him tightly, kiss. If this is your relative, he should have separate dishes and hygiene items, however, they should always be individual.

It is worth remembering that the disease in the acute stage can also be transmitted by airborne droplets. Therefore, if possible, it is worth disinfecting open parts of the body, which could be seeded with microparticles of secretion (face, neck), rinse your mouth.

Barrier contraceptives and genital antiseptic treatment after contact partially protect against genital herpes. But the best defense would be the elimination of random connections.

If infection cannot be avoided, consult your doctor and regularly take the recommended course of antiviral therapy. You can resort to alternative medicine methods, turn to a homeopath. Such measures will help keep herpesvirus under control and will be a good prevention of its reactivation and the development of serious complications.

Forecast

Timely initiated antiviral therapy significantly increases the chances of a favorable prognosis, even with severe forms of herpetic encephalitis. If untreated, herpetic encephalitis leads to death or severe disability in the vast majority of cases. Currently, a fourth to fifth of inflammation of the brain substance caused by the herpes virus ends with an unfavorable outcome. The fulminant form of the disease is especially dangerous, as well as the more serious consequences of the spread of the inflammatory process to the soft membranes of the brain (meningoencephalitis). 

Mortality from untreated HSV encephalitis is approximately 70%, and 97% of survivors will not return to their previous level of function. [53], [54]

Among the most significant negative prognostic factors are old age, coma / lower level of consciousness during manifestation, limited diffusion according to DWI and delayed intake of acyclovir. 

The sluggish process is dangerous for the duration of the latent period, as a result of which, by the time of seeking help, the patient already has extensive and irreversible lesions of cerebral structures.