What Is Herpes Encephalitis?

Herpes simplex encephalitis, also known as herpes virus encephalitis, is the most common viral infectious disease of the central nervous system caused by herpes simplex virus. It often involves the temporal lobe, frontal lobe and limbic system of the brain, causing brain tissue Hemorrhagic necrosis and allergic brain damage. It can be seen in both primary herpes simplex virus infection and recurrent patients. The disease is sporadic and is the most common form of non-epidemic viral encephalitis. According to statistics, it accounts for about 10% to 20% of viral encephalitis. It is severe and has a poor prognosis. The pathogenic herpes simplex virus (HSV) is divided into type I and type II. These two types of viruses, after being inoculated at the peripheral site, were tested for viral DNA by PCR technology, which confirmed that they could be latent in the body for a longer period of time. Type HSV is latent in the olfactory bulb, olfactory tract and sensory ganglion of the trigeminal nerve and is likely to induce encephalitis. Type HSV is latent in the root ganglia of the posterior iliac pulp and easily induce repeated genital herpes infection. Therefore, HSV is often one of the pathogens that induce opportunistic infections under host immunosuppressive conditions.

Herpes simplex encephalitis

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Herpes simplex encephalitis

herpes simplex encephalitis

Herpes simplex encephalitis; herpes simplex encephalitis; herpes simplex encephalitis; herpes simplex encephalitis; herpes simplex encephalitis;

Infectious Diseases> Viral infections> Herpes virus infection

Neurology> Central nervous system infection

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Herpes simplex encephalitis can occur at any age; it is sporadic; it is the most common form of non-epidemic viral encephalitis, and according to statistics, it accounts for about 10% to 20% of viral encephalitis; the condition is serious and the prognosis is relatively difference.

Given that HSV-1 is mainly related to oral infections and HSV-2 is mainly caused by genital infections, it is clear that HSV-1 is easier to access and invade the brain, so more than 95% of herpes viral encephalitis is caused by HSV-1 infection; and HSV-2 is common in neonatal patients.

Herpes is a common and infectious skin disease with an ancient history; related records have even been seen in ancient Greece. In the 18th century, the presence of genital herpes was noted clinically. After the 19th century, due to the densely populated and large-scale population movements caused by the Industrial Revolution, the chance of transmitting herpes through general contact and sexual contact increased, leading to an increase in the incidence of herpes-like diseases; physicians gradually realized its infectious and sexually transmitted routes Since then, it has been found that herpes virus has the characteristics of latent infection.

HSV is a DNA virus. Baringer and Swoveland in 1973 showed that in non-selective human autopsy materials, 85% to 90% of the corpses could display type I HSV genome in the trigeminal sensory ganglia.

Baringer and Pisani used PCR technology in 1994 to study autopsy data of patients who died of diseases that are not known to be neurological diseases. They found that HSV genomes exist in the medulla oblongata, pons, and olfactory bulbs, but how HSV dormant in the human body causes encephalitis. Not completely clear.

The herpesvirus family is divided into three subfamilies of , , and , including 114 members, which have certain host specificity and infect humans or other animals, respectively. The human herpes virus currently includes at least eight members (Table 1).

The pathogen of herpes simplex is human herpes simplex virus, which belongs to the human herpesvirus family subfamily, and the herpes simplex virus genus is divided into two subtypes, HSV-1 and HSV-2. HSV-1 subtype mainly invades the upper part of the waist, especially the face and brain tissue, while HSV-2 type mainly invades the lower part of the waist, especially the genitals, so it is called genital herpes; however, this distinction is not strict.

Herpes simplex virus is spherical and consists of a nucleocapsid and a virus envelope. The nucleocapsid is in the shape of an icosahedron and is composed of 162 shell particles. The core contains a viral genome, which is a linear double-stranded DNA molecule with a length of 15226kb. The homology between the two subtype genomes of HSV-1 and HSV-2 The source is only 47% to 50%. The herpes simplex virus genome encodes at least 70 different proteins. Mature viral nucleocapsids contain at least seven proteins. The surface of the nucleocapsid has an inner membrane whose physical structure is not completely clear. It contains four kinds of protein components, which are related to the transcription and replication of viral genes. The outer envelope of herpes simplex virus is a double-layer lipoprotein. Glycoprotein components are complex and include at least six types. Among them, the antigen specificity of glycoprotein gG is the serological basis for identifying HSV-1 or 2 types. After the herpes simplex virus invades the host cell, viral DNA enters the nucleus and replicates. At the same time, viral DNA transcripts enter the cytoplasm and direct the synthesis of viral structural proteins in the cytoplasm. Subsequently, the progeny virus DNA returns to the cytoplasm to assemble as Infectious mature virus particles. During the replication of herpes simplex virus, mature virus particles account for only a few, and the rest are rapidly degraded or become non-infectious immature virus particles because they have not been processed and packaged in a timely manner.

Human herpes simplex virus is not resistant to the outside world. It can be inactivated by heating at 56 for 30min, UV irradiation for 5min, ether, and other fatty solvents; however, its biological activity can be stored for a long time at -70 .

In an in vitro culture environment, herpes simplex virus can infect almost all kinds of embryonic and newborn animal-derived fibroblasts and epithelial cells, and quickly produce lesions visible to the naked eye. Therefore, in some difficult cases, the method of in vitro culture to isolate the virus can be Used to help clinical diagnosis.

The pathogenesis of herpes simplex virus encephalitis is more complicated. Recent studies have shown that part of the mechanism of brain tissue damage caused by viral infection is the result of damage to immune pathology.

Because type I HSV is mostly encephalitis in children and adults, and it mainly involves the medial temporal lobe, the lower frontal lobe, the adjacent island lobe and the cingulate gyrus, and can involve the olfactory bulb and olfactory tract, while the occipital lobe and cerebellum do not Involvement, suggesting that brain inflammation and infection of the olfactory mucosa with HSV may spread through the olfactory system and cause the above-mentioned typical damage distribution.

Other scholars have proposed that the HSV line spreads from the trigeminal sensory ganglia along the nerve supplying the dura mater to the medial and lower frontal lobe below it (Davis and Johnson, 1979), but this theory is yet to be confirmed.

In children and young people, primary HSV infection can cause encephalitis; it can be a consequence of viremia, but it can also be caused by the herpes virus invading the brain directly along the olfactory nerve through the nasopharynx. Animal experiments have shown that HSV-2 is more toxic to the nervous system than HSV-1. Given that HSV-1 is mainly related to oral infections and HSV-2 is mainly caused by genital infections, it is clear that HSV-1 is easier to access and invade the brain, so more than 95% of herpes viral encephalitis is caused by HSV-1 infection; and HSV-2 is common in neonatal patients. Encephalitis caused by herpes simplex virus in adults is characterized by the most severe temporal lobe damage. Most patients have a history of herpes simplex or have positive serum HSV-1 antibodies. The occurrence of encephalitis mainly comes from the reactivation of HSV-1 latent infection in vivo. When the body's immune function is low, HSV lurking in the trigeminal ganglion (half-lunar ganglia) or spinal ganglion invades the central nervous system along the axon, causing brain tissue damage; or the virus is dormant in the central nervous system for a long time, under certain conditions Encephalitis occurs when activated. Such patients may not have a viremia course.

The pathology of this disease is highly characteristic. It is a change of acute necrotizing encephalitis, showing asymmetric diffuse whole brain damage, and forming hemorrhagic necrosis of different sizes. Lesions can first damage one hemisphere and then extend to the opposite side. Half of the cases are confined to one side, and about one-third of the cases are confined to the temporal lobe; even if the patient's bilateral hemispheres are damaged, one side is often the weight.

Gross observation of the early congestion and swelling of the brain. And due to severe swelling on one side, the asymmetry of the two sides of the brain, and caused the displacement of the midline structure, resulting in a temporal lobular hernia. The areas of cerebral necrosis are the medial temporal lobe, the anterior part of the hippocampus, the inferior temporal gyrus, the fusiform gyrus, the hook gyrus, and the frontal orbital gyrus, especially the posterior orbital gyrus. , Island leaves, cingulate gyrus, hippocampus and amygdala. The lesions not only affected the cortex and penetrated into the white matter, resulting in unclear boundaries of gray matter. Those who survived for 1 to 2 weeks had disintegrated necrotic tissue, and those who survived for more than a few months could see temporal lobe shrinkage and cystic changes in the cortical necrosis area.

Under the microscope, the early neural tissue was loose necrosis accompanied by meningoencephalitis. The infiltration of a large number of inflammatory cells in the brain is mainly lymphocytes, and there are large mononuclear and plasma cells. Nerve cells can show phagocytosis, necrosis, and disappearance. It can be seen that macrophages engulf the cells formed by lipids. Vascular wall necrosis, red blood cells leak out of blood vessels, and some are surrounded by inflammatory cells to form a blood vessel sheath. Pia mater congestion and inflammatory response are also mainly lymphocytes. There may be a small amount of lymphocytes and exuding red blood cells in the subarachnoid space. Typical changes are eosinophilic inclusions in the nucleus, which are found in nerve cells, astrocytes, and oligodendrocytes. In HE staining, eosinophilic inclusions can be found under high magnification. It was dark brown in color using immunohistochemical (ABC) staining. Electron microscopy revealed virus particles (Rao Mingli et al., 1987).

Herpes simplex encephalitis can cause complications such as coma and severe hernia.

1. Intracranial hypertension.

2. Hernia.

3. Some cases showed decortical rigidity at an early stage.

1. Individual patients with early cerebrospinal fluid (CSF) examination can be normal. Generally, they are colorless and transparent, with a clear appearance and increased pressure. The number of cells is (20 200) × 106 / L, most of which are below 0.4 × 109 / L. Most of them are lymphatic and monocytes, but they can also be early. It is neutrophil; due to the hemorrhagic and necrotic nature of brain tissue lesions, the cerebrospinal fluid in some cases contains more red blood cells, which can reach (50 to 500) × 106 / L or more; the protein is mild to moderately increased, and the protein quantification is 0.5 to 2.0g / L; sugar content is normal or low. These changes can only provide infectious lesions.

2. Polymerase chain reaction (PCR) technology detection, extremely sensitive to the diagnosis of HSV pathogens, is particularly important for early diagnosis, but false negatives can still appear 1 to 2 days after the onset of disease and 10 to 14 days after the onset of disease. Because HSV antibodies appear relatively late in CSF, they are usually easy to detect at 1 week after onset, but can exist for weeks to months, so retrospective diagnosis is still valuable.

3. Indirect immunofluorescence detection of HSV antibodies in serum is also helpful for pathogenic diagnosis. Immunological examination showed that the titer of serum neutralizing antibody or complement-binding antibody gradually increased to more than 4 times; the herpes simplex virus antiviral antibody titer of cerebrospinal fluid was more than 1:80, and the antibody titers of early and late double specimens increased by more than 4 times.

4. Viral antigens can be detected using immunohistochemical techniques; however, clinical biopsy is more difficult. Virological testing is the gold standard for diagnosing this disease. However, at the time of the onset of encephalitis, most patients did not show herpes lesions on the body surface, and the virus was often difficult to detect in the cerebrospinal fluid. Although electron microscopy can be used to detect nerve cell nuclear inclusions and virus particles in brain biopsy specimens; PCR technology can be used to detect HSV DNA in cerebrospinal fluid specimens, which is helpful for early diagnosis, but attention should be paid to its specificity.

The EEG is abnormal, and the two sides can be asymmetric, which is obvious on one side of the cerebral hemisphere. CT and MRI showed hemorrhagic necrosis of the temporal lobe and frontal lobe, or diffuse lesions of the brain tissue.

EEG examination

Diffuse, high-amplitude slow waves often occur, with unilateral or bilateral temporal frontal region abnormalities as obvious, and even spikes and spikes in the temporal region can appear.

Imaging changes

CT scan: normal and local low-density areas can also be seen; MRI can help find lesions with long T1 and T2 signals in the brain parenchyma.

Brain histopathology

An important feature of brain histopathology is hemorrhagic necrosis under light microscope, and Cowdry A type inclusion bodies under electron microscope, showing oligodendrocytes and nerve cell nuclei in or near the necrotic area, and Togo in one cell nucleus. Inclusion body. The pathogenic examination is that intracellular virus particles can be found under an electron microscope; brain tissue samples can also be used for PCR, in situ hybridization, etc. to check viral nucleic acids, or to isolate and culture viruses.

The diagnosis of herpes simplex encephalitis is based on comprehensive analysis of clinical manifestations and laboratory test results. The following points suggest the possibility of herpes encephalitis:

1. Acute or subacute onset of the patient, the first symptoms of general discomfort or upper respiratory tract infection, often a few days after the onset of fever, headache, fever or behavioral abnormalities as the first symptoms.

2. Then there are signs of disturbance of consciousness, mental abnormality and brain parenchymal damage; if there is herpes damage on the upper lip or olfactory hallucinations and taste hallucinations in the history, this disease should be considered.

3. Cerebrospinal fluid pressure increased, protein and white blood cells increased slightly to moderately, mainly lymphocytes; CSF found a large number of red blood cells has diagnostic value (but to exclude puncture injury or subarachnoid hemorrhage and other diseases), increased protein content and sugar And chloride is normal.

4. EEG abnormalities, asymmetry on both sides, obvious on one side of the hemisphere; CT and MRI showed hemorrhagic necrosis of temporal lobe and frontal lobe, or diffuse lesions of brain tissue.

5. The diagnosis of HSV encephalitis should be carried out in time for infectious etiology. At present, the detection of HSV antigen in CSF by PCR technology is most important for early diagnosis. If the test result is negative within 1 to 2 days after the onset of the disease, a PCR test of CSF for repeat lumbar puncture should be repeated after 24 to 48 hours. If it is still negative, then other pathogens or other diseases should be considered.

The clinical manifestations of herpes encephalitis are not specific, and only about 1/4 of the patients are accompanied by the appearance of skin herpes (cold herpes); if encephalitis occurs in patients with primary herpes infection, there is no previous history to follow; Although HSV-2 is common in neonatal patients, the signs of genital herpes may not be detected in their biological mothers, so the clinical diagnosis of herpestic encephalitis is sometimes difficult. Brain biopsy revealed eosinophilic inclusions in the nucleus, virus particles were seen under electron microscopy; culture of HSV virus was diagnostic.

Other viral encephalitis

The pathogens of viral encephalitis are diverse, including herpes virus, arbovirus and enterovirus. However, except for a few epidemic encephalitis such as Japanese encephalitis, the clinical manifestations of other sporadic viral encephalitis are relatively light, with few signs mainly based on significant damage to the temporal and frontal lobe; serum and cerebrospinal fluid examination The identification of specific antibodies against the virus is helpful.

Japanese encephalitis is severely ill and progresses rapidly. It often starts with sudden high fever and rapidly appears as brain damage such as disturbance of consciousness, convulsions, and convulsions; and the disease is concentrated in the summer and autumn mosquito season. Can help diagnose.

Shingles virus encephalitis: This disease is rare. It mainly invades and lurks in the nerve cells of the spinal nerve posterior root ganglia or the brain cells of the sensory ganglia, and rarely invades the central nervous system. The clinical manifestations are symptoms and signs of blurred consciousness, ataxia, and focal brain damage. The extent of the lesion is light and the prognosis is good. Patients often have a history of shingles in the thoracolumbar region. CT showed no signs of hemorrhagic necrosis. Serum and cerebrospinal fluid were positive for the virus antigens, antibodies, and viral nucleic acids, which can be identified.

Enterovirus encephalitis: more common in summer and autumn, it can be epidemic or sporadic. Clinical manifestations of fever, conscious disturbance of balance, recurrent seizures, and limb paralysis. Early gastrointestinal symptoms, viral isolation in the cerebrospinal fluid, or a positive PCR test can help diagnose.

Cytomegalovirus encephalitis: Rarely clinically, it is common in patients with immunodeficiency or long-term use of immunological agents.

Purulent meningoencephalitis

Pyogenic meningoencephalitis is characterized by severe systemic infection and poisoning symptoms. Peripheral blood leukocytes are significantly increased, cerebrospinal fluid is purulent, and bacterial smears or cultures are positive.

Acute disseminated encephalomyelitis

The disease has received increasing attention and is seen in the course of acute eruptive viral infectious diseases (such as measles, rubella, smallpox, chickenpox, etc.); it can also be seen in other acute viral infections (such as infectious mononucleosis, influenza, etc.) The recovery period is called post-infection encephalitis; those who have occurred within 2 to 3 weeks after pertussis, rabies and other vaccination are called post-vaccination encephalitis; it can even occur due to deworming treatment, such as L-imidazole encephalitis may be related to the immune response. Acute disseminated encephalomyelitis is characterized by symptoms and signs of the parenchyma, meninges, brain stem, cerebellum, and spinal cord. Symptoms and signs are diverse. Severe patients may have conscious disturbances and mental symptoms.

The pathological features are disseminated demyelination of the brain and spinal cord, and infiltration of inflammatory cells distributed around small veins. Clinical manifestations vary with the location and severity of the lesion, and may include high fever, headache, vomiting, convulsions, coma, coma, signs of meningeal irritation, and signs of focal damage; cerebrospinal fluid detection protein and cell numbers increase. Pay attention to find out when the patient's neurological symptoms occur, often suggesting clinical diagnosis.

Toxic encephalopathy

Often in the early or extreme stages of acute bacterial infections, they are more common in sepsis, pneumonia, bacterial dysentery, typhoid fever, diphtheria, pertussis and so on. The patients are mainly children between 2 and 10 years of age. They are caused by congestive edema caused by the body's allergic reaction to infection toxins. Clinical manifestations include fever, headache, vomiting, delirium, convulsions, coma, meningeal irritation, etc .; Cerebrospinal fluid pressure Increased, protein can be slightly increased, cells generally do not increase, sugar and chloride are normal. After the primary disease improves, the brain symptoms gradually disappear, and generally there are no sequelae.

General treatment

Care should be strengthened to prevent complications such as bedsores and lung infections; meanwhile, treatments such as cooling, antispasmodic and dehydration should be taken according to the condition. Patients with intracranial hypertension who are ineffective in the treatment of drugs can be used for emergency decompression of ventricular drainage and bone flap when necessary.

Antiviral therapy

As the disease occurs in the central nervous system, the earlier the antiviral treatment is, the better; however, since the virus only causes the appearance of typical symptoms at the end of intracellular replication, the timing of antiviral treatment is often late, affecting the efficacy and prognosis. The ideal antiviral drugs can selectively inhibit the metabolism of viral nucleic acids and proteins without affecting the host cells at all; however, the current antiviral drugs have not been able to do this, and most of them have certain toxic and side effects. The following are more commonly used in clinical practice.

Acyclovir, which only works on virus-infected cells and does not affect uninfected cells, has become the drug of choice. The dose is 5-10mg / kg body weight, intravenous infusion once per / 8h, 14 to 21 days as a course of treatment; relapse often occurs within 10 days. Adverse reactions include tremor, rash, hematuria, transient renal insufficiency, and elevated transaminase. Recently, the number of acyclovir-resistant strains has been increased, especially in HSV-1.

Vidarabine, a dose of 15 mg / (kg · d) for 10 days. When used, it must be diluted and slowly infused intravenously so that its concentration does not exceed 700 mg / L and the infusion time is not less than 12 hours. Adverse reactions include nausea and vomiting, and hematopoietic dysfunction.

Ribavirin (ribavirin) is intravenously infused at a dose of 0.5 to 1 g / d, and the child is 20 to 30 mg / kg of body weight for 7 to 10 days.

Adrenocorticotropic hormone

Despite some controversy, in view of the involvement of immune damage in the pathogenesis of this disease, most scholars still advocate the use of hormones to treat this disease. Corticosteroids can reduce the inflammatory response, detoxify and stabilize the lysosomal system, reduce capillary permeability, protect the blood-brain barrier, eliminate brain edema, and overcome the rebound effect caused by dehydrating agents. Once the disease is diagnosed, hormones can be used early, in large quantities, and for short courses. Dexamethasone is the first choice. Generally, 15 to 20 mg is used. It is intravenously infused after dilution, once a day, and gradually reduced after 10 to 14 days.

Interferon and its inducer

Interferon has inhibitory effects on many viruses. It is commonly used clinically for 3 to 5 million U, 1 time / d, intramuscular injection, about 4 weeks as a course of treatment.

Interferon-inducing agents, such as polymyocytes, cause the body to produce endogenous interferons, and the efficacy of this interferon in the treatment of this disease is uncertain.

Traditional Chinese Medicine

Traditional Chinese medicine treats viral encephalitis mainly with clearing heat and detoxifying, and adopts the principles of aromatizing turbidity and promoting blood circulation. Recipes include Xijiao Dihuang Decoction, Baihu Decoction, Qingwen Baidu Yin Decoction, Yinqiaosan, etc .; proprietary medicines include Zixuedan and Angong Niuhuang Pill.

The herpes virus encephalitis case fatality rate can reach as high as 70%, and most of them die within 2 weeks after the onset of illness. Those with deep coma, severe intracranial hypertension, and late antiviral treatment often have a poor prognosis. Half of the survivors have varying degrees of neurological sequelae, such as memory loss or memory loss, language disorders, mental disorders, labor loss, and even vegetative growth.

Patients with herpes simplex in a child care institution should be instructed to be isolated at home, and they can return after treatment is cured. Pregnant women with genital herpes should give birth by caesarean section. Pregnant women with a recent history of genital herpes should take amniotic fluid samples to test for IgM HSV antibodies. Those who are positive indicate that the fetus has suffered from intrauterine infection. You can discuss with the couple of patients whether to consider choosing 0.1% eye drops and isolate them from the mother. To avoid being nurtured by the mother until the mother is cured; the mother and her newborn should be isolated from other mothers and newborns during the postpartum period and during postnatal observation in the hospital.

Adhere to the pre-marital medical examination system, avoid multiple sexual intercourse, and promote a safe sex life; if necessary, use condoms during intercourse to help control or reduce the prevalence of genital herpes infections. Acyclovir was used immediately after organ transplantation (including bone marrow transplantation). For patients with frequent recurrent herpes, try to remove or avoid predisposing factors. The above measures are helpful to prevent the occurrence of herpes simplex infection or the outbreak of the original hidden infection. Currently, vaccines to prevent herpes simplex have entered clinical trials.

Aciclovir, Adenosine arabinoside, adenosine, ribavirin, dexamethasone, interferon, polymyocyte, purple Xuedan, An Gong Niuhuang Wan

Plasma cells, herpes simplex virus antibodies, cerebrospinal fluid pressure, interferon