Overview of Herpes Simplex Virus
Herpes simplex virus infection is an acute disease of the central nervous system often manifested by fever, headache, mental behavioral abnormalities, impaired consciousness, cognitive impairment, epilepsy, etc. Herpes simplex virus infection is caused by antiviral therapy, supplemented by supportive therapy and rehabilitation.
Definition
Herpes simplex virus encephalitis is an acute central nervous system disease caused by herpes simplex virus infection.
It is the most common viral infection of the central nervous system.
Herpes simplex virus most often damages the temporal lobe, frontal lobe, and limbic system of the brain, causing inflammation of brain tissue and, in severe cases, hemorrhagic necrosis.
The main manifestations are fever, headache, vomiting, mental behavioral abnormalities, memory loss, impaired consciousness, and seizures.
Typing or Classification
According to the virus serotype, it can be divided into herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2).
HSV-1 encephalitis: accounts for about 90% of cases and is seen mainly in adults.
HSV-2 encephalitis: about 10% of cases, mainly in newborns.
Incidence
The incidence of this disease in foreign countries is 4-8 cases per 100,000 people, and the prevalence is 10 cases per 100,000 people, and accurate data are lacking in China.
The disease can develop at any age, and about 2/3 occurs in adults over 40 years old.
It is globally distributed and can occur in all seasons of the year.
There is no obvious gender difference.
Causes
Pathogenesis
The disease is caused by herpes simplex virus infection.
Herpes simplex viruses usually first cause infection in the mouth, respiratory tract, or genitals.
In most cases, the body quickly develops an immune response against the virus and recovers, but the virus is not completely eliminated.
The virus can remain latent in the ganglia (e.g. trigeminal ganglia, etc.) for a long period of time without showing clinical symptoms. When the body’s immunity declines, the latent virus is activated again and enters the brain through the nerve axons, causing intracranial infections and leading to edema, softening, hemorrhage and necrosis of brain tissue.
A small number of patients infected with the virus can directly cause intracranial infection, the pathogenesis of which is still unclear.
Neonates infected with the virus (mainly HSV-2) through exposure during the birth canal mostly cause direct intracranial infections.
Transmission
Source of infection
Patients with herpes simplex virus encephalitis.
Mothers of newborns with genital herpes.
Asymptomatic infected persons in the incubation period .
Healthy carriers of the virus.
Route of transmission
Close contact.
Sexual contact.
Susceptible population
People are generally susceptible.
Symptoms
Main Symptoms
Incubation period
The incubation period for primary infection ranges from 2 to 21 days, with an average of 6 days.
Infection caused by reactivation of the latent virus depends on the patient’s immunity, and the time of onset cannot be determined.
In some patients with strong immunity, the virus may also remain latent in the body for a long period of time, without onset of disease for life.
Prodromal stage
Mostly acute onset, with herpes of the mouth and lips presenting in about 1/4 of patients.
Fever, body temperature can be as high as 38.4~40℃.
There may be general discomfort, headache, muscle pain, drowsiness, abdominal pain and diarrhea.
The course of the disease is from a few days to 1~2 months.
Symptomatic period
The disease often progresses rapidly within a few days, manifested by neurological deficits, psychiatric disorders and seizures.
Focal neurological deficits
Hemianopsia: When looking at something with one or both eyes, one side of the visual field is missing, and it is impossible to see the whole visual field.
Hemiparesis: One side of the limb is weakened, immobile, or completely paralyzed, accompanied by loss of sensation in the limb, which is more obvious in the lack of sensitivity to pain and hot and cold stimuli.
Ataxia
Unsteady standing, staggering gait, legs apart, walking to one side or swaying.
They may not know the distance of their steps or the depth of their feet, as if they were stepping on cotton.
Aphasia: The main manifestation is that the expression and comprehension of language are affected.
Mental and behavioral abnormalities
May be the first or only symptom in some patients.
Personality changes: changes in personality, daily behavior patterns and the way of dealing with people.
Memory loss: memory loss, impaired memory integrity, short-term memory, long-term memory.
Signs of meningeal irritation
Headache, stiff neck, aggravated by movement, especially noticeable when head is bowed.
Projectile vomiting.
Infants and children show agitation, screaming, crying.
Impaired consciousness
The initial manifestation is indifference, slow response and lazy behavior, which gradually develops into blurred consciousness and answering questions.
With the aggravation of the disease, lethargy, coma, or decorticate state may appear.
In some patients, coma may occur rapidly in the early stages of the disease.
Decorticate state
Presenting a special posture with upper limbs flexed and lower limbs straightened.
Can unconsciously open and close the eyes (also known as open-eye coma).
No conscious activity, no speech, inability to move around, no response to external stimuli such as calling and pain.
Seizures.
About 1/3 of patients experience generalized or partial seizures.
They may be characterized by loss of consciousness, generalized convulsions, often accompanied by rolling of the eyes, clenching of the teeth, and bruising or paleness of the face.
They may also be characterized by involuntary twitching of the eyelids, corners of the mouth, fingers, and toes.
Complications
Cerebral edema/brain herniation
Severe patients may die due to increased intracranial pressure caused by extensive parenchymal necrosis and cerebral edema, or even brain hernia formation.
Early symptoms include headache, nausea, vomiting, drowsiness or unresponsiveness. In severe cases, respiratory irregularities or sudden arrest and coma may occur.
Pressure Sore
Patients with unfavorable limb movement and prolonged bed rest cause pressure damage to the skin.
It is characterized by redness, purple, blisters and ulceration of the skin at the pressure site.
Cognitive impairment
Extensive parenchymal necrosis and recurrent seizures can cause irreversible brain dysfunction, leading to long-term cognitive dysfunction.
The main manifestation is the decline of cognitive function in various aspects, such as calculation, memory, and executive ability.
Medical Treatment
Department of Medicine
Neurology
Headache, hemianopsia, aphasia, memory loss, limb movement disorder, motor incoordination and other symptoms, it is recommended to consult a doctor in time.
Pediatrics
Infants and children with recurrent fever, vomiting, screaming and crying, or drowsiness are advised to seek prompt medical attention.
Emergency Department
If there are symptoms such as neck stiffness and limitation of movement, severe headache, generalized convulsions, drowsiness or coma, it is recommended to go to the Emergency Department as soon as possible or call the 120 emergency number.
Preparation
Preparation for medical consultation: registration, preparation of information, common problems
Tips for seeking medical treatment
If you have a high fever, you can take physical measures to lower the temperature while waiting for medical treatment, such as warm towels to wipe the skin of the neck and armpits, and record the changes in body temperature. Self-application of antipyretic drugs before seeking medical treatment is not recommended as it may aggravate the symptoms or mask the condition.
If the patient loses consciousness, the patient’s mouth should be cleared of foreign objects and his/her head should be tilted to the side to prevent choking.
If the patient’s whole body is convulsing, remove dangerous objects from the surrounding area, and do not forcibly pry open the mouth or stuff towels or chopsticks in the patient’s mouth.
Children may not be able to accurately describe their symptoms. Parents can help to record the symptoms they have experienced so that they can give more reference to the doctor.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there a fever? How long has the fever been present? What is the highest temperature?
Any headache, vomiting? To what extent?
Are there any symptoms such as limb weakness, unsteady gait, involuntary tremor?
Any memory loss, amnesia?
Any sudden change in personality or behavior?
Are there any limb convulsions with confusion?
List of medical history
Any recent contact with patients with herpes simplex virus infection.
Any history of herpes orofacialis, herpes genitalis?
Does the mother of the neonatal patient have a history of genital herpes infection?
Checklist
Test results from the last 6 months, which can be brought to the doctor’s office
Routine blood work, cranial CT/MRI, EEG, cerebrospinal fluid examination.
Medication list
Medication used in the last 3 months, if available in boxes or packages, may be brought to the doctor’s office
Antipyretic and pain medications: ibuprofen, acetaminophen, diclofenac, etc.
Antiepileptic drugs: diazepam, carbamazepine, sodium valproate, oxcarbazepine.
Antiviral medications: acyclovir, ganciclovir, cidofovir, famciclovir.
Diagnosis
Diagnosis is based on
Medical history
History of contact with a patient with herpes simplex virus infection.
History of oral and labial herpes and genital herpes.
History of genital herpes infection in the mother of the newborn.
Clinical manifestations
Symptoms
Rapid onset with fever, headache, vomiting, aphasia, hemiparesis, mental behavioral abnormalities, memory loss, impaired consciousness, and seizures.
Physical signs
The doctor uses a physical examination to see if there are any abnormalities in vital signs, movements, and pathologic reflexes.
Vital signs: Check if blood pressure, heart rate, pulse, and respiration are normal and stable.
Motor function test: Observe whether you can lift your arms, sit up, stand, walk, etc., and whether you need assistance.
Skin sensory examination: Slide a cotton swab over the patient’s skin or gently prick the skin with a blunt needle to assess the degree of sensory impairment according to the sensitivity to sensation.
Cognitive function examination: It can be assessed by general knowledge quiz, calculation, picture recognition, etc.
Meningeal irritation sign examination: observe whether headache occurs when the neck is flexed in supine position.
Tendon reflex examination
Observe the muscle contraction of the upper arm and thigh when the tendons of the elbow and knee joints are struck.
The disease may be characterized by enhanced or diminished muscle contractions.
Laboratory examination
Purpose of examination: to understand the general condition, the presence of infection, and to make preliminary judgment on the type of pathogen that causes encephalitis.
Examination items: including blood routine, blood sugar, blood lipid, coagulation function, erythrocyte sedimentation rate examination.
Results: White blood cell count may be mildly high.
Electroencephalography
Examination purpose: to determine whether epilepsy is present and the type of epilepsy.
Examination results: diffuse high amplitude slow wave, with unilateral or bilateral temporal and frontal region abnormality more obvious, and even sharp wave and spike wave in temporal region may appear.
Precautions: Keep quiet and relax during the examination; follow the doctor’s instructions for opening and closing the eyes, speeding up the breathing rate, etc.; no cell phones or other electronic products.
Imaging Examination
Cranial CT examination
Purpose of examination: to determine whether there is any focal abnormality or bleeding.
Findings: may be normal, or there may be low density foci in one or both temporal and frontal lobes; if there are punctate high-density foci in the low density foci, it suggests hemorrhage.
Precautions: In the first 4 to 5 days after the onset of symptoms, patients with this disease may not have obvious abnormalities on CT; CT examination has a certain amount of radiation and is contraindicated in pregnant women.
Magnetic resonance imaging (MRI) of the head
Purpose of examination: It can do early diagnosis and clarify the location of the lesion.
Examination results: about 90% of patients have focal edema in the medial temporal lobe, frontal lobe orbital surface, insula cortex and cingulate gyrus within the 1st week of the onset of the disease.
Precautions: Those who have dentures, steel plates in the body, cardiac stents and other metal implants need to inform the radiologist to decide whether MRI examination can be performed according to the specific material of the metal and the magnetic resonance machine.
Cerebrospinal fluid examination
Purpose of examination: Diagnosis of viral encephalitis and differential diagnosis with other encephalitis.
Results
Cerebrospinal fluid pressure is normal or mildly increased.
There is a significant increase in lymphocytes and also erythrocytosis (hemorrhagic necrosis of brain tissue).
Protein is increased in the cerebrospinal fluid, but sugar and chloride are normal.
Increased titers of specific IgM and IgG antibodies and positive DNA (high sensitivity and specificity).
Precautions
Decubitus flat lying for 4~6 hours after surgery, avoid premature activity causing dizziness and headache, nausea and vomiting.
Avoid activities that increase the pressure in the abdominal cavity, such as coughing and defecation.
Brain tissue biopsy
Purpose of examination: the gold standard for the diagnosis of herpes simplex virus encephalitis.
Findings: Eosinophilic inclusion bodies can be seen in the nuclei of neuronal cells, and herpes virus particles can be found in the cells under electron microscopy.
Differential diagnosis
Herpes zoster virus encephalitis
Similarities: Both may present with fever, headache, vomiting, confusion, ataxia, mental abnormality and other symptoms.
Differences
Herpes zoster virus encephalitis is most common in middle-aged and older adults with a history of herpes zoster in the chest and lumbar region.
Cranial CT shows no hemorrhagic necrosis and has a better prognosis.
Enteroviral encephalitis
Similarities: both may present with fever, impaired consciousness, seizures and limb paralysis.
Differences
Enteroviral encephalitis is most common in summer and fall, with gastrointestinal symptoms such as loss of appetite and diarrhea at the beginning of the disease course.
Enterovirus nucleic acid can be detected in the cerebrospinal fluid, which can be used as a differential.
Cytomegalovirus encephalitis
Similarities: headache, confusion, memory loss and other symptoms may occur.
Differences
Cytomegalovirus encephalitis is common in patients with immunodeficiency, such as AIDS, or in patients with long-term immunosuppression. It has a subacute or chronic onset and rarely presents with fever.
Diffuse or focal white matter abnormalities can be seen on cranial MRI, and cytomegalovirus nucleic acid can be detected in the cerebrospinal fluid, which can be used as a differential.
Treatment
Therapeutic goal: there is no specific treatment, control of intracranial pressure, high fever and convulsive seizures as the focus of treatment.
Treatment principle: mainly include antiviral drug treatment, supplemented by symptomatic treatment and rehabilitation therapy.
Symptomatic supportive treatment
Bed rest, close monitoring of body temperature, consciousness, pulse, respiration and blood pressure.
Physical hypothermia may be given to those with fever.
Suspend eating and drinking if vomiting.
Avoid straining to defecate and coughing; if defecation is laborious, laxatives can be given to loosen stools.
When there is coma, respiratory difficulties, timely oxygen, tracheal intubation, ventilator-assisted ventilation.
If there is swallowing disorder, nutritional support can be provided through nasal feeding tube or intravenous route.
Keep the skin clean, turn over regularly, and use air cushion or soft cushion on the pressure-prone parts to prevent pressure sores.
Medication
Antiviral therapy
Commonly used drugs: acyclovir, ganciclovir, phosphonic acid and so on.
Cautions
Drugs cannot eradicate the virus, but can inhibit viral replication. They should be used according to the doctor’s instructions and the course of treatment to prevent recurrence.
It may cause delirium, tremor, rash, hematuria, abnormal liver and kidney functions.
Adrenocorticotropic hormone therapy
Therapeutic purpose: For patients with severe or with intractable intracranial hypertension, it can inhibit inflammatory reaction and reduce intracranial edema.
Commonly used drugs: dexamethasone, methylprednisolone, prednisone and so on.
Precautions
Peptic ulcer, elevated blood glucose, elevated blood pressure, insomnia, etc. may occur.
Blood sugar and blood pressure need to be monitored during the use of the drug.
Antiepileptic drugs
Purpose of medication: to control seizures and avoid further aggravation of brain damage.
Commonly used drugs: diazepam, carbamazepine, sodium valproate, oxcarbazepine, etc.
Precautions
Adverse reactions such as dizziness, memory loss, generalized rash, nausea and vomiting may occur.
Strictly follow the doctor’s requirements, take the medication on time, according to the dosage and regularly, and prohibit stopping, reducing or changing the medication without authorization.
Other medications
Antipyretic and analgesic drugs, such as ibuprofen and diclofenac, may be given if fever and headache are obvious.
If there are serious mental symptoms, olanzapine, clozapine and other drugs can be used for treatment.
Those with increased intracranial pressure can be given timely dehydration and hypotensive treatment, such as mannitol, furosemide and so on.
Rehabilitation treatment
Treatment principle: After the condition is stabilized, an individualized rehabilitation program is formulated according to the dysfunction that occurs.
Exercise therapy
Limb function training
Passive training: move the upper and lower limbs with the assistance of the therapist during the period of bed rest, to the extent that it can be tolerated, which can prevent muscle atrophy, avoid muscle tension and stiffness, and maintain the range of motion of the joints.
Active training: under the guidance of the therapist, turn over, get up, keep sitting, stand up, walk training.
Pay attention to safety and moderate labor and leisure during training to prevent postural abnormality and avoid fall, over-fatigue and aggravation of the condition.
Sensory function training
Superficial sensory training: focusing on tactile stimulation of the skin, such as pain, touch, alternating temperature stimulation of ice and warm water, touching and recognizing daily necessities.
Deep sensory training: Sensory training must be combined with motor training, such as squeezing and weight bearing on joints during training, to obtain the correct motor experience in the process of completing the movement.
Speech function training
Train patients to respond correctly from listening, speaking, reading and writing to improve their speech.
Train the muscles of the face and throat to improve the clarity and fluency of pronunciation.
Cognitive function training
Adopt “one-to-one” or multi-person group training.
Memory, calculation and thinking skills are trained through memorization of numbers, math problems, and reasoning problems.
Daily life ability training
Improve the patient’s ability to live independently and reduce the burden on the caregiver.
Training in practical daily living actions such as dressing, getting up, eating, washing, and handling urine and feces.
Physical factor therapy
Biofeedback, neuromuscular electrical stimulation therapy, etc. to restore muscle strength and motor function.
Hyperbaric Oxygen Therapy
The purpose of treatment: to improve the lack of oxygen in brain tissue, reduce cerebral edema, lower intracranial pressure, shorten the course of the disease and reduce the sequelae.
Precautions
Avoid carrying flammable and explosive articles, such as lighters and matches.
Do chewing and swallowing during the process of raising and lowering the pressure. If there is an earache that cannot be eliminated, the doctor should be informed to stop it in time.
Chinese medicine treatment
Medication
Clearing heat and removing phlegm are the principles of treatment.
For those with phlegm-heat congestion, it is appropriate to remove fire and phlegm; for those with phlegm blocking the orifices, it is appropriate to remove phlegm and open the orifices; and for those with phlegm-stasis obstruction, it is appropriate to remove phlegm and open the orifices and activate blood circulation and remove blood stasis. For those with phlegm and blood stasis blocking the collaterals, it is recommended to clear phlegm and open the orifices, and activate blood circulation.
Commonly used medicines: clearing the plague and defeating poison drink, cleansing phlegm soup, Angong Niuhuang Pill, Niuhuang Qingxin Pill, Zixue Dan and so on.
Acupuncture and moxibustion
Acupuncture and moxibustion are mainly used to treat the symptoms, and the commonly used acupoints are as follows:
High fever and convulsion: Acupuncture Da Shi, Qu Chi, He Gu;
Aphasia, needling Mute Gate, Tongli, Lianquan, Hegu, Yongquan.
Chinese medicine treatment should be carried out under the guidance of a Chinese medicine practitioner in a regular hospital.
Prognosis
Cure
In untreated patients, the disease mortality rate is as high as 60% to 80%.
Most patients with milder disease and timely treatment can be cured.
About 10% of the patients may be left with sequelae such as paralysis and decreased intelligence of different degrees.
Since the virus cannot be completely cleared from the body, it may cause recurrent herpes simplex virus encephalitis, with a recurrence time of several weeks to several years and a recurrence rate of 5% to 26%.
Hazards
The disease can be severe and life-threatening due to hemorrhagic necrosis of the brain, causing coma, respiratory distress, and persistent seizures.
Patients may be left with limb paralysis, visual field changes, memory loss, etc., which affects the quality of life.
Long-term use of antiepileptic drugs can cause gastrointestinal discomfort and liver function damage.
Daily
Daily Management
Dietary management
Diet should be light and less spicy and stimulating food.
Combine the diet reasonably to ensure balanced nutrition.
Eat more foods rich in group fibers to prevent constipation.
Lifestyle Management
Pay attention to rest, maintain a good daily routine, avoid staying up all night and exertion.
After being discharged from the hospital, patients should insist on home rehabilitation training and moderate physical exercise.
Patients with cognitive impairment should avoid going out alone or wearing identification tags to prevent loss.
Patients who have been bedridden for a long time should be helped to change their body position frequently to avoid prolonged skin pressure.
When patients with sensory disorders take a bath, do not use too hot water and do not rub or friction the skin too hard to prevent injury.
Psychological support
Patients need to pay attention to their own mental health, release pressure in time, avoid anxiety, depression and other bad emotions.
Family members should also pay attention to the patient’s mental state, listen patiently, and communicate and interact with the patient more often.
If necessary, professional psychological counseling.
Disease monitoring and follow-up
Monitor the recovery of seizures, headache, limb movement and sensation to understand the changes in the condition.
Follow up regularly according to the doctor’s instructions. Blood tests, head MRI and other tests may be done during follow-up, so please be prepared for them in advance.
Prevention
Wash hands frequently and wear masks in public places.
Avoid unclean sex.
Adopt a healthy lifestyle and improve immunity.
Actively prevent and treat genital herpes during pregnancy.