Overview
Neurological lesions caused by various pathogens invading the intracranial brain parenchyma, meninges, and blood vessels are mainly characterized by fever, chills, headache, vomiting, convulsions, limb paralysis, coma, etc. The causative pathogens include bacteria, fungi, viruses, parasites, and other types of pathogens, which are mainly treated with medication, symptomatic supportive therapy, and surgery.
Definitions
Neurologic lesions caused by various pathogens such as bacteria, fungi, viruses, and parasites that invade the brain parenchyma, meninges, and blood vessels within the skull are called intracranial infections.
It can lead to inflammatory reactions in the brain parenchyma, meninges, and intracranial blood vessels, resulting in fever, chills, headache, vomiting, convulsions, paralysis, coma, and other symptoms.
Types
Classified according to different pathogens
Bacterial infection: the most common, mainly including purulent meningitis (meningococcus, pneumococcus, hemophilus, staphylococcus aureus, streptococcus, Escherichia coli), tuberculosis bacillus and so on.
Viral infections: mainly include DNA viruses such as herpes simplex virus, varicella-zoster virus, cytomegalovirus, etc. RNA viruses include poliovirus, coxsackie virus, etc.
Fungal infections: including Cryptococcus neoformans infection, Aspergillus, etc.
Parasitic infections: common types include cysticercus, schistosoma, schistosoma, trematode, plasmodium, toxoplasma gondii, amoeba, etc.
Others: including spirochetes, rickettsiae, prions, etc.
Classification according to the different parts of the infection
Encephalitis: mainly invades the brain parenchyma.
Meningitis: mainly invades the soft meninges.
Meningoencephalitis: combined involvement of brain parenchyma and meninges.
Pathogenesis
The incidence of intracranial infections varies considerably depending on the pathogenic microorganisms infecting them, and data on the incidence of only some types are available.
Herpes simplex encephalitis: the most common infectious disease of the central nervous system, accounting for 5% to 20% of all encephalitis and 20% to 68% of viral encephalitis. The global incidence is 1.5 to 7 per 100,000 people per year.
Septic meningitis: 1.2 million new cases of septic meningitis occur globally each year. There are huge regional variations. In developed countries, the lethality of Streptococcus pneumoniae and Neisseria meningitidis is 30% and 7%, respectively, while in developing countries it can be as high as 50%.
Causes
Causes
Intracranial route of pathogen entry
Bloodstream infection: Pathogens enter the bloodstream through insect bites, animal bites that damage the mucous membranes of the skin, or directly into the bloodstream through the use of unclean syringes or blood transfusions. Pathogens can also enter the skull retrogradely through the veins in facial infections. Pathogens infecting pregnant women can be transmitted to the fetus via the placenta.
Direct infection: pathogens spread into the skull after penetrating craniocerebral trauma or infection of adjacent tissues.
Retrograde infection of the nerve trunk: herpes simplex virus-like neuropathogens, etc. first infect the skin, respiratory tract or gastrointestinal tract mucosa, enter the nerve trunk via nerve endings, and then enter the skull retrogradely.
Neuropathologic changes caused by pathogens
Pathogens can directly cause inflammation, degeneration, and necrosis of the brain parenchyma.
It can also cause nerve fiber and vascular lesions and aggravate brain parenchyma injury by inducing an immune response.
Risk factors
Age: Infants, young children and the elderly are at higher risk.
Mosquito bites: Living in areas infested with mosquitoes and ticks and in hot seasons carries a relatively higher risk of occurrence.
Immunocompromised: People taking immunosuppressive drugs, people infected with human immunodeficiency virus (HIV), people with congenital immunodeficiency diseases, and people with chronic diseases such as diabetes mellitus and kidney disease.
Symptoms
Main Symptoms
Clinical manifestations are characterized by systemic and neurological symptoms, and intracranial infections caused by different pathogens may have different accompanying symptoms.
Systemic symptoms
Fever.
Night sweats.
Headache.
Muscle pain.
Nausea, vomiting.
Mental depression and weakness.
Neurological symptoms
In mild cases, there may be no obvious neurological symptoms. In severe cases, there may be brain parenchyma injury, brainstem injury, meningeal irritation, elevated intracranial pressure and brain hernia.
Parenchymal brain injury
Limb weakness, paralysis, muscle atrophy.
Decreased sensation and numbness of limbs and facial skin.
Difficulty in verbal communication.
Mental symptoms: abnormal behavior, character and personality changes, etc.
Brain stem injury
Facial paralysis.
Choking on drinking water, difficulty in swallowing.
Slurred or labored pronunciation.
Ptosis of the eyelids, exophthalmos, inflexible eye movements, etc.
Difficult to control crying or laughing.
Meningeal irritation manifestations
Neck stiffness.
Headache, especially when the head is lowered, is significantly worse.
Projectile vomiting.
In infants and young children, agitation, screaming and crying.
Blurred vision.
Increased intracranial pressure and brain herniation
Infants and young children may present with bulging fontanels.
Coma.
Dilated pupils.
Cardiac arrest.
Concomitant Symptoms
Mumps virus encephalitis with enlarged parotid glands.
Herpes virus encephalitis with herpes on the skin.
In coxsackievirus and echovirus encephalitis, the following symptoms may accompany it.
Skin rash.
Myocarditis: chest tightness, chest pain, palpitations, and weakness may be present.
Hand, foot and mouth disease: fever, maculopapular rash and/or herpes on the hands, feet, mouth and buttocks area, without pain, itching, crusting, etc.
Diarrhea.
Complications
Persistent status epilepticus.
Damage to brain cells may result in the formation of epileptic foci with persistent abnormal discharges and persistent status epilepticus.
It manifests as persistent and frequent seizures that cannot be terminated automatically.
Systemic infection
Infections of the urinary system and lungs due to bed rest, impaired coughing and swallowing reflexes.
Often present with cloudy urine, fever, cough, sputum and other manifestations.
Hydrocephalus
Brain parenchyma injury, cerebrospinal fluid turbidity can cause tissue adhesion, obstruction, the formation of hydrocephalus.
In infants and young children, this may be characterized by bulging fontanels, increased head circumference, and downward rotation of the eyeballs, exposing the white sclera in the upper part of the eye.
Adults may present with difficulty in lifting legs, unsteady walking, frequent urination, and urinary incontinence.
Cerebral hyponatremia
Damage to the inferior colliculus leads to abnormal secretion of antidiuretic hormone, which in turn leads to hyponatremia and water intoxication due to vomiting.
Manifestations include low urine output, mild swelling, frequent vomiting, recurrent convulsions and coma.
Consultation
Neurology
Prompt medical consultation is recommended if symptoms such as persistent headache, vomiting and limb weakness occur.
Pediatrics
Prompt medical consultation is recommended for infants and young children with recurrent fever, vomiting, screaming and crying or drowsiness.
Infectious diseases
Prompt medical consultation is recommended when symptoms such as fever, chills, cough, rash, diarrhea and vomiting occur.
Emergency Medicine
In case of severe headache, generalized convulsions, coma, etc., it is recommended to go to the Emergency Department as soon as possible or call the 120 emergency number.
Preparation
Preparing for medical treatment: registration, preparation of documents, and 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.
The patient may not be able to accurately describe his/her own symptoms. Family members can help to record the symptoms that have occurred so as to give the doctor more reference.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is the headache severe? When does it get worse?
Any recent rash, diarrhea, parotid gland enlargement, etc.?
Is there a fever? How long has the fever been present? What is the highest degree?
Any limb twitching, weakness, abnormal sensation?
Is the appetite normal? What is the mental status?
List of medical history
Any history of herpes zoster, tuberculosis, etc.?
Any history of craniocerebral trauma, head and face surgery, diabetes mellitus, malignant tumor.
Any recent mosquito bites, visits to infected areas, or contact with patients with intracranial infections?
Have immunizations been administered?
Are there any immunodeficiency diseases or use of immunosuppressants?
Checklist
Test results of the last six months, which can be brought to the doctor’s office
Laboratory tests: blood count, blood biochemistry
Imaging tests: cranial CT, cranial MRI
Other tests: cerebrospinal fluid test, electroencephalography
List of medications
Medication used in the last 3 months, if available, please bring the box or package with you to the doctor.
Antiviral drugs: acyclovir, ganciclovir, famciclovir
Anti-infectives: ceftazidime, penicillin, rifampin
Others: acetaminophen, prednisolone, carbamazepine, mertiomacrolate
Diagnosis
Diagnosis is based on
Medical History
Recent immunizations, mosquito bites, travel to an infected area, or exposure to patients with intracranial infections.
History of herpes zoster, tuberculosis infection, craniocerebral trauma, and head and face surgery.
History of diabetes mellitus, malignant tumors, immunodeficiency diseases, use of immunosuppressive drugs.
Clinical manifestations
Symptoms
Presence of systemic symptoms of infection and toxicity such as fever, chills, cough, nausea, diarrhea, and malaise.
Typical symptoms such as severe headache, vomiting, coma, paralysis, blurred vision, convulsions.
Vital Signs
The doctor uses a physical examination to see if there are any abnormalities in vital signs, motor, sensory, and swallowing functions, and nerve reflexes.
Vital signs: Check whether blood pressure, heart rate, pulse, pupils, and breathing are normal and stable.
Motor function check: Observe whether you can complete movements such as lifting hands, sitting up, standing, walking, 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.
Swallowing function test: Observe whether there is choking when drinking water to assess the swallowing function.
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 increased or decreased muscle contraction.
Meningeal irritation test
Observe whether headache occurs when the neck is flexed in the supine position or whether the angle of straightening the knee is in place when the hip is flexed.
The disease may present with headache on flexion of the neck and a knee extension angle of less than 135°.
Laboratory tests
Blood tests
Initial determination of whether an infection has occurred and the type of pathogen.
Bacterial infection: increased white blood cell count with a predominance of neutrophils.
Viral infections: lymphocytosis, normal or mildly elevated white blood cell count.
Parasitic infections: increased eosinophil count.
C-reactive protein (CRP)
CRP is tested to determine the presence of an acute phase infection.
An elevated CRP concentration indicates that the infection is in the acute phase. It can be used as an adjunctive test.
Cerebrospinal fluid test
Important in determining the presence of intracranial infection and the type of pathogen.
Bacterial infection Viral infection Fungal infection Parasitic infection
Cerebrospinal fluid pressure ↑↑↑↑ or -↑ or –
Cerebrospinal fluid pressure
↑
↑
↑ or –
↑ or –
Protein content ↑↑↑↑ or –
Protein content
↑
↑
↑
↑ or –
Glucose content ↓↓-
Glucose content
↓
↓
–
–
Chloride content ↓ – –
Chloride content
↓
–
–
– –
Elevated cell types leukocytes lymphocytes leukocytes may be normal or elevated lymphocytes
Elevated cell types
Leukocytes
Lymphocytes
Leukocytes may be normal or elevated
Lymphocytes
Note: ↑ indicates increase, ↓ indicates decrease, – indicates no significant change
Precautions for examination
Adjust the body position according to the doctor’s requirements during the examination.
Do not cough or move your body once the puncture needle has entered the body.
After the puncture, lie down with the pillow removed for 4 to 6 hours to prevent headache caused by the change of intracranial pressure.
Keep the local skin clean and dry to prevent infection at the puncture site.
Imaging
This includes cranial CT and cranial MRI.
Cranial MRI is the imaging method of choice for encephalitis.
It can show swelling and hemorrhagic changes in the involved areas, mostly with nodular or ring-like enhancement.
Precautions
Cranial CT: Remove any metal objects, such as necklaces and earrings, from the body before the examination.
MRI: Remove any metal or magnetic objects from the body beforehand; people with pacemakers, metal or magnetic objects in their bodies are not allowed to undergo the examination.
Smear test or culture
For bacterial and fungal infections.
Nasopharyngeal swabs, peripheral blood and cerebrospinal fluid can be used as pathogen collection samples.
The isolation and culture of the collected samples can greatly improve the positive rate and accuracy of the test, and drug sensitivity test can be performed at the same time. If the results of routine blood and cerebrospinal fluid tests are negative, sometimes the culture can also obtain the causative organisms.
Immunological examination
Applicable to viral and fungal infections.
Through enzyme-linked immunosorbent assay or polymerase chain reaction, specific antigen, antibody and complement can be detected to assist in determining the type of pathogen.
Tuberculin test
Suitable for tuberculosis infection.
Positive tuberculin test suggests that intracranial infection may be related to tuberculosis bacteria, but there are many factors affecting the result, and the result should not be used alone for judgment.
Pathology
Pathologic examination of the brain parenchyma is the gold standard for diagnosing intracranial infections when it is difficult to identify the causative agent with other tests.
The detection of viral particles by electron microscopy is the gold standard for the diagnosis of herpes simplex virus encephalitis.
This test is invasive, may cause brain damage, and is not commonly used.
Electrophysiologic examination
Includes electroencephalogram, cerebral evoked potentials.
Viral encephalitis is characterized by diffuse high-amplitude slow waves, with more pronounced abnormalities in the temporofrontal region unilaterally or bilaterally, and even spike and spike waves in the temporal region.
Differential diagnosis
Differential diagnosis is mainly associated with diffuse gliomatosis, carcinomatous meningitis, and cerebral arteriovenous malformations.
Diffuse gliomatosis
Similarities
Nausea, vomiting, headache, limb paralysis, aphasia, coma, etc. may occur.
Differences
Cerebrospinal fluid (CSF) examination: intracranial infections may show elevated pressure and changes in the number and type of cells; patients with diffuse cerebral gliomatosis have no obvious changes.
Cranial magnetic resonance examination: intracranial infection lesions are variable in location and extent. Diffuse cerebral gliomas have multiple irregular patchy and macroscopic changes, and characteristic corpus callosum involvement is seen.
Carcinomatous meningitis
Similarities
Both present with nausea, vomiting, headache, limb paralysis, aphasia, and coma.
Differences
Patients with carcinomatous meningitis have a history of tumors elsewhere, and cerebrospinal fluid tests can detect cancer cells.
Cerebral arteriovenous malformation
Similarities
Nausea, vomiting, headache, limb paralysis, aphasia, coma, etc. are all present.
Differences
The cerebrospinal fluid of patients with cerebral arteriovenous malformations is usually not significantly altered.
Cranial magnetic resonance imaging and digital silhouette angiography may show irregular blood vessel clusters and abnormal blood flow changes in the brain.
Treatment
Treatment purpose: anti-infection, relieve symptoms, control the development of the disease, reduce the rate of disability and death.
Principle of treatment: Drug treatment is the mainstay, supplemented by supportive therapy, and some types need to be treated with surgery.
General treatment
Bed rest, reduce physical exertion.
Keep the respiratory tract open, and in serious cases, use the ventilator to assist breathing.
Adequate fluid replacement to maintain water electrolyte balance.
Physical cooling is the mainstay of fever, and ice packs can be placed in the groin, armpits and neck, and cooling beds or cold mattresses can also be used.
Anti-infective drug treatment
Anti-infective drugs should be selected according to different pathogens and drug susceptibility test results. All drugs should be used according to medical advice.
Antiviral therapy
Commonly used drugs are acyclovir and ganciclovir.
Acyclovir: used for encephalitis caused by herpes simplex virus.
Ganciclovir: used for encephalitis caused by cytomegalovirus infection.
These drugs may cause renal impairment and bone marrow suppression and are contraindicated in pregnant and breastfeeding women.
Antibacterial drugs
Frequently available drugs include ceftriaxone, cefotaxime, penicillin, ampicillin, chloramphenicol, vancomycin, etc.
Precautions for the use of drugs
Sensitive antibiotics should be selected according to the results of drug sensitivity test.
For patients with a history of drug allergy, the drug should be used with caution to avoid allergic reactions.
Adverse reactions such as nausea and vomiting, diarrhea, and rash may occur with use.
Antifungal drugs
Frequently available drugs include amphotericin B, fluconazole, 5-fluorocytosine, etc.
May cause adverse reactions such as high fever, chills, thrombophlebitis, headache, nausea, vomiting, leukopenia or thrombocytopenia.
Antiparasitic drugs
Commonly used drugs include praziquantel, albendazole and so on.
Precautions for the use of drugs
The dosage should be carefully adjusted according to the number of parasites and the degree of disease. Avoid causing severe acute inflammatory reaction and cerebral edema.
May cause headache, nausea, abdominal pain, diarrhea, fatigue, liver function abnormalities, skin rash and other adverse reactions.
Anti-tuberculosis drugs
Commonly used drugs include isoniazid, rifampicin, pyrazinamide, streptomycin and so on.
They can cause anorexia, nausea, vomiting, flu-like symptoms, peripheral neuritis, effects on the auditory nerve, liver and kidney function.
Symptomatic supportive treatment
Glucocorticoids
Can control the inflammatory response, reduce edema, limited to patients with severe or persistent cranial hypertension.
Commonly used drugs: dexamethasone, methylprednisolone.
Cautions: not long-term use, pay attention to peptic ulcer, osteoporosis and other adverse reactions.
Dehydration diuretic
Can relieve cerebral edema and reduce intracranial pressure.
Commonly used drugs: mannitol, furosemide and so on.
Precautions: need to monitor the urine volume and electrolytes during the use of drugs to avoid hyponatremia, renal function injury, etc..
Antiepileptic drugs
To control seizures and avoid further aggravation of craniocerebral injury.
Commonly used drugs: midazolam, carbamazepine, sodium valproate, oxcarbazepine and so on.
Precautions
Adverse reactions such as dizziness, memory loss, generalized rash, nausea and vomiting may occur.
Long-term medication may be required.
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
If emotional instability and irritability exist, drugs such as diazepam and lorazepam may be used for sedation.
Naproxen, ibuprofen, aspirin, etc. may be used as appropriate for severe headache.
If vomiting is frequent, metoclopramide may be used for symptomatic treatment.
Electrolyte disorders due to vomiting, insufficient intake and cerebral hyponatremia should be supplemented with electrolytes.
Attention should be paid to strengthening dietary nutrition, and fat emulsion can be infused intravenously if necessary.
Surgical treatment
Cerebrospinal fluid shunt surgery can be performed when persistent intracranial hypertension occurs and conservative treatment is ineffective.
For intracerebroventricular parasitic foci, surgical resection can be considered when the foci are small.
Prognosis
The prognosis of intracranial infections is related to the causative agent, the patient’s condition, and the promptness of effective treatment.
Usually, viral intracranial infections have a certain degree of self-healing, and most patients can recover completely. Bacterial intracranial infections have a higher incidence of sequelae and mortality than the former. Tuberculous intracranial infections can be cured in most cases, but the morbidity and mortality rates are higher in infants and young children. Fungal and parasitic intracranial infections are poorly treated and have a poor prognosis.
The prognosis is better for young adults, mild disease, timely diagnosis and treatment.
Infants, young children, the elderly, and those with immunosuppression have poor therapeutic effects and a poor prognosis.
Some patients may be left with sequelae such as mental retardation, limb paralysis, epilepsy and hydrocephalus.
Patients with severe disease and poor basic condition may cause death.
Daily
Daily management
Dietary management
Diet should be light, with high protein and high vitamin diet.
Eat more fresh vegetables and fruits.
Eat more high quality protein, such as milk, soy products, eggs, lean meat and other foods.
Avoid cold, greasy and spicy stimulating foods, such as chili peppers, coffee and strong tea.
Abstain from alcohol.
For those who are unable to eat, a nasal diet must be used to provide nutritional support.
Exercise management