Brain Inflammation is an inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues. The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood-brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells. However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response. Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood-brain barrier.
Inflammation of Brain(Encephalitis )
Inflammation of the brain that is caused especially by infection with a virus (such as herpes simplex or West Nile virus) or less commonly by bacterial or fungal infection or autoimmune reaction
Causes of Inflammation of Brain
In most cases, encephalitis is caused by a viral infection (infectious encephalitis). The most common viruses that can cause encephalitis are:
- the herpes simplex virus (the virus that also causes cold sores)
- the measles virus
- the varicella virus (chickenpox)
- the rubella virus (German measles)
Other viruses that less commonly cause encephalitis include the mumps virus, the Epstein-Barr virus (glandular fever), echovirus, Coxsackie virus, human immunodeficiency virus (HIV) and cytomegalovirus (CMV).
Some people can experience encephalitis in the days or weeks following a viral infection (post-infectious encephalitis). Although rare, this is due to a problem with the immune system which causes it to attack the brain.
Sometimes people can experience encephalitis when their immune system mistakenly attacks their brain without them previously having had a viral infection. This is called autoimmune encephalitis. Often, the cause of the problem with the immune system is unknown.
Very rarely, encephalitis can be caused by bacterial or fungal infections.
Several different viruses that can cause encephalitis are spread by insect bites. These are more commonly found outside the UK.
Looking for reasons of Inflammation of Brain
Karim Belarbi, lead author of the 2012 UCSF paper and now based at the French research institute INSERM, says that “one of the impacts we saw was an elevated proportion of neurons getting activated in response to behavior.”
One hypothesis for this, he adds, is that elevated TNF-α increases levels of AMPAR—a neuronal receptor for an excitatory neurotransmitter called glutamate. More glutamate receptors mean more sensitivity to glutamate in the surrounding tissue, which in turn makes the neurons more liable to being activated by stimuli, and eventually too much so. Another possible route to excessive activation, Belarbi says, is that TNF-α-mediated inflammation alters the properties of helper brain cells called astrocytes, which normally regulate glutamate levels, the loss of that glutamate regulation could lead to a buildup of the neurotransmitter and, again, an oversensitization of neurons.
Note that neuroinflammation, according to these hypotheses, impairs cognition by causing the overactivation of neurons. “If you want to have good cognition, you need neuronal activation at the optimum level,” Belarbi suggests. “I like to think of it in terms of a signal to noise ratio: Too little neuronal activation means the signal is too low. Too much neuronal activation means the noise is too high. Either way, you will lose cognition.”
Other hypothesized effects of inflammation that would impair cognition include suppression of the production of new hippocampal neurons (neurogenesis) and reduction in microglial cells’ normal ability to help repair and maintain neuronal connections (synapses).
Symptoms of encephalitis
Overall symptom
- a headache
- fever (high body temperature)
- the general feeling of being unwell
After the initial symptoms, the headache can become severe and people can also experience:
- nausea (feeling sick) and vomiting (being sick)
- mild to moderate neck stiffness
- drowsiness and confusion
- problems with memory
- speech problems
- changes in personality and uncharacteristic behaviour
- epilepsy (seizures)
Other symptoms can include sensitivity to bright light and a lack of co-ordination
The symptoms of encephalitis can range from mild to severe.
Mild symptoms include
Severe symptoms include
- fever of 103°F (39.4°C) or higher
- confusion
- drowsiness
- hallucinations
- slower movements
- coma
- seizures
- irritability
- sensitivity to light
- unconsciousness
Infants and young children show different symptoms. Call a doctor immediately if your child is experiencing any of the following:
- vomiting
- bulging fontanel (soft spot in the scalp)
- constant crying
- body stiffness
- poor appetite
According to EULAR, the symptom is following
The symptoms of encephalitis include
- Fever
- A sore throat
- Weakness
- Disorientation
- Loss of consciousness
- Seizures
- Delusions
- Hallucinations
- Agitation
- Personality changes
In case the encephalitis is accompanied by meningitis, symptoms may also include
- A headache
- Stiff neck
- Nausea and vomiting
- Intolerance to bright light
There may be other symptoms present as well – depending on the area of the brain affected. Some of these include:
- Difficulty in speaking
- Difficulty in understanding words
- Involuntary muscle movements such as tremors
- Loss of coordination
- Weakness or partial paralysis
The viruses that most commonly cause encephalitis include
- Arboviruses – These are viruses carried by insects and can cause Eastern equine encephalitis, Western equine encephalitis, La Crosse encephalitis, St. Louis encephalitis and West Nile encephalitis.
- Herpes simplex viruses – Both HSV-1 which causes cold sore and HSV-2 which causes genital herpes can cause encephalitis.
- Varicella zoster virus, the cause of chicken pox and shingles
- Epstein-Barr virus – the cause of mononucleosis
- Childhood viruses that cause measles, rubella and mumps.
There are certain factors that increase the risk of developing viral encephalitis. These include
- Newborns and the elderly are susceptible
- Exposure to mosquitos
- Having a weak immune system
- No immunity against childhood diseases
- Traveling to places where this condition is endemic
Diagnosis of Inflammation of Brain
Your doctor will first ask you about your symptoms. They may perform the following tests if encephalitis is suspected.
Brain Scans
A scan of the brain can help show whether you have encephalitis or another problem such as a stroke, brain tumor or brain aneurysm (a swelling in an artery).
The two main types of scan used are:
- a CT scan – several X-rays are taken from different angles and are put together by a computer to create a detailed image of the brain
- an MRI scan – strong magnetic fields and radio waves are used to produce a detailed image of the brain
Lumbar puncture
A lumbar puncture is a procedure to remove some fluid from around the spinal cord (the nerves running up the spine) so it can be checked for signs of encephalitis.
For the procedure:
- you lie on one side and bring your knees up towards your chin
- local anesthetic is used to numb your lower back
- a needle is inserted into the lower part of your spine and a sample of fluid is removed
The sample will be checked for signs of infection or a problem with your immune system, which are the main causes of encephalitis
Electroencephalograph (EEG)
An EEG uses electrodes (small metal discs with wires) attached to the scalp to record brain activity. An EEG does not detect the virus that causes encephalitis, but certain patterns on the EEG may alert your neurologist to an infectious source of your symptoms. Encephalitis can lead to seizures and coma in later stages. That’s why the EEG is important in determining the areas of the brain that are affected and the types of brain waves that occur in each area.
Blood tests
A blood test can reveal signs of a viral infection. Blood tests are rarely performed alone. They usually help diagnose encephalitis along with other tests.
Brain biopsy
In a brain biopsy, your doctor will remove small samples of brain tissue to test for infection. This procedure is rarely performed because there’s a high risk of complications. It’s usually only done if doctors can’t determine the cause the brain swelling or if treatment isn’t working.
Treatment of Inflammation of Brain
Anti-viral medications can help treat herpes encephalitis. However, they aren’t effective in treating other forms of encephalitis. Instead, treatment often focuses on relieving symptoms. These treatments may include:
- rest
- painkillers
- corticosteroids (to reduce brain inflammation)
- mechanical ventilation (to help with breathing)
- lukewarm sponge baths
- anticonvulsants (to prevent or stop seizures)
- sedatives (for restlessness, aggressiveness, and irritability)
- fluids (sometimes through an IV)
Treatment (which is based on supportive care) is as follows:[rx]
- Antiviral medications (if virus is cause)
- Antibiotics, (if bacteria is causing)
- Steroids are used to reduce brain swelling
- Sedatives for restlessness
- Acetaminophen for fever
- Pyrimethamine-based maintenance therapy is often used to treat Toxoplasmic Encephalitis (TE), which is caused by Toxoplasma gondii and can be life-threatening for people with weak immune systems.
- The use of highly active antiretroviral therapy (HAART), in conjunction with the established pyrimethamine-based maintenance therapy, decreases the chance of relapse in patients with HIV and TE from approximately 18% to 11%.[rx] This is a significant difference as a relapse may impact the severity and prognosis of disease and result in an increase in healthcare expenditure.[rx]
You may need to be hospitalized during treatment, especially with brain swelling and seizures.
- Recently the use of anti-inflammatory drugs for the treatment of concussion has been closely examined. As it is now becoming more evident that lingering neuroinflammatory mechanisms contribute to the secondary damage following a concussion, the use of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an attractive option.
- That being said, there is evidence to suggest NSAIDs may not be the best pharmacotherapy for managing the neurobiological factors underlying concussive injuries. It has been shown that chronic treatment with ibuprofen, one of the most commonly used NSAIDs, worsens the cognitive alterations in rodents exposed to an experimental TBI (Browne et al Rx).
- Other NSAIDs, such as minocycline – are capable of reducing apoptotic damage in several forms of CNS injury, such as spinal cord injury, but do not show any beneficial effects when examining recovery times from mild TBI (Stirling et al Rx; Rx). Taken together, these data demonstrate that preventing an inflammatory response to a concussion is not a viable treatment, despite its effectiveness in treating other traumatic injuries occurring in the CNS.
- Nesfatin-1 – provides hope for the use of anti-inflammatory drugs in the treatment of concussive injuries. However, it should be noted that the beneficial effects of Nesfatin-1 administration were preceded by 5 consecutive days of peripheral administration and there was no time-response relationship (rx). Therefore, it remains unclear whether acute, post-concussive treatment with Nesfatin-1 would provide any lasting protection or if a continuous presence of Nesfatin-1 is required as would result from preventative dosing. Further studies are needed to investigate the potential therapeutic effects of peripherally administered endogenous anti-inflammatory agents following concussions.
- Steroids – are representative anti-inflammatory drugs that act specifically through glucocorticoid receptors (GRs). Despite the development of many new drugs, steroids are still broadly used to treat intractable diseases and pathological states, including inflammation, autoimmune disorders, and cancers.
- Although steroids have demonstrated remarkable clinical efficacy, the exact mechanisms underlying such effects have only recently been unveiled. GR is a prototype ligand-activated transcription factor that belongs to the nuclear receptor (NR) family and regulates gene expression by either transcriptional activation [rx] or transcriptional repression (transrepression) [rx].
- In polysaccharide and lipid metabolism, steroid-activated GR forms a dimer, migrates into the nucleus and binds glucocorticoid response elements (GREs) to induce target gene transcription [rx]. However, GREs are absent from the promoter regions of most inflammatory genes [rx], meaning that glucocorticoid-mediated anti-inflammation acts indirectly.
- Indeed, the anti-inflammatory mechanism of steroids was found to act via transrepression, with ligand-activated GR indirectly suppressing the activity of inflammation-related transcription factors by inhibiting the binding of co-activators that promote transcription or by recruiting co-repressors to inhibit transcription [rx].
- Current treatments for multiple sclerosis include interferon-B, Glatiramer acetate, and Mitoxantrone, which function by reducing or inhibiting T Cell activation but have the side effect of systemic immunosuppression [rx]
- In Alzheimer’s disease, the use of non-steroidal anti-inflammatory drugs decreases the risk of developing the disease. Current treatments for Alzheimer’s disease include NSAIDs and glucocorticoids. NSAIDs function by blocking the conversion of prostaglandin H2 into other prostaglandins (PGs) and thromboxane (TX). Prostaglandins and thromboxane act as inflammatory mediators and increase microvascular permeability.
Integrative Therapies
- Note: There is a currently a lack of scientific data on the use of integrative therapies for the treatment or prevention of viral encephalitis. The therapies listed below have been studied for viral infections in general, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies.
- Unclear or conflicting scientific evidence –
- Alizarin – Limited available evidence suggests that alizarin may improve various herpes infections. Additional study is needed before a firm recommendation can be made. Avoid if allergic or hypersensitive to alizarin or any plants in the Rubiaceae family. Alizarin may be toxic and should not be handled for long periods of time, rubbed in the eyes, or eaten. Avoid if pregnant or breastfeeding.
- Astragalus – Astragalus products are derived from the roots of Astragalus membranaceus or related species, which are native to China. In traditional Chinese medicine, astragalus is commonly found in mixtures with other herbs and is used in the treatment of numerous ailments, including heart, liver, and kidney diseases, as well as cancer, viral infections, and immune system disorders. Anti-viral activity has been reported with the use of astragalus in laboratory and animal studies. Limited human research has examined the use of astragalus for viral infections in the lung, heart (pericarditis, myocarditis, endocarditis), liver (hepatitis B and C), cervix (papilloma virus), and in HIV disease. Studies have included combinations of astragalus with the drug interferon, or as a part of herbal mixtures. However, most studies have been small and poorly designed. Due to a lack of well-designed research, firm conclusions cannot be drawn.
- Avoid if allergic to astragalus – peas, or any related plants, or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant or autoimmune diseases (like HIV/AIDS). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.
- Blessed thistle – Blessed thistle leaves, stems, and flowers have traditionally been used in “bitter” tonic drinks and in other preparations taken by mouth to enhance appetite and digestion. Evidence of activity of blessed thistle against herpes viruses, influenza, or poliovirus is currently lacking in available preliminary research. Effects of blessed thistle (or chemicals in blessed thistle called lignans) against HIV are not clear. Human research of blessed thistle as a treatment for viral infections is lacking.
- Avoid if allergic – to blessed thistle, mugwort, bitter weed, blanket flower, chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed, Echinacea or any plants of the Asteraceae or Compositae families. Use cautiously with peptic ulcer disease. Avoid with a history of bleeding diseases or gastroesophageal reflux disease (GERD), or if taking drugs for blood thinning, stroke, stomach diseases, or to control stomach acid. Avoid if pregnant or breastfeeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures.
- Cranberry – Cranberry is popular as a food and is often consumed as relish, sauce, jam, juice, or dried berries. Limited laboratory research has examined the antiviral activity of cranberry. Reliable human studies supporting the use of cranberry in this area are currently lacking. Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium genus. Sweetened cranberry juice can affect blood sugar levels. Use cautiously with a history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.
- Focusing – Early research showed that increased experiential involvement (an indication of focusing taking place) did not have an effect on antibody titers to Epstein-Barr virus. More studies in the area of immune function and antibody production are required before a recommendation can be made in this area.
- Green tea – Preliminary research suggests that green tea decreases viral load in carriers of the HTLV-1 virus. Additional well-designed controlled research is needed before a recommendation can be made for or against the use of green tea in the treatment of HTLV-1 carriers. Avoid if allergic or hypersensitive to caffeine or tannin. Use cautiously with diabetes or liver disease.
- Sorrel – Historically, sorrel has been used as a salad green, spring tonic, diarrhea remedy, weak diuretic, and soothing agent for irritated nasal passages. Sorrel has been used with other herbs to treat bronchitis and sinus conditions in Germany since the 1930s. There is currently a lack of well-conducted published studies that demonstrate antiviral or antibacterial activity of sorrel. In an available laboratory study, sorrel did not demonstrate activity against herpes simplex virus-1, herpes simplex virus-2, HIV, B. subtilis, E. coli, Proteus morganii, Pseudomonas aeruginosa, P. vulgaris, Serratia marcescens, or Staphylococcus aureus.
- Avoid with a known allergy to sorrel – Avoid large doses of sorrel because there have been reports of toxicity and death, possibly due to oxalates found in sorrel. Tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. High alcohol sorrel formulations may also cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.
- Turmeric – The rhizome (root) of turmeric (Curcuma longa Linn.) has long been used in traditional Asian medicine to treat gastrointestinal upset, arthritic pain, and “low energy.” Evidence suggests that turmeric may help treat viral infections. However, there is currently not enough human evidence in this area. Well-designed trials are needed to determine if these claims are true. Avoid if allergic or hypersensitive to turmeric, curcumin, yellow food colorings, or plants belonging to the Zingiberaceae (ginger) family. Use cautiously with a history of bleeding disorders, immune system deficiencies, liver disease, diabetes, hypoglycemia, or gallstones. Use cautiously with blood-thinners, such as warfarin and blood sugar-altering medications. Avoid in medicinal amounts if pregnant or breastfeeding. Turmeric should be stopped prior to scheduled surgery.
- Vitamin A – The role of vitamin A in the prevention, transmission, or treatment of HIV is controversial and not well established. A clear conclusion cannot be formed based on the available scientific research. Vitamin A supplementation has also been suggested to help prevent Nov infection in children and reduce the symptoms associated with Nov infections. Additional research is needed in this area.
Complications of Inflammation of Brain
Most people who are diagnosed with severe encephalitis will experience complications. Complications resulting from encephalitis can include:
- loss of memory
- behavioral/personality changes
- epilepsy
- fatigue
- physical weakness
- intellectual disability
- lack of muscle coordination
- vision problems
- hearing problems
- speaking issues
- fatigue
- coma
- difficulty breathing
- death
Complications are more likely to develop in certain groups, such as:
- older adults
- people who have had coma-like symptoms
- people who didn’t get treatment right away
What is the long-term outlook?
Your outlook will depend on the severity of the inflammation. In mild cases of encephalitis, the inflammation will likely resolve in a few days. For people who have severe cases, it may require weeks or months for them to get better. It can sometimes cause permanent brain damage or even death.
People with encephalitis may also experience:
- Problems with balance, coordination and dexterity.
- Speech problems.
- Weakness and problems with movement.
- Swallowing problems
- Fits (seizures)
- A chronic headache
- Personality changes
- Memory problems
- Behavioral problems
- Mood problems, anxiety, and depression
- Difficulty concentrating
- paralysis
- loss of brain function
- problems with speech, behavior, memory, and balance
Depending on the type and severity of encephalitis, it may be necessary to receive additional therapy, including
- physical therapy – to improve strength, coordination, balance, and flexibility
- occupational therapy – to help redevelop everyday skills
- speech therapy – to help relearn muscle control needed for talking
- psychotherapy – to help with coping strategies, mood disorders, or personality changes
References
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542678/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520152/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479815/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001842/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260471/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188748/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320802/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313590/
- https://en.wikipedia.org/wiki/Encephalitis
- https://en.wikipedia.org/wiki/Neuroinflammation
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