What is Autoimmune Encephalitis?
Autoimmune encephalitis, often referred to as AIE, is a condition where the body’s immune system causes inflammation in the brain. This condition is one of the most common types of non-infectious brain inflammation. Over the last decade, doctors started to consider AIE when a person exhibits particular neurological symptoms that can’t be attributed to a typical infection, even though the exact cause of AIE still is not clearly understood. Research indicates it may be due to autoimmune antibodies attacking proteins in synapses, which can cause widespread inflammation in the brain.
Common symptoms of AIE include new memory loss, periods of psychosis, changes in overall mental state, or seizures. These symptoms usually present themselves gradually, over a few weeks to three months. AIE can affect different parts of the nervous system, including the limbic system, the spinal cord, and/or the entire neuraxis, which is the central line of the nervous system. It can be confirmed by various methods such as laboratory testing (detecting antibodies), scans of the brain, and electrical studies of the brain activity (electroencephalogram).
It’s important to note that while classical paraneoplastic encephalitis is often linked to cancer, AIE may or may not be related to cancer. Therefore, after a diagnosis of AIE, patients are usually screened for cancer because of the potential association. Even though these tests can take time, if a patient’s symptoms strongly suggest AIE, doctors often start treatment early because the condition tends to respond well to treatment and patients tend to get better. Most knowledge about treatments for AIE come from studying a specific form known as Anti-N-methyl-D-aspartate receptor (anti-NMDA) encephalitis.
What Causes Autoimmune Encephalitis?
While experts are still working to understand it fully, it’s thought that autoimmune encephalitis happens when your body’s immune system overreacts to a protein found in your nerve cells. Unlike a related condition, paraneoplastic encephalitis, autoimmune encephalitis is caused by harmful antibodies.
These antibodies cause inflammation when they target certain specific nerve cell proteins. To date, we know they target things like proteins at the nerve cell connections, proteins that regulate the movement of ions in and out of cells, and proteins inside cells that receive signals. Once these antibodies attach to these proteins, they cause them to change shape, which leads to inflammation.
Risk Factors and Frequency for Autoimmune Encephalitis
Information about autoimmune encephalitis is often under-reported. This is because the disease may appear in different ways and can be caused by many different antibodies. Encephalitis appears in adults at different rates, between 0.7 to 12.6 per 100,000, and can affect both adults and children.
So far, most reports and studies about autoimmune encephalitis have focused on a specific type called Anti-NMDAR encephalitis. In a large study, 80% of patients with Anti-NMDAR encephalitis were female, and the average age of diagnosis was 21 years old. Moreover, 38% of patients in the study had an underlying tumor, most commonly an ovarian teratoma.
- Autoimmune encephalitis can be caused by many different antibodies and can appear differently, making it under-reported.
- The disease can be found in both adults and children and appears at a rate of 0.7 to 12.6 per 100,000 in adults.
- Most research on autoimmune encephalitis has focused on Anti-NMDAR encephalitis.
- In a large study, 80% of patients with Anti-NMDAR encephalitis were female.
- The average age of diagnosis for Anti-NMDAR encephalitis was 21 years old.
- In the same study, 38% of patients had an underlying tumor, usually an ovarian teratoma.
Signs and Symptoms of Autoimmune Encephalitis
The symptoms of this condition can be vague and vary a lot, making it hard to diagnose. Many times, people don’t experience the usual symptoms, so doctors use tools like imaging, blood tests, and EEGs (tests that measure the electrical activity in the brain) to make a diagnosis. The condition can impact different parts of the brain in different ways, causing a range of symptoms. It’s important to note that different types of this condition have been linked to certain specific antibodies – proteins that the body produces in response to harmful substances.
About 70% of people with this condition first have symptoms like a headache or fever that make it seem like they might have a virus. The condition then moves into a more serious phase with symptoms that appear quickly or gradually. These might include memory problems, changes in mental state, shifts in behavior, hallucinations, bizarre and agitated behavior, rigid posture, seizures, or strange movements. People may get better and worse in cycles as the disease progresses.
If the condition advances further, people might become less conscious and have difficulty breathing normally, requiring a machine to help them. When evaluating someone with these symptoms, it’s important to ask about other signs of illness like fever, weight loss, or night sweats. These could suggest that the symptoms are due to a different disease or even a cancer-related process. A full neurological exam is necessary to look for specific neurological deficits and to rule out other possible causes of encephalitis.
- Difficulty diagnosing due to vague symptoms
- Symptoms can vary greatly
- Diagnosis involves imaging, blood tests, and EEGs
- Initial symptoms resembling a viral infection
- Subsequent symptoms can include changes in mental state, behavior shifts, hallucinations, seizures, and unusual movements
- Progression may involve cycling between improvement and worsening
- More serious progression can involve decreased consciousness and difficulty breathing
Testing for Autoimmune Encephalitis
Diagnosing autoimmune encephalitis is a multi-step process and can often take anywhere from a few weeks to three months. It’s important to first rule out infectious encephalitis, which can be life-threatening. After other causes have been ruled out, it’s still tricky to accurately diagnose autoimmune encephalitis. This diagnosis relies on a range of tools including symptoms of brain function or behaviour changes, lab tests, brain scans, and EEG, which measures electrical activity in the brain.
A group of experts developed a set of criteria to help doctors identify autoimmune encephalitis and start the right treatment. These criteria include the sudden onset of changes in consciousness or personality, new symptoms related to the central nervous system, seizures not explained by a previously diagnosed seizure disorder, high white blood cell count in the spinal fluid, and MRI scans suggesting inflammation in the brain. It’s important to note, all criteria must be met to make a diagnosis.
The MRI scan shows signal changes in specific brain areas on a specific setting (T2 weighted FLAIR images). Autoimmune limbic encephalitis diagnosis becomes firmer when the symptoms appear quickly (less than 3 months), the MRI brain scan shows abnormalities restricted to the middle part of the brain, there’s a high white blood cell count in the spinal fluid or EEG shows slow-wave or epileptic activity in the temporal lobes, and other causes have been reasonably ruled out.
It’s important to note, if one of the first three criteria isn’t met, a definitive diagnosis can only be made if antibodies against specific proteins are detected in both the blood and spinal fluid. Some studies showed that in all patients with a specific type of encephalitis where antibodies were detected in the spinal fluid, 14% of the cases didn’t have detectable antibodies in the serum. Therefore, doctors recommend collecting both spinal fluid and blood to maximize the chance of detecting antibodies.
Once an autoimmune encephalitis diagnosis is made, patients should be screened for tumors. There is a connection between certain tumors and the type of autoimmune antibody detected. This can involve CT scans of the chest, stomach, and pelvis to look for potential tumors in these areas. Women should also have gynecological exams and scans of the breasts and ovaries, while men should have ultrasound scans for testicular evaluation. If these initial scans do not reveal any tumors, doctors may consider a specialized full-body scan called an FDG-PET.
Treatment Options for Autoimmune Encephalitis
Autoimmune encephalitis, a condition where the immune system attacks the brain, can be managed using a combination of treatments. The main aim of the treatment is to reduce the harmful antibodies causing the disease. The decision to commence treatment should not be postponed until the antibody is detected, as starting treatment earlier often leads to better results.
For effective management of autoimmune encephalitis, a team made up of neurologists, rheumatologists, and oncologists is typically involved. The initial treatment usually comprises corticosteroids, intravenous immunoglobulins, and a procedure called plasma exchange, where the blood’s liquid portion (plasma) is replaced.
It’s recommended to consider plasma exchange for people with severe symptoms such as abnormal bodily functions (dysautonomia), severe and uncontrollable seizures, or a condition that causes difficulty breathing (central hypoventilation syndrome). If these initial treatments don’t work, then additional therapies with medications like rituximab and cyclophosphamide may be considered.
Furthermore, if a tumor connected to the disease is discovered, it’s crucial to remove it by means of surgery or treat it with chemotherapy. This is because tumor removal or chemotherapy can speed up the patient’s recovery and prevent potential relapses.
What else can Autoimmune Encephalitis be?
Because this condition can show up in various ways, it may look like other health issues. This is why doctors also look at other possible causes. Most patients start to show more signs of the syndrome within a few days or weeks. Since it usually begins with a fever and a headache, it’s imperative to rule out sicknesses that can cause inflammation in the brain. As it advances and causes changes in behavior, physicians should also consider whether the encephalopathy might be caused by toxins or metabolic imbalances. If patients display particular deficits in their neurological function, stroke becomes a more likely scenario. It is crucial for these patients to have a complete examination, including a scan of the brain, to determine their diagnosis. Other causes of seizures or behavioral disturbances, like growths within the brain, are also possible.
Certain autoimmune brain inflammations usually start with severe mental health symptoms, which can lead to patients being admitted to a psychiatric unit for inpatient care. Healthcare providers should pay close attention to how the patient’s condition progresses since they usually start to show added signs of the syndrome within a few days or weeks. A cautious examination might reveal minor neurological deficits. These should make doctors consider the possibility of autoimmune brain inflammation. Patients might also present with demyelinating disorder, such as Multiple Sclerosis, or other autoimmune conditions like Lupus or Neurosarcoidosis, which can affect numerous systems in the body and require further tests including cerebrospinal fluid (CSF) studies and scans of the brain. Conditions relating to the degeneration of the nervous system, such as Alzheimer’s disease, typically show up slowly over time and should also be investigated with scans of the brain. Occasionally, mental health symptoms can be caused by inherited or metabolic disorders. If there’s family history of such, additional studies will be needed.
What to expect with Autoimmune Encephalitis
Autoimmune encephalitis, a condition where the immune system mistakenly attacks the brain, usually responds well to immunosuppression treatments and removing the linked tumor. However, the cancer stage can affect the outcome. Based on a study, 94% of patients received initial therapy that involved either immunosuppression or tumor removal. This led to improvements within four weeks for 53% of the patients, and most of them had positive results within the first 24 months. These outcomes continued to get better up to 18 months after the first symptoms appeared.
Factors that predicted good outcomes included early treatment and avoiding a stay in the intensive care unit (ICU). Patients need to be monitored closely after recovery, as the condition can return. Regular scans every 4 to 6 months are recommended for at least four years. Generally, there is a better prognosis for patients who have cell-surface antibodies compared to those with intracellular antibodies.
Possible Complications When Diagnosed with Autoimmune Encephalitis
Autoimmune encephalitis, while often responsive to treatment, can result in some significant complications if not treated promptly. These could include problems with cognition, sleep issues, excessive and uncontrollable movements, malfunctioning of the body’s automatic functions like heart rate or digestion, lasting memory loss (specifically with anti LG1 encephalitis), coma, and severe and continuous seizures.
A research study conducted by Xu and colleagues highlighted that a condition called central hypoventilation syndrome, where the body ‘forgets’ to breathe, is a major risk factor for needing ventilator assistance during hospital stay for patients with encephalitis caused by anti-NMDAR. This brings out the importance of keeping a keen eye on this syndrome.
- Cognitive impairment
- Sleep disorders
- Hyperkinesia
- Autonomic dysfunction
- Persistent amnesia (anti LG1 encephalitis)
- Coma
- Status epilepticus
- Central hypoventilation syndrome (specifically in anti-NMDAR encephalitis)
Preventing Autoimmune Encephalitis
Teaching patients about their condition, how it develops, evolves over time, and its potential link to deeper health issues is essential. It’s important for patients to know that the nature of this disease can vary, which might cause a delay in diagnosis. Patients should also continue to visit their neurologist or oncologist frequently after leaving the hospital, due to the risk of the disease returning and the need to check for deeper health issues.
It’s recommended for these patients to have medical scans every six months for a minimum of four years to check for any growth or spread of tumors, which may not be initially noticeable and can lead to brain-related symptoms. Family involvement in making healthcare decisions can be very beneficial because they might observe unusual changes in patient’s behavior or potential seizure episodes that may be missed otherwise.
Furthermore, it’s crucial for patients to understand the long-term effects of steroid therapy and the role of treatments that suppress the immune system. These treatments can expose them to a risk of infections or bring about general side effects.
