What is Paraneoplastic Limbic Encephalitis?
Paraneoplastic syndrome is a rare condition caused by the immune system’s reaction to cancer, often appearing without clear signs. It can result in different symptoms and complications. They could range from inflammation of the brain (encephalitis), Lambert-Eaton myasthenic syndrome (a disorder affecting the nerves and muscles), common belly problems tied to a specific type of cancer called neuroblastoma (including serious constipation and constant gas), spine disorders (myelopathies), movement irregularities, new-onset high blood sugar, bile flow problems within the liver (intrahepatic cholestasis), and several hormone-related symptoms.
A specific type of this syndrome, called paraneoplastic limbic encephalitis (LE), involves swelling and damage to brain areas involved in emotion, behavior, long-term memory, and smell. If you have this condition, you might experience memory issues, psychosis (severe mental disorder), mood and behavior problems, cognitive decline, strange movements, altered levels of alertness, dysautonomia (problems with the nervous system that control your heart rate, blood pressure, temperature control, etc.), and seizures. Involvement of the “amygdala,” a part of the brain, can cause emotional problems and aggressive behavior, while impact on the hypothalamus, another part of the brain, can affect hunger and sexual desire.
Let’s talk about what makes this condition happen. There are two main categories of bodies that can cause paraneoplastic LE. The first includes antibodies that target the surfaces of cells or synaptic antigens (proteins that help neurons communicate). These reactions can bring about damage mediated by the immune system (the body’s defense against harmful substances). The second category targets antigens inside cells, especially those associated with cancer; these antibodies don’t directly cause the disease. Instead, damage is primarily brought about by cell-mediated toxicity, a process in which the immune system targets cells for destruction. This second group is more frequently associated with paraneoplastic syndromes.
The most appropriate treatment for paraneoplastic LE is to treat the underlying cancer if it can be found. If no cancer is found, doctors often continue looking for it while providing treatments – like immunotherapy – that help manage the symptoms of the syndrome.
What Causes Paraneoplastic Limbic Encephalitis?
Paraneoplastic LE, a type of neurological disorder, is usually caused by the presence of cancer in the body. Here’s what happens: our body generates antibodies to fight cancer, but sometimes these antibodies mistakenly target the body’s normal cells, leading to health complications including neurological complications.
It’s important to note that some antibodies are more often associated with a hidden, underlying cancer than others.
Some types of cancers are more likely to cause paraneoplastic LE. A common example is small cell lung cancer (SCLC).
Researchers have identified some key antibodies that are often found in patients with paraneoplastic LE. The list includes HU, Ma-1/2, Amphiphysin, and others, and they are frequently associated with certain types of cancers such as SCLC, testicular tumor, breast cancer, and thymoma.
While these antibodies are common indicators of paraneoplastic LE, it’s possible for some individuals not to show these markers. Plus, this condition can also be linked to solid tumors, whether they’re original or have spread from other parts of the body. Interestingly, this can happen even when the cancer is hidden and has yet to show symptoms.
In males around age 40, testicular tumors are the most common cause of paraneoplastic LE. However, overall, lung cancer is the most common cause.
But, not all occurrences of LE are caused by cancer. This condition can also show up in people with other autoimmune diseases like Type 1 diabetes, and systemic sclerosis, or infections.
Risk Factors and Frequency for Paraneoplastic Limbic Encephalitis
Autoimmune encephalitis, which includes a subtype known as paraneoplastic LE, is becoming more common. Paraneoplastic LE is a rare condition but it’s important to consider it as a possible reason for changes in mental status in young people, including children. In fact, it occurs in fewer than 1 in 10,000 patients. It’s worth noting that among those affected by it, 50% may have lung cancer, 20% may have testicular tumors, and 8% might have a breast cancer diagnosis.
The age at which paraneoplastic LE begins can vary, depending on the type of cancer a person has. For instance, SCLC (small cell lung cancer) is usually seen in older people, while testicular cancer is more common in younger men.
- Autoimmune encephalitis is increasingly common, with paraneoplastic LE as a subtype.
- Paraneoplastic LE is rare but can cause changes in mental status in young people, including children.
- It occurs in less than 1 in 10,000 patients.
- Half of the patients with this condition may have an underlying lung cancer, 20% may have testicular tumors, and 8% might have been diagnosed with breast cancer.
- The age of onset varies depending on the type of underlying cancer. For example, SCLC is more common in older people, while testicular cancer usually affects younger men.
Signs and Symptoms of Paraneoplastic Limbic Encephalitis
Limbic Encephalitis (LE), which includes a subtype related to cancer, could show various symptoms based on the specific antibodies at play and the areas of the brain affected. This condition usually appears suddenly or rapidly and is characterized by a sudden development of various mental and neurological symptoms.
Key areas in a patient’s medical history that need closer examination include:
- New psychiatric symptoms like the onset of mental delusion. These could include changes in personality, episodes of depression or mania, delusions, hallucinations, or catatonia. It’s important to distinguish these symptoms from primary mental conditions because they’re often confused with them. This is especially true for patients with a type of LE caused by anti-NMDA antibodies.
- Onset of seizures, particularly those that are resistant to treatment. These usually signal involvement of the medial temporal lobe, the area of the brain most susceptible to causing seizures. Different types of LE may cause different seizure characteristics and EEG patterns. For example, facial-brachial dystonic seizures indicate a type of encephalitis caused by anti-LGI1 antibodies, while the extreme delta brush EEG pattern is often seen in cases of LE caused by anti-NMDAR.
- Movement disorders, primarily in younger patients, like orofacial dyskinesia, often indicate Anti-NMDAR LE. Morvan syndrome is common in patients with Anti-CASPR2 LE.
- Cognitive impairment is a consistent feature of paraneoplastic LE.
- Sleep disorders such as insomnia, REM sleep behavioral disorders, periodic sleep movements, oversleeping and inconsistent sleep are frequently encountered but often underestimated aspects of this condition.
Often, LE is diagnosed before the underlying cancer is detected and it’s sometimes mistaken for issues related to chemotherapy. So, when suspected of this syndrome, doctors must carry out a thorough medical history and physical examination to identify the underlying cancer. Cognitive function can be assessed using tools such as the Mini-Mental State Examination, clock test or assessment of daily life activities. In some cases, LE might be part of a larger condition affecting the limbic system, brain stem, and spinal cord.
Testing for Paraneoplastic Limbic Encephalitis
If doctors think that you might have a condition called paraneoplastic LE, they will perform various tests to confirm this. The first of these is a blood test, particularly checking for the presence of certain antibodies, such as anti-Hu, anti-Ta, anti-Ma, anti-GABA B receptor, and anti-NMDA receptor antibodies. However, if these antibodies are not found, it does not necessarily mean that you do not have the disease.
A type of brain scan, called an MRI, can provide supporting evidence. This scan might show certain signals in various parts of the brain, including the temporal lobe, hippocampal areas, insula, amygdala, or cingulate gyrus. However, it’s worth noting that these MRI findings may sometimes only become noticeable after the first symptoms of the syndrome have already appeared.
Another test, called a lumbar puncture, should ideally not show up any cancer cells or signs of infection. Though, it might show signs of inflammation, such as increased white blood cell count or proteins, increased production of immune proteins (immunoglobulins), and distinct proteins called oligoclonal bands.
An electroencephalography (EEG), another type of brain scan, often shows sharp and slow waves. If other tests are not conclusive, a PET-CT scan may be done to identify any abnormal cellular activities within the limbic system, an important part of the brain related to memory and emotions.
Diagnosing paraneoplastic LE can be challenging as many patients don’t exhibit common signs of the disease. A study identified four criteria to diagnose this condition, such as matching symptoms, timing between cancer and neurological signs, absence of other oncological complications, and meeting at least one other criteria like inflammation in spinal fluid, abnormalities in the temporal lobe in an MRI, and signs of seizure activity in the temporal lobe seen in an EEG.
However, some patients may not meet all these criteria, in such cases, this condition can be confirmed through further examination of the nervous system. In addition, doctors can use other sets of criteria to help diagnose this syndrome. For example, the Graus and Saiz criteria include a sudden onset of seizure or confusion, evidence of neuropathology or radiological involvement of the limbic system, exclusion of other causes and identification of related tumor within five years of diagnosing the syndrome.
Treatment Options for Paraneoplastic Limbic Encephalitis
Managing the main cause, which is typically a tumor, is usually the first step in treating paraneoplastic limbic encephalitis (LE). This often leads to slow improvements in the symptoms, even if scans show that the condition is still present. The main treatments for the tumor include chemotherapy or surgery.
Alongside these treatments, your doctor might provide supportive care to manage your symptoms and improve your quality of life. They might also recommend a variety of other possible treatments, like high doses of corticosteroids, which are powerful anti-inflammation drugs, plasma exchange, a process that helps clean your blood, or high doses of immunoglobulin, which helps boost your immune system. Options can also include drugs that hinder your immune system from causing further harm, like azithromycin and rituximab. In some situations, particularly resilient cases linked to anti-NMDA receptors (a type of protein), a medication called Bortezomib may be considered.
Sometimes, a mix of these medications might be used depending on the specific situation. However, studies usually find that treating the main tumor is more effective than solely the symptoms management. Steroids, for example, might not always be effective.
During plasma exchange, the liquid part of your blood (plasma) is replaced with another solution, which could be either human albumin or fresh frozen plasma. But it’s important to know that there could be potential complications like low blood pressure, allergic reactions, mild anemia (low red blood cell count), hypocalcemia (low calcium levels), and problems related to the placement of the catheter for the procedure.
What else can Paraneoplastic Limbic Encephalitis be?
In cases of symptoms suggesting Paraneoplastic limbic encephalitis, a condition tied to cancer, doctors need to rule out other potential conditions. These may include:
- Infectious encephalitis, comprising of viral (specifically herpes simplex), fungal, and tuberculous infections.
- Systemic autoimmune diseases like systemic lupus and Behcet disease.
- Toxic-metabolic causes such as substance abuse and Wernicke encephalopathy.
- Rapidly progressive neurodegenerative disorders like Creutzfeld-Jakob disease.
- Neoplastic diseases, especially lymphoma.
- Neurological issues from chemotherapy or other significant medical diseases.
Doctors need to consider these conditions and conduct the necessary medical tests to make an accurate diagnosis.
What to expect with Paraneoplastic Limbic Encephalitis
It’s crucial to diagnose and treat malignant tumors, which are harmful, cancerous growths, as soon as possible. Doing so can improve the patient’s chances of getting better and speed up their recovery. However, different antibodies (a type of protein produced by the body’s immune system) present in the blood can affect the possible outcomes and speed of recovery.
Here are some of the antibodies and their respective effects:
- Patients with anti-Hu antibodies, typically those having multiple neurological symptoms, usually have a lesser chance of a positive outcome.
- Patients with anti-Ta antibodies, another type of antibodies, are also often associated with a poor recovery path.
- Individuals with no detectable antibodies in their blood generally have a better chance of recovering.
- Patients with anti-GABA B receptor antibodies, another immune system response, might respond better to medications that suppress the immune system compared to patients with anti-Hu antibodies.
Possible Complications When Diagnosed with Paraneoplastic Limbic Encephalitis
Attaining complete recovery of brain function in autoimmune encephalitis can be tricky at times. However, in the subtype of the disease linked to cancer, also known as paraneoplastic autoimmune encephalitis, symptoms frequently get better after the associated tumor is effectively treated with medicine or surgery.
Recovery from Paraneoplastic Limbic Encephalitis
After leaving the hospital, some patients may need to continue rehabilitation for a long time. In fact, certain patients may even require several months of ongoing rehabilitation.
Preventing Paraneoplastic Limbic Encephalitis
Paraneoplastic limbic encephalitis, or LE, is a condition that’s important to understand. It often shows up as many different behavioral and mental health symptoms, which can sometimes be confusing. This confusion can even lead doctors to mistakenly think it’s a mental health issue. This mix-up can cause a delay in getting the right treatment and can make the condition worse. So, if there are any changes in how your brain works or your mental health, it’s very important that both you and your doctors keep in mind the possibility of LE.
Education is key here and it also helps you become aware of activities that could potentially increase the chance of getting a tumor. These include things like smoking. Being proactive and avoiding these risk factors can help catch the condition early and improve your chances of getting better.
