What is Paraneoplastic Cerebellar Degeneration?
Paraneoplastic syndromes are rare symptoms that happen in some patients with certain kinds of cancer. These symptoms are not caused by the cancer spreading, but rather by hormones, active proteins or molecules known as peptides that the cancer cells produce. Examples of these hormones include the antidiuretic hormone (ADH), which helps the body manage the water balance, and the parathyroid hormone-related peptide (PTHrP), which is involved in calcium balance. Additionally, paraneoplastic syndromes can also occur due to an immune reaction. This is when the body’s immune system produces antibodies or cells that attack not just the cancer, but also healthy cells. Syndromes like Lambert Eaton syndrome, paraneoplastic cerebellar degeneration, and limbic encephalitis are caused by such immune reactions.
Paraneoplastic syndromes can also arise due to cytokines, which are proteins that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection, and trauma. These syndromes can be seen in multiple types of cancer, including breast cancer, small cell lung cancer, Hodgkin lymphoma, mesothelioma and kidney cancer, among others.
It’s essential for doctors to recognize these syndromes because they can be the first signs of an underlying cancer. Failing to identify them may lead to delayed cancer diagnosis and poorer outcomes for the patient. These syndromes are not related to the cancer spreading, the symptoms of metastatic disease (cancer that has spread to other parts of the body), or side effects from treatment.
There is a subset of paraneoplastic syndromes that affects the nervous system. These syndromes, known as paraneoplastic neurological syndromes (PNS), are caused by antibodies known as onconeural antibodies. These antibodies are produced by the immune system to fight the cancer but can also attack different parts of the nervous system, leading to various neurological symptoms.
One of the more commonly seen paraneoplastic neurological syndromes is paraneoplastic cerebellar degeneration (PCD). This condition is caused by an immune-mediated injury to cells in a part of the brain called the cerebellum, which coordinates movement. PCD is associated with multiple types of cancer, but most commonly with breast and pelvic cancers. It can also occur in patients with Hodgkin lymphoma, stomach cancer, prostate cancer, and small cell lung cancer. PCD can get worse quickly over weeks and can result in severe disability.
What Causes Paraneoplastic Cerebellar Degeneration?
Paraneoplastic cerebellar degeneration occurs when your body’s immune system produces specific antibodies, called onconeural antibodies, in response to a cancerous tumor. These onconeural antibodies mistakenly attack some of the brain’s cells, specifically the Purkinje cells in the cerebellum part of your brain. This can lead to sudden or gradually developing problems with your cerebellum’s functions.
Risk Factors and Frequency for Paraneoplastic Cerebellar Degeneration
Paraneoplastic cerebellar degeneration is a particularly uncommon condition, believed to affect less than 1% of individuals who have cancer. Because it is so rare, we don’t have a lot of specific data about it. However, it is thought to occur more often in women. This belief comes from the fact that many patients with this condition have high levels of a certain substance called anti-yo antibodies, which is primarily associated with breast and gynecological cancers.
Signs and Symptoms of Paraneoplastic Cerebellar Degeneration
Paraneoplastic cerebellar degeneration is a condition that often begins slowly with mild symptoms such as an unsteady walk, blurry or double vision, and difficulty with detailed hand movements. Over time, these symptoms typically become worse and patients might also experience issues with balance and coordination of their limbs and torso. Some people may also have problems linked to the brain stem, resulting in uncontrolled eye movements, difficulty speaking, and trouble swallowing.
In certain cases, the condition can progress slowly over weeks or months, but in other cases, the symptoms might get worse quickly over just a few days. There are instances where patients might first experience symptoms similar to a mild flu – low-grade fever, general discomfort, and nausea or vomiting – before they begin to have movement related issues. It’s also worth noting that symptoms related to the brain and nervous system can emerge months or even years before a cancer diagnosis.
In people with a personal or family history of cancer or autoimmune disease who start showing signs of balance and coordination problems, doctors will be on the lookout for paraneoplastic cerebellar degeneration since these factors can increase one’s likelihood of developing the condition.
- Starts with mild symptoms such as unsteady walk, blurry or double vision, difficulty with detailed hand movements
- Progresses to problems with balance and coordination of limbs and torso
- Potential brain stem related problems like uncontrolled eye movement, speech difficulty, swallowing difficulty
- Symptoms can get worse slowly over weeks or months, but can also progress quickly over days
- Patient might first experience flu-like symptoms before movement related issues
- Cerebellar symptoms can emerge months to years before a cancer diagnosis
- Higher risk in people with personal or family history of cancer or autoimmune disease
Testing for Paraneoplastic Cerebellar Degeneration
If your doctor suspects that you might have a condition known as paraneoplastic cerebellar degeneration (PCD), one of the first things they’ll do is schedule you for brain imaging. This helps your doctor see what’s going on inside your brain and rule out other conditions that could be causing your symptoms, such as brain tumors or strokes. The kind of brain imaging you’ll receive may include computed tomography scans (CT scans), which are a type of X-ray that can show detailed images of your brain, and magnetic resonance imaging (MRI), which uses magnetic fields and radio waves to create pictures of the inside of your brain.
A particular type of brain imaging called a Fluorodeoxyglucose-positron emission tomography scan (FDG-PET scan) can show increased activity in the brain which is an early sign of the disease. Also, the use of positron emission tomography-computed tomography (PET/CT) is vital to identify any underlying cancer, which is usually the root cause of PCD.
Another test your doctor might perform is a cerebrospinal fluid (CSF) analysis, which involves taking a small sample of the fluid that surrounds your brain and spinal cord. This fluid can show signs of inflammation or other abnormalities. However, the changes seen with CSF in PCD aren’t specific and could be the result of different conditions, so your doctor will likely need to do additional tests to confirm a diagnosis.
Your doctor will also want to test for substances known as paraneoplastic antibodies. These are proteins that your immune system produces in reaction to cancer. Multiple types of these antibodies can occur in PCD, and each of them is typically associated with a specific type of cancer. For example, Anti-Yo antibodies often appear in people who have breast cancer or ovarian cancer, while Anti-Hu antibodies might indicate lung cancer, prostate cancer, or testicular cancer.
To confirm a diagnosis of PCD, a patient must exhibit severe cerebellar symptoms (issues related to balance and limb coordination) for less than 12 weeks, have a normal brain MRI, and have a moderate disability, as measured by a medical tool called the Modified Rankin Scale (MRS). There must be clinical evidence of both limb and trunk balance problems, along with a diagnosis of cancer within five years of the onset of symptoms. If your doctor identifies specific paraneoplastic antibodies in your blood, they can confirm a PCD diagnosis.
If all classic symptoms are present, but the antibodies aren’t detected, your doctor might still think you likely have PCD. In such a case, you would need further scans to look for any present cancer, and your blood would be tested again for any paraneoplastic antibodies. If there’s no identifiable cancer causing your symptoms but the suspicion of PCD is high, your doctor will probably recommend regular check-ups to keep an eye on any changes in your health.
Treatment Options for Paraneoplastic Cerebellar Degeneration
Paraneoplastic cerebellar degeneration (or PCD) is managed primarily by identifying and treating any underlying cancer as soon as possible. In addition to targeting the underlying cancer, doctors may recommend treatments to help manage the immune system’s response. Some of these treatments could include systemic corticosteroids, which are medications that reduce inflammation or swelling; intravenous immunoglobulins, which are antibodies given through a vein to help boost the immune system; plasma exchange, a procedure in which liquid part of the blood (or plasma) is removed, treated, and then returned to the body; and medications like cyclophosphamide, tacrolimus, or rituximab, that can help regulate the activity of the immune system.
Patients who received treatment for their underlying cancer generally saw their conditions improve, whether or not they also received the above mentioned therapies to manage the immune system’s response. But, it’s important to note that every patient’s response to these treatments can vary.
As of now, there haven’t been any randomized controlled clinical trials, which are considered to be the highest standard of scientific research, specifically for treating PCD. The rarity of this disease could be a possible reason why these trails have not happened so far.
What else can Paraneoplastic Cerebellar Degeneration be?
When dealing with a condition like central ataxia (a type of imbalance), it’s necessary for doctors to consider and eliminate other, more common, causes. These might include brain lesions (abnormal tissue areas) or damage to the blood vessels in parts of the brain that help with balance and coordination.
Similarly, they must be able to tell the difference between paraneoplastic cerebellar degeneration (a rare neurological disorder that often occurs in the presence of a cancerous tumor) and other brain conditions that may look similar.
These could encompass:
- Demyelinating disorders, such as multiple sclerosis (a condition where the body’s immune system attacks the brain’s nerves)
- Autoimmune disorders including glutamic-acid-decarboxylase-associated cerebellar degeneration, sarcoidosis, systemic lupus erythematosus, and Behcet disease (conditions where your immune system fights your own body, often causing inflammation)
- Unusual brain infections: Creutzfeldt-Jakob disease (rare, fatal brain disorder), progressive multifocal leukoencephalopathy (rare infection that causes inflammation and damage to the brain)
- Metabolic disorders: vitamin B12 deficiency (a lack of a crucial nutrient), alcohol-related Wernicke encephalopathy (brain damage due to alcohol abuse), celiac disease (digestive disorder provoked by eating gluten)
What to expect with Paraneoplastic Cerebellar Degeneration
Paraneoplastic cerebellar degeneration, a condition that affects the brain, often carries a poor prognosis. People with this condition typically experience worsening symptoms over a span of weeks to months. Most people’s symptoms stabilize after about six months from when they first appear. However, by this point, many people are considerably disabled from the disease, often needing a wheelchair for mobility or becoming bed-bound.
Research has shown that patients with specific types of antibodies known as anti-yo and anti-Hu antibodies often have more severe symptoms. These antibodies also make the disease more challenging to treat. Consequently, this group of patients generally has a lower overall survival rate compared to patients with other types of antibodies, specifically anti-Tr antibodies and anti-Ri-antibodies.
Possible Complications When Diagnosed with Paraneoplastic Cerebellar Degeneration
Not recognizing and treating paraneoplastic cerebellar degeneration quickly enough can lead to serious disability. Damage to a part of the brain known as the cerebellum can’t be reversed once the disease gets to a severe stage, often referred to as the burnout state. Also, if the cancer that’s causing the cerebellar degeneration isn’t found and treated soon enough, it can progress and cause serious illness or potentially even death.
- Delay in treating paraneoplastic cerebellar degeneration can cause severe disability
- Damage to the cerebellum becomes irreversible at the burnout stage of the disease
- Late discovery and treatment of the underlying cancer can lead to it progressing
- Progression of the cancer can cause serious illness or death
Preventing Paraneoplastic Cerebellar Degeneration
Diseases affecting the cerebellum, an area of the brain, can lead to problems with walking, frequent falls, and potentially cause serious injuries and disabilities. One of these conditions, called Pediatric Cerebellar Disease (PCD), is quite rare and there currently aren’t any widely-accepted treatment guidelines. There aren’t any known ways to prevent this condition, and the results of treatment vary greatly from person to person.
However, like with any condition that impacts the brain or nervous system, it’s crucial to take note of symptoms early on and seek medical help promptly. This will aid in a faster diagnosis and potentially lead to better end results in terms of managing the condition.
