What are Paraneoplastic Neurological Syndromes?

Bandeau PNS

Paraneoplastic neurologic syndromes (PNS) are a group of conditions that affect the nervous system (brain, spinal cord, nerves and/or muscles) in patients with cancer. The term "paraneoplastic" means that the neurological syndrome is not caused by the tumor itself, but by the immunological reactions that the tumor produces. It is believed that the body’s normal immunological system interprets the tumor as an invasion. When this occurs, the immunological system mounts an immune response, utilizing antibodies and lymphocytes to fight the tumor. The end result is that the patient’s own immune system can cause collateral damage to the nervous system, which can sometimes be severe.


SYMPTOMS

Symptoms of PNS can develop rapidly, over the course of a few days or weeks, or they may develop slowly. In about 60% of patients with PNS, the symptoms occur before the diagnosis of cancer is made. For about 40% of patients already known to have cancer, the initial symptoms of PNS may appear to resemble other complications of cancer. 

Broadly speaking, paraneoplastic neurologic syndromes (PNS) are categorized by the area of the nervous system that is principally affected; the type of symptoms manifested; or the type of immunological response.

Signs and symptoms vary depending on the body part being injured, and may include:

¤ Difficulty walking

¤ Difficulty maintaining balance

¤ Loss of muscle coordination

¤ Loss of muscle tone or weakness

¤ Loss of fine motor skills, such as picking up objects

¤ Difficulty swallowing

¤ Slurred speech or stuttering

¤ Memory loss and other thinking (cognitive) impairment

¤ Vision problems

¤ Sleep disturbances

¤ Seizures

¤ Hallucinations

¤ Unusual involuntary movement

The signs and symptoms of paraneoplastic syndromes of the nervous system are similar to those of many conditions, including cancer, cancer complications and even some cancer treatments. But if you have any signs or symptoms suggesting a paraneoplastic syndrome, see your doctor as soon as possible. Early diagnosis and appropriate care can be extremely important.


DIAGNOSIS

In the majority of patients with PNS, the tumor is localized to one site without having metastasized (spread) to distant parts of the body. Usually, the size of the tumor at this stage is small. For this reason, it can be very difficult to find the tumor. The combination of symptoms, lab studies, and the paraneoplastic antibodies that may be found in the blood and/or spinal fluid, helps to make the diagnosis of a paraneoplastic neurologic syndrome. The specific antibodies, if detected, can help focus the search for the tumor to one or a few organs.

Patients with a suspected paraneoplastic syndrome should receive a complete panel of laboratory studies, including blood, urine, and CSF. In addition, the use of an MRI, EEG (electroencephalogram), and EMG (electromyogram) can further display abnormalities that help to diagnose PNS.

It should be understood that there are three types of antibodies that associate with neurological syndromes. There is one type that associates with specific neurological syndromes but not with cancer. Another type includes antibodies that almost always associate with the presence of cancer. The third type of antibodies includes those that may occur with or without cancer. Therefore, it is important to understand the relative value of each category of antibodies in suggesting that the neurological syndrome is paraneoplastic or not.

Once a diagnosis of or a suspicion of a paraneoplastic syndrome is apparent, other tests are used to identify the location and type of tumor. These include CT scanning (usually of the chest, abdomen, and pelvis), mammography, ultrasound, PET scan, and blood tests for specific tumor markers (such as the CA125, for ovarian cancer). The type of paraneoplastic antibody often helps to direct the search of the tumor to a specific organ (for example, most patients with Hu antibodies have lung cancer).


TREATMENT

Except for a few PNS of the peripheral nerves and neuromuscular junction, there is no general consensus yet for treating many of these syndromes. However, there are several principles in which most investigators agree upon:

The tumor is the main trigger for all PNS. Therefore, in general, prompt identification and treatment of the tumor is essential. Thus, the first therapeutic option is usually surgery, radiation, or chemotherapy (singly or in combination).

Because many PNS are immune-mediated, immunotherapy should be considered based on the type of antibody involved. PNS in which the antibody attacks the cell-surface of neurons respond better to immunotherapies than PNS in which the antibodies react with proteins that are inside the neurons (or intracellular antigens). The usage, timing, and type of immunotherapy will vary depending on the specific type of PNS and/or whether the tumor is being treated at the same time.

In a patient who has been in remission from a cancer treated within the prior five years, symptoms that appear to be a PNS imply a high likelihood of tumor recurrence. Repeat cancer screening should be undertaken. Similarly, a relapse or sudden worsening of neurological symptoms in a patient known to have a PNS, but whose cancer was thought to be in remission, should raise a high index of suspicion for cancer recurrence.