What is PCD?

Email: Richard_Hopper@gse.harvard.edu

(Modified Dec.12/98)

What is Paraneoplastic Cerebellar Degeneration (PCD)?

A paraneoplastic syndrome is an autoimmune disease, similar to diseases such as Lupus, rheumatoid arthritis or psoraisis. A ‘neoplasm’ is a cancer, whereas a ‘paraneoplasm’ is an antibody produced by a patient’s own immune system to keep cancer at bay - sort of like nature’s chemotherapy. In most cases these cancer-fighting antibodies focus their attack on the cancer cells. A paraneoplastic syndrome occurs when a cancer victim produces antibodies that end up attacking not only the cancer, but also healthy cells. In rare instances the paraneoplastic antibodies attack the cerebellum, the area of the brain located at the lower back of the head, just above the brain stem and below the cerebral cortex. The cerebellum is responsible for all the wonderful things we take for granted: balance, swallowing, voice volume, fine motor coordination, eye movement, etc.

What happens to a person with PCD is that his/her own immune systems produce hostile antibodies which are transported through the circulatory system. These antibodies are found in blood plasma, but somehow make their way past the brain-blood barrier into the spinal fluid and "bathe" the cerebellum. The problem with PCD suffers is that the cancer antibodies attack the layer of cells in the cerebellum called the perkinje cells. Perkinje cells are the communicator cells for the cerebellum - sort of like transmitters of information to the cerebral cortex, the larger "thinking" part of the brain. The antibodies kill off perkinje cells, causing atrophy or degeneration of the cerebellum, thereby disturbing the communication path to the cerebral cortex. This cerebellar degeneration causes a host of symptoms which can vary from patient to patient, but which include ataxia (uncontrolled gait and loss of fine
motor coordination), dysarthria (slurred speech), dysphagia (difficulty swallowing), hypotonia (loss of muscle tone), nystagmus (repeated uncontrollable movement of the eyes), vomiting and vertigo (the two are not necessarily related, but can be), uncontrollable voice volume, Parkinson’s tremors and a variety of other physical symptoms. In some cases patients can also experience dementia, blindness, and memory loss. Patients generally exhibit a unique combination of these and other neurological symptoms.



What can be done to treat PCD?

The most important thing is to get a rapid diagnosis. PCD is most common in patients with lung, breast, ovarian, or lymphatic cancers. Some patients are diagnosed with PCD before locating their primary cancer. The syndrome can also appear well after tumor excision, chemotherapy, and radiation have already taken place. Some patients have great difficulty identifying the location of their cancer. These patients are said to have "occult" or hidden cancers that are hard to detect even after many scans, blood tests, and biopsies. PCD effects almost as many women as men, but is very slightly more common in males. There have been some reported cases where the symptoms have abated upon tumor excision, chemotherapy, radiation, etc. It is therefore important to locate the source of the cancer and work to eradicate it, if at all possible.

There are other diseases such at Kreutzfeld Jacob disease (related to the "mad cow" disease), Freidricks Ataxia, or cerebellar tumors which can also cause severe ataxia. It is therefore important to get a proper diagnosis through antibody testing. Until recently the antibody test was generally done on spinal fluid which is extracted through a lumbar puncture, and now diagnosis can be done with a simple blood test--speeding-up diagnosis and treatment.

In addition to treatment of the primary cancer, PCD patients can also undergo "plasmapheresis" a sort of blood dialysis in which the plasma is replaced with saline solution or other fluid in an effort to flush out the antibodies that are causing the harm. This blood cleansing technique can ease the symptoms of PCD, and can sometimes arrest any progression of neurological dysfunction so it is important that patients avail themselves of this treatment as soon as possible.

Some patients respond to steroids such as Cortisone, Prednisone, or Prelone. Some doctors may wish to try using a steroid-stimulating hormone called ACTH as an alternative. There is also the possibility of treatment with IVIG, or intravenous gamma globulin, as well as Cytoxin, a chemotherapy drug called cyclophosphamide.



How else might we combat the neurological deficits of PCD?

Physical therapy, speech therapy, and occupational therapy can help patients to recover some function. Another effective technique is aquatherapy. Aquatherapy is assisted "walking" in a pool with the help of therapists and flotation devices. The water helps helps patients with severe ataxia to feel a greater sense of freedom and ease of motion. Some aquatherapy centers have open hours in which patients can use the specially equipped pool with friends or family members who have received some basic training in appropriate techniques.

PCD patients are also hypercoagulopathic, meaning that their blood clots easily, presenting a risk of pulmonary embolisms and the like. Physical therapy important on this basis alone: regular exercise will help the patient lessen his/her risk of blood clots by staying as active as possible; aquatherapy can be one way to do that.



What sort of research is being done on PCD?

Much of the research on PCD is limited, as it is an extremely rare disorder. The primary concern of physicians is understandably treatment of the underlying cancer. Many physicians hold the belief that Paraneoplastic Cerebellar Degeneration is an untreatable sign of imminent death and therefore find it to be an unfruitful area for research.
This is an unfortunate attitude, since understanding the antibodies related to paraneoplastic syndromes might actually help us to better fight cancer. If paraneoplastic antibodies are meant to kill cancer cells, then why not learn to harness their power to produce a controlled assault on cancer cells rather than brain cells, thereby creating a new therapy to fight cancer? One physician concerned with just this topic is Dr. Jerome Posner of Memorial Sloan Kettering Cancer Center in New York City (Neuro-Oncology).

Some hospitals doing research on PCD are: