Patients receiving chemotherapy for various types of cancer have long complained about neurological side effects they believed were related to the chemo treatments themselves. These symptoms included memory loss, headaches, difficulty concentrating, word-finding problems, mental fatigue and even learning disabilities. Until recently, these complaints were often dismissed as being unrelated to the chemotherapy. Doctors felt they were due to depression about being sick, having cancer, eating poorly, being stressed out, disturbed daily schedules or even "ICU syndrome." However, emerging information is documenting the full scope of the adverse cognitive impact chemotherapy has on the brain. 

In some studies, upwards of 80% of patients treated with chemotherapy reported that they suffer from some form of impaired cognition. This has come to be referred to as "Chemo Brain." These (usually delayed) consequences can compromise the quality of life in a significant portion of cancer survivors. Consistent with these observations is new research demonstrating that treatment with a single chemotherapeutic agent, 5-fluorouracil (5-FU), even when used by itself is able to cause a syndrome of delayed degeneration within the nervous system. 5FU is a widely prescribed chemo drug frequently used in combination with other agents for the treatment of many cancers including cancers of the colon, rectum, breast, stomach, pancreas, ovary and bladder.

Little is known about the brain-related side effects of chemotherapy. Why one patient may be affected and not another is not fully understood. Questions remain including whether these effects are related to dosing regimens, combinations, relationship to specific cancer types, prior brain damage, breakdown of the blood-brain barrier or inflammation. Researchers at the University of Rochester and Harvard Medical School demonstrated in mice studies that administration of 5-FU caused both acute central nervous system damage as well as damage that worsened over time. They discovered this damage was not self repairing. One of the manifestations was an impairment in the rate at which the animals were able to process information.

In addition to toxicity to the dividing cells within the brain, 5-FU damaged cells called oligodendrocytes. They are brain cells responsible for producing the myelin sheath of neurons. This is like the plastic coating on a lamp cord. When damaged, the wires short out and the lamp doesn't work. The same thing happens in the brain. Messages between nerve cells can't be transmitted.

In other studies, Mark Noble, PhD, exposed several different types of healthy brain cells as well as a variety of human cancer cell lines to three commonly used chemotherapy drugs - carmustine, cisplatin and cytosine arabinoside - at levels characteristically experienced in patients. These drugs are used to treat certain types of breast cancer, lung cancer, colon cancer, Hodgkin and non-Hodgkin lymphoma, leukemia and brain tumors.

Cancer treatments are partially based on the assumption that the drugs are less toxic to normal cells than to cancer cells. Normal cells also usually recover more rapidly from chemo than do cancerous cell types. It thus came as a big surprise that these drugs were far more toxic to healthy brain cells than to the cancer cells. Worse still, these drugs were found to be toxic to both non-dividing cells, dividing stem cells and precursors at even very low concentrations. Because neurogenesis (formation of new nerve cells) occurs in the hippocampus - a major hub in memory function - and it is interrupted by these drugs, this locus might be one area where the cognitive side effects of chemotherapy arise.

These findings provide some scientific rationale for the cognitive symptoms many patients receiving chemotherapy describe. However, because chemotherapy is a cornerstone of cancer treatment, no one should forego this potentially life-saving therapy. It should be discussed with your doctor ahead of time and mental function should be monitored during and after therapy. This information should also stimulate the development of strategies to protect brain cells from these drugs.