Central Neurotoxicity, Memory Loss, and Their Relationship to Chemotherapy

Neurotoxicity

Related: Confusion, Cognitive Problems, Memory Problems, and Seizures

Description: The body's nervous system is divided into two systems, the central nervous system and the peripheral nervous system. The central nervous system is also divided into two major parts the brain and spinal cord. Different parts of the brain control different functions. Cancer treatments, including chemotherapy, can produce certain effects on these areas of the brain, including impaired cognitive skills, chemo-induced seizures, and memory loss.

• The cerebral cortex is a sheet of tissue that makes up the outer layer of the brain. This area of the brain is responsible for thought, voluntary movement, language, reasoning, perception.
• The cerebellum is located behind the brain stem and controls functions of movement, balance and posture.
• The brain stem is a general term for the area of the brain between the thalamus and spinal cord. Structures within the brain stem are responsible for the most basic functions of life such as breathing, heart rate and blood pressure.
• The hypothalamus is located at the base of the brain and is only the size of a pea. One important function of the hypothalamus is the control of body temperature. The hypothalamus acts like a "thermostat" by sensing changes in body temperature and then sending out signals to adjust the temperature.
• The thalamus receives sensory information and relays this information to the cerebral cortex. The cerebral cortex also sends information to the thalamus, which then transmits this information to other areas of the brain and spinal cord.
• The limbic system is a group of structures that are important for controlling the emotional response to a given situation.
• The hippocampus is one part of the limbic system that is important for memory and learning.
• The basal ganglia are a group of structures that are important in coordinating movement.
• The midbrain functions to help control vision, hearing, eye movement and body movement.

What is Central Neurotoxicity?

The above is a very basic description of the brain and its functions. We are describing central neurotoxicity as side effects of cancer therapy that interfere with the functions of the central nervous system. Particularly focusing on chemotherapy brain effects of confusion, cognitive problems, memory problems and memory loss, seizures, balance and movement.

Central neurotoxicity can also be caused by a variety of conditions including disease, infection, or injury. If there is a question regarding the cause of the neurological symptoms further evaluation may be needed. Below are listed some common exams that may be used to evaluate the central nervous system.

Common Neurologic Examinations:

• Physical Examination - During a physical examination by the health care professional a neurologic examination may be performed. This can be very brief or more detailed depending on concerns and findings. In general the physical examination is divided into 4 parts; cranial nerve assessment, motor function assessment, sensory function assessment, and assessment of reflexes.
• Cranial nerve assessment: There are 12 cranial nerves and these arise from the brain. Each nerve has its own function and the assessment of the nerves is done by evaluating each function. For example, testing the gag reflex with the tongue depressor is testing the 9th and 10th cranial nerves.
• Motor function assessment is checking a person's gait, muscle strength and coordination. The test where a person is asked to touch their nose then the finger of the examiner, with eyes open then with eyes closed is an example of how coordination may be evaluated.
• Sensory function assessment is checking sensations such as pain, temperature, position sense, crude and fine touch along certain pathways. A test that may be used to evaluate this is asking the person to close their eyes and then using a wisp of cotton, ask the person if they can feel the cotton brushed on the skin.
• Testing reflexes helps to assess the status of the central nervous system, this indicates whether the pathway from the spinal cord to the area stimulated and back is intact. The briskness of response is evaluated.
• Computerized Tomography (CT) Scan - A CT scan may be done of your brain, or another part of your body, if your healthcare provider suggests. This exam is more specific than plain x-rays, as a computer takes pictures, from different angles, to show a cross-sectional view of your brain, or other organs. How it works:
• As you lie on a movable table, a scanner inside of a machine moves around you. X-rays are taken at different angles, as the computer records the pictures. The computer then puts the pictures in a specific order, so that the specialist can interpret the findings.
• Sometimes, you may be given a contrast (dye) solution, either taken by mouth (oral) or injected into a large vein (IV). This helps to improve the picture, and show any abnormalities as the dye passes through your body. Your doctor may want you to drink oral contrast if he or she wants to examine your abdomen or pelvis at the same time another part of your body is examined.
• You may be required to fast (not eat) after midnight the day of the exam, if your abdomen is to be examined. Your healthcare provider will give specific instructions to you.
• Electroencephalogram (EEG) - An EEG is a procedure that records your brain waves during certain activities. The procedure may take only 45 minutes to an hour, and tests your brain waves while you are asleep, awake, or concentrating on certain actions. It is sometimes used during anesthesia. It may be a valuable tool to diagnose your condition. Your healthcare provider may order this test if he or she thinks you may have:
• An infection in your brain
• A seizure disorder
• Changes in your mental status
• A Brain tumor
• Electromyography (EMG) - This test may be ordered by your doctor if you have been experiencing nerve pain, or muscle weakness. An EMG will show the conduction of the nerves and muscles, usually in your arms or legs. An EMG may be ordered if:
• You have a neuromuscular disease, such as Myasthenia Gravis, or Amyotrophic Lateral Sclerosis (ALS, or Lou Gering's disease)
• You have pain, numbness or tingling in your extremities - perhaps as a result of carpal tunnel syndrome, or a disease, such as amyloidosis
• Certain nerve injuries from sports-related activities (Burner's disease)
• Magnetic Resonance Imaging (MRI) - While x-rays are very good at looking at bones and solid structures, an MRI looks, very specifically, at the soft organs, cartilage, eyes and tissues of your body. You may receive an MRI:
• Of the spine - if you are having severe back pain, pain that goes down your leg, and your healthcare provider is worried about the stability of your spine. You may have this done if you have cancer that has gone to your bones (metastasized), or if there is a tumor on your spine. You may also have thinning of the bones (osteoporosis), and you are at risk for breaking a bone or fracturing one or more of the bones in the vertebral column, called vertebrae.
• There are 33 vertebrae, each joined by ligaments. Damage to one or more of these bones may damage the spinal cord, and cause serious problems.
• Of the brain - to look at the brain tissue, to check for cancer, or cancer that may have spread, or if swelling is present. This is also important if your doctor thinks you may have an infection in your eyes or head.
• Of a joint - if you have had injury (from playing sports, walking, or falling down), and you have a lot of pain. This will show if any ligaments or cartilage have been damaged in your body. You may receive an MRI of the shoulder, knee, or any other joints in your body.
• There is no special preparation in many cases, but you should not wear metal to the exam. Avoid all metal inside the MRI machine, including:
• Metal snaps on clothing
• Zippers
• Jewelry
• Watches.
• If you have a pacemaker, metal plates in your body from surgery, or any other type of metal in your body, notify your healthcare provider.
• There is a loud "whirring" noise associated with the MRI machine, which many people find upsetting. While you are undergoing the procedure:
• It helps to wear earplugs or headphones to block out the noise of the machine.
• If you are anxious, close your eyes and take slow, deep, even breaths. Think of things that have relaxed you in the past.
• This procedure takes about 1/2 hour to 1 hour to complete.

Cognitive Problems

Description: "Cognitive development" occurs when a person develops the ability to think in a complex manner. Cognition is best described as a higher level of functioning. Cognition is important for:

• Language - the ability to be able to speak correctly, form words, and think through problems at a "higher" level of functioning.
• Emotional development - the ability to handle stressful situations, concentrate and make decisions appropriately
• Moral development- knowing right from wrong
• Social development - learning how to interact with others

Cognitive problems are those related to memory, concentration and a state of alertness. If you are having cognitive problems, you may be unable to solve simple dilemmas, count your change when you return from the grocery store, or tell right from wrong. You may have trouble focusing your thoughts on certain activities.

Symptoms:

• You may be unable to remember things, and have difficulty concentrating and following directions. You may feel "disoriented".
• You forget to do things that you normally would not forget to do (go grocery shopping, do the laundry).
• You may have trouble learning new things, or you may forget how to do things that you have done over and over again.
• You may feel agitated, or "jumpy", with abrupt changes in your mood and behavior (mood swings). You may feel depressed.
• You may have trouble handling money, or may forget what happened in a day.
• If there is an underlying physical cause of your cognitive problems, you may develop confusion. With mild confusion, you may not notice much change in your behavior. With severe confusion, you still may not notice that your behavior has changed, or is inappropriate. Your family and friends may notice the difference.

Many factors can contribute to the experience of cognitive problems. It is important to treat conditions contributing to cognitive problems, whether it is due to medications, illness, or your disease. Changes in cognition may last minutes, days, or longer.

Cancer Therapies Associated with Cognitive Problems:

• Chemotherapy medications that contribute to confusion such as hydroxyurea, high dose ifosfamide or methotrexate.
• Biologic therapies such as: high dose interleukin-2, interferon.

Physical Conditions That Contribute to Cognitive Problems:

• Stress and anxiety - These affect your memory, concentration and your ability to learn things. With high levels of stress and anxiety, you may be unable to focus on important tasks, and perform your usual activities. It may be hard for you to concentrate, and function normally.
• Fatigue, or extreme tiredness- can cause problems with memory and concentration.
• Electrolyte disorders - such as high blood calcium levels (hypercalcemia); high or low blood sodium levels (hypernatremia or hyponatremia). Slightly elevated blood calcium levels may lead to a state of disorientation, or inability to concentrate. High blood calcium levels may lead to confusion.
• Dehydration- may lead to inability to concentrate.
• Heart problems- (your heart isn't pumping properly, causing less oxygen to travel to your tissues). This may make you confused, or disoriented
• Anemia- or low blood hemoglobin concentration may cause impaired memory. Hemoglobin carries oxygen to your tissues. With less oxygen, it becomes harder to concentrate.
• A severe infection in your blood or central nervous system, may lead to a state when you are not as alert.
• Brain cancer, or cancer cells in your central nervous system (such as lymphoma, or cancer that has spread to the brain), may lead to a confused state, or difficulty thinking.
• Endocrine or metabolic disorders - such as extremely high or low blood sugar levels in those with diabetes, or thyroid disorders

Other medications that contribute to cognitive problems are used to treat:

• Pain.
• Heart problems.
• Stomach upset.
• Infections - Infection in the blood, which produces a fever, may cause you to be less alert, or even confused.
• Alcohol use or abuse- the use of alcohol, and withdrawal from alcohol.

Symptom Management:

Things you can do (the patient):

• Changes in cognition should be evaluated if it begins to affect your lifestyle. If you have any changes in memory, thinking, or concentration, discuss them with your healthcare provider

If you notice that you are starting to have difficulty with details and memory:

• Keep one note pad or diary in your possession at all times. Write down everything that is important to you. Keep lists of things you need to do in the same place.
• Keep a detailed calendar of events at all times.
• With the help of friends or family members, try to keep a timeline, as to when you started having difficulty remembering things, and doing certain activities.
• Take a friend or family member with you to all your doctor's appointments. It helps to have someone else present, to clarify questions during and after the visit.
• Ask your family and friends for help. If you need assistance with certain activities, such as cooking, cleaning, and the laundry. It is okay to ask, especially if they have offered. You may need assistance in the home form awhile.
• Try to form a daily routine, and stick to it. Inform family and friends of your routine.
• If you are having trouble remembering names, ask a friend or family member, and repeat the name a few times. Although you may feel embarrassed, it is okay to admit that you are "forgetful", and ask the person for their name. (Ex: "Hi, I am ______. I know we have met before, but I am a little forgetful. What is your name again?")
• Keep your mind busy with crossword puzzles, or reading. Exercise your brain, just as you are supposed to exercise your body!
• If you take any new medications, or change your diet, make sure you tell all your healthcare providers. Certain medications may interact with one another, causing you to be confused.

Sometimes you may feel confused if you are having problems with cognition. If you are experiencing periods of confusion:

• Notify your healthcare provider if this is a new problem for you. If there is a medication or physical illness that is causing your change in thinking and memory, they may be able to help.
• Do not be left alone by yourself. It is important to have friends or family members around to assist you, when you need it.
• Make sure to keep familiar people around, to help re-orient you to your surroundings.
• Make sure you keep your environment quiet. Eliminate background TV or radio noises. Try to focus your attention while performing your tasks - and take your time doing so.
• If you are upset or agitated, your healthcare provider may prescribe certain medications to relax you.
• Wearing hearing aids and glasses may help to decrease the amount of confusion you are experiencing.
• Hallucinations may occur with certain causes of confusion or memory impairment, especially if it is related to medications. Discuss what you are experiencing. It helps to have someone around to explain or make "sense" of your possible visions and illusions. The visions that you see are very real to you, and may cause you to be frightened.
• If your hallucinations were an unfavorable side effect of medications, record the suspected name of the drug to tell other healthcare providers in the future.
• Pneumonia and the flu can cause infections in adults, which may cause you to have problems with cognition. If you are over the age of 65 years, or have an altered immune system due to chemotherapy, chronic disease or steroid use, the Centers for Disease Control (CDC) recommends that you receive a flu vaccine every year, and a pneumonia vaccine every 5 years. Discuss this with your healthcare provider if this is right for you.
• Also to prevent pneumonia and lung infections: You need to circulate air from the bottom of their lungs and out of your lungs (oxygenation). Using an incentive spirometer for 15 minutes a day, twice a day, can help promote oxygenation.
• If you are still smoking, you should quit. Discuss with your healthcare provider techniques that can help you quit.
• Try to exercise, as tolerated, to maintain your optimal level of functioning. People with impaired cognition may forget to exercise. Make a daily walk with a friend or a family member a part of your routine. Even light walking may help you to promote the flow of oxygen in your lungs and blood (oxygenation), which will help your cognition. .
• Make sure to get enough sleep at night. People who do not sleep well at nighttime may have difficulty concentrating in the daytime. If you have trouble sleeping:
• Do not eat or exercise within 2 hours of bedtime
• Make the room dark
• If you have an electronic clock, or one with an illuminated face, turn the face away from you.
• Use the bed only for sleeping
• Keep a consistent schedule. Make sure you go to bed each night and wake up each morning, at the same time.
• Minimize daytime naps. If you must take a nap, do not sleep for more than an hour at a time. Longer naps will make you feel more tired, and interrupt nighttime sleep.
• If these techniques do not work, consult your healthcare provider.
• Stress and anxiety may cause cognitive problems, especially if the stress and anxiety are prolonged. If you feel anxious, or "stressed out", use relaxation techniques to decrease the amount of anxiety you have. Place yourself in a quiet environment, and close your eyes. Take slow, steady, deep breaths, and try to concentrate on things that have relaxed you in the past.
• Participating in support groups may be helpful to discuss with others what you are going through. Ask your healthcare provider if he or she is aware of any support groups that would benefit you.
• If you experience symptoms or side effects or therapy, especially if severe, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Medications That May Be Prescribed By Your Doctor:

Treatment of cognitive problems is based upon getting rid of the underlying cause.

Antibiotics - If your doctor or healthcare provider suspects that you have an infection, he or she may order antibiotic pills or intravenous (IV).

• Commonly prescribed antibiotics for infections include azithromycin (Zithromax^®), and levofloxacin (Levaquin^®). These medications have broad-spectrum coverage, and are specifically good for lung infections, or pneumonia, that may have caused your confusion.
• If you are prescribed antibiotics, take the full prescription. Do not stop taking pills once you feel better.

Antidepressants - are used to treat depression in adults. People who are tired and depressed are at a higher risk for health problems. Depression may also lead to confusion and problems with cognition.

Antidotes - People who have experienced drug toxicity from narcotics, anti-anxiety medications, or chemotherapy drugs may receive an "antidote", to reverse the effects. Drug toxicity can cause impaired cognition.

Bisphosphonates - Cancer cells that spread to the bone can secrete (produce) substances that can cause other cells found in the bone, called osteoclasts, to dissolve or "eat away" a portion of the bone. These tumors or lesions weaken the bone and can lead to complications. Some of the complications resulting from this bone breakdown are bone pain, fractures and hypercalcemia, (increased levels of calcium in the blood). Mild hypercalcemia can lead to changes in memory and concentration, while significantly high levels of blood calcium can lead to confusion and problems with cognition.

• Bisphosphonates, such as pamidronate (Aredia^®), and zoledronate (Zometa^®) may be used to treat hypercalcemia (high blood calcium), and to decrease pain.

Corticosteroids work by decreasing inflammation (swelling) in many areas of the body. The corticosteroids prevent infection- fighting white blood cells (polymorphonuclear leukocytes) from traveling to the area of swelling in your body. This means you are more prone to infection while on steroids.

• You may be taking steroids if you have cancer that has spread to your brain. The swelling in the areas where the tumors are located could be causing your confusion.
• You may take steroids if you have a lung problem, such as Chronic Obstructive Lung Disease (COLD), and it is worse, which is altering your blood oxygen levels.
• It is important to note that while steroids are used to treat certain things that cause confusion, a side effect of this medication is mood swing. If you, a friend or a family member notice any changes in your behavior, notify your healthcare provider.

Erythropoeitin is a substance that your body produces naturally. This is a protein normally produced by the kidneys, which helps make red blood cells. Epoetin alfa and darbepoetin alfa are similar drugs that act like this natural substance to stimulate red blood cell production. During chemotherapy, patients may not be able to produce enough red blood cells, a condition known as anemia. Erythropoetic agents can treat anemia by increasing the number of red blood cells in the body.

Hemoglobin is the iron-containing substance in red blood cells that delivers oxygen throughout the body. Anemia and resulting decrease in circulating oxygen may contribute to confusion and cognitive problems. The normal hemoglobin range is approximately 12 to 18 g/dL, and varies according to age and gender. Doctors may prescribe erythropoetic agents to chemotherapy patients whose hemoglobin levels have fallen below normal levels.

Narcotics -Long-periods of pain can cause you to have problems with cognition. However, a side effect of narcotics may be a "confused" state. It is important to control your pain, to decrease your chances of being confused, or have trouble with cognition. However, be careful of narcotic medications that may cause you to be confused.

• Make sure you discuss with your healthcare provider common side effects, such as constipation, drowsiness, nausea and vomiting, and how to control these side effects.

Non-steroidal anti-inflammatory (NSAID) agents and acetaminophen - such as naproxen sodium and ibuprofen, may provide relief of headaches, and generalized pain. These may be appropriate medications in people with pain, who may be experiencing cognitive problems. Unlike narcotics, NSAIDS and acetaminophen rarely cause confusion.

• If you are to avoid NSAID drugs, because of your type of cancer or chemotherapy you are receiving, acetaminophen (Tylenol^®) up to 4000 mg per day (two extra-strength tablets every 6 hours) may help.
• It is important not to exceed the recommended daily dose of acetaminophen, as it may cause liver damage. Discuss this with your healthcare provider.

When to Contact Your Doctor or Health Care Provider:

• Fever of 100.5° F (38° C) chills or sore throat (possible signs of infection if you are receiving chemotherapy).
• Increased confusion, or falling "down"
• If you are having more trouble handling money, or lose track of the days.
• If are experiencing more difficulty learning things than you usually do, or if you forget things that you have done repeatedly in the past.
• Feeling your heart beat rapidly, or experience palpitations
• Dizziness or lightheadedness, "feeling faint", especially if severe