Paraneoplastic Syndromes

Paraneoplastic syndromes of the nervous systems are a group of rare disorders that is prevalent in some people having cancer. Paraneoplastic syndromes not only affects nervous system but also other systems such as endocrine system, skin (dermatologic), blood (hematologic) and joints (rheumatologic). 

The most common symptoms of cancer, such as tiredness, reduced hunger and weight loss, may be associated with paraneoplastic events.

The syndrome is believed to occur when the immune system is activated against not only cancer cells but also against some parts of brain, spinal cord, peripheral nerves or muscle. These syndromes are mostly experienced by people suffering from lung, breast, ovary, and blood cancer. 

Depending upon the areas where nervous system is affected, paraneoplastic syndrome can cause uncoordinated muscle movement, altered sensory perception, impaired memory or thinking skills or even problems in sleep. 

The injury in nervous system in some cases is reversible when treated with cancer chemotherapy and immunosuppressant. The diseases can also progress to an extent that the injury is irreversible. However, the treatment of cancer and other medical intervention may prevent further injury and improve symptoms and quality of life.

The signs and symptoms of paraneoplastic syndromes of the nervous systems progresses rapidly, often within days to weeks. The symptoms differ depending on the body part being affected. Some of the symptoms include:

• Difficulty in muscle coordination, walking  and maintaining balance
• Loss of muscle tone, fine motor skill (for example picking up objects)
• Dysphagia (Difficulty in swallowing)
• Dysarthria (Slurred speech)
• Dyskinesia (Abnormal involuntary movement)
• Impaired memory and cognition
• Vision problem
• Sensory disturbances
• Convulsions or seizures

The neurological disorders are characterized as paraneoplastic syndrome only if the syndromes co-occur with cancer. 

The similar neurological disorders associated with immune system disease are not identified as paraneoplastic syndrome. Paraneoplastic syndrome of the nervous system include following symptoms: 

Cerebellar degeneration: It is the deterioration of neurons in cerebellum of the brain. This part of the brain regulates motor activity and balance.   

The signs and symptoms are:

• Ataxic gait (unsteady walking, lack of muscle coordination)
• Nystagmus (involuntary eye movement)
• Difficulty in maintaining posture
• Double vision
• Dysphagia
• Dysarthria
• Lightheadedness, nausea

Limbic encephalitis: It is characterized by inflammation of limbic system of brain responsible for controlling basic emotions, behaviors and certain memory functions. People may experience:

• Alteration in mood
• Dementia (memory loss)
• Seizures
• Hallucination
• Insomnia 

Encephalomyelitis: It is the inflammation of the brain and spinal cord. The sign and symptoms experienced depend on the area affected.

Opsoclonus-myoclonus syndrome: This syndrome is experienced as a result of dysfunctional cerebellum or its connection. The symptoms include:

• Opsoclonus (rapid, irregular eye movements)
• Myoclonus (spasmodic muscle jerks) 

Stiff person syndrome: It is also known as stiff man syndrome with progressive stiffening of muscles and affects your spine and lower extremities. It may also cause painful muscle spasm. 

Myelopathy: It refers to the condition when spinal cord is injured. The symptoms experienced depend on the level of spinal coed injury which may include:

• Alteration in bowel and bladder function
• Severe weakness and numbness
• If spinal cord is injured in neck region, all four limbs are severely affected

Lambert-Eaton myasthenic syndrome: It is seen when communication between muscles and nerves is interrupted. It is usually associated with lung cancer. Its signs and symptoms are: 

• Muscle weakness
• Fatigue
• Dysphagia
• Dysarthria
• Nystagmus and double vision
• Dry mouth
• Impotence
• Decreased sweating

Myasthenia gravis: It is characterized by interrupted impulse transmission between nerve and muscle and generally associated with thymoma (cancer of thymus gland). Symptoms include:

• Rapid muscle weakness
• Difficulty in swallowing
• Slurred speech
• Difficulty in breathing
• Double vision

Neuromyotonia: Neuromyotonia, also known as Isaacs’ syndrome and peripheral nerve hyperexcitability, refers to abnormal impulses in peripheral neurons that control muscle movement resulting in muscle twitching, muscle rippling (that looks like a "bag of worms"), progressive rigidity, muscle spasm and other muscle impairments. 

Peripheral neuropathy: This condition is characterized by damage of neurons that transmit signals from central nervous system to the rest of your body. If sensory nerves of the peripheral nervous system are damaged, you can have pain anywhere in your body. 

Dysautonomia: Dysautonomia refers to the condition where neurons in autonomic nervous system (ANS) are injured. 

ANS regulate involuntary body functions such as heart rate, blood pressure, sweating, and bowel and bladder functions. The most common symptoms experienced are low blood pressure and nausea, bloating, and weight loss.

When to see a Doctor?

Visit your doctor immediately if you experience signs and symptoms similar to paraneoplastic syndrome.

Paraneoplastic syndromes of the nervous system are caused by a cancer that leads your body to attack its own nervous system.

Making a diagnosis of paraneoplastic syndromes of the nervous system is done by performing several tests.

Many people experience neurological problems even when cancer has not been diagnosed. Visit your doctor as soon as you experience the symptoms of neurological paraneoplastic syndrome. 

Your primary care doctor may refer you to a neurologist (specialist in nervous system disorders) or oncologist (cancer specialist).  

• Clinical exam: Your doctor will perform general physical and neurological exam. The test conducted helps to evaluate reflexes, muscle strength and tone, vision and hearing, coordination balance, mental status. 
• Blood tests: Blood test is done to detect antibodies, if present, commonly associated with paraneoplastic syndrome. It may be done to identify an infection, hormonal or metabolic disorder which could explain your signs and symptoms. 
• Spinal tap (lumbar puncture): A sample of cerebrospinal fluid or CSF (the fluid that surrounds your brain and spinal cord) is obtained by inserting a needle into your lower spine and aspirating a small amount of CSF for laboratory analysis. Paraneoplastic antibodies may be detected in CSF while they may not be seen in blood.
• Imaging tests: Imaging tests are used to identify a tumor associated with your neurological symptoms. Computerized tomography (CT) scans, magnetic resonance imaging (MRI) or positron emission tomography (PET) are employed in diagnosis. PET-CT, a combination of PET and CT, is employed to detect small cancers which are associated with paraneoplastic neurological syndrome. 

If the cause is not identified, you may be recommended a follow-up image testing every three to six months until the cause has been identified. 

What your doctor wants to know?

A clear talk with your doctor can optimize the therapy and improve the outcomes. Prepare yourself to answer some essential questions from your doctor. Your doctor might ask you typical questions like: 

• Have you experienced muscle weakness or lack of coordination?
• Have you had unusual muscle movements?
• Do you have vision problem?
• Do you have difficulty while swallowing, speaking, breathing or chewing?
• Have you had seizure? How long have they lasted?
• Do you experience numbness or tingling in your limbs?
• Have you seen or heard things that others are unaware of?
• Do you take any other medicine? 
• Does your family have history of cancer?
• Do you smoke?
• Have you had significant mood change?

Treatment of neurological paraneoplastic syndromes is guided by the specific type of paraneoplastic syndrome you have been experiencing. 

Treatment of neurological paraneoplastic syndromes includes treatment of cancer and in some instances, use of immnosuppresant.

• Medication: You may be prescribed with corticosteroid or immunosuppressant, to suppress immune system, along with chemotherapy:
  • Corticosteroids such as prednisone are given to suppress inflammation. The serious side effects of corticosteroids on long term use are osteoporosis (weakening of bone), diabetes, and hypertension.
  • Immune suppressing drugs like cyclophosphamide or azathioprine are given to delay the production of white blood cells (disease-fighting cells)
  • Anti-epileptic drug may be prescribed to control seizures.
  • Drugs such as 3, 4-diaminopyridine may be prescribed to increase the release of chemical messenger that transmits signal from neurons to muscles.
  • Drugs such as pyridostigmine may be given to inhibit the breakdown of chemical messenger thereby enhancing ‘nerve to muscle’ transmission.

• Plasmapheresis: It is also known as plasma exchange. In this process, the blood cells and plasma (fluid part of blood) are separated by cell separator. The blood cells are returned to your body while the plasma containing unwanted antibodies is discarded and replaced with other fluids.
• Intravenous immunoglobulin (IVIG): Immunoglobulin contains healthy antibodies from donor which destroys the damaging antibodies present in your blood. 
• Physical therapy: It is indicated in people with significant disability due to paraneoplastic syndrome. Specific exercises may help in recovering the damaged muscle function. 
• Speech therapy: It is indicated for those who have difficulty in speaking or swallowing. 

Lifestyle modifications are necessary in order to cope with paraneoplastic syndromes of the nervous system.

Gather as much as information as possible about your condition to improve coping skill.

Join a support group.

People with family history of autoimmune disease are at increased risk to have paraneoplastic syndrome of the nervous system.

The paraneoplastic syndrome of nervous system is more likely to occur in people with lung, ovary, breast, testis or lymphatic cancer.