Introduction:
Individuals with cancer often experience various neurological impairments. These impairments can result from chemotherapy, malnutrition, infections, or immune-mediated response to tumors. When this immune-mediated response to tumor cells is generated, they sometimes attack the healthy nervous system leading to paraneoplastic neuropathy. The occurrence of neuropathy is a tell-tale sign of cancer, which predates or occurs at various stages of cancer. Therefore, the severity of symptoms may vary based on the type of cancer, immune response, etc.
What Are Neoplastic and Paraneoplastic Neuropathy?
Paraneoplastic neuropathy or termed paraneoplastic neuropathic syndrome is a group of uncommon disorders affecting the nervous system in some cancer patients. When the tumor cell dies, it releases an oncoantigen that triggers an immune response. The immune system releases antibodies to attack the nervous system and tumor cells due to similar antigens in nerve cells. The antibodies released are onconeural and neuronal surface antibodies. The damaged tissue has infiltrates of lymphocytes. The affected nerve tissue includes the brain, spinal cord, and peripheral nerves. It is called neoplastic or peripheral neuropathy when only the peripheral nerves are involved. This condition can be reversible when detected early and adequate cancer care is provided. However, the nerve tissues are sometimes damaged, making the condition irreversible.
What Are the Risk Factors of Neoplastic and Paraneoplastic Neuropathy?
Old-aged and middle-aged people are found to have developed this condition. More often, lung, ovary, breast, testis, or lymphatic system cancer. Most commonly found in small-cell lung cancer.
What Are the Types of Neoplastic and Paraneoplastic Neuropathy?
The classification is divided into 'definite' and 'possible' types based on ease of diagnosis.
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Definite type involves cancer development within five years of neurological disorder diagnosis.
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The possible type involves symptom improvement after providing cancer treatment.
The classification based on clinical presentation is
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The classic syndrome includes limbic encephalitis, subacute sensory neuronopathy, subacute cerebellar degeneration, encephalomyelitis, lambert-eaton myasthenic syndrome, opsoclonus-myoclonus syndrome, chronic gastrointestinal pseudo-obstruction, dermatomyositis.
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The non-classic syndrome includes brain stem encephalitis, optic neuritis, stiff person syndrome, acquired neuromyotonia, motor neuron disease, acute necrotizing myopathy, myasthenia gravis, acute or subacute sensorimotor neuropathy, and acute dysautonomia.
There are other conditions whose classification remains controversial as their presence does not always indicate cancer. They are small fiber neuropathy, cryoglobulinemia, hyperexcitability syndrome, etc.
Classic Syndrome:
Limbic encephalitis causes the brain's limbic area to swell due to the presence of anti-Hu antibodies. Personality changes, irritability, and depression are common features.
Neurons of sensory nerve roots close to the spinal cord cause subacute sensory neuropathy. Symptoms begin on one side and progress to the other within days or weeks. Pain is felt like an electric shock, the feeling of walking on sand, etc.
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Cerebellar degeneration is caused due to antibodies that attack brain cells called Purkinje cells. These antibodies cause damage to the brain that is associated with balance and muscle coordination.
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Encephalomyelitis is a neurological condition with inflammation of the brain and spinal cord damaging the myelin.
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Opsoclonus-Myoclonus syndrome is characterized by rapid eye movements and sleep disturbance. It is caused by enzymes responsible for the glutamic acid conversion to GABA.
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Lambert- Eaton myasthenic syndrome is the most common. In this syndrome, the nerves get affected. The signals from nerves to muscles are disrupted due to low levels of acetylcholine.
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Chronic gastrointestinal pseudo-obstruction is a rare but severe disease with impaired muscle contraction that pushes food forward in the digestive tract.
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Dermatomyositis is a muscle disorder causing inflammation and skin rash.
Non-classic Syndrome:
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Brain stem encephalitis is a rare and severe brain or central nervous system inflammation.
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Optic neuritis is due to inflammation of the optic nerve. It causes pain in eye movement and loss of vision.
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Stiff person syndrome is a rare progressive nerve condition that causes muscle stiffness and spasms. It mostly affects the spine and lower limbs.
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Acquired neuromyotonia is a condition where the never over stimulates the muscle, causing hyperexcitability, spasms, and sweating.
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Motor neuron disease is a rare group of disorders where the spine and brain lose function over time.
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Acute necrotizing myopathy is a rare and newly described myositis with muscle necrosis. It causes skeletal muscle weakness on both sides of the body of proximal muscles such as the hip, thigh, arms, and legs.
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Myasthenia gravis is a condition where muscle weakness and rapid fatigue of voluntary muscle are seen. There is no treatment for the condition. The communication between nerve and muscle is affected.
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Acute or subacute sensorimotor neuropathy is a condition where difficulty in feeling or moving is experienced. When peripheral nerves are affected, it is called peripheral neuropathy.
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Acute dysautonomia is a condition affecting the autonomic nervous system. It commonly affects involuntary functions like heartbeat, digestion, and breathing. When the autonomic system gets affected, there is increased blood pressure, loss of bladder control, and trouble breathing.
The list of conditions keeps getting updated as the paraneoplastic conditions still need to be defined, and the exact mechanism remains unknown.
What Are the Symptoms of Neoplastic and Paraneoplastic Neuropathy?
The symptoms can develop within a few days or weeks. The symptoms include.
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Fever, loss of weight, and appetite.
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Difficulty walking.
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Difficulty maintaining balance.
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There is loss of muscle coordination.
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There is loss of muscle tone and weakness.
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Loss of motor skills like picking up things.
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Difficulty in swallowing.
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Difficulty in speaking, vision and memory loss.
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Sleep disturbance, hallucinations, seizures.
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Nausea and vomiting, fatigue.
What Is the Diagnostic Test of Neoplastic and Paraneoplastic Neuropathy?
A positive diagnosis of paraneoplastic neuropathy is often an indicator of underlying cancer. The various tests are,
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Medical history and physical examination.
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A neurological examination is done to assess brain and muscle function.
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Imaging studies like CT (computed tomography) and MRI (magnetic resonance imaging) are carried out to detect cancers.
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Blood tests are carried out to detect antibodies and for cancer antigen detection.
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Spinal fluid is used to assess antibodies.
What Is the Treatment Methodology of Neoplastic and Paraneoplastic Neuropathy?
There are no specific treatment options available for paraneoplastic neuropathy. The line of treatment includes
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Casual, which includes tumor removal and immunomodulation.
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Symptomatic, which includes drug therapy, disability treatment, and neuropathic pain.
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Corticosteroids are used to reduce swelling and inflammation.
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Immuno suppressors are used to reduce the immune response.
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Plasmapheresis is done to reduce the level of antibodies in plasma.
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Physiotherapy and speech therapy improves motor and speech disabilities, respectively.
What Is the Prognosis of Neoplastic and Paraneoplastic Neuropathy?
There is no specific treatment for the disease. Outcomes depend on,
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Treating the tumor.
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Detection and management of symptoms in the early stage to manage disability.
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The stage at which cancer develops can decide treatment outcomes.
Conclusion:
Paraneoplastic syndromes include disorders affecting any central and peripheral nervous system. The complications experienced may be of a broad range from minor to debilitating. Early detection of symptoms with cancer screening and adequate treatment can improve quality of life and prevent disability.
