Diagnosis of LEMS can be difficult because symptoms often overlap with those of a common autoimmune disease called myasthenia gravis. But, there are essential differences that clinicians can use to diagnose. A detailed history and physical exam can uncover signs that point to LEMS as the suspect. A blood test can reveal antibodies that are characteristic of the disorder.
Medical History and Clinical Exam
Medical history is a core part of every doctor-patient encounter. It helps determine what condition is causing the patient’s symptoms. For healthcare providers like physicians, nurse practitioners, and physician assistants, taking a thorough medical history is a skill that must be learned. To make it easier to identify the patient’s issues in an organized manner, the history is divided into categories such as the history of present illness (the patient’s current complaints), family and social history, current medications, and a review of systems. In this last category, the healthcare provider conducts a targeted physical examination of the body to detect signs of illness or injury. For people with LEMS, the first symptoms are usually fatigue and muscle weakness, which progressively worsen over time. These are typically in the legs but can move up to the arms and hands. LEMS can also cause problems with your autonomic nervous system, which unconsciously regulates many body functions. These might include drooping eyelids or dry mouth. It can be hard to notice these symptoms on a physical exam which causes common LEMS misdiagnoses because they happen slowly and aren’t as alarming as extreme fatigue and weakness. Often the first clue is when your healthcare provider sees you have high amounts of antibodies against calcium channels in your blood. These are found in about 85% of people with LEMS. If your clinician suspects LEMS, they will likely order a few more tests to be sure.
If you’re concerned that your symptoms might be cancer, or if they don’t clear up after your initial imaging tests, your doctor will want to take a closer look at the muscles in your body. This exam is called an electromyography or EMG test. It involves inserting electrodes into the affected muscles to record electrical signals from their activity, which your physician can then evaluate. Muscle weakness is the most apparent sign of LEMS. It usually starts in the proximal leg muscles, making it difficult to climb stairs or get out of a chair. Eventually, it affects the arms, hands, head, and neck. This pattern of weakness may resemble that of MG. Still, atypical autonomic symptoms (dry mouth, erectile dysfunction in men, orthostatic hypotension, and impaired sweating) make it more likely to be LEMS. Before an EMG, you’ll probably need to stop taking certain medications. You might also experience some temporary, minor bruising where the needle electrode was inserted into the muscle. Your physician will discuss the results of your EMG with you at a follow-up appointment. Your doctor will also want to perform a nerve conduction velocity (NCV) test, which uses surface electrodes to measure the speed of electrical signals through your nerves. This will help to differentiate a nerve disorder from a muscle one.
If the medical history and physical exam suggest LEMS, the neurologist should check for antibodies to calcium channels on the nerve side of the neuromuscular junction. These are called VGCC (voltage-gated calcium channel) antibodies. In LEMS, these antibodies make less acetylcholine available at the neuromuscular junction. This causes weakness. A blood test to measure VGCC antibodies can be done as an outpatient before or on the day of the clinic appointment. When this test is positive, it indicates that antibodies are present and a person has LEMS. The neurologist should also order a low-frequency repetitive nerve stimulation of the muscle to look for signs of post-activation facilitation, often seen in people with LEMS. This involves stimulating the muscle and then measuring the response for 10 seconds. Suppose the amplitude of the CMAP increases after the muscle is stimulated. In that case, it’s a sign that VGCC antibodies are present and that the weakness may be due to these antibodies at the neuromuscular junction. LEMS can be caused by cancer, which is why your neurologist should do screening for small-cell lung cancer in addition to checking for VGCC antibodies. If cancer is found, it’s essential to be treated as soon as possible. If the underlying cancer can’t be removed, it can lead to more severe complications like heart problems and other diseases that may shorten your life.
In people with idiopathic LEMS, immune system dysregulation is the cause. Variations in specific genes often increase the risk of autoimmune diseases, including LEMS. Cancer can produce substances that disrupt nerve-muscle communication in people with idiopathic LEMS who have cancer. This is a type of paraneoplastic syndrome. If physical symptoms and EMG indicate a possible diagnosis of LEMS, the neurologist may order additional tests to confirm it. For example, they will test muscle responses by stimulating muscles for 10 seconds and then repeating the stimulation. In LEMS, the muscle response usually increases by more than 60 percent. This is called an increment, a vital sign of the condition. Another important blood test is for antibodies to voltage-gated calcium channels (VGCCs). These are located on the nerve side of the neuromuscular junction. People with idiopathic LEMS have high levels of these antibodies. People with cancer that causes LEMS also develop these antibodies, but it’s unknown why some do, and others don’t. If a person is diagnosed with idiopathic LEMS, monitoring them closely for signs of cancer is essential. A person screened regularly and for a more extended period is more likely to get a cancer diagnosis earlier in the disease process when it is easier to treat. This is why doctors recommend frequent screening for lung cancer in people with idiopathic LEMS.