Two experts debate the preferred testing options for Lambert-Eaton myasthenic syndrome presenting with small cell lung cancer.
David Gerber, MD: Steve, this brings up many questions because there have been cases in my practice where I have been the one to clinically recognize neuromuscular junction pathology, either myasthenia or LEMS [Lambert-Eaton myasthenic syndrome]. The patients never come in and say, “I have fatigable, proximal lower-extremity weakness.” They say, “I’m tired.” When you’re a medical oncologist, people can be tired because they have frequent appointments, they’re anemic from chemotherapy, or they are hypoxic from the small cell lung cancer in their chest. The most recent patient I diagnosed told me that she had been telling her outside oncologist for 6 months that she was tired, and nothing was being done, and I asked her to get up from the examination chair and go over to the table. She had to push with her hands for 5 seconds to get out of the chair. I said, “That’s not fatigue; that’s something different,” and we went from there. It makes me wonder, in the era of telemedicine, which we’ve done a lot more of in the last 2 years, how do we make sure we’re not missing those things? It’s hard to sense what is going on in the body. The other questions I had were in general when it comes to diagnosis. In many institutions, there’s not only a single antibody test, but you can order a paraneoplastic panel with 20 or more different antibodies looking for LEMS, myasthenia, or other cerebellar dysfunction types of conditions. What are your thoughts on the comprehensive panel versus a single test?
Steven Vernino, MD, PhD: You’re right about telemedicine. As neuromuscular doctors interested in muscles, it’s terrible because you can’t see the muscles and you can’t test them directly. It’s particularly difficult with Lambert-Eaton syndrome because unlike myasthenia, these patients don’t have much facial weakness or changes in their speech. Many of our patients with myasthenia have a droopy eyelid, or they have a very nasal speech, which tips you off. If the weakness is predominantly in the hip girdle muscles, and they’re usually sitting at their computer, you don’t see that. I like your approach with the patient in front of you who’s complaining of a nonspecific weakness, fatigue, or tiredness, and having them stand up and walk across the room. I also like to ask for specifics on telemedicine. “What things can or can’t you do that you used to be able to?” It’s interesting to ask about getting out of a chair and going up the stairs because those are activities that require some good proximal lower-extremity strength. When someone says they can’t get out of a chair or go up the stairs, that’s a clue that there’s some real weakness as opposed to just feeling tired. Tired people will say, “if I have to, I can get up the stairs, but I don’t want to do it constantly.” People who really have weakness can’t. Those are good and important things.
With respect to antibody testing, it’s a critical piece to think about. We have access to a whole battery of tests. Small cell lung cancer has been associated with more than one paraneoplastic disorder, ranging from ataxia, encephalitis, neuropathies, as well as Lambert-Eaton myasthenic syndrome. It’s difficult to know whether there are more than one of those going on at the same time. Our general approach, if you’re coming from the cancer side, or we have a constellation of symptoms that’s hard to put your finger on, is a panel of antibody testing because you have the highest yield. Any individual antibody in that panel is probably rare. We talk about things like anti-Hu and anti-Yo antibodies as being pathognomonic for particular disorders, but they are rarely encountered. You’re more likely to pick something up if you look at a broad panel. Conversely, if we’re in the room on the neuromuscular side of things, and you’ve done the EMG [electromyography] and we know there’s a neuromuscular junction disorder, we might limit our testing to antibodies for myasthenia or Lambert-Eaton myasthenic syndrome rather than other antibodies that are more relevant for brain- or spinal cord-related paraneoplastic syndromes.
It’s great to have that kind of sensitive testing available, where we can do a whole panel and be sure not to miss anything, but it does raise some concerns about specificity. Patients with small cell lung cancer may have low levels of various antibodies, even without a symptomatic or definable neurological condition occurring. That is not surprising, it reflects that the immune system is responding to these cancers appropriately and doing its job to generate antibodies and cell-mediated response against the tumor cells, which is good. It’s helping to fight off cancer. We must ensure we’re using our clinical judgment as well. When we talk about misdiagnosis of Lambert-Eaton syndrome, there’s a lack of recognition of the disease and underdiagnosing. But there’s also the risk that if you send the big antibody panel for everybody who’s a little fatigued or tired, you’ll occasionally turn up some antibodies. We’ll see many cases where someone has a low level of voltage-gated calcium channel antibodies, and someone has labeled them with Lambert-Eaton myasthenic syndrome when they had none of the symptoms or physical findings to go along with that.
These tests are useful tools, but the antibody is not 100% diagnostic of the condition. It’s very sensitive, if you have Lambert-Eaton you’re likely to have the antibodies, but in our practice, many people who have the antibodies don’t have Lambert-Eaton syndrome. We must put these things into context: our clinical judgment, the antibody testing, and the ancillary testing, whether it be electrodiagnostic testing or imaging.
David Gerber, MD: It’s almost analogous to the rheumatologist whose clinic panel is filled with asymptomatic people with positive ANA [antinuclear antibody], and not knowing where to go next.
Transcript edited for clarity.