The antibodies bind particularly to the part of the receptor known as the "domain III S5–S6 linker peptide". Antibodies may also bind other VGCCs. Some have antibodies that bind synaptotagmin, the protein sensor for calcium-regulated vesicle fusion. Many people with LEMS, both with and without VGCC antibodies, have detectable antibodies against the M1 subtype of the acetylcholine receptor;  their presence may participate in a lack of compensation for the weak calcium influx.Apart from the decreased calcium influx,  a disruption of active zone vesicle release sites also occurs, which may also be antibody-dependent, since people with LEMS have antibodies to components of these active zones (including voltage-dependent calcium channels). Together, these abnormalities lead to the decrease in muscle contractility. Repeated stimuli over a period of about 10 seconds eventually lead to sufficient delivery of calcium, and an increase in muscle contraction to normal levels, which can be demonstrated using an electrodiagnostic medicine study called needle electromyography by increasing amplitude of repeated compound muscle action potentials.The antibodies found in LEMS associated with lung cancer also bind to calcium channels in the cancer cells, and it is presumed that the antibodies originally develop as a reaction to these cells. It has been suggested that the immune reaction to the cancer cells suppresses their growth and improves the prognosis from the cancer. Diagnosis
The diagnosis is usually made with nerve conduction study (NCS) and electromyography (EMG), which is one of the standard tests in the investigation of otherwise unexplained muscle weakness.
Signs and symptoms
Symptoms:

Paroxysmal—appears suddenly, and in episodes of short duration: lasts only seconds to minutes
Positional—is induced by a change in position, even slight
Vertigo—a spinning dizziness, which must have a rotational component
Torsional nystagmus—a diagnostic symptom where the top of the eye rotates toward the affected ear in a beating or twitching fashion, which has a latency and can be fatigued (vertigo should lessen with deliberate repetition of the provoking maneuver): nystagmus should only last for 30 seconds to one minute
Pre-syncope—(feeling faint) or syncope (fainting) is unusual, but possible
Visual disturbance—due to associated nystagmus, making it difficult to read or see during an attack
Nausea—is often associated
Vomiting—is common, depending on the strength of vertigo itself and the causes for this illnessMany people will report a history of vertigo as a result of fast head movements. Many are also capable of describing the exact head movements that provoke their vertigo. Purely horizontal nystagmus and symptoms of vertigo lasting more than one minute can also indicate BPPV occurring in the horizontal semicircular canal. The spinning sensation experienced from BPPV is usually triggered by movement of the head, will have a sudden onset, and can last anywhere from a few seconds to several minutes. The most common movements people report triggering a spinning sensation are tilting their heads upward in order to look at something and when rolling over in bed.People with BPPV do not experience other neurological deficits such as numbness or weakness. If those symptoms are present, a more serious etiology, such as posterior circulation stroke or ischemia, must be considered.