About LEMS

Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of the neuromuscular junction8

Neuromuscular junction (NMJ) disorders may be the result of exposure to certain toxins, immune-mediated diseases, or genetic disorders.8

Chart showing neuromuscular junction disorders
Chart showing neuromuscular junction disorders

While all neuromuscular junction disorders are uncommon, the immune-mediated disorders—
LEMS and MG—are the ones most often encountered in the EMG lab.8

NORMAL NEUROMUSCULAR
FUNCTION

Watch this brief video animation to better understand the normal mechanism of action between neurons and muscle receptors.

KEY FACTS ABOUT LEMS

Symptoms

LEMS is a rare, immune-mediated neuromuscular disorder characterized by a clinical triad of signs and symptoms: proximal muscle weakness, autonomic symptoms, and hyporeflexia or areflexia.12 See more on the LEMS Symptoms Map.

Burden

LEMS results in diminished physical functionality as well as impairments in activities of daily living (ADL) and patients’ quality of life.5

Prevalence

LEMS is estimated to affect up to 3,600 individuals in the United States.11

COMORBIDITY

Historically, more than half of LEMS cases are associated with an underlying cancer, usually small cell lung cancer (SCLC).13 Studies suggest that LEMS patients with SCLC display a more rapidly progressing course of LEMS vs those with LEMS not associated with SCLC.14,15  Because LEMS symptoms can precede cancer detection by months or even years16, lives may be saved by earlier diagnosis of LEMS.

PATHOPHYSIOLOGY

Patients with LEMS experience severe muscle weakness due to reduced acetylcholine (ACh) release from presynaptic motor nerve terminals.17

LEMS mechanism of disease
    1. In patients with LEMS, autoantibodies target voltage-gated calcium channels on the presynaptic motor neuron, reducing calcium influx during an action potential17
    2. Reduced intracellular calcium limits presynaptic vesicle fusion and release of ACh17
    3. Disrupted ACh transmission lessens activation of ACh receptors on the muscle fiber potential17
    4. Reduced ACh signaling results in diminished muscle fiber contraction and muscle weakness17

LEMS MECHANISM OF DISEASE

Watch this brief video animation to better understand how LEMS disrupts communication between neurons and muscle receptors

LEMS POP Quiz

LEMS is caused by: (select all that apply)


Submit
Answer:

LEMS is caused by autoantibodies to presynaptic VGCCs that effectively decrease acetylcholine release and disrupt neuromuscular transmission, resulting in muscle weakness.17

DISEASE BURDEN

LEMS patients’ health-related quality of life is lower compared to MG patients and the general population18

A questionnaire-based survey compared the health-related quality of life (HRQoL) of patients with Lambert-Eaton myasthenic syndrome (LEMS, n=46) with the HRQoL of patients living with myasthenia gravis (MG, n=92) and the general population (n=92).18

The results revealed that LEMS patients reported comparatively more unfavorable outcomes in the following domains18

Icon for Physical functioning
Physical functioning
Icon for emotional well being
Emotional well-being
Icon for general health perception
General health perception
icon for pain
Pain

Furthermore, patients with LEMS reported experiencing a higher overall burden of disease compared to patients with MG.18

Participants were also surveyed for satisfaction with LEMS treatments

of respondents indicated they were satisfied with their treatments*, 4% experienced
no symptoms under medication, and 67% experienced minimal symptoms18

*The survey did not specify a parcular treatment.18

of respondents reported using FIRDAPSE® (amifampridine)18

†Other therapies reported by survey included pyridostigmine, steroids, and IVIG.18

BURDEN OF DISEASE FLASH CARD

Get a downloadable version of this content
and more using the link below.

Progression of LEMS symptoms contributes to worsening disease burden5

IN A 2012 SURVEY OF PATIENTS LIVING WITH LEMS5:

man getting up icon

75% reported partial or total restriction of activities of daily living5, such as rising from a chair or climbing stairs6

symptom icon

50% reported severe leg weakness; other frequently reported symptoms included dry mouth and difficulty focusing eyesight5

comparable icon

Based on EQ-5D scores, the health-related quality of life for LEMS patients is comparable to the most severe forms of multiple sclerosis5

In a 2001 study, ~25% of LEMS patients required a wheelchair all the time or for mobilization outside the home19

A CHALLENGING DIAGNOSIS

LEMS patients often experience a long diagnostic journey5

The mean time to a LEMS diagnosis is 4.4 years

REASONS FOR THE DELAYS IN DIAGNOSIS:

  • Nonspecific and fluctuating symptoms12
  • Slow progression of disease12
  • Similar clinical presentation to other conditions12,20

Despite the significant burden it places on patients and their families, LEMS is often underrecognized5

THE DIAGNOSTIC CONUNDRUM

Studies reveal that more than half of patients with LEMS received a different diagnosis first12,20

THE DIAGNOSTIC CONUNDRUM

In a cohort of 241 adult patients with LEMS, 58% were diagnosed with another disorder at least once before receiving the correct diagnosis.12

THE DIAGNOSTIC CONUNDRUM

Clinical presentation of LEMS resembles other common diagnoses12,20

The symptoms of LEMS are often mistaken for common diseases and disorders, such as myasthenia gravis (MG), multiple sclerosis (MS), Guillain-Barré syndrome, amyotrophic lateral sclerosis (ALS), and depression.12,20

INITIAL DIAGNOSES PRIOR TO CONFIRMATION OF LEMS (n=140)12

  • MG
  • Muscular abnormalities
  • Peripheral nerve abnormalities
  • Intracranial/spinal cord abnormalities
  • Depression
  • Other

More than 1/3 of LEMS patients were previously diagnosed as having MG12

Prevalence of misdiagnoses among patients with LEMS12

  • MG
  • Muscular abnormalities
  • Peripheral nerve abnormalities
  • Intracranial/spinal cord abnormalities
  • Depression
  • Other

More than 1/3 of LEMS patients were previously diagnosed as having MG12

LEMS POP QUIZ

LEMS is often misdiagnosed as: (please select one)


Submit
Answer:

The patient journey to a diagnosis of LEMS is often long and arduous.5 Reasons for the delay include the fact that the way LEMS presents is similar to all of the above conditions.12,20