Introduction

Lambert-Eaton Myasthenic Syndrome (LEMS) is one of the rarest autoimmune diseases. It rarely occurs in adults, but even more in children (anyone under 18 years of age). LEMS is an autoimmune condition, which means that the body’s immune system gets confused and attacks itself. This attack occurs where the nerve and muscle connect- the neuromuscular junction- causing miscommunications between the nerves and muscles.  This leads to complications with movement and strength-based activities.

The manifestation of LEMS in adults typically occurs in older people with lung cancer or in those who are middle-aged. Although LEMS is inherently a rare condition, its occurrence and diagnosis in children are even less common, primarily because it is often associated with cancers that are seldom seen in that age group. Nonetheless, LEMS can be identified as the primary diagnosis in paediatric patients.

Likewise, the prognosis for individuals with LEMS, especially in paediatric cases, can be enhanced if it is identified quickly and appropriate treatment is started and followed through.  This article aims to explore the journey of diagnosing LEMS in children, detailing aspects from clinical symptoms to long-term outcomes.^1,2

Understanding lambert-eaton myasthenic syndrome

The miscommunication occurring between nerves and muscles in LEMS is a result of the immune system's attack on the voltage-gated calcium channels situated at the neuromuscular junction. These play a crucial role in regulating muscle function and movement. Consequently, individuals diagnosed with LEMS suffer from muscle weakness. 

LEMS is usually associated with cancer in the body, commonly lung cancer. In cases of children diagnosed with LEMS, the condition typically arises from an autoimmune response rather than cancer. Nevertheless, children with LEMS often undergo a follow-up period of four years after their diagnosis, as research indicates that the signs and symptoms of LEMS may appear six months to five years before a cancer diagnosis is made.³

Clinical features in children

The clinical characteristics of LEMS observed in children are all associated with varying degrees of muscle weakness. Therefore, there are occasions when symptoms may resemble those of other neuromuscular conditions, such as myasthenia gravis, which can lead to children being inaccurately diagnosed with more prevalent neuromuscular disorders before receiving the correct diagnosis of LEMS. The characteristics that are observed in children diagnosed with LEMS include, but are not limited to:⁴

• Increased susceptibility to fatigue, alongside an improvement of strength after exertion (a hallmark sign of LEMS)
• Difficulty walking
• Difficulty climbing stairs
• Difficulty standing up
• Gradual muscle weakness (more focused in the legs)
• Reduced reflexes
• Dry mouth
• Constipation

Challenges in diagnosis

The biggest challenge that is faced in the diagnosis of LEMS is the fact that it can often be misdiagnosed, as several other neuromuscular disorders have symptoms which could overlap. This is particularly the case within paediatric cases, due to the highest percentage of origin of LEMS being autoimmune, compared to being related to an existing cancer. Naturally, these possible misdiagnoses can lead patients down management plans that are not effective, and to unnecessary treatments. Due to delayed correct treatment, the patient could experience increased symptoms, increased disability and increased long-lasting negative effects.

To ensure increased positive outcomes, specifically when focusing on children, a high level of suspicion of a diagnosis of LEMS should be considered if any children are presenting to healthcare professionals with unexplained progressive muscle weakness.⁵

Diagnostic approach

To confirm a LEMS diagnosis, several components must be tested and their results must align, as there is no single specific test that can prove a LEMS diagnosis. These are:⁴

• Physical examination: focusing on the neurological examinations needed to elicit neurological signs
• A full, comprehensive clinical history
• Nerve stimulation tests: specifically, electromyography (EMG) to investigate neuromuscular abnormalities within the muscle itself. The results should show a low response when the person is at rest, and then an increased response after doing some exercise
• Blood tests: specialised blood tests that are required to rule out other neuromuscular disorders and specific antibodies related to the voltage-gated calcium channels

Management strategies

Similar to many conditions that can have long-lasting effects, the management of LEMS can be easily split into three main categories: medications, physical therapy, and ongoing support.

Medications

LEMS occurs when the immune system mistakenly targets the neuromuscular junctions, leading to the use of immunosuppressive therapy to reduce the immune response, allowing it to subside and refrain from attacking inappropriate areas in the body. Examples of these immunosuppressive therapies include corticosteroids, azathioprine, and intravenous immunoglobulin (IVIG).

Another group of medications that might be used is those that enhance the communication between nerves and muscles. One of these medications is called amifampridine (or called 3,4-diaminopyridine, or 3,4-DAP). This type of medication improves muscle strength by ultimately increasing calcium within channels in the body by blocking voltage-gated potassium channels.⁴

Physical therapy

Since LEMS affects the body, it is essential to maintain mobility and strength from the time of diagnosis and throughout ongoing management, so that daily activities can be performed without causing weakness from overexertion.⁶

Ongoing support

Physical therapy plays a crucial role in ongoing consultations with healthcare providers to guarantee effective symptom control. In the case of LEMS in children, it is essential to maintain communication with the pediatric neurology team.

Another crucial category of professionals to maintain ongoing communication with is those involved in psychological care. From support groups for teenagers with LEMs to family sessions to best help the development of your child, there are so many niche groups of people where this support can be found. It can be something as simple as a non-professional-led meet-up, to as structured as psychologist appointments for the child and/or family.

It may seem insignificant to continually pursue these avenues; however, they can make such a clear impact upon the growth of positive outcomes for children (and ultimately anyone) with LEMS to ensure optimised management.^7,8,9

Summary

Pediatric-onset LEMS is a rare but serious neuromuscular disorder that requires early diagnosis for optimal outcomes. The paediatric-onset of LEMS is a very rare neuromuscular condition; however, it does have some unique signs. It occurs when the immune system mistakenly attacks the nerve and muscle connection, leading to communication issues that result in muscle weakness and complications with movement. In adults, LEMS is often linked with lung cancer, while in children, it usually arises from an autoimmune response rather than cancer. Early diagnosis and treatment can improve the prognosis for children diagnosed with LEMS.

LEMS causes miscommunication at the neuromuscular junction due to the immune system attacking voltage-gated calcium channels, leading to weakness in muscles. Children with LEMS may experience symptoms such as increased fatigue, difficulty walking, climbing stairs, and standing, gradual weakness in the legs, reduced reflexes, dry mouth, and constipation. The diagnosis can be challenging, often leading to misdiagnosis, as other neuromuscular disorders like myasthenia gravis share similar symptoms. These misdiagnoses can result in ineffective management and unnecessary treatments, worsening the patient's condition. To diagnose LEMS, various tests are required, including a physical examination focused on neurological signs, a comprehensive clinical history, nerve stimulation tests, and specialised blood tests to rule out other disorders. There is no single test that confirms LEMS, making a detailed diagnostic approach crucial. Management of LEMS includes medications, physical therapy, and ongoing support.

Immunosuppressive therapy, such as corticosteroids and azathioprine, is used to reduce the immune response. Additionally, medications such as amifampridine enhance communication between nerves and muscles. Physical therapy is important for maintaining mobility and strength, enabling children to perform daily activities without excessive fatigue. Ongoing support involves regular consultations with healthcare providers, particularly pediatric neurologists, and psychological care. Support groups and family sessions can be beneficial for emotional well-being. While these avenues may seem small, they significantly contribute to positive outcomes for children with LEMS. Overall, awareness and quick diagnosis are essential for effective management of LEMS in pediatric patients.

FAQs

How is LEMS different from myasthenia gravis in children?

The pattern and progression of weakness in myasthenia gravis is typically from the section of the limb closest to the body, progressing to the section of the limb furthest from the body, whereas in LEMS, there is a general muscle weakness mainly focused in the lower limbs.⁴

What is lambert-eaton myasthenic syndrome, and how does it affect children?

LEMS is a neuromuscular disorder where the immune system gets confused and attacks a part of the body that controls the communication between the nerves and muscles in the body. It is particularly prominent in the legs.

Is LEMS in children related to cancer, like in adults?

LEMS in children is typically not related to the presence of cancer cells already in the body, as it is in adults who have LEMS. In children, LEMS is more commonly an autoimmune condition; however, some studies show LEMS will present in paediatrics anywhere from 6 months to five years before being diagnosed with some type of cancer.