Lambert-Eaton Myasthenic Syndrome (LEMS).pptx

PPT on the LEMS including signs, symptoms and treatment.

1. Lambert-Eaton Myasthenic Syndrome (LEMS)

2. Introduction Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder affecting the neuromuscular junction, leading to muscle weakness and fatigue. It results from the body's immune system mistakenly attacking voltage-gated calcium channels (VGCC) on presynaptic nerve terminals, impairing acetylcholine release. LEMS is most commonly associated with small-cell lung cancer (SCLC), where it can present as a paraneoplastic syndrome, but it can also occur without malignancy. The condition primarily affects adults, with a higher prevalence in men over 60 years. Early diagnosis and management are essential to prevent complications and improve the quality of life.

3. Neuromuscular Junction Highly specialized synapse between a motor neuron nerve terminal and its muscle fiber responsible for converting electrical impulses generated by the motor neuron into electrical activity in the muscle fibers . Axon terminals contain synaptic vesicles and mitochondria. Synaptic vesicles contain ACh .

4. Sliding Filament Theory Calcium ions bind to troponin on the actin filaments of the muscle fibers . This binding moves tropomyosin , which blocks the interaction between actin and myosin . Myosin heads attach to the actin filaments, forming a cross-bridge . Using energy from ATP , the myosin heads pull the actin filaments toward the center of the sarcomere, causing the muscle fiber to contract . This process is known as the sliding filament theory because the actin and myosin filaments slide past each other, shortening the muscle.

5. Etiology Paraneoplastic LEMS (linked to cancer, particularly small-cell lung cancer, or SCLC): 50-60% of LEMS cases are associated with cancer, especially SCLC. This happens because the cancer cells cause the immune system to create antibodies that also attack the calcium channels in the nerves. Non-paraneoplastic (idiopathic) LEMS : This form occurs without a detectable cancer and is often associated with other autoimmune conditions like rheumatoid arthritis or lupus.

6. Clinical Features of LEMS Muscle weakness : Mainly affects the proximal muscles (shoulders, hips, thighs). Patients may struggle with climbing stairs, getting out of a chair, or lifting objects. Fatigue : Muscle weakness gets worse with activity but improves after rest (similar to myasthenia gravis). Autonomic dysfunction : LEMS can also affect autonomic nerves. Dry mouth, constipation, difficulty in urination, and impotence. Improvement after exercise : A unique feature of LEMS— brief exercise improves muscle strength (this is due to increased calcium influx in nerve terminals after activity). In time, the excess calcium is cleared off by mitochondria. Thus, this effect is temporary

7. Hyporeflexia - Depressed or absent deep tendon reflexes are a common sign. However, the patient may present with normoreflexia after exercise. Bulbar Involvement - It is rare and may present as ptosis, diplopia or dysphagia. In contrast to MG, ptosis and ophthalmoplegia are very mild in LEMS. Respiratory Failure   -  It is extremely rare and occurs very late into the disease. It is associated with increased mortality.

8. Diagnosis Clinical features such as proximal muscle weakness associated with areflexia and autonomic dysfunction should raise suspicion for LEMS. Serology Antibodies directed against P/Q-type VGCC, as detected in a radioimmunoassay, are present in approximately 85% to 95% of individuals with LEMS. However, it is noteworthy that P/Q-type VGCCs are not exclusive to LEMS, as they have also been linked to various other neurological conditions and autoimmune disorders.

9. Electrodiagnostic Testing EDS typically begins with nerve conduction studies (NCS) and electromyography (EMG). Sensory studies conducted as part of NCS typically show normal results, with unaffected nerve conduction velocities. In contrast, motor unit amplitudes are generally significantly reduced. Repetitive nerve stimulation (RNS) is an essential component of EDS, which commonly reveals a decremental response during low-frequency repetitive nerve stimulation and an incremental response at high-rate stimulation. Although these findings are generally consistent and reproducible, varying results have also been reported.  Screening for Malignancy Due to the strong association with malignancy, a diagnosis of LEMS warrants an immediate and extensive investigation for an underlying malignancy. The initial recommended imaging study is a computed tomography (CT) or magnetic resonance imaging (MRI) chest scan. A positron emission tomography (PET) scan is also used for initial screening if CT is negative. If the initial evaluation does not reveal any malignancy, it is recommended to continue cancer screening every 3 to 6 months for a minimum of 2 years.

10. Management Medical Management Immunotherapy : Immunosuppressive treatments like corticosteroids, azathioprine, or intravenous immunoglobulin (IVIG) can reduce the autoimmune attack on VGCC. Plasmapheresis : This may be used to remove circulating antibodies in severe cases. 3,4-diaminopyridine (3,4-DAP) : A potassium channel blocker that enhances acetylcholine release, improving neuromuscular transmission. Pyridostigmine : An acetylcholinesterase inhibitor that can be used to increase acetylcholine levels, although it is less effective in LEMS compared to myasthenia gravis. Cancer treatment : For paraneoplastic LEMS, treating the underlying malignancy (e.g., chemotherapy or radiotherapy for SCLC) is crucial and can lead to symptom improvement.

11. Physiotherapy Management 1. Strengthening Exercises To improve proximal muscle strength, particularly in the lower limbs, as weakness in these muscles is one of the main symptoms of LEMS. Target Muscles: Focus on strengthening the quadriceps, hamstrings, hip flexors, gluteal muscles, and core muscles. Exercises: Isometric Exercises: Progressive Resistance Training (PRT) Closed-chain exercises Frequency and Intensity: 2-3 times per week of moderate-intensity strengthening exercises. Rest days are important to allow muscle recovery. Start with low intensity and gradually increase the load as tolerated. The progression should be slow, as LEMS patients can fatigue easily.

12. Isometric

13. Progressive Resistance Training

14. Aerobic and Cardiovascular Training Low-impact Aerobic Exercises : Activities like walking, stationary cycling, and swimming are recommended. Swimming or Aquatic Therapy : Aquatic exercises reduce the impact on the joints and muscles while allowing for full body movement. The buoyancy of the water supports the body, making it easier to move even with significant muscle weakness. Frequency and Intensity: Start with 15-20 minutes of aerobic activity, 3-4 times per week. Progress gradually based on patient tolerance. Aim for a moderate level of exertion (around 12-14 on the Borg scale).

15. Functional Training and Mobility Exercises Exercises should be tailored to improve the patient's ability to perform tasks such as rising from a chair, climbing stairs, or walking. Sit-to-Stand Exercises : It is often difficult for LEMS patients due to proximal muscle weakness. Stair Climbing : If the patient has stairs in their home, stair training (using a handrail if needed) Gait Training : Treadmill training or overground walking exercises. Focus on step length, stride consistency, and overall gait symmetry. Balance Training : Since proximal muscle weakness can lead to instability, working on balance is critical to reduce the risk of falls. Frequency and Intensity: Functional and balance exercises can be done 3-4 times per week . Start with simple tasks and gradually increase the complexity as the patient improves.

16. Fatigue Management and Energy Conservation Techniques Pacing Strategies : Teach patients how to pace themselves during activities. Encourage them to take frequent breaks and alternate between more demanding and less demanding tasks. Example : Advise the patient to break up tasks like cleaning the house into shorter intervals with rest in between. Energy Conservation Techniques : Educate patients on techniques to conserve energy during daily activities. Example : Sitting while performing tasks like cooking or folding laundry, using assistive devices such as reachers or shower chairs to reduce physical strain. Activity Scheduling : Help the patient prioritize high-energy tasks in the morning or during times when they feel most rested and energized.

17. Respiratory Muscle Training In some severe cases of LEMS, respiratory muscles may become weak, though this is less common than in MG. Breathing Exercises : Diaphragmatic Breathing : To strengthen the diaphragm and improve lung capacity. Incentive Spirometry : To encourage deeper breaths and improve lung function. Chest Physiotherapy : If the patient has difficulty with mucus clearance, percussion or postural drainage techniques may be helpful.

18. Patient Education : Teach the patient about LEMS, the importance of staying active within their limits, and how to monitor their own fatigue levels. Assistive Devices : Introduce walking aids such as canes or walkers if the patient has severe proximal weakness or balance issues. These devices can help reduce the risk of falls and improve mobility. Example : A four-wheeled walker with a seat may help patients who need to rest frequently while walking. Family and Caregiver Education : In cases where the patient needs assistance, provide training to family members or caregivers on how to support the patient during daily tasks and exercise.

19. Outcome Measures and Progress Monitoring Muscle Strength Testing : Regular testing of proximal muscle strength using a dynamometer or manual muscle testing. 6-Minute Walk Test (6MWT) Timed Up and Go Test (TUG) Fatigue Severity Scale (FSS) : This questionnaire helps monitor the patient’s fatigue levels and adjust therapy accordingly.