Q 2.15. Myasthenia Gravis (MG) MG vs other neuro-muscular junction disorders. Diagnosis and treatment.

 

 

Clinical case: 

Patient Profile: 

– Age: 48 

– Gender: Female 

– Occupation: High school teacher 

Chief Complaints: 

– Progressive muscle weakness, predominantly in the upper limbs 

– Ptosis (drooping of the eyelids) 

– Diplopia (double vision) 

History of Present Illness: 

The patient, a 48-year-old high school teacher, presents with a 6-month history of fluctuating muscle weakness, which worsens towards the evening. Initially, she noticed difficulty holding her arms up while writing on the board and experienced episodes of double vision, which she initially attributed to fatigue. However, the symptoms have progressively worsened, affecting her ability to perform daily tasks. 

 

Neurological Examination: 

 Cranial Nerves: Ptosis observed, with fatigable weakness upon sustained upward gaze, suggesting ocular muscle involvement. 

– Motor Examination: Mild bilateral weakness in the proximal upper limb muscles, more pronounced after repetitive use. 

Reflexes: Normal. 

– Sensation: Intact. 

– Coordination: No ataxia noted. 

 

Clinical Progression: 

Over the past few months, the patient’s symptoms have shown a clear pattern of fatigability. The muscle weakness is not present at rest but becomes evident with sustained muscle use. There is a notable improvement in muscle strength after periods of rest. 

 

Discussion: 

This case illustrates a typical presentation of myasthenia gravis (MG), a chronic autoimmune neuromuscular disorder characterized by varying degrees of weakness of the voluntary muscles. MG commonly affects ocular, bulbar, and limb muscles and can present with ptosis, diplopia, and fluctuating muscle strength, which are hallmark signs of the disease. The progression of symptoms throughout the day and improvement with rest are indicative of the fatigable nature of MG. Neurological examination findings, such as fatigable muscle weakness without sensory or reflex abnormalities, are key to suspecting MG in a clinical setting. 

 

Educational Note for Medical Students: 

In patients presenting with fluctuating muscle weakness and ocular symptoms, consider MG in the differential diagnosis. Neurological examination focusing on muscle strength and fatigability, along with a detailed patient history, can provide critical clues for diagnosis. Further diagnostic tests, such as serum acetylcholine receptor antibody levels and electromyography, would be warranted to confirm the diagnosis of MG. Treatment typically involves immunosuppression and symptomatic management, with a focus on improving quality of life and minimizing the impact of symptoms on daily activities. 

 

  • Definition: MG is the most common autoimmune disease affecting the neuromuscular junction. 

Characteristics: 

  • Muscle Weakness: It presents as painless fatigable muscle weakness. 

  • Autoantibodies: MG is caused by autoantibodies against neuromuscular junction proteins. 

    • Nicotinic Acetylcholine Receptor (AChR): Autoantibodies can target AChR. 

    • Muscle-Specific Tyrosine Kinase (MuSK): Another subset of patients has autoantibodies against MuSK. 

  • Epidemiology: Affects approximately 100 patients per million population. 
  • Bimodal Age of Onset: 

    • Early-Onset: Typically affects women under 40 years. 

    • Late-Onset: More common in older men. 

    • Prevalence is increasing, especially in the elderly. 

  • Neuromuscular Physiology: Acetylcholine (ACh) is the key neurotransmitter at the neuromuscular junction. Nerve impulses open voltage-gated calcium channels (VGCC), leading to calcium influx. This triggers ACh vesicle fusion and neurotransmitter release. ACh binds to nicotinic AChRs on the postsynaptic membrane, causing short-lived ion channel openings. If the depolarization reaches a critical threshold, voltage-gated sodium channels open, generating an action potential. 

  •  

 

Myasthenia gravis (MG) associated with thymoma represents a unique clinical entity that requires careful consideration and management. Thymomas are tumors arising from the thymus gland, and their association with MG is well-established, occurring in approximately 30% of cases.  

Key Points to Note: 

  • Pathophysiology: The exact mechanism linking thymoma and MG remains unclear, but it is believed to involve an autoimmune response against acetylcholine receptors at the neuromuscular junction. Thymomas may harbor autoreactive T-cells that trigger immune dysfunction. 

  • Clinical Presentation: Patients typically present with symptoms of MG, including muscle weakness, fatigue, and ptosis (drooping eyelids). However, MG associated with thymoma may exhibit a more severe and refractory course compared to non-thymomatous MG. 

  • Diagnosis: Diagnosis involves a combination of clinical evaluation, serological testing for anti-acetylcholine receptor antibodies, and imaging studies to identify thymoma. Thymoma-associated MG often presents with thymic enlargement on imaging. 

  • Treatment: Management of MG associated with thymoma necessitates a multidisciplinary approach involving neurologists, oncologists, and thoracic surgeons. Treatment options may include thymectomy (surgical removal of the thymus), immunosuppressive therapy, and tumor-directed treatment. 

  • Prognosis: Thymectomy has been shown to improve outcomes in patients with thymoma-associated MG, although the response to treatment can vary. Close monitoring for disease recurrence and long-term complications is essential. 

 

Other Neuromuscular Junction Disorders: 

  1. Lambert-Eaton Myasthenic Syndrome (LEMS): 

  • Cause: Autoantibodies against voltage-gated calcium channels (VGCC). 

  • Presentation: Muscle weakness, especially in proximal muscles. 

  • Distinguishing Feature: Improvement with repetitive muscle use (unlike MG). 

  • Treatment: Symptomatic and immunomodulatory . 

  1. Neuromyotonia: 

  • Cause: Autoantibodies against voltage-gated potassium channels (VGKC). 

  • Features: 

  • Muscle Hyperexcitability: Continuous muscle fiber activity. 

  • Myokymia: Visible muscle rippling. 

  • Treatment: Symptomatic and immunomodulatory . 

 

Diagnosis and Treatment: 

  • Diagnosis: 

    • Clinical Assessment: Based on characteristic symptoms and signs. 

    • Serological Testing: Detect autoantibodies (AChR, MuSK, VGCC, VGKC). 

    • Electromyography (EMG): Repetitive nerve stimulation shows decremental response in MG. 

  • Treatment: 

    • Acetylcholinesterase Inhibitors: Enhance ACh availability. 

    • Immunosuppression: Corticosteroids, azathioprine, mycophenolate. 

    • Thymectomy: Beneficial in some cases. 

    • Plasmapheresis and Intravenous Immunoglobulins: For acute exacerbations. 

    • Supportive Measures: Manage respiratory function, ocular symptoms, and swallowing difficulties . 

Remember, early recognition and appropriate management are essential for improving patient outcomes. 

 

Does it make sense?  

Lambert-Eaton Myasthenic Syndrome (LEMS) and Myasthenia Gravis (MG) are both autoimmune disorders that affect the neuromuscular junction, but they have distinct differences: 

 

Target of the Immune Response: 

  – In MG, the immune system targets the acetylcholine receptors at the neuromuscular junction. 

  – In LEMS, the immune system targets the voltage-gated calcium channels on the presynaptic nerve terminal. 

 

Muscle Weakness: 

  – MG typically presents with muscle weakness that worsens with activity. 

  – LEMS often shows muscle weakness that may improve with exercise. 

 

Associated Conditions: 

  – LEMS is often associated with an underlying malignancy, such as small cell lung cancer. 

  – MG is not commonly associated with cancer. 

 

Autonomic Symptoms: 

  – LEMS can present with autonomic symptoms like dry mouth or erectile dysfunction, which are not typical in MG. 

 

Reflexes: 

  – Patients with LEMS usually have reduced or absent reflexes, a feature not commonly seen in MG. 

 

Response to Medications: 

  – MG often responds well to acetylcholinesterase inhibitors. 

  – LEMS may require medications that facilitate the release of acetylcholine from the presynaptic terminal. 

 

Understanding these differences is crucial for accurate diagnosis and treatment of these conditions. For medical students, it’s important to note these distinctions when evaluating patients with muscle weakness and other related symptoms. 

 

References: 

1 pn.bmj.com 

2 jnnp.bmj.com 

3 mayoclinic.org 

4 msdmanuals.com 

5 teesneuro.org 

6 doi.org 

 

 

Verified by Dr. Petya Stefanova