Lambert-Eaton Myasthenic Syndrome (LEMS)

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness, fatigue, and autonomic dysfunction. It is also known as Lambert-Eaton syndrome or Eaton-Lambert syndrome.

Causes and Pathophysiology

LEMS is caused by an autoimmune response against the voltage-gated calcium channels (VGCCs) at the neuromuscular junction. The immune system produces antibodies that bind to the VGCCs, reducing the release of acetylcholine and leading to impaired muscle contraction.

Symptoms

The symptoms of LEMS may include:

• Muscle weakness, particularly in the proximal muscles (e.g., shoulders, hips)
• Fatigue
• Autonomic dysfunction, such as:
  • Dry mouth
  • Impaired pupillary reflexes
  • Orthostatic hypotension
  • Urinary retention or incontinence
• Decreased or absent deep tendon reflexes
• Difficulty walking or climbing stairs
• Drooping eyelids (ptosis)
• Double vision (diplopia)

Diagnosis

The diagnosis of LEMS is based on a combination of clinical evaluation, laboratory tests, and electrophysiological studies. Diagnostic criteria may include:

• Characteristic symptoms and physical examination findings
• Presence of VGCC antibodies in the blood
• Electromyography (EMG) showing a decremental response to repetitive nerve stimulation
• Nerve conduction studies (NCS) showing slowed nerve conduction velocities

Treatment and Management

Treatment for LEMS typically involves a combination of medications and therapies, including:

• 3,4-Diaminopyridine (3,4-DAP), which increases acetylcholine release at the neuromuscular junction
• Prednisone or other corticosteroids to reduce inflammation and suppress the immune system
• Azathioprine or other immunosuppressive agents to reduce antibody production
• Plasmapheresis or intravenous immunoglobulin (IVIG) to remove antibodies from the blood
• Physical therapy to maintain muscle strength and mobility

Prognosis and Complications

The prognosis for LEMS varies depending on the underlying cause, response to treatment, and presence of complications. Potential complications may include:

• Respiratory failure due to severe muscle weakness
• Autonomic dysfunction leading to orthostatic hypotension or urinary retention
• Increased risk of falls and injuries due to muscle weakness
• Association with small cell lung cancer (SCLC) in approximately 60% of patients, which may require separate treatment and management

Epidemiology and Demographics

LEMS is a rare disorder, affecting approximately 1-2 people per million. It can occur at any age, but typically presents in middle to late adulthood. Men are more commonly affected than women, and there may be an association with other autoimmune disorders or cancer.