What is the differential diagnosis for a 4-month progressive weakness and fatigue in a previously active individual, presenting with initial thumb weakness, subsequent difficulty jogging, chest pressure, decreased exercise tolerance, weight loss, early satiety, and increasing leg weakness, particularly in the hip flexors and quadriceps?

Amyotrophic Lateral Sclerosis (ALS): Given the progressive weakness, initially in the thumb and then spreading to other parts of the body, including the legs, ALS is a strong consideration. The sensation of body parts feeling 'disconnected' and the worsening fatigue throughout the day also align with ALS symptoms. However, the weight loss and early satiety are less typical and might suggest a concurrent condition.

Myasthenia Gravis: Characterized by muscle weakness that worsens with activity and improves with rest, myasthenia gravis could explain the difficulty with jogging and stair climbing. However, the weight loss and gastrointestinal symptoms are not typical.
Lambert-Eaton Myasthenic Syndrome (LEMS): Similar to myasthenia gravis but often associated with autonomic dysfunction and can have a more gradual onset. Weight loss and gastrointestinal symptoms could be part of a paraneoplastic syndrome associated with LEMS.
Inflammatory Myopathies (e.g., Polymyositis, Dermatomyositis): These conditions cause progressive muscle weakness and could explain the difficulty with physical activities. Weight loss and gastrointestinal symptoms can occur, especially if there's an associated malignancy or systemic inflammation.

Spinal Cord Compression or Tumor: A mass in the spinal cord could cause progressive weakness, especially if it affects the cervical or thoracic regions. The sensation of body parts feeling 'disconnected' could be indicative of sensory level changes.
Multiple Sclerosis: Although less likely given the progressive nature without clear relapses, multiple sclerosis can cause a wide range of neurological symptoms, including weakness, fatigue, and sensory disturbances.
Neurosyphilis: A condition that can mimic many neurological diseases, including those causing progressive weakness and fatigue. It's crucial to consider in patients with risk factors.

Mitochondrial Myopathies: A group of disorders affecting the mitochondria, leading to muscle weakness and fatigue. These conditions are rare and often have a more insidious onset.
Pompe Disease: A genetic disorder causing glycogen accumulation in muscles, leading to progressive weakness. It's rare and typically presents in infancy, but late-onset forms can occur in adults.
Kennedy's Disease (Spinal and Bulbar Muscular Atrophy): A rare X-linked recessive disorder causing progressive muscle weakness, atrophy, and fasciculations, primarily in men.