Differential Diagnosis for the 42-year-old Male Patient

Single Most Likely Diagnosis

• Amyotrophic Lateral Sclerosis (ALS): The progression from lower limb weakness to upper limb weakness, along with muscle wasting and the absence of the ankle jerk, points towards a motor neuron disease. The presence of both upper and lower motor neuron signs (wasting and weakness for lower motor neuron, and absent ankle jerk for upper motor neuron) in the absence of sensory findings is highly suggestive of ALS.

Other Likely Diagnoses

• Progressive Muscular Atrophy (PMA): A form of motor neuron disease that primarily affects the lower motor neurons, leading to muscle wasting and weakness. The initial presentation in one limb with progression to others could fit PMA, although the absence of ankle jerk might suggest some upper motor neuron involvement.
• Multifocal Motor Neuropathy (MMN): Characterized by asymmetric muscle weakness and wasting, often starting in one limb. However, MMN typically responds well to immunomodulatory treatment, and the absence of sensory symptoms and the specific pattern of progression might make ALS more likely.

Do Not Miss Diagnoses

• Spinal Cord Compression or Tumor: Although the sensory examination is normal, any progressive neurological deficit warrants consideration of a compressive lesion, especially given the tobacco use which increases the risk of cancer. A tumor could cause both motor and sensory symptoms, but the absence of sensory findings does not rule out a slowly progressive compressive lesion.
• Vitamin Deficiency (e.g., Vitamin B12 Deficiency): Can cause subacute combined degeneration of the spinal cord, leading to upper motor neuron signs, but typically also involves sensory symptoms. However, early on, the presentation might be predominantly motor.

Rare Diagnoses

• Kennedy's Disease (Spinal and Bulbar Muscular Atrophy): An X-linked recessive disorder that affects males, characterized by bulbar and limb muscle weakness and atrophy, but typically includes symptoms like gynecomastia and tremor, which are not mentioned here.
• Inherited Motor Neuropathies (e.g., Charcot-Marie-Tooth Disease): These conditions can cause progressive muscle weakness and wasting but usually have a family history and often involve sensory nerves as well. The pattern of progression and the absence of sensory findings make this less likely.