Paraplegia is loss of motor power in both lower limbs. Quadriplegia is loss of motor power in all four limbs. Motor weakness/paralysis occurs in upper motor neuron lesion, lower motor neuron lesion, neuromuscular junction disorder, and muscle disease. Differential diagnosis of motor weakness, clinical approach to acute paraplegia, approach to clinical disability due to stiffness of limbs, clinical approach to slow progressive/chronic LMN paraplegia, myopathy, and myasthenia are covered in this chapter. Diseases due to neuromuscular disorder (myasthenia) is characterized by fluctuating motor weakness, fatigability, usually starts with diplopia ptosis. The main features of episodic enduring motor weakness (not fluctuating motor weakness) and cramps associated with muscle weakness.