Pt2 (II-4 in Figure 1A), now 60 years old, was first referred to us at 52, for insidiously progressive walking difficulties, initiated at 46 years with stiffness and weakness at the right lower limb, followed within 3-5 years by involvement of the right upper, and then left lower and upper limbs. He also reported symptoms consistent with nocturnal lower-limb myoclonus. The neurological examination at 52 years showed spastic tetraparesis, more prominent on the right side and lower limbs, bilateral pes equinovarus, normal strength, bilateral Babinski sign. His gait was paraparetic with bilateral thigh adduction; however he could still walk unassisted. He showed no muscle wasting, with the exception of bilateral atrophy of the temporalis muscle. He was diagnosed as having “primary lateral sclerosis” and started riluzole and baclofen, with no tangible benefit. Over the subsequent two years he developed mild spastic hypophonia, and moderate dysphagia for liquids, with worsening of the limb spasticity. At 56 he became wheelchair-bound, severely dysphonic and dysphagic, with severe tetra-spasticity, flexed posture, bilateral ankle clonus, bilateral Babinski, bilateral hypotrophy of temporalis, interosseus and tibialis anterior muscles. Sensory examination and neurovegetative tests were normal, as were the eye movements. The EMG showed neurogenic abnormalities, without spontaneous fibrillation. Nerve conduction studies showed motor axonal neuropathy at the lower limbs, whereas the peripheral sensory conduction was normal. Taken together, these findings indicate severe motor-neuron disease (MND) of limb and bulbar districts. Symptoms have slowly progressed over time. The patient has no cognitive deterioration.