Snapshot A 61-year-old male presents with left-sided hand weakness and trouble with walking. He is not sure why these symptoms occur. On physical exam, tongue fasciculations are appreciated. He has slow speech. The left upper extremity shows forearm atrophy and depressed reflexes. The right lower extremity is hypertonic, with 3+ reflexes, and positive Babinski sign. Introduction A progressive neurodegenerative disease affecting both upper and lower motor neurons there are sporadic (~90% of cases) and familial causes sensation is intact bowel and bladder are spared Certain cases may be due to superoxide dismutase type 1 (SOD-1) mutations results in the generation of free radicals, eventually leading to cell death Epidemiology Age of onset: ~60 years of age in sporadic cases ~50 years of age in familial cases Presentation Symptoms progressive weakness affecting any segment of the body asymmetric limb weakness (most common) upper and lower motor neuron signs upper motor neuron (UMN) signs spasticity or stiffness hyperreflexia dysarthria dysphagia lower motor neuron (LMN) signs atrophy fasciculations hyporeflexia weakness Evaluation LMN signs determined by physical exam, electrophysiologic, or neuropathologic studies UMN signs determined by physical exam Symptom progression spread or signs No other disease process can explain the patient's findings EMG shows widespread denervation and fibrillation potential Differential Benign fasciculations Spinal muscular atrophy Poliomyelitis Multiple sclerosis Syringomyelia Treatment Riluzole only medication to slow disease progression and improve survival may decrease excitotoxic damage to neurons Edaravone Supportive treatment Dextramethorphan/quinidine for pseudobulbar affect Baclofen and tizanidine for spasticity Complications Weight loss Respiratory failure Sialorrhea Depression Prognosis Main cause of death is respiratory failure