Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)

1. ALS Volunteers Inclusion Criteria: * Diagnosis of possible (excluding volunteers with UMN signs ONLY), probable, probable-laboratory supported, or definite ALS, either sporadic or familial according to revised El Escorial criteria * Disease duration of less than or equal to two years from symptom onset * Age 30-80 years at the time of disease onset * Ability to provide informed consent * Ability to comply with study procedures * Medically safe to have lumbar puncture (lumbar puncture volunteers only) Exclusion Criteria: * Clinical evidence of chronic liver or renal failure * Presence of a bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (lumbar puncture volunteers only) * Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (lumbar puncture volunteers only) 2. Suspected ALS (PMND) Volunteers Inclusion Criteria: * Diagnosis of suspected ALS defined as presence of UMN or LMN signs alone and the diagnosis of Clinically Probably Laboratory-Supported ALS CANNOT be proven by evidence in clinical grounds in conjunction with electrodiagnostic, neurophysiologic, neuroimaging or clinically laboratory studies * Disease duration of less than or equal to four years from symptom onset * Age 30-80 years at time of disease onset * Ability to provide informed consent * Ability to comply with study procedures * Medically safe to have lumbar puncture (lumbar puncture volunteers only) Exclusion Criteria: * Clinical evidence of chronic liver or renal failure * Genetically confirmed diagnosis of hereditary spastic paraparesis or spinal motor atrophy (SMA) disease * Presence of a bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (lumbar puncture volunteers only) * Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (lumbar puncture volunteers only) 3. Neurological Disease Mimic Volunteers Inclusion Criteria: Diagnosis of one of the following: Pure Lower Motor Neuron Disease (LMND) mimics: * Multi-focal motor neuropathy * Autoimmune motor neuropathy * Cervical or lumbosacral radiculopathies Peripheral mononeuropathies: * Ulnar neuropathy * Carpal tunnel syndrome/median neuropathy * Peroneal neuropathy * Sciatic neuropathy * Spinal muscular atrophy * Spinobulbar muscular atrophy (Kennedy's disease) * Charcot Marie-Tooth Disease (CMT) Pure Upper Motor Neuron Disease (UMND) mimics: * Cervical myelopathy * Multiple sclerosis * Hereditary spastic paraparesis * Age 30-80 years * Ability to provide informed consent * Ability to comply with study procedures * Medically safe to have lumbar puncture (lumbar puncture volunteers only) Exclusion Criteria: * Diagnosis of suspected, possible, probable or definite ALS either sporadic or familial * Presence of positive family history of ALS * Clinical evidence of chronic renal or liver failure * Presence of a bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (lumbar puncture volunteers only) * Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (lumbar puncture volunteers only) 4. Healthy Control Volunteers Inclusion Criteria * Absence of a known neurological disorder. * Age 30 - 80 years. * Ability to provide informed consent. * Ability to comply with study procedures. * Medically safe to have lumbar puncture. Exclusion Criteria: * History of ALS, myopathy, neuropathy, ALS mimic disorder or other neurodegenerative disease. * Presence of positive family history of ALS. * Clinical evidence of chronic liver or renal failure. * Presence of bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (LP research volunteers only). * Research participant must not be taking anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (LP research volunteers only).