Amyotrophic Lateral Sclerosis (ALS) with Laboratory Abnormalities of Unknown Significance (LAUS) --Where Does It Begin and Where Does It End? (P4.144)

OBJECTIVE: Define the prevalence/natural history of ALS-LAUS at an ALS Multidisciplinary Clinic in the Southeastern USA BACKGROUND: ALS-LAUS, characterized by upper and lower motor neuron signs together with LAUS, was categorized as a diagnostic classification category by the World Federation of Neurology Research Group on Motor Neuron Disease/ALS. Lower motor neuron syndromes(LMNS) with LAUS may be separated out as ALS-Mimics. DESIGN/METHODS: Patient Database review from 2010-2014 of 457 patients referred for ALS diagnosis. RESULTS: ALS-LAUS was seen in[79/457=17.2[percnt]]of evaluated patients with probable-laboratory supported, clinically probable and clinically definite ALS by Revised El Escorial criteria. GM1-ganglioside/HS6S/SGPG auto-immune Antibodies(Abs)[12/79=15.2[percnt]], Monoclonal Gammopathy of Unknown Significance(MGUS)/Waldenstrom[16/79=20.3[percnt]], Voltage-Gated Calcium or Potassium Channel Abs[7/79=8.8[percnt]], hypo/hyper-gammaglobulinemia/cryoglobulinemia[12/79=15.2[percnt]], Acetylcholine Receptor/Ganglionic Acetylcholine Receptor/low-density lipoprotein receptor-related protein(LRP4)agrin receptor/Skeletal muscle Abs[3/79=3.8[percnt]], Anti-phospholipid/Sjogren’s Abs[2/79=2.5[percnt]]comprise a pattern of possibly immune-mediated motor neuron pathogenesis[52/79=65.8[percnt]]. Concurrent infection with Virus[WNV,HCV,HPV,Rubella][5/79=6.3[percnt]] and borrelia burgdorferi[1/79=1.3[percnt]]was identified. Methylmalonic acidemia[4/79=5.1[percnt]]and aluminum toxicity[4/79=5.1[percnt]]were identified and treated. In addition to standard riluzole, patients with ganglioside Abs[10/12=83.3[percnt]], MGUS/Waldenstrom[2/16=12.5[percnt]], VGCC/KC Abs[4/7=57.1[percnt]], hyper-or hypo-gammaglobulinemia/cryoglobulinemia[1/12=4.8[percnt]] were treated with IVIg and/or other regimens. On IVIg treatment, ALSFRS-R deterioration showed no change over 12 months in 1/2 MGUS/Waldenstrom patients and slowed in 3/10 ganglioside Abs patients. Pulmonary embolism rate [5/79=6.3[percnt]-ALS-LAUS;20/377=5.3[percnt]-ALS] was comparable in both groups. Overall, the course of patients with ALS-LAUS is significantly slower[p=0.05][0.5+0.5 ALSFRS-R units/month compared with 0.9+0.6 units/month. CONCLUSIONS: Further detailed analysis of progression rate by site of onset, sex, age, treatment will require assimilation of clinic-based datasets of properly analyzed ALS-LAUS patients from multiple clinic sites. The appropriate role of IVIg in ALS-LAUS patients requires further study following explication of the natural history of these patients compared with non-ALS-LAUS patients. The determination as to whether auto-antibodies to additional antigens may play a role in the progression rate of ALS-LAUS compared with sporadic ALS needs to be systematically studied. Study Supported by: Carolinas ALS Research Fund Disclosure: Dr. Brooks has received personal compensation for activities with Biogen Idec, Avanir Pharmaceuticals, Acorda Therapeutics, Cytokinetics, Synapse, and the National Institute of Neurological Disorders and Stroke. Dr. Bravver has nothing to disclose. Dr. Langford has nothing to disclose. Dr. Alwan has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Lucas has nothing to disclose. Dr. Nichols has nothing to disclose. Dr. Belcher has nothing to disclose. Dr. Lary has nothing to disclose. Dr. Nemeth has nothing to disclose. Dr. Russo has received personal compensation for activities with Teva Neuroscience and Biogen Idec as a consultant. Dr. Wright has nothing to disclose. Dr. Ward has nothing to disclose. Dr. Holsten has nothing to disclose. Dr. Fischer has nothing to disclose. Dr. Bockenek has nothing to disclose. Dr. Desai has received personal compensation for activities with Purdue Pharma and UCB Pharma as a speaker. Dr. Lindblom has nothing to disclose. Dr. Pacicco has nothing to disclose. Dr. Sanjak has nothing to disclose.