TY - JOUR
T1 - Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS
AU - Carew, J. D.
AU - Nair, G.
AU - Andersen, P. M.
AU - Wuu, J.
AU - Gronka, S.
AU - Hu, X.
AU - Benatar, Michael
N1 - Funding Information:
Dr. Carew receives research support from the NIH, AHRQ, the Cardiovascular Research Foundation, and the Carolinas HealthCare Foundation. Dr. Nair and Ms. Gronka report no disclosures. Dr. Andersen receives research support from the Swedish Science Council, the Swedish Hållsten's Brain Research Foundation and Swedish Brain Power; Dr. Andersen has served as a paid consultant for Hoffman La Roche. Ms. Wuu receives research support from NIH, FDA, CDC, MDA, ALS Association, Consolidated Anti-Aging Foundation and the Woodruff Health Sciences Center (Emory University). Dr. Hu has received research support from the NIH/NHLBI. Dr. Benatar is funded by FDA grants FD003517 and FD003710 , ALS Association grants 1491, 1712, and 1862 , and Muscular Dystrophy Association grant 172123 ; and is a paid consultant for Cytokinetics and Bayhill Therapeutics. Dr. Benatar receives publishing royalties for Neuromuscular Disease: Evidence and Analysis in Clinical Neurology (Humana Press, 2006), BluePrints in Neurology (Lippincott Williams & Wilkins, 2002), and Field of Vision: A Manual and Atlas of Perimetry (Humana Press, 2010); and has received research support from CytRx Corporation, the Centers for Disease Control and Prevention, the Woodruff Health Sciences Center (Emory University), and the NIH; he has participated in medico-legal cases.
Funding Information:
Study funding: Supported by the Muscular Dystrophy Association (grants 4365 and 172123) , the ALS Association (grants 1491 and 1712) , the Swedish Brain Research Foundation, the Hållsten's Brain Research Foundation, the Swedish Science Council, and the Swedish Association for the Neurologically Disabled.
PY - 2011/10/4
Y1 - 2011/10/4
N2 - Objective: It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neurodegeneration precedes the appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was used to measure ratios of neurometabolites in the cervical spine of asymptomatic individuals with a mutation in the SOD1 gene (SOD1+) and compare their neurometabolic ratios to patients with ALS and healthy controls. Methods: A cross-sectional study of 1H-MRS of the cervical spine was performed on 24 presymptomatic SOD1+ volunteers, 29 healthy controls, and 23 patients with ALS. All presymptomatic subjects had no symptoms of disease, normal forced vital capacity, and normal electromyographic examination. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylaspartate (NAA) were determined. Results: NAA/Cr and NAA/Myo ratios are reduced in both SOD1+ subjects (39.7%, p < 0.001 and 18.0%, p = 0.02) and patients with ALS (41.2%, p < 0.001 and 24.0%, p = 0.01) compared to controls. Myo/Cr is reduced (10.3%, p = 0.02) in SOD1+ subjects compared to controls, but no difference was found between patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with ALS (24.0%, p = 0.002), but not in presymptomatic SOD1+ subjects compared to controls. Conclusions: Changes in neurometabolite ratios in the cervical spinal cord are evident in presymptomatic SOD1+ individuals in advance of symptoms and clinical or electromyographic signs of disease. These changes reflect a reduction in NAA/Cr and NAA/Myo. Neurometabolic changes in this population resemble changes observed in patients with clinically apparent ALS. This suggests that neurometabolic changes occur early in the course of the disease process.
AB - Objective: It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neurodegeneration precedes the appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was used to measure ratios of neurometabolites in the cervical spine of asymptomatic individuals with a mutation in the SOD1 gene (SOD1+) and compare their neurometabolic ratios to patients with ALS and healthy controls. Methods: A cross-sectional study of 1H-MRS of the cervical spine was performed on 24 presymptomatic SOD1+ volunteers, 29 healthy controls, and 23 patients with ALS. All presymptomatic subjects had no symptoms of disease, normal forced vital capacity, and normal electromyographic examination. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylaspartate (NAA) were determined. Results: NAA/Cr and NAA/Myo ratios are reduced in both SOD1+ subjects (39.7%, p < 0.001 and 18.0%, p = 0.02) and patients with ALS (41.2%, p < 0.001 and 24.0%, p = 0.01) compared to controls. Myo/Cr is reduced (10.3%, p = 0.02) in SOD1+ subjects compared to controls, but no difference was found between patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with ALS (24.0%, p = 0.002), but not in presymptomatic SOD1+ subjects compared to controls. Conclusions: Changes in neurometabolite ratios in the cervical spinal cord are evident in presymptomatic SOD1+ individuals in advance of symptoms and clinical or electromyographic signs of disease. These changes reflect a reduction in NAA/Cr and NAA/Myo. Neurometabolic changes in this population resemble changes observed in patients with clinically apparent ALS. This suggests that neurometabolic changes occur early in the course of the disease process.
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U2 - 10.1212/WNL.0b013e318231526a
DO - 10.1212/WNL.0b013e318231526a
M3 - Article
C2 - 21940617
AN - SCOPUS:82255179751
VL - 77
SP - 1370
EP - 1375
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 14
ER -