Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1370-1375 |
| Number of pages | 6 |
| Journal | Neurology |
| Volume | 77 |
| Issue number | 14 |
| DOIs | |
| State | Published - Oct 4 2011 |
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ASJC Scopus subject areas
- Clinical Neurology
- Arts and Humanities (miscellaneous)
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Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. / Carew, J. D.; Nair, G.; Andersen, P. M.; Wuu, Joanne; Gronka, S.; Hu, X.; Benatar, Michael G.
In: Neurology, Vol. 77, No. 14, 04.10.2011, p. 1370-1375.Research output: Contribution to journal › Article
}
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, Joanne
AU - Gronka, S.
AU - Hu, X.
AU - Benatar, Michael G
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
VL - 77
SP - 1370
EP - 1375
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 14
ER -