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Do serum uric acid levels reflect oxidative stress in the progression of ALS?
Journal of the Neurological Sciences 287 (2009) 294
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Letter to the Editor Do serum uric acid levels reflect oxidative stress in the progression of ALS?
Dear the Editor: We read with great interest article of Keizman et al [1]. Authors show low serum uric acid (UA) levels in patients with amyotrophic lateral sclerosis (ALS) as compared to well-matched controls [1]. We also studied prognostic variables in ALS patients. We would like to argue the relationship between serum UA levels and disease progression. Forty-nine patients with definite or probable ALS fulfilled the El Escorial revised criteria were analyzed for prognostic factors, including age, sex, disease duration, ALS Functional Rating Scale (FSR), serum UA levels, serum creatinine (Cr) levels, body mass index (BMI) and forced vital capacity (FVC). Those variables were measured twice at the initial examination and one year later. Three patients were diagnosed as familial ALS. ALS patients who had hypertension, renal dysfunction, gout, a percutaneous enterogastrostomy and UAlowering medication were excluded. Serum UA and Cr levels were compared between ALS patients and 50 age-, sex- and BMI-matched healthy controls. As compared to controls, serum UA and Cr levels were decreased significantly in ALS patients. Annual decline rate of FRS was correlated with decline rate of serum Cr levels, BMI and FVC. The first data of serum UA, serum Cr, BMI and FVC were not associated with decline rate of FRS. Annual changes of serum UA levels were varied, and no significant differences existed between those changes and FRS decline rate (Table 1). Table 1 Clinico-laboratory variables in ALS patients and healthy controls.
Age years Sex (male/female) Initial FRS Decline rate of FRS, %/year Serum UA mg/dL Varied rate of serum UA, %/year Serum Cr mg/dL Decline rate of serum Cr, %/year BMI kg/m2 Decline rate of BMI, %/year FVC % Decline rate of FVC, %/year
ALS patients (n = 49)
Controls (n = 50)
58.8 ± 12.7 32/17 40.2 ± 3.8 28.3 ± 10.2 4.1 ± 1.2⁎
59.1 ± 12.3 30/20
7.8 ± 2.7 0.51 ± 0.19⁎ 23.8 ± 17.3⁎⁎ 21.6 ± 3.3 10.2 ± 9.6⁎⁎ 91.0 ± 19.8 31.7 ± 28.0⁎⁎
5.8 ± 1.5 0.74 ± 0.20
Keizman et al. [1] conclude that monthly decline rate of FRS is correlated to relative decrease of serum UA levels (ΔUA) that is defined as the control's level minus the patient's level at the 2nd blood test. Our study also disclosed that serum UA levels differed significantly between ALS patients and controls. However, serum UA levels and those annual changes were not found to affect disease progression in our patients. Our question is whether serum UA values at the first or the second blood examination are linked to disease progression (ΔFRS) in patients of Keizman et al. Whether differences between the 1st and the 2nd serum UA levels of their 46 patients are associated with ΔFRS? Annual decline of serum Cr levels, BMI and FVC strongly suggest progression of muscle atrophy in our patients. Those variables are reported as independent prognostic survival factors in ALS patients [2]. Serum UA and Cr levels depend on skeletal muscle damages and volumes, besides renal function. We would like to know serum Cr levels in patients and well-matched controls of Keizman et al. One possibility is proposed that muscle damages in ALS patients may influence ΔUA between patients and controls. Our data and the study of Keizman et al [1] support low UA levels in sera of ALS patients. Nevertheless, annual changes of serum UA levels were not associated with disease progression in our patients. Thus, we need to interpret cautiously how serum UA levels contribute to oxidative stress in the progression of ALS. Serum UA changes from early stage of ALS patients should be monitored. References [1] Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress? J Neurol Sci Jun 22 2009 Electronic publication ahead of print. [2] Paillisse C, Lacomblez I, Dib M, Bensimon G, Garcia-Acosta S, Meininger V. Prognostic factors for survival in amyotrophic lateral sclerosis patients treated with riluzole. Amyotroph Lateral Scler Other Mot Neuron Disord 2005;6:37–44.
Ken Ikeda ⁎ Kiyokazu Kawabe Yasuo Iwasaki Department of Neurology, Toho University Omori Medical Center, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan ⁎Corresponding author. Tel.: +81 3 3762 4151; fax: +81 3 3768 2566. E-mail address: [email protected] (K. Ikeda).
21.9 ± 3.6
FRS = ALS Functional Rating Scale. UA = uric acid. Cr = creatinine. BMI = body mass index. FVC = forced vital capacity. Data are shown as mean ± SD. ⁎ p < 0.01 by unpaired Student's t-test. Significant differences of serum UA and Cr between ALS patients and controls. ⁎⁎ p < 0.01 by Spearman's rho correlation. FRS decline rate is correlated with decline rate of serum Cr levels, BMI and FVC. 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.08.008
22 July 2009
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Letter to the Editor Do serum uric acid levels reflect oxidative stress in the progression of ALS?
Dear the Editor: We read with great interest article of Keizman et al [1]. Authors show low serum uric acid (UA) levels in patients with amyotrophic lateral sclerosis (ALS) as compared to well-matched controls [1]. We also studied prognostic variables in ALS patients. We would like to argue the relationship between serum UA levels and disease progression. Forty-nine patients with definite or probable ALS fulfilled the El Escorial revised criteria were analyzed for prognostic factors, including age, sex, disease duration, ALS Functional Rating Scale (FSR), serum UA levels, serum creatinine (Cr) levels, body mass index (BMI) and forced vital capacity (FVC). Those variables were measured twice at the initial examination and one year later. Three patients were diagnosed as familial ALS. ALS patients who had hypertension, renal dysfunction, gout, a percutaneous enterogastrostomy and UAlowering medication were excluded. Serum UA and Cr levels were compared between ALS patients and 50 age-, sex- and BMI-matched healthy controls. As compared to controls, serum UA and Cr levels were decreased significantly in ALS patients. Annual decline rate of FRS was correlated with decline rate of serum Cr levels, BMI and FVC. The first data of serum UA, serum Cr, BMI and FVC were not associated with decline rate of FRS. Annual changes of serum UA levels were varied, and no significant differences existed between those changes and FRS decline rate (Table 1). Table 1 Clinico-laboratory variables in ALS patients and healthy controls.
Age years Sex (male/female) Initial FRS Decline rate of FRS, %/year Serum UA mg/dL Varied rate of serum UA, %/year Serum Cr mg/dL Decline rate of serum Cr, %/year BMI kg/m2 Decline rate of BMI, %/year FVC % Decline rate of FVC, %/year
ALS patients (n = 49)
Controls (n = 50)
58.8 ± 12.7 32/17 40.2 ± 3.8 28.3 ± 10.2 4.1 ± 1.2⁎
59.1 ± 12.3 30/20
7.8 ± 2.7 0.51 ± 0.19⁎ 23.8 ± 17.3⁎⁎ 21.6 ± 3.3 10.2 ± 9.6⁎⁎ 91.0 ± 19.8 31.7 ± 28.0⁎⁎
5.8 ± 1.5 0.74 ± 0.20
Keizman et al. [1] conclude that monthly decline rate of FRS is correlated to relative decrease of serum UA levels (ΔUA) that is defined as the control's level minus the patient's level at the 2nd blood test. Our study also disclosed that serum UA levels differed significantly between ALS patients and controls. However, serum UA levels and those annual changes were not found to affect disease progression in our patients. Our question is whether serum UA values at the first or the second blood examination are linked to disease progression (ΔFRS) in patients of Keizman et al. Whether differences between the 1st and the 2nd serum UA levels of their 46 patients are associated with ΔFRS? Annual decline of serum Cr levels, BMI and FVC strongly suggest progression of muscle atrophy in our patients. Those variables are reported as independent prognostic survival factors in ALS patients [2]. Serum UA and Cr levels depend on skeletal muscle damages and volumes, besides renal function. We would like to know serum Cr levels in patients and well-matched controls of Keizman et al. One possibility is proposed that muscle damages in ALS patients may influence ΔUA between patients and controls. Our data and the study of Keizman et al [1] support low UA levels in sera of ALS patients. Nevertheless, annual changes of serum UA levels were not associated with disease progression in our patients. Thus, we need to interpret cautiously how serum UA levels contribute to oxidative stress in the progression of ALS. Serum UA changes from early stage of ALS patients should be monitored. References [1] Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress? J Neurol Sci Jun 22 2009 Electronic publication ahead of print. [2] Paillisse C, Lacomblez I, Dib M, Bensimon G, Garcia-Acosta S, Meininger V. Prognostic factors for survival in amyotrophic lateral sclerosis patients treated with riluzole. Amyotroph Lateral Scler Other Mot Neuron Disord 2005;6:37–44.
Ken Ikeda ⁎ Kiyokazu Kawabe Yasuo Iwasaki Department of Neurology, Toho University Omori Medical Center, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan ⁎Corresponding author. Tel.: +81 3 3762 4151; fax: +81 3 3768 2566. E-mail address: [email protected] (K. Ikeda).
21.9 ± 3.6
FRS = ALS Functional Rating Scale. UA = uric acid. Cr = creatinine. BMI = body mass index. FVC = forced vital capacity. Data are shown as mean ± SD. ⁎ p < 0.01 by unpaired Student's t-test. Significant differences of serum UA and Cr between ALS patients and controls. ⁎⁎ p < 0.01 by Spearman's rho correlation. FRS decline rate is correlated with decline rate of serum Cr levels, BMI and FVC. 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.08.008
22 July 2009