Objective-To determine 1) the reproducibility of metabolite measurements by 1 H MRS in the motor cortex; 2) the extent to which 1 H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS.Methods-Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice 1 H MRSI. 1 H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain.Results-The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS.Conclusion-Metabolite changes measured by 1 H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.ALS is a neurodegenerative disorder that causes rapid loss of motor neurons in the brain and spinal cord leading to paralysis and death. Diagnosis is based solely on clinical data, and there is no definitive diagnostic test for ALS and no surrogate marker for directly measuring disease progression. Therefore, an objective and quantitative method would be extremely helpful to evaluate viability and functioning of upper motor neurons in ALS, identify individuals at an early stage of the disease, and monitor responses to treatment. In addition to NAA, 1 H MRS measures resonances from choline (Cho)-and creatine (Cre)-containing compounds in the brain. Cre represents a combination of creatine and phosphocreatine, a putative marker of gliosis, 3,6 and Cho is thought to be a marker associated with membrane phospholipids. 7In most previous MRS studies of ALS,4,[8][9][10][11][12][13][14][15][16][17][18][19][20] sampling of metabolite signals from the motor cortex was limited, because measurements were restricted to a rectangular region within the brain that was sufficiently distant from the skull to avoid interferences with an intense signal from extracranial lipids. Furthermore, because the selected regions of interest were generally large, including unavoidably some white matter and nonmotor tissue, results from these studies may have been skewed to the extent that white matter and nonmotor regions contributed to the metabolite signal from the motor cortex. With use of a multiplana...

Although diabetic ketoacidosis is characterized by increased renal excretion of glucose, ketone bodies, and nitrogenous compounds, there are few quantitative studies pertaining to renal function during this state. Therefore, renal function was studied in 10 adult patients in moderate to severe diabetic ketoacidosis before insulin administration. Admission plasma concentrations were: glucose 21.4 (9.2–39.4) mM or 386 (166–710) mg/dl, acetoacetate 3.0 (1.3–7.4) mM, beta-hydroxybutyrate 7.9 (2.9–15.2) mM, acetone 4.4 (1.3–8.9) mM, and HCO3 12.8 (9.5–17.8) mM. Arterial blood pH was 7.28 (7.21–7.38). Partial rehydration was achieved with 0.45% saline. Inulin was used to measure GFR. Renal clearance of acetoacetate, beta-hydroxybutyrate, acetone, glucose, and urinary excretion of nitrogenous compounds were determined. Partial rehydration reduced plasma glucose concentration, primarily because of renal excretion, amounting to 384 ± 73 μmol/min or 69 ± 13 mg/min. Partial rehydration had no effect on plasma ketone bodies, on bicarbonate or urea concentrations, or on arterial pH. Partial rehydration had no effect on ketone body or nitrogenous compound excretory rates. Reabsorptive rates of acetoacetate, beta-hydroxybutyrate, acetone, and glucose increased linearly with their filtered loads, and no maximal renal tubular transport rates were demonstrated for any ketone body or glucose. Because renal absorption of ketone bodies was less than 100%, ketonuria increased as filtered loads increase. Unlike ketone bodies, glucose reabsorptive rate was directly related to GFR. Total renal excretion of nitrogen in the forms of urea, ammonium, creatinine, and uric acid amounted to 16 ± 2 mg/min. This huge loss of body nitrogen reflected ongoing protein catabolism and not heightened renal excretion of preformed compounds, as the plasma concentrations of urea, creatinine, and uric acid did not change during the study. Urea nitrogen accounted for 12 ± 2 mg/min (72%) of the total nitrogen excreted. Ammonium excretion was markedly augmented, ranging from 76 to 537 μmol/min, and was inversely related to arterial pH. We conclude that the fall in plasma glucose concentration is primarily caused by renal glucose excretion, and that the absence of a maximal renal tubular reab-sorption rate for either acetoacetate (AcAc) or beta-hydroxybutyrate (β-OHB) serves to mitigate urinary losses of sodium and potassium during diabetic ketoacidosis.

Clinical states of hyperglucocorticoidism are associated with renal metabolic alkalosis, yet the systemic and renal acid-base response to chronic administration of glucocorticoid steroids (dexamethasone, triamcinolone) possessing little or no mineralocorticoid activity has not been investigated. In balance studies studies in dogs administration of triamcinolone (Tcn), 1.0 mg . kg-1 . day-1 for 6-9 days (group I, n = 5), resulted in a persistent reduction in urine pH and increase in net acid excretion (NAE), and in the excretion of urinary unmeasured anions (C+NH4,Na;K minus A-Cl,HCO3,Pi), which were identified as organic anions and sulfate. A significant degree of metabolic acidosis occurred initially (delta [HCO3-]p, -3.4 meq/liter, P less than 0.05, day 1). As Tcn administration was continued, the cumulative increment in net acid excreted exceeded the cumulative increment in urinary unmeasured anion excreted and [HCO-3]p returned to pre-Tcn control values and remained stable thereafter. In the steady state of Tcn administration plasma potassium concentration and renal potassium clearance were not significantly different from pre-Tcn control, in contrast to the findings of hypokalemia and increased renal potassium clearance during chronic administration of deoxycorticosterone (DOC). Triamcinolone did not result in antinatriuresis or antichloruresis. Chronic administration of a 10-fold smaller dose of Tcn (0.1 mg . kg-1 . day-1) in an additional group (group III) also resulted in a persisting reduction in urine pH and an increase in net acid excretion that exceeded unmeasured anion excretion and resulted in a small increase in steady-state plasma bicarbonate concentration. These results suggest that chronic administration of potent glucocorticoid steroids results in 1) a persisting increase in endogenous acid production, and 2) stimulation of renal hydrogen ion secretion that was of greater degree than accounted for by the increment in endogenous acid production and that was not accompanied by renal mineralocorticoid effects on sodium and potassium transport.

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