The combined use of conventional MRI and MR spectroscopic imaging increases the diagnostic accuracy in amyotrophic lateral sclerosis.

PURPOSE: We aimed to assess, in amyotrophic lateral sclerosis (ALS), the diagnostic accuracy of the combined use of conventional MRI signal changes (namely, hypointensity of the precentral cortex and hyperintensity of the corticospinal tracts on T2-weighted images), and N-Acetyl-Aspartate (NAA) reduction in the motor cortex at Magnetic Resonance Spectroscopy (MRS), which are affected by limited diagnostic accuracy when used separately. METHODS: T2-hypointensity and NAA/(Choline+Creatine) ratio of the precentral gyrus and T2-hyperintensity of the corticospinal tracts were measured in 84 ALS patients and 28 healthy controls, using a Region-of-Interest approach. Sensitivity and specificity values were calculated using Fisher stepwise discriminant analysis, and cross-validated using the leave-one-out method. RESULTS: Precentral gyrus T2 signal intensity (p<10(-4)) and NAA peak (p<10(-6)) were significantly reduced in patients, and their values did not correlate significantly to each other both in patients and controls, while no significant differences were obtained in terms of T2-hyperintensity of the corticospinal tract. Sensitivity and specificity of the two discriminant variables, taken alone, were 71.4% and 75.0%, for NAA peak, and 63.1% and 71.4% for T2-hypointensity, respectively. When using these two variables in combination, a significant increase in sensitivity (78.6%) and specificity (82.1%) was achieved. CONCLUSIONS: Precentral gyrus T2-hypointensity and NAA peak are not significantly correlated in ALS patients, suggesting that they reflect relatively independent phenomena. The combined use of these measures improves the diagnostic accuracy of MRI in ALS diagnosis.

A randomized controlled clinical trial of growth hormone in amyotrophic lateral sclerosis: clinical, neuroimaging, and hormonal results.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease with motor neuron degeneration. Riluzole is the only available treatment. Two-thirds of ALS patients present with growth hormone (GH) deficiency. The aim of this study is to determine if add-on of GH to riluzole, with an individually regulated dose based on Insulin-like growth factor 1 (IGF-I) production, was able to reduce neuronal loss in the motor cortex, reduce mortality, and improve motor function of ALS patients. Patients with definite/probable ALS, in treatment with riluzole, aged 40-85 years, and with disease duration ≤3 years were enrolled. The study was randomized, placebo controlled, and double blind. Before treatment, patients were tested with a GH releasing hormone (GHRH) + arginine test. The initial dose of GH was 2 IU s.c. every other day, and was progressively increased to a maximum of 8 IU. Primary endpoint was N-acetylaspartate/(creatine + choline) (NAA/Cre + Cho) ratio in motor cortex assessed by magnetic resonance spectroscopy performed at months 0, 6, and 12. Secondary endpoints were mortality and ALS functional rating scale revised (ALSFRS-R). The NAA/(Cre + Cho) ratio decreased in all patients who completed the trial. No significant difference was noted between treated and placebo group. At baseline, although IGF-I levels were within the normal range, 73% of patients had GH deficiency, being severe in half of them. Compared with bulbar onset, spinal-onset patients showed more depressed GH response to the GHRH + arginine stimulation test (10.4 ± 7.0 versus 15.5 ± 8.1 ng/mL; p < 0.05). Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] increased from 2.1 ± 1.0 at baseline to 4.6 ± 1.9 at 12 months (p < 0.001). Insulin-like growth factor (IGF) binding protein 3 (IGFBP-3) decreased from 8,435 ± 4,477 ng/mL at baseline to 3,250 ± 1,780 ng/mL at 12 months (p < 0.001). The results show that GH exerted no effect on cerebral NAA or clinical progression assessed by ALSFRS-R. Two-thirds of ALS patients had GH deficit, with higher levels in the bulbar-onset group. During follow-up, patients showed progressive increase in HOMA-IR and decrease in IGFBP-3 levels.

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.