Structural white matter changes in adolescents and young adults with maple syrup urine disease.

OBJECTIVE: To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. METHODS: Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. RESULTS: In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. CONCLUSION: Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.

Single dose NTBC-treatment of hereditary tyrosinemia type I.

NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3cyclohexanedione) is the mainstay of treatment in tyrosinemia type 1 (HT 1). The current recommendation is to divide the total daily dose of NTBC into two doses. We monitored the plasma NTBC concentrations in a series of seven patients who were changed from multiple divided doses to a single daily dose of NTBC. Two additional patients were started on a single daily dose of NTBC after the diagnosis of HT 1 was established. In three patients, NTBC kinetics were performed over 6 and 24 hours, respectively. The use of multiple divided doses or a single daily dose did not significantly affect plasma NTBC concentrations or the mean daily dose needed to attain therapeutic plasma NTBC concentrations. Moreover, kinetic studies demonstrated that plasma NTBC concentrations were completely stable over a period of 24 hours with a single dose regimen, as expected given the known NTBC plasma half life of 54 hours. Although these preliminary results need to be confirmed in more patients, our findings show that administration of NTBC in a single daily dose may be as effective as a multiple-dose regimen in reaching therapeutic plasma NTBC concentrations and suppressing succinylacetone formation in patients with HT 1. In fact, single dose treatment may increase patients' compliance with the drug treatment and improve metabolic control.

Continuous venovenous hemofiltration rapidly lowers toxic metabolites in a patient with MSUD and imminent cerebral herniation.

Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism. During catabolic stress encephalopathy and brain swelling that can culminate in brain herniation may occur. Beyond the neonatal period, these metabolic decompensations normally can be treated with a conservative dietary emergency regimen. Nevertheless in exceptionally severe cases also older patients may require extracorporeal interventions. We present the case of a 12-year-old patient with cerebral edema and imminent cerebral herniation. Continuous venovenous hemofiltration (CVVH) caused a prompt decrease of the toxic metabolite levels as well as an improvement of the patient's condition.

[Effects of autogenic training in elderly patients]. / Effekte von Autogenem Training bei Alteren.

Autogenic training (AT) is a widely available relaxation method with beneficial outcome on physiological and psychological functioning. In our study, we wanted to test the effects of an AT course in cognitively impaired, frail elderly. After a 3 month waiting period (control), AT courses (intervention) of 3 months duration were offered in 2 nursing homes. Thirty-two frail elderly took part in the study, 24 of them had a psychiatric diagnosis (mean age 82.1 +/- 7.2 years, CAMCOG 75.5 +/- 15.7, MMSE 23.3 +/- 4.3, HAMD 10.0 +/- 3.6, NOSGER 57.2 +/- 18.4, AT-SYM 32.9 +/- 17.6 points). Eight participants dropped out during the waiting period, 8 during the course. From the 16 participants, 15 (94%) were able to learn the AT according to subjective, 9 (54%) according to objective criteria. The ability to practice the AT successfully correlated with the CAMCOG (p = 0.001) and the NOSGER (p = 0.01) score. Participants with a dementia syndrome had major difficulties, whereas age, depressiveness, and number of complaints (AT-SYM) had no influence on the ability to learn the AT. There was no intervention effect, measured with the HAMD, NOSGER, AT-SYM and MMSE. In the pre-post comparison of training sessions, a significant improvement in general well being was found (p < 0.001). Mentally impaired, frail elderly participants are able to learn the AT. Cognitive impairment is disadvantageous for a successful participation.