ABSTRACT
There is evidence from in vitro and animal experiments that oral creatine (Cr) supplementation might prevent or slow down neurodegeneration in Huntington's disease (HD). However, this neuroprotective effect could not be replicated in clinical trials, possibly owing to treatment periods being too short to impact on clinical endpoints. We used proton magnetic resonance spectroscopy ((1)H-MRS) as a surrogate marker to evaluate the effect of Cr supplementation on brain metabolite levels in HD.Twenty patients (age 46+/-7.3 years, mean duration of symptoms 4.0+/-2.1 years, number of CAG repeats 44.5+/-2.7) were included. The primary endpoint was metabolic alteration as measured by (1)H-MRS in the parieto-occipital cortex before (t1) and after 8-10 weeks (t2) of Cr administration. Secondary measures comprised the motor section of the Unified Huntington's Disease Rating Scale and the Mini Mental State Examination. (1)H-MRS showed a 15.6% decrease of unresolved glutamate (Glu)+glutamine (Gln; Glu+Gln=Glx; p<0.001) and a 7.8% decrease of Glu (p<0.027) after Cr treatment. N-acetylaspartate trended to fall (p=0.073) whereas total Cr, choline-containing compounds, glucose, and lactate remained unchanged. There was no effect on clinical rating scales. This cortical Glx and Glu decrease may be explained by Cr enhancing the energy-dependent conversion of Glu to Gln via the Glu-Gln cycle, a pathway known to be impaired in HD. Since Glu-mediated excitotoxicity is presumably pivotal in HD pathogenesis, these results indicate a therapeutic potential of Cr in HD. Thus, longterm clinical trials are warranted.
Subject(s)
Aspartic Acid/analogs & derivatives , Brain/drug effects , Creatine/pharmacology , Down-Regulation/drug effects , Glutamic Acid/metabolism , Huntington Disease/drug therapy , Neuroprotective Agents/pharmacology , Administration, Oral , Adult , Aspartic Acid/metabolism , Brain/metabolism , Brain/physiopathology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/physiopathology , Creatine/therapeutic use , Down-Regulation/physiology , Energy Metabolism/drug effects , Energy Metabolism/physiology , Female , Glutamine/metabolism , Humans , Huntington Disease/diagnosis , Huntington Disease/metabolism , Magnetic Resonance Spectroscopy , Male , Middle Aged , Neurologic Examination , Neuroprotective Agents/therapeutic use , Pilot Projects , Treatment OutcomeABSTRACT
The aim of this study was to compare low-field MRI (0.2 T) and conventional radiography for the detection of acute fractures of the distal part of the extremities. X-ray and MRI examinations of 78 (41 fractures, 37 without fracture) patients with the clinical suspicion of an acute fracture in the distal part of the extremities were compared. Four experienced radiologists, two for each of the two modalities, independently analyzed the images. Interobserver variability and receiver operating characteristic (ROC) analysis for both methods were established. The MRI and conventional radiography revealed an accuracy of 81.4 and of 79.5%, respectively, in the detection of acute fractures. The diagnostic accuracy of MRI to detect fractures in the hand and forefoot proved to be significantly inferior to conventional X-ray examinations. On the other hand, MRI achieved a better accuracy for the examination of bones near a large joint. The interobserver variability for both methods was rated as moderate. In ROC analysis both methods were rated as good. There was no statistical difference of the accuracy between low-field MRI and conventional radiography in the detection of acute fractures of the distal part of the extremities. Consequently, a routine use of low-field MRI as an alternative to conventional radiography to diagnose acute fractures of the extremities seems not to be justified.
