Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.

Measurement of NAA concentrations and NAA/Cho ratios appear to be most suitable for detection of motor cortex degeneration by single-volume proton magnetic resonance spectroscopy. Reduced NAA/Cho ratios correspond to aspects of the clinical presentation and reflect disease progression in follow-up measurements.

Purpose: To quantify the macromolecular content in different anatomic brain regions and to evaluate an age dependency of the macromolecular concentrations. Material and Methods:A short echo time Stimulated Echo Acquisition Mode (STEAM) sequence was used without and with inversion recovery metabolite nulling in 8 -12 healthy volunteers. Quantitation was achieved by an extended LCModel, and macromolecular resonances at 0.9, 1.4, 2.1, and 3.0 ppm were evaluated. Results:In the cerebellum, the 1.4, 2.1, and 3.0 ppm resonances were highest compared to all other regions (P Ͻ 0.02); the 0.9 ppm resonance was significantly higher than that of pons (P Ͻ 0.01). In the motor cortex, the 0.9, 1.4, and 2.1 ppm resonances were higher than those of white matter and pons (P Ͻ 0.02). Pons and white matter did not differ significantly from each other. A significant correlation of the macromolecular concentrations with the age could not be found. Conclusion:There were higher macromolecular concentrations in the cerebellum and motor cortex than in pons or white matter. These were probably due to the higher portions of gray matter in these volumes of interest (VOIs) than in the other regions. SHORT ECHO TIME PROTON MAGNETIC resonance spectroscopy (MRS) of the brain allows for the detection of so-called macromolecules with a molecular weight of above 3500 Da, forming a broad substructure below the signal from metabolites with lower molecular weights (1-6). Several approaches have been made to evaluate the macromolecular contributions in the baseline of the spectra to achieve a reliable quantitation of the metabolites (6 -10). Other studies pointed out a potential pathologic relevance of increased macromolecular resonances, e.g., in stroke, brain tumors or multiple sclerosis (3,(11)(12)(13). Although a correlation of metabolite concentrations with anatomic regions is well known (14 -19), there is only one work concerning regional alterations of the macromolecules with respect to supratentorial gray and white matter (6). More knowledge about variations of the macromolecules within different supra-and infratentorial anatomic regions of the brain is essential to avoid misinterpretations of macromolecular signals in healthy and pathological conditions. This study was focused on the macromolecular content of different anatomic brain regions, such as the cerebellum, motor cortex, pons, and parietal white matter in healthy subjects. Correlations between the macromolecular concentration and age were analyzed and compared with the work of Hofmann et al (6). The metabolite concentrations obtained from the different regions were compared to the literature. Possible factors influencing the measurements of the macromolecules such as relaxation effects and partial volume problems were considered. To evaluate the quality of the quantification method, the results for the macromolecular concentrations of the metabolite-nulled and not-nulled spectra were compared. MATERIALS AND METHODS SubjectsTwelve healthy male volunteers, aged 28 -62 years (median a...

Spectroscopic data fail to provide further evidence for altered energy metabolism in KD. Metabolite changes in the brainstem indicate a reduction of the neuronal marker NA or elevated Cho. These findings may reflect neuronal loss or gliosis consistent with the known pathologic features. In a subset of patients, altered metabolite ratios best explained by neuronal loss suggest subclinical involvement of the motor region. The extent of metabolite changes does not correlate with the trinucleotide repeat length.

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Purpose: To investigate whether glutamine and glutamate (Glx) were elevated in Kennedy Disease (KD), and whether pathological proteins were spectroscopically visible as altered macromolecular (MM) resonances. Materials and Methods:Ten patients with KD and twelve healthy volunteers were investigated using a stimulated echo acquisition mode (STEAM) spectroscopy sequence with metabolite-nulling. Results:The concentrations of Glx remained unchanged in KD. An increased myo-inositol (Ins), and elevated MM at 0.9 ppm were found within the motor area. The N-acetyl-aspartate (NAA)/creatine (Cr) ratio was negatively correlated to the number of cytosine adenosine guanine (CAG) repeats in the motor area. Conclusion:The elevated MM at 0.9 ppm may be attributed to a pathologically altered protein in KD. Additionally, the changes of Ins point to a clinically unexpected involvement of the motor cortex. The correlation of NAA/Cr with the number of CAG repeats indicates a link between metabolites and genetic failure.

A cross-sectional neuropsychological study of cognitive functions in 20 male patients with genetically proven spinal and bulbar muscular atrophy (SBMA) was performed, with a comparison of their cognitive performance with that of 20 age- and education-matched control subjects. Neuropsychological assessment covered executive functioning, memory, and attentional control. The SBMA patients revealed deficits in verbal and non-verbal fluency as well as concept formation. Additionally, they showed significant memory deficits in all of the investigated domains of working memory, short-term and long-term memory. With respect to attentional control, the SBMA patients underperformed in relevant subtests, although performance differences did not reach significance overall. We conclude that fronto-temporal cognitive functions are impaired in SMBA, although at a subclinical level. Thus, functional deficits in SBMA are not confined to motor neurons but also affect extramotor networks.

Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [(11)C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.