The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.

Nonetheless, whilst radiologists and clinicians must always be cautious when evaluating the macroscopic peculiarities of a brain tumour, the value of imaging cannot be overestimated when any sort of pathology is encountered. Moreover, besides the classic CT and MRI findings, new MRI-related techniques, such as magnetic resonance spectroscopy (MRS), are able to extract a different kind of information from cerebral neoplasms, and they could be important widespread diagnostic alternatives in the very near future.

Background/Aims: To evaluate ¹H-labelled magnetic resonance spectroscopy (MRS) in patients with a low Mini Mental State Examination (MMSE) score identified during a dementia community-based survey. Methods: A population sample of 1,500 individuals (>64 years old) was randomly selected. Two hundred and fifteen individuals (MMSE ≤24) were sorted into clinical groups: dementia, Alzheimer’s disease, mild cognitive impairment (MCI), normal. Up to 56 of these individuals attended the MRS appointment. Two single-voxel sequences (TR 1,500, TE 35/144 ms) were carried out in the posterior cingulate gyrus of each individual, and the ratios N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, NAA/mI and NAA/Cho were compared statistically. The ability of MRS to distinguish clinical groups was assessed by receiver-operating characteristics analysis. Cognition effects on metabolite ratios were estimated, with gender and cognition as categorical variables and age as a continuous covariate. Results: NAA/Cr and NAA/Cho ratios were lower in dementia or Alzheimer’s disease than in MCI and normal groups. The NAA/Cr ratio at TE 35 ms performed best when distinguishing dementia or Alzheimer’s disease from non-demented subjects (cut-off point 1.40). MRS could not distinguish between MCI patients and normal subjects. Dementia was an independent predictor of metabolite values. Conclusion: In a population sample, conventional MRS still proved to be a useful tool for dementia discrimination, but it is potentially far less useful as a surrogate marker for MCI.

Hypertension is associated with cognitive decline in elderly persons. We studied asymptomatic hypertensive subjects using brain magnetic resonance (MR) spectroscopy to evaluate metabolite impairments before the appearance of symptoms in patients with different treatment outcomes. In all, 14 healthy controls and 37 asymptomatic hypertensive patients (17 controlled and 20 resistant) underwent brain structural MR and MR spectroscopy of the posterior paralimbic (PPL) area and left frontal white matter. Ischemic burden (IB), global cortical atrophy and microbleeds were analyzed with visual scales. Metabolite ratios involving N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (mI) were computed. Ultrasound measurements, including intima-media thickness, plaques and hemodynamic ratios, were obtained. Intergroup differences in IB, atrophy and metabolite ratios, and the atrophy and IB relationship were assessed with parametric and nonparametric statistical tests. In addition, the impacts of demographic, analytic and clinical factors, ischemia and atrophy, and ultrasound measurements on metabolite ratios were assessed. The significance level was set at Pp0.05. Higher atrophy scores presented with higher total or frontal IB (Po0.05). However, there was no intergroup difference in atrophy and IB. PPL mI/Cr was increased in resistant hypertension (Po0.021), whereas frontal NAA/Cr (Po0.007) showed opposite trends between controlled (increased ratios) and resistant (decreased ratios) hypertension. Unlike PPL mI/Cr, frontal NAA/Cr showed significant correlations with the lipid profile and ultrasound measurements. PPL mI/Cr increases in resistant hypertension, and frontal NAA/Cr diverges between controlled and resistant hypertension before physical and neuropsychological symptoms appear.