Cerebellar neurometabolite abnormalities in pediatric attention/deficit hyperactivity disorder: A proton MR spectroscopic study

We designed a case–control proton magnetic resonance spectroscopic study comparing the cerebellar and prefrontal regions of a group of 17 ADHD (attention deficit/hyperactivity disorder) medicated children and a group of 17 control children matched for laterality, gender and age. As we had found decreased gray matter volume in the right prefrontal region and the left cerebellar hemisphere in a previous voxel-based morphometry study conducted on an independent ADHD sample, we tested the hypothesis that these regions should show neurometabolite abnormalities. MRI (magnetic resonance imaging) was performed with a 1.5 T system; spectral acquisition was performed with a single-voxel technique and a PRESS sequence. Two volumes of interest were selected in the right prefrontal region and the left cerebellar hemisphere. NAA (N-acetylaspartate), Cre (creatine), Cho (choline), MI (myo-inositol) and Glx (glutamate-glutamine) resonance intensities were absolutely quantified. In the left cerebellar hemisphere, ADHD children showed significant decreased MI and NAA absolute concentrations with high effect sizes (p = 0.004, ES = 1.184; p = 0.001, ES = 1.083). The diminished absolute concentration of the NAA could be related to a gray matter volume decrease in the same cerebellar region found in the previous voxel-based morphometry MRI study, while the reduced MI absolute concentration could express a decreased glial density. This is the first proton MR spectroscopic study examining the cerebellum and it provides additional support for the role of cerebellum in the ADHD neurobiology.     

High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression

Background

Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS).

Method

Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study〔active ((n = 19) vs. sham(n = 15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls.

Results

In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS (p < 0.001). After successful treatment, m-Ino increased significantly in left PFC and the levels no longer differed from those of age-matched controls. In addition to a positive correlation between clinical improvement and an increment in m-Ino ratio, a correlation between clinical improvement and early age onset was observed.

Conclusions

Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.     

首发抑郁症患者海马质子磁共振波谱成像研究

目的:探讨首发抑郁症患者海马的磁共振质子波谱(1HMRS)特点.方法:应用1HMRS成像技术检测21例未用药首发抑郁症患者和14例健康志愿者海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,计算NAA/Cr和Cho/Cr比值.结果:首发抑郁症患者组双侧海马NAA/Cr比值低于对照组,差异有统计学意义(右侧:0.88±0.29/1.37±0.51,P=0.004;左侧:0.76±0.33/1.40±0.99,P=0.034);Cho/Cr比值两组间无统计学差异(P＞0.05);双侧海马NAA/Cr和Cho/Cr与抑郁严重度无相关性(P＞0.05).结论:首发抑郁症患者可能存在双侧海马神经元活力和功能下降.     

1H MRS in acute traumatic brain injury

The objective of this study was to demonstrate ¹H MR spectroscopy (MRS) changes in cerebral metabolites after acute head trauma. Twenty-five patients (12 children, 13 adults) were examined with quantitative ¹H MRS after closed head injury. Clinical grade (Glasgow Coma Scale [GCS]) and outcome (Rancho Los Amigos Medical Center Outcome Score [ROS]) were correlated with quantitative neurochemical findings. N-acetylas-partate (NAA), a neuronal and axonal marker, was reduced (P < .03?.001). In children, a reduced NAA/creatine plus phosphocreatine (Cr) level and the presence of detectable lipid/lactate predicted bad outcome (sensitivity, 89%; specificity, 89%). The first MRS examination of all patients correlated with ROS versus NAA (r = .65, P < .0001). Although most patients showed MRS abnormalities, striking heterogeneity of ¹H MRS characterized the individual patients. ¹H MRS identifies multiple patterns of diffuse brain injury after blunt head trauma. There was a strong correlation between MRS and outcome. Future prospective studies will be needed to determine the clinical usefulness of MRS in predicting outcome from closed head injury.     

Proton magnetic resonance spectroscopic changes of the primary motor cortex and supplementary motor area in hemiparetic patients with corticospinal tract injury due to deep intracerebral hematoma

This study was conducted to investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and supplementary motor areas (SMA) of 9 hemiparetic patients with documentable hemiparesis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of interest (VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH). 1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were compared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were significantly lower than those of normal volunteers. These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway.     

Axonal recovery after severe traumatic brain injury demonstrated in vivo by 1H MR spectroscopy

Proton magnetic resonance spectroscopy (MRS) suggested almost complete axonal recovery 21 months after trauma in a patient with severe diffuse axonal injury. MRS while the patient was comatose showed evidence of severe diffuse axonal injury in occipitoparietal white matter, but occipital grey matter was relatively spared. At 21 months N-acetylaspartate was normal. At 33 months examination showed a Functional Independence Measure of 83 and a Rancho Los Amigos Scale of Cognitive Function of 7–8, a remarkable improvement considering all the initial findings, except those of MRS.     

Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging.

BACKGROUND: The brain regions involved in the pathophysiology of bipolar disorder have not been definitively determined. Previous studies have suggested possible involvement of the hippocampus and of prefrontal regions. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) allows measurement of N-acetylaspartate (NAA, marker of neuronal integrity), choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in multiple brain regions. The objective of this study was to assess possible NAA reductions in hippocampus and prefrontal regions in patients with bipolar disorder. METHODS: We studied 17 patients with bipolar disorder and 17 age- and gender-matched healthy subjects on a 1.5-T nuclear magnetic resonance (NMR) machine. With (1)H-MRSI we measured ratios of areas under the metabolite peaks of the proton spectra (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions. RESULTS: Patients showed significant reductions of NAA/CRE bilaterally in the hippocampus. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. CONCLUSIONS: This study shows that patients with bipolar disorder have a regional reduction of NAA relative signals, suggesting neuronal damage or malfunction of the hippocampus. As suggested by other studies, neuronal pathology in the hippocampus may be involved in the pathophysiology of bipolar disorder and in susceptibility to psychosis.     

Primary Lateral Sclerosis: Clinical,radiological and molecular features

Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder. Despite the well-recognisable constellation of clinical manifestations, the initial diagnosis can be challenging and therapeutic options are currently limited. There have been no recent clinical trials of disease-modifying therapies dedicated to this patient cohort and awareness of recent research developments is limited. The recent consensus diagnostic criteria introduced the category ‘probable’ PLS which is likely to curtail the diagnostic journey of patients. Extra-motor clinical manifestations are increasingly recognised, challenging the view of PLS as a 'pure' upper motor neuron condition. The post mortem literature of PLS has been expanded by seminal TDP-43 reports and recent PLS studies increasingly avail of meticulous genetic profiling. Research in PLS has gained unprecedented momentum in recent years generating novel academic insights, which may have important clinical ramifications.