Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI

OBJECTIVE: To determine 1) the reproducibility of metabolite measurements by (1)H MRS in the motor cortex; 2) the extent to which (1)H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. METHODS: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice (1)H MRSI. (1)H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. RESULTS: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. CONCLUSION: Metabolite changes measured by (1)H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.     

Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

OBJECTIVES: After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. METHODS: Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. RESULTS: In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.     

Effect of Creatine Supplementation on Metabolite Levels in ALS Motor Cortices

Mitochondrial pathology is an early observation in motor neurons and skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). To clarify the relevance of this finding, we determined the effects of a 1-month oral administration of creatine on (1)H NMR-visible metabolites in the motor cortices of 15 controls and 15 patients with sporadic ALS, most of whom had mitochondrial pathology in skeletal muscle. In the motor cortex of the ALS group the N-acetylaspartate (NAA)/creatine (Cr(t)) metabolite ratio was lower than in our control group, indicating NAA loss. Upon creatine supplementation we observed in the controls a decline in the NAA/Cr(t), NAA/choline (Cho), glutamate + glutamine (Glx)/Cr(t), and Glx/Cho metabolite ratios. In contrast, in the ALS patient group the NAA/Cr(t) and the NAA/Cho metabolite ratios remained unchanged, while the Glx/Cr(t) and Glx/Cho metabolite ratios decreased. These data are compatible with the interpretation that creatine supplementation causes an increase in the diminished NAA levels in ALS motor cortex as well as an increase of choline levels in both ALS and control motor cortices. Because NAA is synthesized by mitochondria in an energy-dependent manner and the NAA/Cho metabolite ratios in the ALS motor cortices were found to be correlated to the degree of mitochondrial pathology in ALS skeletal muscle, our results can be explained by a deficiency of enzymes of mitochondrial respiratory chain in the ALS motor cortex which might affect motor neuron survival.     

磁共振波谱检测肌萎缩侧索硬化的上运动神经元损害

目的探讨质子磁共振波谱(proton magnetic resonance spectroscopy,1 H-MRS)检测肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)的上运动神经元损害(upper motor neuron,UMN)的特点和诊断准确性。方法收集ALS患者31例和健康对照32名,采用1 H-MRS检测脑中央前回皮质下、内囊后肢和大脑脚感兴趣区代谢产物N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)的水平,计算NAA/Cr、NAA/(Cho+Cr)、Cho/Cr比值,采用受试者工作特征(receiver operating characteristic,ROC)曲线分析1 H-MRS对ALS患者UMN损害的诊断价值。结果 ALS患者各锥体束走行部位和部位组合的NAA/Cr和NAA/(Cho+Cr)较对照组显著降低(P0.05)。NAA比值预测ALS的UMN损害的ROC曲线下面积(area under the curve,AUC)为0.67~0.91,其中内囊后肢、大脑脚两部位的平均NAA/(Cho+Cr)和三部位的平均NAA/(Cho+Cr)的AUC、灵敏度、特异度分别为0.91、0.828、0.906和0.90、0.769、0.875。结论 1 H-MRS可检出ALS患者锥体束走行的生化代谢异常,是评估ALS的UMN损害的客观影像学指标,其诊断准确性中等,多水平检测和综合指标的选择有助于提高其诊断效力。     

The GH–IGF system in amyotrophic lateral sclerosis: correlations between pituitary GH secretion capacity,insulin‐like growth factors and clinical features

Background and purpose: The growth hormone (GH) and insulin‐like growth factor (IGF) system may be involved in neurodegenerative processes, and some abnormalities have been reported in amyotrophic lateral sclerosis (ALS). Our aim was to investigate the GH–IGF axis in patients with ALS and evaluate correlations between this endocrine system and clinical features. Methods: Serum levels of GH, IGF‐ I, IGF‐ II, insulin, IGF‐binding protein 1 (IGF‐BP1), and IGF‐binding protein 3 (IGF‐BP3) were measured in 25 patients with ALS and 25 age‐, gender‐, and BMI‐matched healthy controls. A GHRH plus arginine test was performed in patients and controls. Clinical status of patients was evaluated with the ALS Functional Rating Scale – Revised (ALSFRS‐R) and upper motor neuron (UMN) score. Results:  GHRH plus arginine test showed GH deficiency (GHD) in 13 (52%) patients with ALS; severe GHD was found in 6 (24%) and partial GHD in 7 (28%) patients. IGF‐I levels were significantly higher in patients with ALS than in healthy controls (182.9 ± 90.8 vs. 139.4 ± 58.1 ng/ml; P = 0.015). IGF‐I levels were higher in patients with ALS with UMN score >10 than those with UMN score <10 (217.8 ± 100.8 vs. 155.5 ± 74.6 ng/ml, P = 0.05). IGF‐II levels were significantly lower in patients with ALS than in healthy controls (720.9 ± 215 vs. 1001.9 ± 475.4 ng/ml; P = 0.03). Conclusions: The results demonstrate an impairment of the GH–IGFs system in ALS. The degenerative process in ALS might lead to a compensatory increase in IGF‐I in an attempt to provide additional support to motor neurons or degenerating muscle fibers. The decrease in IGF‐II levels may also be of pathological significance.     

肌萎缩侧索硬化症病人大脑中央前回运动区磁共振波谱分析

目的 :1H MRS是否可确定ALS病人大脑皮质运动区神经元受损 ,是否适用于监测ALS病情。方法 :病例组包括 9例ALS病人。对照组包括 5例健康人 ,同时测定大脑皮质运动区的NAA、Cho、Cr。结果 :ALS病例组中NAA/Cr显著低于对照组 (P <0 0 5 ) ,Cho/Cr显著高于对照组 (P <0 0 1)。结论 :NAA/Cr下降和Cho/Cr升高 ,提示ALS病人大脑皮质运动区存在神经元破坏和鞘膜功能的异常     

Brain metabolites in definite amyotrophic lateral sclerosis

Abstract Biomarkers beyond clinical assessment are needed in patients who suffer from amyotrophic lateral sclerosis (ALS). Here, single-voxel proton magnetic resonance spectroscopy (¹H MRS) of the gray matter of the motor cortex and the white matter including the pyramidal tracts was used to investigate concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, glutamate, and glutamine in patients with definite ALS in a longitudinal design (three measurements at study inclusion, after 3 and 6 months). A volume-corrected analysis of gray and white matter fractions within the volumes of interest (VOI) was performed for the identification of the absolute metabolite concentrations. The patient group showed a significant decline of the compound NAA over time in the motor cortex areas both of the clinically more and less affected hemisphere between first measurement and month 6 and for the less affected side additionally between first measurement and month 3. For the NAA/(Cr + Cho) ratio, significant decline in the less affected hemisphere was observed from the first measurement to month 3 and to month 6 as well as from month 3 to month 6. In contrast, neither NAA nor the NAA/(Cr + Cho) ratios in the white matter areas showed any significant alterations. All other compounds showed no significant changes over time. In summary, the longitudinal changes of cortical metabolite concentrations in the course of ALS could be assessed by optimized ¹H MRS techniques at group level, so that ¹H MRS parameters, in particular volume-corrected values of NAA in the clinically less affected hemisphere, seem to have the potential to serve as a surrogate marker for monitoring ALS disease progression.     

Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy

BACKGROUND: Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of the degree of cerebral involvement in ALS. OBJECTIVE: To test the hypothesis that the NAA/Ins ratio may provide an index of cerebral involvement in patients with ALS. DESIGN: High-field (3.0-T) magnetic resonance spectroscopy was performed to determine the NAA/creatine plus phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in the motor cortex. PARTICIPANTS: Seventeen patients with ALS and 15 healthy control subjects were studied. RESULTS: In patients with ALS, the greatest abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04), NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047). Correlation of the ALS Functional Rating Scale with NAA/Ins approached statistical significance (R = 0.43, P = .07). CONCLUSION: The NAA/Ins ratio may provide a meaningful biomarker in ALS given its optimal sensitivity and specificity profile.     

Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis

We studied 25-hydroxyvitamin D (vitamin D) levels in patients with amyotrophic lateral sclerosis (ALS) and the effect of vitamin D supplementation. Vitamin D levels were checked in 37 consecutive patients with ALS. Demographic data, vitamin D supplementation, change in Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score, and side effects from vitamin D were noted over a 9 month follow-up period. ALSFRS-R scores were compared between patients who took vitamin D and those who did not. The median age was 55 years and median time since symptom onset was 61 months. The mean vitamin D level was 22.3 ng/mL (normal range, 30–80 ng/mL). Eighty-one percent of patients had a vitamin D level lower than 30 ng/mL and 43% had a vitamin D level lower than 20 ng/mL. Twenty patients took 2000 international units of vitamin D daily. After adjustment for age and baseline vitamin D levels in a linear regression model, the ALSFRS-R score decline was smaller in patients taking vitamin D at 9 months (p = 0.02) but was not significantly different at 3 or 6 months. Median vitamin D levels rose from 18.5 to 31.0 ng/mL at 6 months in the group taking vitamin D. No side effects secondary to vitamin D supplementation were reported. Vitamin D supplementation at 2000 international units daily was safe over a period of 9 months and may have a beneficial effect on ALSFRS-R scores. Further studies are warranted to determine whether there is a benefit in vitamin D supplementation for all ALS patients.     

Riluzole does not have an acute effect on motor thresholds and the intracortical excitability in amyotrophic lateral sclerosis

Intracortical excitability in amyotrophic lateral sclerosis (ALS) is impaired. The effectiveness of the glutamate antagonist riluzole (Rilutek, Rh?ne-Poulenc Rorer) in ALS has been shown in clinical studies. In healthy subjects it modifies intracortical excitability in a frequently used double-stimulus paradigm of transcranial magnetic stimulation (TMS). Under riluzole intracortical inhibition is enhanced in healthy individuals, although not always significantly, whereas intracortical facilitation has been described as reduced [10, 11]. We wanted to find out whether riluzole affects and potentially rebalances impaired intracortical excitability in ALS. We, therefore, enrolled 13 patients with clinically and electromyographically confirmed ALS into this study. Five patients had to be excluded because motor thresholds were too high to get reliable motor evoked potentials (MEPs). In the remaining 8 patients, mean age was 59.9 +/- 11.9 years (+/- standard deviation) and mean symptom duration 9.6 +/- 2.5 months. Intracortical excitability was assessed before and 1.5 hours after the first intake of a loading dose of 100 mg of riluzole using a conventional paired-pulse TMS paradigm with interstimulus intervals (ISI) ranging from 1-30 ms and intensities adjusted to yield MEPs of 1.0 mV for test pulses and of 90% active motor threshold for conditioning pulses. Patients' baseline results were compared to those of 9 age-matched, healthy control subjects. Before drug intake, motor thresholds did not differ between groups, but there was significantly less intracortical inhibition in the ALS patient group. Riluzole intake did not significantly alter motor thresholds or intracortical excitability in the ALS patients. We conclude that riluzole does not immediately influence intracortical excitability in ALS. Our results are in contrast to the findings of Stefan et al (1998) [14] where a partial normalization of intracortical inhibition in ALS was observed after at least 5 days of drug intake. The difference between that study and our result may indicate a delayed onset of riluzole's influence on intracortical excitability.     

精神分裂症患者前额叶和丘脑的质子磁共振波谱研究

Objective To identify the metabolite levels in prefrontal lobe and thalamus in patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). Methods Thirty-eighty schizophrenics and 38 normal controls were involved in this study. A multi-voxel 1H-MRS was given to all the subjects on prefrontal lobe and thalamus within 24 hours they got in hospital. The N-acetylaspartate (NAA), choline-congtaining compounds (Cho), and creatine compounds (Cr) were measured and the ratios of NAA/Cr, Cho/Cr and NAA/( Cho + Cr) were determined Results In left prefrontal lobe and bilateral thalamus, the NAA/Cr ratio in patients demonstrated lower than that in normal controls ( all P <0. 05). In left prefrontal lobe, the NAA/(Cho + Cr) ratio in patients showed lower than that in normal controls (0. 64 ±0. 13 vs. 0. 74±0. 22,t =2. 26, P<0. 05). Both in patients and in normal controls, there were no significant differences in NAA/Cr, Cho/Cr and NAA/(Cho + Cr) between the two sides (all P >0. 05). Conclusious Abnormalities in neuronal function and/or integrity are present in schizophrenics.There is no significantly lateralized asymmetry for metabolite levels such as NAA, Cho and Cr in either the schizophrenics or the controls.     

三重磁刺激技术对上运动神经元损伤的评价作用

目的研究三重磁刺激技术(TST)的特点,探讨TST在评价运动神经元疾病患者上运动神经元(UMN)损害中的作用。方法选取肌萎缩侧索硬化(ALS)患者12例、下运动神经元综合征(LMNS)患者14例,分别进行双上肢小指展肌TST测定及运动诱发电位(MEP)潜伏期、中枢运动传导时间(CMCT)测定,并将TST波幅比与改良的医学研究委员会(MRC)评分、修订的肌萎缩侧索硬化功能评分量表(ALSFRS-R)评分、肺功能百分比、病程等进行相关性分析。结果 ALS患者12例均完成双侧TST检测,其尺神经TST波幅比为(55.8±32.6)%,较正常参考值下降(F=-3.448,P=0.002),TST波幅比阳性率为70.8%。LMNS患者共13例完成TST检测,其尺神经TST波幅比为(79.4±16.4)%,与正常参考值无统计学差异(F=0.215,P=0.832)。ALS组尺神经TST波幅比〔(55.8±32.6)%〕低于LMNS〔(79.4±16.4)%〕(F=-3.275,P=0.002)。TST波幅比评价UMN体征的敏感度76.5%,高于传统电生理指标;特异度为54.5%,低于传统电生理指标。TST波幅比与改良的MRC评分存在相关性(r=0.431,P=0.035),与ALSFRS-R评分、肺功能、病程、MEP潜伏期以及CMCT均无相关性。结论 TST可以发现亚临床UMN损害,其敏感性高于传统电生理观测指标。TST可以定量评估UMN受损程度,有可能用于ALS患者病情监测。     

全面性发作癫(癎)患者记忆功能与海马质子磁共振波谱改变的相关性分析

目的 探讨原发性癫(癎)全面性发作患者记忆功能损害的特征以及磁共振波谱(magnetic resonance spectroscopy,MRS)检查与记忆功能的关系.方法 对45例癫(癎)全面性发作的患者和20例健康对照组进行临床记忆量表的测量,双侧海马行1H-MRS检测及体积测量,比较2组间记忆量表的各项量表分、记忆商和1H-MRS的各项指标,并对记忆量表的结果与海马1H-MRS结果进行相关分析.结果 癫(癎)组包括服药组(指向记忆15.68±4.79,联想学习18.70±5.84,图像自由回忆13.19±6.22,人像特点回忆12.02±4.31)与未服药组(指向记忆17.19±5.86,联想学习20.00±6.77,图像自由回忆18.44±6.62,人像特点回忆13.19±6.62)以及不同发作频率组的多数项量表分及记忆商(服药组74.64 ±18.52,未服药组79.07±20.20,≥3次/月组78.10±21.22,<3次/月组73.81±17.72)显著低于对照组(t=4.794-10.224,P<0.01);且癫(癎)服药组和发作频率≥3次/月组的各项量表分及记忆商显著低于服药组和发作频率<3次/月组(t=3.267～6.537,P<0.01).癫(癎)组海马体积(左侧2.45±0.25,右侧2.56±0.31)、N-乙酰天门冬氨酸(NAA,左侧12.93±1.73,右侧11.88±1.69)及NAA/胆碱(Cho)+肌酸(Cr,左侧0.48±0.08,右侧0.39±0.07)显著低于对照组,Cho(左侧15.02±0.86,右侧14.94±0.96)、Cr(左侧11.86±0.71,右侧10.71±0.42)显著高于对照组(t=4.103～5.768,P<0.01);癫(癎)组的各项量表分及记忆商与左右侧NAA浓度、NAA/Cho+Cr均呈明显正相关(r=O.489～0.727,P相似文献   

Granulocyte Colony-Stimulating Factor for Amyotrophic Lateral Sclerosis: A Randomized,Double-Blind,Placebo-Controlled Study of Iranian Patients

MethodsForty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 µg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline.ResultsThe rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman''s ρ=0.370, p=0.070).ConclusionsWith the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females.     

Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis

OBJECTIVE: To evaluate proton magnetic resonance spectroscopy for detection and monitoring of upper motoneuron degeneration in patients with amyotrophic lateral sclerosis. METHODS: Seventy patients with amyotrophic lateral sclerosis according to the El Escorial criteria were compared with 48 healthy control subjects. Single-volume proton magnetic resonance spectroscopy (echo time, 272 milliseconds; repetition time, 2000 milliseconds) was performed in both motor cortices for detection of N-acetylaspartate (NAA), phosphocreatine + creatine ([P]Cr), and choline-containing compounds (Cho) to calculate the metabolite ratios NAA/Cho, NAA/(P)Cr, and Cho/(P)Cr. In addition, absolute metabolite concentrations of NAA, (P)Cr, and Cho were obtained in 30 patients and 15 controls with the unsuppressed water signal used as an internal reference. RESULTS: Absolute concentrations of NAA (P<.001) and (P)Cr (P<.05) were reduced in motor cortices of patients, whereas Cho concentrations remained unchanged. The NAA/Cho and NAA/(P)Cr ratios were reduced in all El Escorial subgroups (P<.001). The Cho/(P)Cr ratio was elevated in patients with definite amyotrophic lateral sclerosis (P<.05). Metabolite ratio changes corresponded to the lateralization of clinical symptoms and were weakly correlated with disease duration and disease severity. In follow-up observations of 16 patients during a mean (+/-SD) of 12.1 +/- 8.7 months, NAA/Cho dropped by 9.1% (P<.01), and Cho/(P)Cr increased by 7.0% (P<.01). Changes of metabolite ratios were significantly correlated with progression of disease severity. CONCLUSIONS: 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.     

Focal thinning of the motor cortex mirrors clinical features of amyotrophic lateral sclerosis and their phenotypes: a neuroimaging study

Amyotrophic lateral sclerosis (ALS) is characterised by degeneration of upper (UMN) and lower motor neurons (LMN).We aimed to relate clinical variables to cortical thinning of the primary motor cortex (PMC). The PMC was defined as the region of interest in high-resolution structural MRI scans. We related vertex-wise measures of cortical thinning to UMN involvement, bulbar/limb onset, the total ALS functional rating scale (ALSFRS-R), and its bulbar and upper limb subscore. In total, 93 ALS patients were recruited (60 with classical ALS; 17 with dominant UMN, e.g., primary lateral sclerosis; 16 with pure LMN variant, e.g., progressive muscular atrophy, flail arm or leg syndrome) and compared to 67 age and gender matched healthy controls. The UMN signs in the bulbar regions were associated with bilateral thinning within the bulbar segment on the motor cortex, and UMN signs in spinal regions were associated with thinning in the limb segment of the motor cortex. The site of disease onset (bulbar/lower limb) exhibited the most pronounced thinning in the corresponding part of the motor cortex. According to our analysis, dominant UMN patients demonstrated the most distinct thinning followed by classical ALS patients. Pure LMN variants did not differ from healthy controls. The bulbar subscore of the ALSFRS-R correlated with thinning of the left inferior PMC. Focal morphological changes within the PMC correspond to clinically measured impairments and depend on disease phenotype. Measuring cortical thickness may potentially offer an objective in vivo marker to quantify disease pathology.     

中央前回质子磁共振波谱在肌萎缩侧索硬化患者临床病情评估中的价值

目的 以质子磁共振波谱(1H-MRS)研究肌萎缩侧索硬化(ALS)的上运动神经元病损情况,以期探寻一种评估病情和疾病进程的指标.方法 对110例ALS和24例下运动神经元综合征(LMNS)患者以及89名健康志愿者进行双侧中央前回单体素1H-MRS检查.以上运动神经元受损体征和反射评分、ALS功能评估量表(ALS-FRS)和APPEL ALS量表(AARS)定量评定患者临床症状和体征.结果 与对照组(1.62±0.18)相比,LMNS患者(1.60±0.17)的NAA/Cr无改变,但ALS患者(1.40±0.25)与两组相比均明显降低(与对照组比较,t=-5.007,P=0.000;与LMNS组比较,t=-2.660,P=0.009);在不同分级的ALS患者中,确诊ALS患者较拟诊ALS者和可能ALS者降低更为明显(与拟诊组比较,t=-2.626,P=0.010;与可能组比较,t=-2.537,P=0.013).结合ALS患者临床表现进一步分析发现,上运动神经元体征明显的患者其NAA/Cr较不明显的患者降低更为明显,差异有统计学意义(t=-2.827,P=0.006),相关分析显示,NAA/Cr与患者的反射评分、ALS-FRS、AARS及其各分项均存在显著相关性(P＜0.05).结论 ALS中央前回1H-MRS检测在一定程度上反映患者上运动神经元受损情况,可作为评估患者病情程度的一项临床指标,但其对该病早期诊断和鉴别诊断的价值有限.     

Study with localized proton magnetic resonance spectroscopy of 31 multiple sclerosis lesions: correlations with clinical and MRI features

We have analyzed with localized proton magnetic resonance spectroscopy (MRS) 31 lesions in 28 patients with multiple sclerosis (MS). The course of the disease was either relapsing remitting, secondary progressive, or primary progressive. Four patients had an isolated neurological syndrome suggestive of MS. The decrease in the NAA/Cre ratio and the raise of the Cho/Cre ratio were more pronounced in patients with an acute isolated neurological syndrome, suggesting the predominance of an inflammatory process, and the presence of an axonal dysfunction in the initial course of the lesion. The NAA/Cre ratio was negatively correlated with clinical disability and thus could be used as an index of disease activity. Patients with a secondary progressive course exhibited a significant increase in the Myo/Cre ratio compared to those with a relapsing remitting course. Thus, there may be an association between the evolution towards a progressive disease and axonal loss or the development of gliosis. The isointense lesions to the cerebrospinal fluid on MRI T1 weighted sequences were characterized by a sharp raise in the Cho/Cre ratio suggesting demyelination and/or intense inflammation. Gadolinium enhanced lesions were not characterized by a specific neurochemical profile.     

Low growth hormone response to growth hormone-releasing hormone in child depression.

BACKGROUND: This study examined growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in a large sample of depressed children compared with normal control children. Within-subject comparisons were also performed in control subjects to examine test-retest reliability and in depressed children comparing episode versus clinical recovery. METHODS: The sample included depressed children (n = 82) and normal control children (n = 55) group-matched for age, gender, and pubertal status; the mean ages were 11.2 +/- 1.7 and 11.2 +/- 1.8 years, respectively. We gave GHRH (0.1 mcg/Kg) at 9 AM, and serum GH levels were determined every 15 min from -30 min through +90 min of the GHRH infusion. A subgroup of normal control subjects (n = 11) repeated the protocol for test-retest reliability within a 2-month interval. A subgroup of depressed children (n = 20) were restudied off all medications following full clinical remission from depression. RESULTS: The mean GH response to GHRH was significantly lower in the depressed group (8.7 ng/mL +/- SEM 0.9) compared with normal control children [12.2 ng/mL +/- SEM 1.3; t(135) = 2.59, p =.01 effect size 0.44]. The test-retest reliability of GH response to GHRH was stable (intraclass correlation =.93 for mean post-GH). The GH response to GHRH remained low in subjects restudied during clinical remission from depression. CONCLUSIONS: Depressed children show low GH response to GHRH. The measure appears to be reliable, and the low GH response continues following clinical remission. Further studies are needed to explore the mechanism and relative specificity of this finding.     

Cerebral degeneration predicts survival in amyotrophic lateral sclerosis

Objective

To determine the relationship of cerebral degeneration with survival in amyotrophic lateral sclerosis (ALS).

Methods

Patients with probable or definite ALS underwent magnetic resonance spectroscopic imaging (MRSI) of the brain between July 1996 and May 2002, and were followed prospectively until March 2004. Creatine (Cr), choline (Cho) and the neuronal marker N‐acetylaspartate (NAA) were quantified as ratios in the motor cortex.

Results

In 63 patients compared with 18 healthy people, NAA/Cho was reduced by 13% (p<0.001), NAA/Cr was reduced by 5% (p = 0.01) and Cho/Cr was increased by 8% (p = 0.01). NAA/Cho was used for survival analysis, given its larger effect size and superior test accuracy (a sensitivity of 67% and a specificity of 83%). Median survival after MRSI was 24 months. Multivariate analysis showed reduced survival for lower NAA/Cho (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.08 to 0.72, p = 0.01), older age (HR 1.03, 95% CI 1.00 to 1.06, p = 0.04) and shorter symptom duration (HR 0.96, 95% CI 0.93 to 0.99, p = 0.01). Patients with NAA/Cho <2.11 had a reduced survival of 19.4 v 31.9 months (HR 2.05, 95% CI 1.12 to 4.03, p = 0.02).

Conclusions

Cerebral degeneration is predictive of reduced survival in ALS.The extent to which cerebral involvement contributes to shortened life expectancy in amyotrophic lateral sclerosis (ALS) has been difficult to elucidate. The clinical evaluation of upper motor neurone (UMN) integrity as an index of motor cortex degeneration falls short owing to the possible masking of UMN signs by the loss of lower motor neurones (LMNs). Indeed, autopsy series have shown UMN degeneration in cases of LMN‐predominant motor neurone disease that would not have otherwise met the clinical criteria for ALS.¹ The identification of prognostic indicators would aid in selecting patients for clinical trials who are predicted to behave in a homogeneous manner with respect to disease progression and, potentially, pathogenesis. Prognostic indicators would also have clinical value in counselling patients.Proton magnetic resonance spectroscopy (MRS) studies in ALS have consistently shown evidence of neuronal loss or dysfunction in the motor cortex by the finding of decreased N‐acetylaspartate (NAA), a neuronal marker.^2,3We aimed to determine whether cerebral neurochemical abnormalities quantified by MRS correlated with survival.