Proton magnetic resonance spectroscopy study of bilateral thalamus in juvenile myoclonic epilepsy.

PURPOSE: To investigate neuronal dysfunction in the thalami of juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS). METHODS: We performed single-voxel proton MRS over the right and the left thalami of 15 consecutive patients (10 women, 5 men) with JME (mean age 20.3 years) and 16 healthy volunteers (10 women, 6 men) (mean age 24.5 years). All patients had seizure onset in late childhood-teenage, normal neurologic examination, typical electroencephalogram (EEG) of JME and normal magnetic resonance imaging (MRI). We determined N-acetylaspartate (NAA) values and NAA over creatine-phosphocreatine (Cr) values. Mann-Whitney U-test was used to evaluate group differences. RESULTS: Group analysis showed that echo time (TE) 270 integral value of NAA over left thalamus were significantly decreased in JME patients as compared with controls (34.6033+/-15.8386; 48.0362+/-22.2407, respectively, P=0.019). Also group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (right side, 2.21+/-1.07; left side 2.00+/-0.72) as compared with controls (right side, 3.45+/-1.50; left side, 3.08+/-1.60; P=0.011 and P=0.030, respectively). CONCLUSION: In the previous studies, NAA values in patients with JME found that they were not statistically lower in thalami than control group. But, in our study, NAA value was found low as well. It has been known that NAA is a neuronal marker and hence it is a valuable metabolite in the neuron physiopathology. As a result, in the patients with JME we tried to support the theory that the underlying mechanism of the generalized seizures was the abnormal thalamocortical circuity, determining the thalamic neuronal dysfunction in MRS statistically.     

Thalamic dysfunction in juvenile myoclonic epilepsy: a proton MRS study

PURPOSE: To investigate neuronal dysfunction in the thalami of patients with juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS). METHODS: We performed single-voxel proton MRS over the right and the left thalami of 10 consecutive patients (five women) with JME (mean age, 31.6 years) and 10 age-matched healthy volunteers (five men). All patients had seizure onset in late childhood-teenage, normal neurologic examination, typical EEG of JME, and normal high-resolution MR imaging (MRI). We determined ratios of N-acetylaspartate (NAA) over creatine-phosphocreatine (Cr). Values <2 standard deviations from controls were considered abnormal. We performed analysis of variance to evaluate group differences. RESULTS: Group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (left side, 1.58 +/- 0.26; right side, 1.5 +/- 0.15) as compared with controls (left side, 1.98 +/- 0.18; right side, 1.88 +/- 0.15; p = 0.001 and p = 0.007, respectively). Individual analysis showed that nine of the 10 patients had abnormal NAA/Cr in at least one of the thalami. CONCLUSIONS: This study shows evidence of neuronal dysfunction in the thalami of patients with JME, which may have relevance for the mechanisms of seizure generation in this form of generalized epilepsy.     

应用体素的形态学研究复发缓解型多发性硬化患者的全脑灰质萎缩特点

目的 利用基于体素的形态学研究方法比较复发缓解型多发性硬化(relapsingremitting multiple selerosis,RRMS)患者和健康志愿者局部脑灰质的体积差异,推断灰质体积变化可能的病理生理机制.方法 对32例RRMS患者和32名性别、年龄匹配的健康志愿者进行常规MRI和三维T1WI扫描,采用参数统计软件包SPM5进行图像后处理,对RRMS组及对照组数据进行基于体素的统计学比较.利用相关分析检测患者灰质体积的变化与疾病病程、临床残疾程度及脑内可见病灶体积的相关性.结果 与对照组相比,RRMS患者的灰质萎缩区域分布广泛,在两侧丘脑(左侧2031,右侧1711)、尾状核(左侧815,右侧1031)、海马旁回(左侧313,右侧467)及额、颞、顶、枕叶多个皮质区域,灰质体积差异具有统计学意义(t=8.853～11.163,校正后均P＜0.01).RRMS患者两侧丘脑(左侧r=-0.596,右侧r=-0.694)和右侧尾状核(r=-0.409)的体积与脑内可见病灶的体积呈显著负相关(均P＜0.05).结论 RRMS患者灰质萎缩具有分布广泛的特征,尤其在深部灰质更显著.灰质萎缩的关键机制可能是继发于脑内可见病灶的神经元或轴索变性.

Abstract：

Objective To investigate the feature of regional grey matter volume changes in relapsing-remitting multiple sclerosis (RRMS) patients by voxel-based morphometry ( VBM) and presume the possible pathophysiological basis.Methods Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 32 RRMS and 32 sex- and age-matched normal controls.The comparison of grey matter volume between the two groups was analyzed by statistical analysis software SPM5 and VBM.A Pearson correlational analysis was used to assess correlation between gre matter loss and disease duration,expanded disability status scale (EDSS) and visible brain lesion volume.Results Compared with normal controls,RRMS patients had extensive bilateral grey matter atrophy in thalami (left 2031 and right 1711),caudate (left 815 and right 1031) and parahippocampal gyrus (left 313 and right 467),as well as several cortical regions in frontal,temporal,parietal,and occipital lobes (t value were between 8.853 and 11.163,all P ＜ 0.01).Regional grey matter loss in bilateral thalami ( r value were - 0.596 on left and were - 0.694 on right) and right caudate ( r = - 0.409 ) were strongly negatively correlated with visible brain lesion volume in RRMS (all P ＜ 0.05 ).Conclusions By means of VBM,extensive grey matter atrophy are found in RRMS patients,especially in deep grey matter.Axonal degeneration secondary to visible brain lesions may be a key pathogenesis of grey matter atrophy in RRMS.     

复发-缓解型多发性硬化患者丘脑扩散张量成像研究

目的 通过扩散张量成像研究复发-缓解型多发性硬化患者常规MRI表现正常的丘脑扩散参数异常,以及与临床残疾程度和认知损害间的相关性.方法 24例复发-缓解型多发性硬化患者和与之性别、年龄相匹配的健康志愿者分别接受常规MRI和扩散张量成像检查,利用兴趣区法测量影像正常的丘脑扩散参数,比较两组受试者丘脑平均扩散率和部分各向异性间的差异性,并评价患者丘脑扩散参数与临床相关评分及病灶体积之间的相关关系.结果 复发-缓解型多发性硬化组患者丘脑平均扩散率[(85.34+14.68)x10-3mm2/s]低于正常对照组[(98.42±13.10)×10-3mm2/s],组间差异具有统计学意义(t=-3.257,P=0.002);丘脑部分各向异性(0.40±0.04)高于正常对照组(0.36±0.05),差异亦有统计学意义(t=3.163,P=0.003).复发-缓解型多发性硬化组患者丘脑平均扩散率与同步听觉连续加法测验评分呈显著正相关(r= 0.711,P=0.000).结论 对常规MRI表现正常的复发-缓解型多发性硬化患者,扩散张量成像可以发现丘脑异常.而且丘脑扩散异常与患者认知损害存在相关性,提示扩散张量成像作为评价临床功能的重要指标,具有很好的应用前景.     

Dynamic tracking of acute ischemic tissue fates using improved unsupervised ISODATA analysis of high-resolution quantitative perfusion and diffusion data.

High-resolution (200 x 200 x 1,500 microm3) imaging was performed to derive quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps in stroke rats (permanent occlusion) every 30 minutes up to 3 hours after occlusion onset, followed by histology at 24 hours. An improved automated iterative-self-organizing-data-analysis-algorithm (ISODATA) was developed to dynamically track ischemic tissue fate on a pixel-by-pixel basis during the acute phase. ISODATA-resolved clusters were overlaid on the CBF-ADC scatterplots and image spaces. Tissue volume ADC, and CBF of each ISODATA cluster were derived. In contrast to the single-cluster normal left hemisphere (ADC = 0.74 +/- 0.02 x 10(-3) mm2/s, CBF = 1.36 +/- 0.22 mL g(-1)min(-1), mean +/- SD, n = 8), the right ischemic hemisphere exhibited three ISODATA clusters, namely: "normal" (normal ADC and CBF), "ischemic core" (low CBF and ADC), and at-risk "perfusion-diffusion mismatch" (low CBF but normal ADC). At 180 minutes, the mismatch disappeared in five rats (Group I, 180-minute "core" lesion volume = 255 +/- 62 mm3 and 24-hour infarct volume = 253 +/- 55 mm3, P > 0.05), while a substantial mismatch persisted in three rats (Group II, 180-minute CBF-abnormal volume = 198 +/- 7 mm3 and 24-hour infarct volume 148 +/- 18 mm3, P < 0.05). The CBF (0.3 +/- 0.09 mL g(-1)min(-1)) of the "persistent mismatch" (Group II, 0.3 +/- 0.09 mL g(-1)min(-1)) was above the CBF viability threshold (0.2 to 0.3 mL g(-1)min(-1)) throughout and its ADC (0.70 +/- 0.03 x 10(-3) mm2/s) did not decrease as ischemia progressed. In contrast, the CBF (0.08 +/- 0.03 mL g(-1)min(-1)) of the analogous brain region in Group I was below the CBF viability threshold, and its ADC gradually decreased from 0.63 +/- 0.05 to 0.43 +/- 0.03 x 10(-3) mm2/s (ADC viability threshold = 0.53 +/- 0.02 x 10(-3) mm2/s). The modified ISODATA analysis of the ADC and CBF tissue characteristics during the acute phase could provide a useful and unbiased means to characterize and predict tissue fates in ischemic brain injury and to monitor therapeutic intervention.     

MRI Brain T1 Relaxation Time Changes in MS Patients Increase Over Time in Both the White Matter and the Cortex

OBJECTIVE: To test the sensitivity of whole-brain T1 relaxometry to the evolution of pathological changes in multiple sclerosis (MS). BACKGROUND: T1-weighted hypointense lesion load in the brains of patients with MS is associated with axonal loss. Other work has shown that T1 measurements may provide information complementary to existing imaging techniques, such as magnetization transfer imaging. METHODS: The authors studied 14 MS patients twice over a median time interval of 19.5 months (range, 14-22 months). Structural images and whole-brain T1 maps using a novel rapid-scanning technique (3 min/study) were performed at 3 T. Analysis focused on defining changes separately in the lesional and normal-appearing white matter (NAWM) and in the cortical gray matter. RESULTS: At baseline, there was an inverse relationship between disease duration and the NAWM T1 histogram peak height (r = -0.75, P = .03). The total white matter T1 histogram peak height decreased over time (P < .001). This could be accounted for by changes in the NAWM (P < .03). There also was a decrease (6%) in the mean (11 of 14 patients, P = .004) and in the median (7%) (13 of 14 patients, P < .001) neocortical gray matter T1 over the follow-up period. CONCLUSIONS: Brain T1 maps can be generated quickly and are sensitive to pathological changes over time. T1 values in both the gray and the white matter at the baseline visit were related to disease duration, suggesting that the T1 changes are clinically relevant. Although the absolute values will be different, it is likely that similar changes will be able to be detected at 1.5 T. The role of T1 measurement as a magnetic resonance imaging outcome measure in clinical trials now should be explored.     

MRI mean diffusivity detects widespread brain degeneration in multiple sclerosis

We investigated the magnetic resonance imaging (MRI) findings of 32 multiple sclerosis (MS) patients using voxel-based morphometry (VBM) and voxel-based analysis of white matter fluid-attenuated inversion recovery image (FLAIR) high-intensity lesions and diffusion tensor imaging (DTI). Compared with 18 healthy controls, MS patients showed gray matter volume reduction in the thalamus, hypothalamus, caudate, limbic lobe, and frontal lobe. A marked volume reduction of white matter was evident along the ventriculus lateralis and corpus callosum. FLAIR high-intensity lesions were observed beside the ventriculus lateralis. DTI revealed reduced fractional anisotropy areas similar to those of the FLAIR high-intensity lesions. Changes in the volume of increased mean diffusivity (MD) were the most widespread and extended to normal-appearing white matter (p<0.001). Multiple regression analysis revealed that MD values were significantly correlated with both disease duration (r=0.381, p=0.032) and expanded disability status scale scores (EDSS) (r=0.393, p=0.026). This study demonstrated that combined voxel-based analysis for volumetry, FLAIR high-intensity lesions, and DTI could reveal widespread brain abnormalities in MS patients. Furthermore, DTI, especially MD, showed far more widespread brain degeneration than other MRI parameters, and was significantly correlated with both severity and disease duration.     

Apparent diffusion coefficient of pituitary macroadenoma evaluated with line-scan diffusion-weighted imaging

OBJECTIVE: The goal of this study was to evaluate the consistency of pituitary macroadenoma using apparent diffusion coefficient (ADC) with line-scan diffusion-weighted imaging (LSDWI). METHODS: Patients with pituitary macroadenoma (n=19) were studied prospectively. The LSDWI was performed using a maximum b factor of 1000 s/mm2. The consistency of macroadenoma was rated as soft, intermediate or hard at transsphenoidal surgery. The ADC values of tumors were compared with the tumor-consistency ratings. RESULTS: A soft consistency was found at surgery in 13 patients (mean ADC: 0.84+/-0.1x10(-3) mm2/s); an intermediate consistency was observed in six patients (mean ADC: 0.81+/-0.16x10(-3) mm2/s). No tumors of hard consistency were found. There was no significant difference in ADC values between tumors of soft consistency compared with tumors of intermediate consistency (P=0.37). CONCLUSIONS: A relationship between tumor consistency and the ADCs of soft and intermediate macroadenomas was not shown in this study using LSDWI.     

Cerebral blood flow in children with intractable epilepsy

A good correlation of Doppler internal carotid blood velocity determinations with hemispheric blood flow measurements by the 133-xenon inhalation method was demonstrated in 14 epileptic patients without abnormal CT findings. The highest correlation was seen between the flow of gray matter (F1) and the internal carotid end-diastolic velocity (d) (left side r = 0.841, right side r = 0.817). As end-diastolic velocity (d) well correlated with the value obtained by the 133-xenon inhalation method, the d value was compared between 77 healthy children and 13 patients with intractable epilepsy. The mean d value of both internal carotid arteries in patients was 16.7 +/- 2.9 mm (mean +/- SD), and that of healthy children 20.9 +/- 4.3 mm, the difference being statistically significant. The low cerebral blood flow in patients might be due to multiple antiepileptic drugs administered and/or mental retardation and cerebral hypofunction related to seizures.     

Decrease in heart ventricular ejection fraction during multiple sclerosis

Recent studies have shown that mitoxantrone is effective in patients with active multiple sclerosis (MS) and that cardiac monitoring is usually required. However, right and left ventricular ejection fractions (VEFs) have never been studied in MS patients as compared with control subjects. Radionuclide angiocardiography (RA) was performed to assess right and left VEFs at rest in 40 consecutive patients with active definite MS [15 men and 25 women; mean age 33.9 +/- 10 years; mean disease duration 8 +/- 6.5 years; 18 had relapsing-remitting and 22 had secondary progressive forms of the disease; mean Expanded Disability Status Scale (EDSS) score 4.8 +/- 1.9]. The control group consisted of 40 subjects free of neurological or cardiovascular disease (17 men and 23 women; 44.6 +/- 13.4 years of age). The VEF values obtained in the control group defined the normal limits (right VEF 32-54%; left VEF 50-74%). A statistically significant decrease of right (P=0.02) and left (P < 0.0001) VEFs was found in MS patients as compared with control subjects. RA showed pathological results for right (7.5%), left (10%) and both (7.5%) VEFs in 25% of MS patients. No correlation was found between VEF and sex, age, disease duration, disease course, EDSS score or previous treatment. Autonomic impairment, which frequently occurs in MS patients, may have accounted for the decrease in VEFs. Further physiological studies are required to determine factor responsible for the decrease of VEFs in MS.     

Brain diffusion during hyperventilation: diffusion-weighted MR-monitoring in patients with temporal lobe epilepsy and in healthy volunteers

Hyperventilation (HV) can be used to provoke epileptiform activity and occasionally seizures in generalised and in focal epilepsies. Based on the hypothesis that HV might alter brain diffusion in the epileptogenic areas of patients with temporal lobe epilepsy (TLE), we examined these alterations using quantitative diffusion MR imaging (DI) in four patients with TLE and unilateral hippocampal sclerosis (TLE-HS) and six patients with TLE without hippocampal sclerosis (TLE-pure), and in 10 healthy volunteers. Brain diffusion was measured at baseline and immediately after 4 min of HV. In all patients with TLE HV was repeated two times, 4 min each, followed by subsequent DI. The apparent diffusion coefficient (ADC) was quantified in predefined regions of interest. In controls, the ADC did not differ between baseline and HV and between right and left side. Compared to controls TLE-HS patients showed significantly higher ADC at baseline in the hippocampus of the ictogenic side (111+/-13 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.029). During HV ADC decreased significantly in the ictogenic hippocampus compared to controls (-17.3+/-7.1 vs. -3.34+/-8.7, P=0.004). In TLE-pure patients ADC of the ictogenic hippocampus was higher than in normals (99.3+/-14.2 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.031) but there was no significant decrease during HV. Serial HV did not further enhance this decrease. No significant HV-induced changes were seen in other brain areas. In conclusion, our results show that HV can induce dynamic changes of brain diffusion in patients with sclerotic hippocampi but not in non-sclerotic hippocampi. These findings may be utilized for lateralisation of the epileptogenic hippocampus during presurgical evaluation of TLE.     

MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment in multiple sclerosis

OBJECTIVES: MRI T2 hypointensity in multiple sclerosis (MS) gray matter, suggesting iron deposition, is associated with physical disability, disease course, lesion load, and brain atrophy. Ambulatory dysfunction limits quality of life; however correlation with conventional MRI remains poor. METHODS: Normalized intensity on T2-weighted images was obtained in the basal ganglia, thalamus, red nucleus, and dentate nucleus in 47 MS patients and 15 healthy controls. Brain T1-hypointense and FLAIR-hyperintense lesion volume, third ventricle width, brain parenchymal fraction and timed 25 foot walk (T25FW) were measured in the MS group. RESULTS: T2 hypointensity was present throughout gray matter in MS vs. controls (all p<0.01). Dentate T2 hypointensity was the only MRI variable significantly correlated with T25FW (Pearson r=-0.355, p=0.007) and was also the best MRI correlate of physical disability (EDSS) score in regression modeling (r=-0.463, R(2)=0.223, p=0.004). CONCLUSIONS: T2 hypointensity is present in subcortical gray matter nuclei in patients with MS vs. normal controls. Dentate nucleus T2 hypointensity is independently related to ambulatory impairment and disability, accounting for more variance than conventional lesion and atrophy measures. This study adds more weight to the notion that T2 hypointensity is a clinically relevant marker of tissue damage in MS.     

Does Reversal of Ischemia on Diffusion‐Weighted Imaging Reflect Higher Apparent Diffusion Coefficient Values?

This study investigated whether ischemia on diffusion-weighted imaging (DWI) that reverses has higher apparent diffusion coefficients (ADCs). A patient treated with thrombolytics was evaluated with serial magnetic resonance imaging studies before treatment, at 3 and 14 days and at 4 weeks. A 100.01-cm3 left frontoparietal stroke on baseline DWI was only 18.11 cm3 (18%) on 4-week fluid attenuated inversion recovery. The mean ADC was 7.43 x 10(-3) mm2/s in the 6 regions that reversed and 7.31 x 10(-3) mm2/s in the 6 regions that persisted (P < .036). With thrombolytic treatment, large ischemic lesions on DWI may reverse, and these areas display higher mean ADCs.     

A case of cerebral venous thrombosis with reversible brain parenchymal lesions: usefulness of diffusion weighted imaging and measurement of apparent diffusion coefficient]

A 47-year-old man with a history of thrombophlebitis of his left leg for several years presented with a mild left hemiparesis and ipsilateral hypesthesia. Magnetic resonance imaging showed subacute thrombosis of the superior sagittal sinus and a cortical vein of the right cerebral hemisphere. A linear hyperintense area was found in the white matter of the right postcentral gyrus on T 2- and diffusion weighted axial imagings on the 7 days after the onset. The patient was treated conservatively, and his clinical course was uneventful. His neurological dysfunctions recovered within approximately three weeks after the onset. The white matter lesion in the right postcentral gyrus also disappeared one month later. The apparent diffusion coefficients (ADCs) in the white matter of the pre- and postcentral gyrus were measured bilaterally on the ADC mapping imaging. In the subacute stage, the ADC values in the white matter of the right pre- and postcentral gyrus were 0.50 x 10(-3) mm2/sec and 0.91 x 10(-3) mm2/sec, respectively. The %ADC indicating the ratio of ADC value of the lesion to that of the contralateral brain tissue was calculated. The %ADCs in the white matter of the pre- and postcentral gyrus were 64.9% and 124.5% respectively. In the chronic stage, the ADC values in the white matter of the right pre- and postcentral gyrus were 0.96 x 10(-3) mm2/sec and 0.99 x 10(-3) mm2/sec, and the %ADCs improved to 106.7% and 106.5% respectively. The lesions in the white matter of the right pre- and postcentral gyrus were reversible. The former was thought to be mainly ascribed to cellular edema and the latter was vasogenic edema. The present case showed when %ADC of the ischemic lesion in cerebral venous thrombosis was higher than 60%-70%, conservative therapy alone is sufficient effective for the improvement of neurological deficits.     

多发性硬化患者颈髓扩散张量成像研究

目的 通过扩散张量成像研究多发性硬化患者常规MRI表现正常脊髓(NASC)的改变,并探讨其临床应用价值.方法 采用平面回波成像技术对13 例多发性硬化患者和13 例健康志愿者施行颈髓扩散张量成像检查,分别测量第2 ~ 5 颈椎(C2 ~ 5)水平前索、后索、侧索及灰质兴趣区的部分各向异性(FA)值及平均扩散率(MD)值,比较两组之间所存在的差异性;相关分析检验多发性硬化组患者FA值和MD 值与扩展残疾状态量表(EDSS)评分之间的关系.结果 与正常对照组相比,多发性硬化组患者C2 ~ 5 前索、侧索、后索和灰质NASC 的FA 值降低、MD 值升高(均P < 0.05);相关分析显示,FA 值与EDSS 评分呈负相关(r = - 0.328 ~ - 0.207,P = 0.001 ~ 0.035),各兴趣区MD 值与EDSS 评分呈正相关(r =0.234 ~ 0.409,P = 0.000 ~ 0.018).结论 多发性硬化患者常规MRI 表现比正常脊髓的FA 值降低,提示存在隐匿性病变.脊髓扩散张量成像对多发性硬化患者临床评价和疗效判断有一定应用价值.     

Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis

BACKGROUND: We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures. OBJECTIVE: To assess the relevance of gray matter changes over time to changes in cognition in RRMS. DESIGN: A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis. SETTING: Two university MS clinics. PATIENTS: Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5). MAIN OUTCOME MEASURES: We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving. RESULTS: We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). CONCLUSION: Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.     

Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T

OBJECTIVES: To assess the presence of perfusion abnormalities in the deep gray matter of patients with relapsing-remitting and primary progressive multiple sclerosis (MS) in comparison with healthy controls and to investigate the impact of perfusion impairment on clinical disability and fatigue. DESIGN: Survey. SETTING: Research-oriented hospital. Patients Twenty-two patients with MS and 11 age- and sex-matched healthy volunteers. Intervention Absolute cerebral blood flow, cerebral blood volume, and mean transit time were measured in the thalamus, putamen, and caudate nuclei. MAIN OUTCOME MEASURES: Decrease of cerebral blood flow in the deep gray matter of patients with MS and correlation between perfusion impairment and the severity of fatigue. RESULTS: The cerebral blood flow value averaged over the thalamus, putamen, and caudate nuclei was significantly lower in patients with primary progressive MS (P<.001) and in patients with relapsing-remitting MS (P = .01) compared with controls, and there was a trend for patients with primary progressive MS to have lower average cerebral blood flow than patients with relapsing-remitting MS (P = .06). With respect to cerebral blood volume, there was a significant difference between patients with primary progressive MS and controls (P<.001) and between the 2 groups of patients (P = .03) but not between patients with relapsing-remitting MS and controls (P>.30). The fatigue score was significantly correlated with cerebral blood flow (r = 0.4; P<.001) and cerebral blood volume (r = 0.5; P = .004). CONCLUSION: The decrease of tissue perfusion in the deep gray matter of patients with MS is associated with the severity of fatigue.     

Patterns of regional gray matter and white matter atrophy in cortical multiple sclerosis

We investigated the patterns of regional distribution of focal lesions, white matter (WM) and gray matter (GM) atrophy in patients with cortical (cort) MS in comparison to classical (c) MS patients. Nine cort-MS, nine c-MS and nine age-matched healthy controls (HC) underwent a brain MRI exam, including FLAIR and high-resolution T1-weighted scans. MS patients underwent neurological and neuropsychological assessment. Between-group differences of GM and WM volumes and their correlations with neuropsychological performances were assessed with voxel-based morphometry. FLAIR and T1 lesion probability maps (LPMs) were also obtained. Performance at neuropsychological tests was worse in cort-MS than in c-MS patients. Compared to HC, MS patients had a distributed pattern of GM and WM atrophy. No GM/WM area was more atrophic in c-MS vs cort-MS patients. Compared to c-MS, cort-MS patients experienced GM atrophy of frontal–temporal–parietal areas and cingulate cortex and WM atrophy of the cingulum bundle, bilateral cerebral peduncles, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. FLAIR and T1 LPMs did not differ between c-MS vs cort-MS patients. A higher susceptibility to neurodegenerative processes in key brain regions known to be related to cognitive functions is likely to underlie the clinical manifestations of cort-MS.     

Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR

In this study we evaluated the correlation between neuropsychological impairment (measured with the Brief Repeatable Battery Neuropsychological Tests) and (juxta)cortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to spin-echo MRI sequences in detecting (juxta)cortical MS lesions. A total of 39 patients with definite MS were evaluated by MRI with a conventional and fast spin echo sequence and fast FLAIR sequence, and neuropsychological tests of the Brief Repeatable Battery Neuropsychological tests were performed. The Z-score of all subtests were used to calculate a Cognitive Impairment Index. The results show that a high number of (juxta)cortical lesions is detected with thin slice FLAIR (30% of all lesions seen). This percentage was not superior to spin-echo, reflecting the thin slice thickness (3 mm) we used. The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques. While the number of non-cortical lesions correlated with the expanded disability status scale (r=0.32, P=0.045), the number of (juxta)cortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index. Our study underlines the high number of (juxta)cortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI. It also stresses the importance of (juxta)cortical lesions on determining neuropsychological impairment. Multiple Sclerosis (2000) 6 280 - 285     

MRI study of thalamus volumes in juvenile patients with bipolar disorder

In vivo imaging studies suggest functional abnormalities of the thalamus in adult patients with bipolar disorder, but the presence of anatomical abnormalities is controversial. Our objective in this study was to compare the thalamus volumes of children and adolescents with bipolar disorder versus healthy controls to determine whether any morphological abnormalities exist early in illness course. We studied 16 patients with bipolar disorder according to DSM-IV criteria (mean age+/-SD=15.5+/-3.4 years) and 21 healthy control subjects (mean age+/-SD=16.9+/-3.8 years). Blinded examiners measured thalamic gray matter volumes with a semiautomated technique. Analysis of covariance, with age, gender, and intracranial brain volume as covariates, revealed no significant differences in left and right thalamic volumes between patients with bipolar disorder and healthy controls. Our findings indicate there are no significant differences in thalamus size between children and adolescents with bipolar disorder and healthy comparison subjects, in contrast to available findings for schizophrenia and first-break psychosis. Any differences in thalamus size that may exist between patients with bipolar disorder and healthy controls must amount to small effect sizes.