Proton magnetic resonance spectroscopy detects a relative decrease of N-acetylaspartate in the hippocampus of patients with dementia with Lewy bodies.

BACKGROUND AND PURPOSE: To characterize the cerebral metabolic changes in dementia with Lewy bodies patients. METHODS: The metabolic ratios of NAA/Cr and Cho/Cr in bilateral hippocampus were determined by proton magnetic resonance spectroscopy in 8 patients and 8 age-matched healthy controls. RESULTS: Dementia with Lewy bodies patients showed significantly lower NAA/Cr ratios in bilateral hippocampus, while the Cho/Cr ratio did not differ from the control group. CONCLUSIONS: Our data show relatively decrease of N-acetylaspartate in the hippocampus of patients with early or intermediate stage DLB. Hence, damage of neurons seems to be an early alteration in DLB.     

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.     

Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy

We performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N-acetylaspartate to choline plus creatine (NAAI[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean l8%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.     

4-Tesla 1H MR spectroscopy in patients with temporal lobe epilepsy]

7 patients with drug-resistant temporal lobe epilepsy (TLE) and localized EEG-focus were investigated with a 4 Tesla whole body MR-scanner. Proton (1H) magnetic resonance (MR) spectra were analyzed quantitatively and compared to the healthy side. MRS allowed the differentiation of the following metabolites in 5 patients: N-acetyl-aspartate (NAA), creatine and phosphocreatine, phosphorylcholine and glycerophosphorylcholine, beta- and gamma-glutamate (GLU). To compare the results with those of an already evaluated normal population, these metabolites were measured also in parietal region. The standard deviation was 42-46% in the patients. Unfortunately, in the temporal region, the field homogeneity was worse than parietal and thus the spectral analysis less distinct especially for GLU with a standard deviation of 45% for NAA and 66% for GLU on the healthy side. Thus, no significant findings were seen on focus side. There was only a tendency to an elevation of glutamate and a reduction of N-acetyl-aspartate.     

A comparative study of the different N-acetylaspartate measures of the medial temporal lobe in Alzheimer's disease

OBJECTIVE: To investigate group differences and correlations and to determine the sensitivity and specificity of different measures of the neuronal marker N-acetylaspartate (NAA) in the medial temporal lobe of Alzheimer's Disease (AD) patients. METHODS: The metabolic ratio NAA/creatine (Cr), the absolute concentration of NAA referenced against brain tissue (BT) water and NAA multiplied with the amount of BT in the proton magnetic resonance spectroscopy (1H-MRS) voxel were assessed in patients and healthy controls with a single-voxel 1H-MRS protocol. RESULTS: All measures were significantly lower in AD patients compared with controls. NAA/Cr and NAA correlated weakly, and there was no correlation of NAA with the amount of BT in the voxel. The highest specificity (87%) at a sensitivity of 80% was observed for NAA multiplied with the amount of BT in the voxel. There was no correlation of the MMSE with any of the NAA parameters. Conclusions: NAA/Cr does not reflect NAA concentration very well. NAA is not correlated with brain atrophy. The BT volume in the 1H-MRS voxel in combination with the concentration of NAA discriminates AD from healthy controls sufficiently.     

Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD

The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.     

Quantifying medial temporal lobe damage in memory-impaired patients

Studies of memory-impaired patients will be most useful when quantitative neuroanatomical information is available about the patients being studied. Toward that end, in the case of medial temporal lobe amnesia, protocols have been developed from histological material that identify the boundaries of relevant structures on magnetic resonance images. Because the size of these structures varies considerably in the normal population, some correction for overall brain size is usually employed when calculating volume measurements. Although different correction procedures have been used to normalize for brain size, there has been little study of how well different methods reduce variability and which methods might be most useful. We measured the volume of the hippocampal region (hippocampus proper, dentate gyrus, and subicular complex) and the volumes of the temporopolar, entorhinal, perirhinal, and parahippocampal cortices in five memory-impaired patients and 30 controls. We then compared three different methods for normalizing the volume measurements: normalization by intracranial volume, normalization by aligning the brain to a standard atlas, and normalization by brain area at the level of the anterior commissure. Normalization by intracranial volume reduced variability in the volume measurements of nearly all brain regions to a greater extent than did normalization by other methods. When normalized by intracranial volume, the patients exhibited a mean reduction in hippocampal volume of about 40% and negligible reductions in the volumes of other medial temporal lobe structures. On the basis of earlier histological analysis of two other patients (L.M. and W.H.), who also had reductions in hippocampal size of about 40%, we suggest that a volume reduction in this range likely indicates a nearly complete loss of hippocampal neurons.     

APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD

OBJECTIVE: To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. METHODS: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (e4/-), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups. RESULTS: Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the e4/- group, and from -24.0 to -48.0% in the e4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (p = 0.03). CONCLUSIONS: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.     

31P magnetic resonance spectroscopy of the medial temporal lobe of schizophrenic patients with neuroleptic-resistant marked positive symptoms

³¹P magnetic resonance spectroscopy was performed in 16 medicated schizophrenic patients with neuroleptic-resistant marked positive symptoms and in 16 healthy volunteers matched for age and sex in order to determine what changes in phosphorus metabolites are detected in such patients as compared to the controls. The schizophrenic patients showed an increased level of phosphodiesters in the bilateral medial temporal lobes. They also showed a decrease in the level of -ATP in the left medial temporal lobe. These findings suggest that schizophrenic patients with prominent positive symptoms refractory to neuroleptics may have a disturbance of bilateral membrane phospholipid and left-sided high-energy phosphate metabolism in the medial temporal lobe.     

New semantic learning in patients with large medial temporal lobe lesions

Two patients with large lesions of the medial temporal lobe were given four tests of semantic knowledge that could only have been acquired after the onset of their amnesia. In contrast to previous studies of postmorbid semantic learning, correct answers could be based on a simple, nonspecific sense of familiarity about single words, faces, or objects. According to recent computational models (for example, Norman and O'Reilly (2003) Psychol Rev 110:611-646), this characteristic should be optimal for detecting the kind of semantic learning that might be supported directly by the neocortex. Both patients exhibited some capacity for new learning, albeit at a level substantially below control performances. Notably, the correct answers appeared to reflect declarative memory. It was not the case that the correct answers simply popped out in some automatic way in the absence of any additional knowledge about the items. Rather, the few correct choices made by the patients tended to be accompanied by additional information about the chosen items, and the available knowledge appeared to be similar qualitatively to the kind of factual knowledge that healthy individuals gradually acquire over the years. The results are consistent with the idea that neocortical structures outside the medial temporal lobe are able to support some semantic learning, albeit to a very limited extent. Alternatively, the small amount of learning detected in the present study could depend on tissue within the posterior medial temporal lobe that remains intact in both patients.     

11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology

OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.     

颞叶内侧结构弥散张量成像及白质纤维束成像在颞叶癫痫诊断中的应用价值

目的 通过磁共振弥散张量成像(DTI)及白质纤维束示踪(DTT)技术定量分析颞叶癫痫患者双侧颞叶内侧结构弥散参数值及局部纤维束变化特点,评价DTI技术对颞叶癫痫的诊断价值.方法 对广州医学院第二附属医院自2010年12月至2011年2月临床诊断为颞叶癫痫的16例患者和20例健康志愿者进行常规MRI及DTI扫描,测量双侧颞叶杏仁体、海马及颞叶皮质的部分各向异性(FA)、相对各向异性(RA)、表观弥散系数(ADC)等数值并进行统计学分析,同时应用DTT技术观察癫痫患者局部纤维束与正常对照者的差异.结果 正常对照者双侧颞叶内侧各结构FA、RA、ADC值比较差异均无统计学意义(P＞0.05).颞叶癫痫患侧、对侧与正常对照者颞叶内侧各结构FA、RA、ADC值比较差异均有统计学意义(P＜0.05),其中ADC值呈颞叶癫痫患侧＞颞叶癫痫对侧＞正常对照者的变化趋势,以海马尾部变化最为显著;而FA、RA值呈颞叶癫痫患侧＜颞叶癫痫对侧＜正常对照者的变化趋势,并且杏仁体、海马体部变化较海马尾部更显著.结论 DTI技术能充分了解癫痫患者颞叶内侧结构的弥散参数值及纤维束变化特点,有助于癫痫病灶定位的准确诊断,同时加深对颞叶内侧结构整体变化的了解亦有助于术前的整体评估及提高手术疗效.     

Network alterations supporting word retrieval in patients with medial temporal lobe epilepsy

Although the hippocampus is not considered a key structure in semantic memory, patients with medial-temporal lobe epilepsy (mTLE) have deficits in semantic access on some word retrieval tasks. We hypothesized that these deficits reflect the negative impact of focal epilepsy on remote cerebral structures. Thus, we expected that the networks that support word retrieval tasks would be altered in left mTLE patients. We measured brain activity with fMRI while participants (13 controls, 13 left mTLE, and 13 right mTLE) performed a verb generation task. We examined functional connectivity during this task in relation to language performance on an off-line clinical test of lexical access (Boston Naming Test, BNT). Using task-seed-behavior partial least squares, we identified a canonical language network that was more active during verb generation than the baseline condition, but this network did not correlate with variability in BNT performance in either controls or patients. Instead, additional networks were identified for each group, with more anterior temporal and prefrontal regions recruited for controls and more posterior temporal regions for both left and right mTLE patients. Our findings go beyond the literature emphasizing differences in laterality of language processes in mTLE patients and, critically, highlight how network changes can be used to account for performance variation among patients on clinically relevant measures. This strategy of correlating network changes and off-line behavior may provide a powerful tool for predicting a postoperative decline in language performance.     

Contralateral medial temporal lobe damage in right but not left temporal lobe epilepsy: a (1)H magnetic resonance spectroscopy study

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) of the hippocampus is useful in lateralising the epileptic focus in temporal lobe epilepsy for subsequent surgical resection. Previous studies have reported abnormal contralateral MRS values in up to 50% of the patients. OBJECTIVE: To identify the contributing factors to contralateral damage, as determined by MRS, and its extension in patients with temporal lobe epilepsy. METHODS: Single voxel MRS was carried out in the hippocampus and lateral temporal neocortex of both hemispheres in 13 patients with left temporal lobe epilepsy (LTLE) and 16 patients with right temporal lobe epilepsy (RTLE). All patients had mesial temporal lobe epilepsy with hippocampal sclerosis. Controls were 21 healthy volunteers of comparable age. RESULTS: Consistent with previous studies, the NAA/(Cho+Cr) ratio was abnormally low in the hippocampus ipsilateral to the focus (p < 0.0001), and there were lower values in both patient groups in the ipsilateral temporal neocortex (p < 0.0001). Patients with RTLE had left hippocampal MRS anomalies (p = 0.0018), whereas the right hippocampus seemed to be undamaged in LTLE patients. CONCLUSIONS: Unilateral mesial temporal lobe epilepsy is associated with widespread metabolic abnormalities which involve contralateral mesial and neocortical temporal lobe structures. These abnormalities appear to be more pronounced in patients with RTLE.     

Category-specificity in the human medial temporal lobe cortex

The medial temporal lobe cortex (MTLC) occupies a pivotal position at the interface between neocortical association areas and the hippocampus. It has been suggested that the MTLC contains functionally distinct regions, with perirhinal cortex (PRc) preferentially supporting object processing and posterior parahippocampal cortex (PHc) preferentially supporting encoding of spatial information. Measuring differential BOLD responsiveness to objects, scenes, and other stimulus categories, we find a double dissociation between an anterior PRc response to objects and a posterior PHc response to scene stimuli. Furthermore, an anatomical ROI based approach was undertaken in an effort to understand the response profile underlying this double dissociation. We did not see any evidence for a sharp border between putatively distinct scene-preferential and object-preferential MTLC regions. Instead, scene-preferential responsiveness was noted to drop off in a graded, linear fashion in successively anterior MTLC regions until object-preferential responsiveness emerged in anterior PRc, although objects produced above baseline responses across the anterior-posterior extent of the parahippocampal gyrus. Other stimulus categories, such as faces and words, led to above baseline activation in either a few confined regions (faces) or none at all (words). Thus, what differentiated regions along the parahippocampal gryus was the relative response to objects and scenes, not simply above baseline responses to either category. This pattern raises the possibility that posterior PHc, and anterior PRc are situated at the ends of a single organizational continuum supported by the entire length of MTLC.     

Non-invasive examinations successfully select patients with medial temporal lobe epilepsy for anterior temporal lobectomy]

We retrospectively analyzed 8 patients with intractable medial temporal lobe epilepsy (MTLE) who underwent the anterior temporal lobectomy with hippocampectomy (ATL) without invasive examinations such as chronic subdural electrode recording. Five patients had a history of febrile convulsion. While all 8 patients had oral automatism, automatism of ipsilateral limbs with dystonic posture of contralateral limbs was demonstrated in 2 patients. Bilateral temporal paroxysmal activities on interictal EEG was observed in 4 patients and all patients had clear ictal onset zone on unilateral anterior temporal region. MRI demonstrated unilateral hippocampal sclerosis in 5 cases. Interictal FDG-PET depicted hypometabolism of the unilateral temporal lobe in all cases, however, ECD-SPECT failed to reveal the hypoperfusion of the unilateral temporal lobe in a case. Postoperatively, 7 cases became seizure free, and one had rare seizure. Non-invasive examinations, especially ictal EEG and concordant FDG-PET findings, in patients with oral automatism in seizure semiology, successfully select patients with MTLE for ATL.     

Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study

INTRODUCTION: Clinical, neuropsychological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal region (DLPFR). This dysfunction has in particular been associated with negative or "deficit" symptoms. Despite these findings, morphological studies have failed to show consistent structural abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere. We used volume-localised proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects. METHOD: Twenty-five patients who fulfilled DSM-IV criteria for schizophrenia and met the criteria for the Deficit syndrome were compared to 26 healthy controls matched for age and gender. Bilateral proton MR spectra were collected from a 2-cm(3) volume in the dorsolateral prefrontal region and the absolute concentrations of N-acetylaspartate, choline (Cho) and creatine+phosphocreatine (Cr+PCr) were measured. RESULTS: There was a significant negative correlation between severity of symptoms and NAA concentration in the schizophrenic patients. This was more marked for positive symptoms and for general psychopathology than for negative symptoms. There was also a significant correlation between NAA concentration and social functioning within the schizophrenic group. There were no significant differences between the two groups for the three metabolites. CONCLUSIONS: The negative association between severity of symptoms and NAA in schizophrenic patients and an association of NAA with social functioning suggest that NAA may be an indicator of disease severity. The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.     

Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients

In this (1)H-MRS follow-up study of the medial temporal lobe (MTL) in patients with AD, the authors report a correlation of N-acetylaspartate (NAA)/creatine (Cr) with cognitive decline. Severely progressed patients showed a reduction, whereas stable or mildly progressed subjects showed a slight increase of NAA/Cr. The reduction of NAA/Cr in the MTL represents a correlate of cognitive deterioration in AD, whereas it is of limited use to detect subtle changes over time in clinically stable patients.