Diffuse structural and metabolic brain changes in Fabry disease

OBJECTIVES: To assess structural and metabolic brain changes in subjects affected by Fabry disease (FD) or carrying the disease mutation. BACKGROUND: FD is an X-linked metabolic disorder due to alpha-galactosidase A deficiency, which leads to storage of glycosphingolipids in many tissues and organs. Previous MR studies have shown structural and metabolic brain abnormalities in FD patients. It is not clear, however, whether tissue damage can be seen in both the brains of hemizygous and heterozygous and whether quantitative MR metrics are useful to monitor disease evolution. DESIGN/METHODS: We studied 4 males and 4 females with FD. Each subject underwent brain proton MRI/MR spectroscopic imaging (MRSI) examinations to obtain measures of total brain volumes, total brain lesion volumes, magnetization transfer ratios (MTr) in WM and central brain levels of N-acetylaspartate (NAA) to creatine (Cr). A second MR examination was performed in five subjects after 2 years. RESULTS: Focal WM lesions were found in 2 males and 1 female. The MTr values were always low in the WM lesions of FD subjects (p < 0.001) and also were low in the normal-appearing WM of 2 affected males. Total brain volumes were never decreased in FD subjects. Brain NAA/Cr values were significantly (p = 0.005) lower in FD subjects than in normal controls and correlated closely with Rankin scale measures (r = -0.79). On follow-up examinations, no significant MR changes were found. However, the small changes in NAA/Cr correlated closely with changes in Rankin scores (r = -0.86). CONCLUSIONS: Subtle structural and metabolic tissue damage can extend beyond WM lesions in FD subjects. Diffuse brain NAA/Cr decrease can be found in FD subjects in relation to the degree of their CNS involvement and its evolution over time.     

Structural and metabolic damage in brains of patients with SPG11-related spastic paraplegia as detected by quantitative MRI

The goal of this work was to assess brain structural and metabolic abnormalities of subjects with SPG11 and their relevance to clinical disability by using quantitative magnetic resonance (MR) metrics. Autosomal recessive hereditary spastic paraplegia (AR-HSP) with thin corpus callosum and cognitive decline is a complex neurological disorder caused by mutations in the SPG11 gene in most cases. Little is known about the process leading to corticospinal and white matter degeneration. We performed conventional MRI/MR spectroscopic imaging ((1)H-MRSI) examinations in 10 HSP patients carrying an SPG11 mutation and in 10 demographically matched healthy controls (HC). We measured in each subject cerebral white matter hyperintensities (WMHs), normalized global and cortical brain volumes, and (1)H-MRSI-derived central brain levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr). Clinical disability was assessed according to patients' autonomy in walking. Conventional MRI showed WMHs in all patients. Global brain volumes were lower in patients than in HC (p < 0.001). Decreased values were diffusely found also in cortical regions (p < 0.01). On (1)H-MRSI, NAA/Cr values were lower in SPG11 patients than in HC (p = 0.002). Cho/Cr values did not differ between patients and HC. Cerebral volume decreases and NAA/Cr in the corona radiata correlated closely with increasing disability scores (p < 0.05). Quantitative MR measures propose that widespread structural and metabolic brain damage occur in SPG11 patients. The correlation of these MR metrics with measures of patients' disease severity suggests that they might represent adequate surrogate markers of disease outcome.     

Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis

Glatiramer acetate (GA) is a disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) with several putative mechanisms of action. Currently, there is paucity of in vivo human data linking the well-established peripheral immunologic effects of therapy with GA to its potential effects inside the central nervous system (CNS). Brain proton magnetic resonance spectroscopy (MRS) allows in vivo examination of axonal integrity by quantifying the resonance intensity of the neuronal marker N-acetylaspartate (NAA). In a pilot study to investigate the effect of GA on axonal injury, we performed combined brain magnetic resonance imaging (MRI) and MRS studies in 18 treatment na?ve RRMS patients initiating therapy with GA at baseline and annually for two years on therapy. A small group of four treatment na?ve RRMS patients, electing to remain untreated, served as controls. NAA/Cr was measured in a large central brain volume of interest (VOI) as well as the normal appearing white matter (NAWM) within the VOI. After two years, NAA/Cr in the GA-treated group increased significantly by 10.7% in the VOI (2.17 +/- 0.26 versus 1.96 +/- 0.24, P = 0.03) and by 71% in the NAWM (2.23 +/- 0.26 versus 2.08 +/- 0.31, P = 0.04). In the untreated group, NAA/Cr decreased by 8.9% at two years in the VOI (2.01 +/- 0.16 versus 1.83 +/- 0.21, P = 0.03) and 8.2% in the NAWM (2.07 +/- 0.24 versus 1.90 +/- 0.29, P = 0.03). Our data shows that treatment with GA leads to axonal metabolic recovery and protection from sub-lethal axonal injury. These results support an in situ effect of GA therapy inside the CNS and suggest potential neuroprotective effects of GA.     

Detection and characterization of neurotoxicity in cancer patients using proton MR spectroscopy

OBJECTIVE: The study objective was to detect abnormalities and identify relationships between brain metabolic ratios determined by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and neuropsychological (NP) function in cancer patients at risk for neurotoxicity. METHODS: Thirty-two patients received (1)H-MRSI using a multi-slice, multi-voxel technique on a 1.5T magnet. Cho/NAA, NAA/Cr, and Cho/Cr ratios were identified in seven pre-determined sites without tumor involvement. A battery of age-appropriate NP tests was administered within 7 days of imaging. Relationships were examined between test scores and metabolite ratios. CONCLUSIONS: This study identifies relationships between brain metabolite ratios and cognitive functioning in cancer patients. (1)H-MRSI may be useful in early detection of neurotoxic effects, but prospective longitudinal studies in a homogeneous population are recommended to determine the prognostic value.     

Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (¹H-MRSI). T1- and T2-weighted MRI images and three-dimensional ¹H-MRSI (480 voxels over 360 cm³, about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18–56 years old, 3–55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This ¹H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.     

Brain metabolic disorders after chemotherapy in the study by magnetic resonance spectroscopy

The purpose of our study was to evaluate CNS pathology due to chemotherapy neurotoxicity, using MRI and localized proton MRS in patients with lung cancer treated with cisplatine, Vinca alkaloids and etoposide. A reduction in N-acetylaspartate was expected as a result of chemotherapy neurotoxicity. METHODS: 31 patients aged 42 to 73 years underwent the following procedures before and after chemotherapy: clinical examination; MRI of the brain (Elscint Prestige 2T), MRS (PRESS sequence, TR 1500 ms, TE 80 ms) with volumes of interest (VOI) of 8 ml localized in the semi-oval center and a cerebellar hemisphere. The analysis of each patient's NAA/Cr and Cho/Cr ratios was carried out separately for the semi-oval center and cerebellum measurements. RESULTS: None of the patients demonstrated any clinical manifestations of the CNS neuropathy. MRI of the brain did not reveal any abnormalities caused by chemotherapy. Pre-treatment NAA/Cr and Cho/Cr ratios in the semi-oval center did not differ significantly from these measured after chemotherapy. However, the analysis of the cerebellar spectra showed a significant decrease in the NAA/Cr ratio (p < 0.05) and a time-related decrease in the Cho/Cr ratio (p < 0.05) after chemotherapy. An analysis of Pearson's correlations showed a very strong linear relationship between NAA/Cr and Cho/Cr ratios (p < 0.001), both in the semi-oval center and cerebellum. CONCLUSION: The decreased NAA/Cr ratio can indicate some neuronal loss caused by chemotherapy. The decrease in the Cho/Cr ratio could be associated with some myelin damage. The MRS results suggest the presence of a sub-clinical selective cerebellar neuropathy caused by chemotherapy. The MRS revealed that reaction to chemotherapy was different at the semi-oval center than that in the cerebellum. The results allow theorizing about an alternative or two-stage brain response to the neurotoxic factor found both in the cerebrum (the semi-oval center) and cerebellum. These initial results indicate that proton MR spectroscopy is a potentially useful modality for detecting an early stage of the CNS pathology caused by neurotoxicity of chemotherapy.     

Long‐Term Study of Brain 1H‐MRS Study in Multiple Sclerosis: Effect of Glatiramer Acetate Therapy on Axonal Metabolic Function and Feasibility of Long‐Term 1H‐MRS Monitoring in Multiple Sclerosis

Glatiramer acetate (GA) has several putative mechanisms of action with the potential of limiting sublethal axonal injury in the central nervous system (CNS). Brain proton magnetic resonance spectroscopy (¹H‐MRS) allows in vivo examination of axonal integrity by quantifying the neuronal marker N‐acetylaspartate (NAA), often expressed as a ratio to creatine (Cr). We showed that treatment with GA led to improvement in NAA/Cr over a 2‐year period. We now report the results of this ongoing study after 4 years of annual brain ¹H‐MRS examinations. Compared to baseline, at year 4, patients receiving continuous GA therapy showed a 12.7% increase in NAA/Cr and (P= .03) in the multivoxel brain volume of interest (VOI) studied and by 9.6% (P= .04) in the normal‐appearing white matter within the VOI. Three patients in the control group who began therapy with GA during the course of the study showed similar increases in NAA/Cr after the first year of therapy. These data support the long‐term effect of GA on maintaining axonal metabolic function and protection from sublethal injury as well as the feasibility of employing brain ¹H‐MRS in long‐term investigative studies in MS.     

Merosin-positive congenital muscular dystrophy: neuroimaging findings

Congenital muscle dystrophy (CMD) is a heterogeneous group of autosomal recessive myopathies. It is known that CMD may affect the central nervous system (CNS). Some authors have shown that merosin-negative CMD patients may have encephalic metabolic disturbances. In order to study metabolic changes within the brain, the authors performed a magnetic resonance spectroscopy (MRS) study in a 1-year-old girl with merosin-positive CMD (MP-CMD). MRS of brain demonstrated that NAA/Cr ratio was decreased (1.52), while Cho/Cr ratio was increased (1.78). These findings suggest that metabolic changes in CNS can also be found in patients with MP-CMD.     

Proton magnetic resonance spectroscopy in dementia with Lewy bodies

Proton magnetic resonance spectroscopy ((1)H-MRS) provides a non-invasive, in vivo insight into the brain metabolism, and has been successfully used in several neurological conditions. Our objective was to characterise the cerebral metabolic changes in dementia with Lewy bodies (DLB) patients using (1)H-MRS. Single Voxel (1)H-MRS was performed in 12 DLB patients with mild to moderate symptoms and 11 age-matched healthy controls. Volumes of interest (VOI) were selected, including white matter (WM) in the centrum semiovale and grey matter (GM) in the parasagittal parietal cortex. Main metabolic peaks corresponding to N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were identified. These areas were measured and referred to that of the water. Metabolic ratios among the different peak areas were also calculated. In comparison with the control group, DLB patients showed significantly lower mean NAA/Cr, Glx1/Cr and Cho/Cr ratios in the WM, while their Ins/Cr and Ins/NAA ratios did not differ from those of the control group. In the GM, no significant differences were found between both groups. Correlations between age at onset, disease duration, Mini-Mental State Examination, the motor section of the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging and metabolic ratios, both for WM and GM, were not significant in DLB patients. Our spectroscopy data show WM involvement, along with GM preservation, in DLB patients with early or intermediate stages. Hence, (1)H-MRS may provide adjunctive information in the ante-mortem diagnosis of DLB.     

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.     

Relation of interictal spike frequency to 1H-MRSI-measured NAA/Cr

PURPOSE: Whereas EEG spiking and decreases of the neuronal marker N-acetyl-aspartate (NAA) both localize well the epileptic focus, the significance of the intensity of these variables is unclear. Therefore we investigated whether the frequency of interictal surface spikes is related to the degree of N-acetyl-aspartate/creatine (NAA/Cr) ratio decrease as measured by proton magnetic resonance (MR) spectroscopic imaging (1H-MRSI) in patients with intractable partial epilepsy. METHODS: We retrospectively studied 14 patients, nine with temporal lobe epilepsy and five with frontal lobe epilepsy. Spikes that occurred during prolonged video-EEG monitoring from electrodes placed according to the International 10-20 system were counted blinded to the 1H-MRSI results. Eight electrode positions (F3/4, C3/4, T3/4, T5/6) were assigned to underlying brain subregions in the 1H-MRSI volume of interest. We converted NAA/Cr ratios into z-scores (NAA/Cr(z)) to compared NAA/Cr values directly across subregions. We calculated Spearman rank-order (p) and Pearson product-moment (r) correlations between spike frequency and NAA/Cr(z) values overall, as well as within each brain subregion. RESULTS: We found an overall negative relation between spike-frequency data and NAA/Cr(z) data (p = -0.341). When analyzing only spiking subregions, this negative relation became slightly stronger (p = -0.442; r = -0.338). When data from the eight sites were considered separately, this negative relation remained in most instances. CONCLUSIONS: Our results reveal a trend toward higher interictal spike frequencies on surface EEG in regions of pronounced neuronal metabolic damage or dysfunction. This suggests that both variables parallel an underlying pathologic substrate, although the pathophysiologic processes may be distinct.     

磁共振氢质子波谱成像在胶质母细胞瘤诊断中的应用

目的 探讨磁共振氰质子波谱成像(~1H-MRSI)在胶质母细胞瘤诊断中的应用价值.方法 经手术病理证实的29例胶质母细胞瘤,术前均行常规MRI及~1H-MRSI检查,根据常规MRI及~1H-MRSI特点预测其病理性质.并总结出本组病例~1H-MRSI特点.结果 29例中,术前预测正确25例,典型的胶质母细胞瘤的~1H-MRSI表现为NAA明显降低,Cho升高,肿瘤内或边缘Cr/NAA比率显著升高,出现Lac峰.结论 肿瘤内或边缘Cr/NAA比率显著升高是胶质母细胞瘤的主要特征,术前~1H-MRSI能为胶质母细胞瘤的诊断提供较高的诊断价值.     

MR evidence of structural and metabolic changes in brains of patients with Werner’s syndrome

Abstract. Objective: To assess CNS abnormalities in patients with Werners syndrome (WS) using MR metrics specific for tissue damage. Background: WS is a rare autosomal recessive disorder that causes premature aging. The CNS involvement in this disease is still debated. Methods: Two siblings who showed signs of neurological involvement underwent MR spectroscopic imaging (MRSI) and magnetization transfer (MT) imaging. Also, on conventional T₁-weighted MR images, measurements of total brain volume were performed. Results: Conventional MR images of both WS patients did not show abnormalities on visual inspection. However, both WS patients showed significantly lower values of normalized total brain volume and MT ratio in the white matter than agematched normal controls. Also, proton MRSI showed significantly lower values of central brain NAA/Cr in WS patients than in normal controls. Conclusions: Our findings suggest that, despite normal appearance on conventional MRI, diffuse structural and metabolic tissue damage can be demonstrated in WS brains by means of sensitive MR methods even in patients with moderate or subclinical CNS involvement.     

Cortical damage in brains of patients with adult-form of myotonic dystrophy type 1 and no or minimal MRI abnormalities

Objective To evaluate, by using quantitative MRI metrics, subtle cortical changes in brains of patients with the adult form of myotonic dystrophy type I (DM1) who showed no or minimal abnormalities on MRI. Background DM1 is an autosomal dominant multisystem disorder caused by the expansion of CTG repeats in the myotonic dystrophy-protein kinase gene. Mild to severe involvement of the CNS can be part of the clinical features of the disease. Several MRI studies have demonstrated that both focal white matter (WM) lesions and diffuse grey matter atrophy can be found in the brains of DM1 patients. However, whether these two processes are related or may occur independently is not clear. Design/Methods Ten genetically-proven DM1 patients who showed no or minimal abnormalities on MRI underwent a new brain MRI examination to obtain computerized measures of total and regional brain volumes normalized to head size and regional measurements of the magnetization transfer ratio (MTr). Results Normalized brain volumes (NBV) were significantly (p < 0.0001) lower in DM1 subjects than in a group of age- and sex-matched normal controls. Normalized cortical volumes (NCV) also were lower (p = 0.003) in DM1 subjects than in normal controls, whereas normalized WM volumes were not different between the two groups (p = 0.3). In agreement with this, values of MTr in the neocortex (cortical-MTr) were significantly (p = 0.006) lower in DM1 patients than in normal controls and this difference was not found in the WM tissue (p = 0.8). Conclusions Neocortical damage seems to be evident in the absence of visible WM lesions suggesting that a neocortical pathology, unrelated to WM lesion formation, occurs in DM1 brains. Received in revised form: 29 January 2006     

Prognostic value of proton magnetic resonance spectroscopic imaging for surgical outcome in patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy

The objective of this study was to assess which features of temporal lobe proton magnetic resonance spectroscopic imaging (1H-MRSI) are associated with satisfactory surgical outcome in patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy. We studied 21 patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy defined by magnetic resonance imaging volumetric measurements who underwent surgical treatment. 1H-MRSI was used to determine the relative resonance intensity ratio of the neuronal marker N-acetylaspartate to creatine + phosphocreatine (NAA/Cr) for mid and posterior temporal lobe regions of the left and right hemisphere, as well as an asymmetry index. Values lower than 2 SDs below the normal mean were considered abnormal. We used Engel's classification to assess surgical outcome with respect to seizure control. Eleven patients (52%) were in class I-II and 10 (48%) were in class III-IV. All 21 were operated on the side of maximal electroencephalographic (EEG) lateralization. Concordant lateralization of decreases in NAA/Cr to the side of surgery and normal NAA/Cr values in the contralateral posterior-temporal region were significantly associated with good surgical outcome: 11 (69%) of 16 patients with 1H-MRSI abnormalities concordant with EEG lateralization and none of the 5 patients with nonconcordant 1H-MRSI had a good outcome (class I-II); 10 (77%) of 13 patients with normal NAA/Cr contralateral to the EEG lateralization versus 1 (12.5%) of 8 of those with NAA/Cr reduction contralateral to EEG lateralization were in class I-II. Regression correlation analysis showed significant linear correlation between the midtemporal NAA/Cr relative asymmetry ratio and surgical outcome; the greater the asymmetry, the better the outcome. We conclude that discriminant 1H-MRSI features associated with favorable surgical outcome in patients with temporal lobe epilepsy and bilateral hippocampal atrophy were (1) concordant 1H-MRSI lateralization, (2) a greater side-to-side asymmetry of NAA/Cr, and (3) an absence of contralateral posterior NAA/Cr reduction.     

Transthyretin amyloidosis: A new mutation associated with dementia

Familial transthyretin (TTR) amyloidosis commonly presents with peripheral neuropathy and involvement of visceral organs. In contrast, signs of central nervous system (CNS) involvement are exceptional. We report that members of a kindred affected by a slowly progressive dementia, seizures, ataxia, hemiparesis, and decreased vision without neuropathy have TTR amyloid deposits in the leptomeninges, the brain parenchyma, and the eye. This condition, previously labeled oculoleptomeningeal amyloidosis, is linked to a mutation at codon 30 of TTR gene, resulting in the substitution of valine with glycine in this family, TTR amyloid deposits were present in the leptomeninges, especially the leptomeningeal vessels, and in the subependymal regions of the ventricular system where they disrupted the ependymal lining and resulted in amyloid-glial formations protruding into and narrowing the ventricular system. Hydrocephalus and atrophy and infarction of cerebral and cerebellar cortexes were also present. Review of the literature shows that amyloid deposition in the leptomeninges is not uncommon in TTR amyloidoses clinically characterized by peripheral neuropathy and lack of CNS signs. The present kindred, which presented exclusively with signs of CNS involvement, expands the phenotype of TTR amyloidosis and raises questions concerning the mechanisms determining phenotypic expression in TTR familial amyloidosis.     

Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy

The purpose of this study was to compare 2hyphen;[¹⁸F]fluoro-2-deoxy−D −glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (¹H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and ¹H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61% and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with ¹H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and ¹H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnorma; MRI and ¹H-MRSI measures do not preclude good surgical outcome.     

Proton magnetic resonance spectroscopic imaging studies in patients with newly diagnosed partial epilepsy

PURPOSE: To assess whether the N-acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr. PATIENTS AND METHODS: Proton magnetic resonance spectroscopic imaging (1H-MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow-up 1H-MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging. RESULTS: Initial 1H-MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow-up 1H-MRSI were seizure-free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 1H-MRSI examination and follow-up 1H-MRSIs showed no significant difference (Z = 135, p = 0.893, 2-tailed) for five seizure-free patients. CONCLUSIONS: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure-free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and observed variable response warrants further investigation.     

壳聚糖、磷脂酰胆碱对轻度认知功能障碍患者脑组织氢质子磁共振波谱成像的影响

目的观察壳聚糖、磷脂酰胆碱对轻度认知功能障碍(MCI)患者海马氢质子磁共振波谱成像(1H-MRSI)的影响。方法对15例MCI患者(MCI组)和15名正常老年人(正常对照组)进行海马1H-MRSI检查。给予MCI组患者壳聚糖、磷脂酰胆碱治疗2个月后对其进行复查,比较N-乙酰天门冬氨酸(NAA)/肌酸(Cr)、胆碱(Cho)/Cr、肌醇(mI)/Cr的比值。结果与正常对照组相比,MCI组服药前、后NAA/Cr比值显著降低,mI/Cr比值显著升高(均P<0.05),Cho/Cr的差异无统计学意义。MCI组治疗后的NAA/Cr比值较治疗前明显升高(P<0.05),mI/Cr比值明显降低(P<0.05),Cho/Cr比值治疗前后的差异无统计学意义。结论1H-MRSI显示,壳聚糖和磷脂酰胆碱能改善脑组织的代谢,可能对MCI有一定的治疗作用。     

Proton spectroscopic imaging shows abnormalities in glial and neuronal cell pools in frontal lobe epilepsy

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE. METHODS: We measured signals from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine + phosphocreatine (Cr) in the supraventricular brain of 14 patients with frontal or frontoparietal epilepsy and their matched controls. The supratentorial brain also was segmented into gray matter, white matter, and cerebrospinal fluid classes. Regional metabolite alterations were compared with localizing and lateralizing results from other examination modalities and with histology from three patients. RESULTS: Spectroscopy lateralized the epileptogenic focus in 10 patients in agreement with video-EEG and functional imaging. In four patients, spectroscopy showed bilateral, focal metabolic abnormality, whereas video-EEG suggested unilateral or midline abnormality. In the epileptogenic focus, Cho and Cr were increased by 23% and 14%, respectively, and NAA was decreased by 11%, suggesting metabolic disturbances both in the glial and in the neuronal cell pools. Two Taylor dysplasia lesions confirmed by histology and one with radiologic diagnosis showed high Cho and low or normal NAA, whereas two dysembryoplastic neurogenic tumors had normal Cho and low NAA. Contralateral hemisphere NAA/(Cho + Cr) was decreased in FLE, indicating diffusely altered brain metabolism. Segmentation of brain tissue did not reveal atrophic changes in FLE. CONCLUSIONS: Spectroscopy is useful in lateralizing frontoparietal epilepsy and shows promise as a "noninvasive biopsy" in epileptogenic lesions.