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.     

Functional magnetic resonance imaging of human absence seizures

We studied a patient with idiopathic generalized epilepsy and frequent absences, using electroencephalogram-correlated functional magnetic resonance imaging. Four prolonged runs of generalized spike-wave discharge occurred during a 35-minute experiment. Time-locked activation was observed bilaterally within the thalami in conjunction with widespread but symmetrical cortical deactivation with a frontal maximum. We demonstrate the reciprocal participation of focal thalamic and widespread cortical networks during human absence seizures and suggest reductions in cortical blood flow, in response to synchronized electroencephalogram activity.     

Magnetic resonance imaging in complex partial seizures

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed on 45 patients with intractable complex partial seizures. MRI was performed with a superconducting whole-body scanner operating at 0.5 tesla (T) and 1.5 T. In patients with temporal lobe epilepsy, 8 of 24 patients had abnormal CT, but 16 of 24 patients showed abnormal MRI. 1.5 T MRI detected more abnormality than 0.5 T MRI when CT was normal. In patients with frontal lobe epilepsy, 5 of 7 patients had normal CT and MRI. In 2 other patients, MRI demonstrated an arachnoid cyst and increased signal intensity area on the T2-weighted images which were not detected by CT. In patients with occipital lobe epilepsy, 5 of 6 patients show abnormal CT and MRI. In patients with tuberous sclerosis, MRI revealed some increased signal intensity areas on the T2-weighted images in the occipital and temporal lobe, which were not detected by CT. Most surface EEG foci corresponded with the side of MRI abnormality. These data indicate that MRI is more informative than CT in complex partial seizures. MRI is the imaging technique of choice in the diagnosis of complex partial seizures.     

Proton magnetic resonance spectroscopic imaging of pediatric low-grade astrocytomas

Despite their uniform histologic appearance, pediatric lowgrade astrocytomas (LGA) often exhibit a rather unpredictable clinical course. It is presently unclear whether certain specific genetic, immunologic and/or metabolic features underlie these observed variations. In order to address this question we examined the tumor distribution of choline compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) in seven children with midline LGA by means of proton magnetic resonance spectroscopy imaging (H-MRSI). Studies were performed with a 1.5 T GE Signa Scanner equipped with the standard head coil; nominal voxel size was 7.5×7.5×15 mm. This spatial resolution allowed us to select and independently evaluate multiple regions of interest (ROI) in the tumor as well as in areas of normal brain from the same individual. Normalized values of the observed signal intensities demonstrated a lower NAA and Cr content in the tumors than in the surrounding normal brain. Intratumoral Cho signals were also below normal values in all but one patient. The average Cho: NAA ratio was consistently higher in the tumor than in the normal brain. However, there was a wide variation (up to fourfold) in the Cho: NAA ratios of different ROIs, even within the same tumor. Our results clearly indicate that pediatric LGAs are metabolically heterogeneous, a feature that may be relevant to the understanding of their variable biologic behavior. Inasmuch as unique metabolic patterns were observed in some LGAs, we believe that systematic HMRSI studies of these patients may help define subsets within the group with specific therapeutic requirements.     

Proton magnetic resonance spectroscopic imaging in pediatric pilomyxoid astrocytoma

Objects A pilomyxoid astrocytoma (PmA) is considered to be either a more aggressive variant of a pediatric pilocytic astrocytoma (PA) or a tumor of a separate entity.Methods We present two cases of pediatric optic-chiasmatic PmA. Proton magnetic resonance spectroscopic imaging (MRSI) of the PmA revealed decreased concentrations of total choline (Cho), creatine (Cr), and N-acetyl aspartate (NAA). In contrast, proton MR spectra of PAs showed elevated Cho and decreased Cr and NAA signals.Conclusion Low metabolite concentrations in PmAs detected by MRSI may therefore help to distinguish PmAs from PAs preoperatively.     

Proton magnetic resonance spectroscopic imaging for metabolic characterization of demyelinating plaques.

We used proton magnetic resonance (MR) spectroscopic imaging to determine the serial changes in MR signals from choline, creatine, lactate, and N-acetylaspartate in and around a large demyelinating lesion followed over a period of 8 months. Elevated lactate and choline signals were observed at the first examination 3 days after the onset of symptoms. Reduced N-acetylaspartate signals were observed a few days afterward. The abnormal metabolite signals varied in different regions of the lesion and extended beyond the borders of abnormal signal intensity seen on conventional MR imaging (MRI). On the last examination at 8 months when the lesion appeared much smaller on MRI, choline signals from the center of the lesion were still high, but were falling. Choline signals outside the lesion on MRI had returned to normal as had lactate signals everywhere. Importantly, there was no recovery of N-acetylaspartate signals in or adjacent to the lesion on MRI. This serial study demonstrates the potential of MR spectroscopic imaging for characterizing the chemical pathological evolution of demyelinating lesions in ways that conventional MRI cannot. We propose that abnormal signals from choline can indicate recent regional demyelination, while persistent abnormal signals from N-acetylaspartate can provide an index of irreversible damage in the nervous system.     

Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration

Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N- acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. Because patients with cerebellar degeneration often show substan- tial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N-acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neurodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients.     

Proton magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy

Proton magnetic resonance spectroscopic imaging (¹H MRSI) has demonstrated decreased N-acetyl compounds (NA) in the epileptogenic hippocampus in patients with temporal lobe epilepsy. We studied 8 patients with frontal lobe epilepsy and found mean NA/creatine (Cr) in the epileptogenic frontal lobe decreased by 27% compared with that of the contralateral homologous region (1.81 ±0.36 vs 2.49 ± 0.60, p < 0.008). In every patient, NA/Cr was decreased in the epileptogenic region by at least 5%. These findings suggest that ¹H MRSI may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.     

Proton magnetic resonance spectroscopic imaging of the brain in childhood autism.

BACKGROUND: Autism is a developmental disorder of unknown neurologic basis. Based on prior work, we used proton magnetic resonance spectroscopic imaging ((1)H- MRSI) to investigate brain structures, including cingulate and caudate, that we hypothesized would reveal metabolic abnormalities in subjects with autism. METHODS: In 22 children with autism, 5 to 16 years old, and 20 age-matched healthy control subjects, (1)H-MRSI assessed levels of N-acetyl compounds (NAA), choline compounds (Cho), and creatine plus phosphocreatine (Cr) at 272 msec echo-time and 1.5 T. RESULTS: In subjects with autism compared with control subjects, Cho was 27.2% lower in left inferior anterior cingulate and 19.1% higher in the head of the right caudate nucleus; Cr was 21.1% higher in the head of the right caudate nucleus, but lower in the body of the left caudate nucleus (17.9%) and right occipital cortex (16.6%). CONCLUSIONS: Results are consistent with altered membrane metabolism, altered energetic metabolism, or both in the left anterior cingulate gyrus, both caudate nuclei, and right occipital cortex in subjects with autism compared with control subjects.     

Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: A series of 100 patients

Surgery is a safe and effective treatment for drug-resistant temporal lobe epilepsy (TLE). However, bilateral electroencephalographic (EEG) abnormalities are frequently present, making presurgical lateralization difficult. New magnetic resonance (MR) techniques can help; proton magnetic resonance spectroscopic imaging (MRSI) can detect and quantify focal neuronal damage or dysfunction based on reduced signals from the neuronal marker N-acetylaspartate, and magnetic resonance imaging (MRI)-based measurements of amygdala-hippocampal volumes (MRIVol) can improve the detection of atrophy of these structures. We performed proton MRSI and MRIVol in 100 consecutive patients with medically intractable TLE to determine how well these techniques agreed with the lateralization by extensive EEG investigation. We found that the EEG, MRSI, and MRIVol findings were highly concordant. The MRSI was abnormal in 99 of 100 patients (bilateral in 54%). The MRIVol was abnormal in 86 of 98 patients (bilateral in 28%). We obtained lateralization in 83% of patients using MRIVol alone, in 86% using MRSI alone, and in 90% by combining MRSI and MRIVol (vs 93% lateralization by EEG). MRSI was abnormal in 12 patients with normal MRIVol. The combination of proton MRSI and MRIVol can lateralize TLE accurately and noninvasively in the great majority of patients. By reducing reliance on EEG, these imaging techniques could reduce prolonged presurgical evaluation and make seizure surgery available to more patients.     

Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T

We performed proton magnetic resonance spectroscopic imaging (MRSI) at high magnetic field (4.1 T) to study N-acetylaspartate, creatine, and choline levels in the brains of normal control subjects and patients with intractable temporal lobe epilepsy. We compared the results of MRSI to those of other presurgical techniques to determine the sensitivity of this method in the lateralization of the epileptic focus. The normal hippocampal creatine—N-acetylaspartate ratio was 0.71 ± 0.14 with no differences between left and right. Using the mean control hippocampal creatine—N-acetylaspartate ratio plus 2 standard deviations to identify statistically significant changes, we found lateralizing metabolic abnormalities corresponding to the operated temporal lobe in all patients. Four patients (40%) had contralateral abnormalities, and 2 of them had bilateral independent seizure onset confirmed by intracranial electroencephalographic studies. Statistically significant increases in the choline—N-acetylaspartate ratio in comparison to healthy volunteers were observed in 8 of the 10 patients. With the creatine—N-acetylaspartate ratio, MRSI demonstrated a 100% sensitivity compared to magnetic resonance imaging, which identified pathology in 70% of the patients. These findings suggest that proton MRSI yields a distinctive metabolic profile in patients with temporal lobe epilepsy and is sensitive in detecting bilateral metabolic abnormalities in some patients. These preliminary findings suggest that MRSI is more sensitive than magnetic resonance imaging in the lateralization of epileptic foci in temporal lobe epilepsy.     

Transient and permanent magnetic resonance imaging abnormalities after complex partial status epilepticus

Epileptic seizures, especially status epilepticus can produce MRI changes. In contrast to convulsive status epilepticus (CSE), permanent parenchymal loss is not well documented with nonconvulsive status epilepticus (NCSE) and the observed MRI changes are transient. We describe a patient with non-lesional right-sided temporal lobe epilepsy with complex partial seizures and repeated episodes of untreated complex partial status epilepticus (CPSE). Diffusion-weighted MRI exhibited marked and extended signal changes within the right temporal, frontal, insular and cingulate regions. The affected areas are considered propagation pathways of temporal lobe epilepsies. After admission, the patient was treated with i.v. antiepileptic drugs. Behavioral, EEG and MRI signal changes resolved. An atrophy of the right temporal lobe not seen in the pre-status MRI examinations was observed 6 weeks after the resolution of MRI hyperintensities. Prior episodes of CPSE had been correctly treated and remained without permanent brain damage. This case report is in favour of immediate and aggressive treatment of partial NCSE in order to avoid irreversible parenchymal loss.     

Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease

OBJECTIVES—10 patientswith Niemann-Pick disease type C (NP-C) were studied by proton magneticresonance spectroscopic imaging (¹H-MRSI) to assess thebiochemical pathology of the brain and to determine whether this methodcan be useful to clinically evaluate these patients.
METHODS—¹H-MRSIpermits the simultaneous measurement of N-acetyl aspartate (NA),compounds containing choline (Cho), creatine plus phosphocreatine(Cre), and lactate (Lac) signal intensities from four 15 mm slicesdivided into 0.84 ml single volume elements. Spectroscopic voxels wereidentified from seven regions of interest.
RESULTS—In patientswith NP-C, NA/Cre was significantly decreased in the frontal andparietal cortices, centrum semiovale, and caudate nucleus; Cho/Cre wassignificantly increased in the frontal cortex and centrum semiovale.Significant correlations were found between clinical staging scalescores and ¹H-MRSI abnormalities.
CONCLUSION—¹H-MRSIshowed diffuse brain involvement in patients with NP-C consistent withthe pathological features of the disease. ¹H-MRSI is anobjective and sensitive tool to neurologically evaluate patients withNP-C.

     

Proton magnetic resonance imaging in ischemic cerebrovascular disease

Proton magnetic resonance imaging (MRI) using a 0.6- or 1.5-Tesla superconductive magnet was compared with high-resolution computed tomography (CT) in 60 patients with transient ischemic attacks (TIAs) or brain infarction. MRI showed focal parenchymal changes in 84% of patients with TIAs, whereas CT showed similar changes in 42%. The sensitivity of MRI was also greater in patients with infarcts, but the difference between CT and MRI was not as great. Infarcts were usually better delineated by MRI regardless of location. However, MRI failed to reveal cortical infarcts that were clearly seen on contrast-enhanced CT scans and was unable to clearly distinguish subacute from chronic hemorrhagic infarcts. MRI changes were best detected with T2-weighted images and usually appeared as multiple areas of increased signal intensity in the subcortical and periventricular white matter. MRI changes often could not be correlated with the clinical history and neurological findings; identical changes have been seen in patients with no history of cerebrovascular disease.     

Proton magnetic resonance spectroscopic observations of epilepsia partialis continua in children

We performed magnetic resonance spectroscopy in three pediatric patients (two boys and one girl, ages 11 to 17 years) with epilepsia partialis continua. Single-voxel proton magnetic resonance spectroscopy was performed on each patient. Data were acquired from voxels of 4 or 8 cm3 from the affected hemisphere and from contralateral homologous regions. The spectral peaks of several metabolites (N-acetyl-aspartate, choline, creatine, and lactate) were measured. Neuropathologic findings revealed Rasmussen's syndrome in two children and gliosis in one. We observed increased lactate-to-creatine ratios and reduced N-acetyl-aspartate-to-creatine ratios in the affected hemispheres in all three children with epilepsia partialis continua. These data support previous reports. The largest increase in the lactate-to-creatine ratio was detected in a patient with Rasmussen's syndrome and ongoing epilepsia partialis continua at the time of measurement. The other two patients had an increase in the lactate-to-creatine ratio and a decrease in the N-acetyl-aspartate-to-creatine ratio in the affected area. The increased lactate-to-creatine ratio was associated with recurrent focal seizures from different underlying pathologies.     

Magnetic resonance imaging in partial complex epilepsy

The yield of magnetic resonance (MR) imaging was investigated in 30 patients with partial complex epilepsy, and the results were compared with those of computed tomography (CT). Magnetic resonance imaging and CT disclosed focal cerebral abnormalities in 13 (43%) and eight (26%) patients, respectively. Two additional focal temporal lesions were identified by double-dose CT scanning, increasing the yield of CT to 33%. Magnetic resonance images were abnormal in all patients with focally abnormal CT scans, and in four patients (50%) they defined the extent of the temporolimbic lesions better than did the CT scans. Two of these patients had gliomas. In addition, MR images were focally abnormal in 85% of the patients in whom scalp electroencephalograms showed focal ictal discharges. These data indicate that MR imaging is more informative than CT in partial complex epilepsy.     

Characterization of untreated gliomas by magnetic resonance spectroscopic imaging

Although there are trends in the morphologic, metabolic, hemodynamic, and structural properties of untreated gliomas that are reflected in MR measurements, there is considerable heterogeneity both within and between lesions of the same histologic grade. The spatial extent of the abnormality in ADC and RA images is similar to the T2 lesion, but there is no obvious difference in intensity between grades. The rCBV is significantly increased in the enhancing volume of grade 4 lesions but is similar or reduced in intensity for most grade 3 lesions. There are clear differences between the enhancing volumes and the regions with increased Cho that may be highly significant for planning focal therapy. The location and intensity of the Lac/Lip peaks are consistent with those representing regions of necrosis for grade 4 lesions. The fact that small Lac/Lip peaks can also be seen in grade 2 and grade 3 lesions suggests that their presence may be indicative of regions that are likely to progress to a higher grade. If this were the case, it would be valuable for directing biopsies. The correlations between rCBV, Cho, and ADC suggest that cellularity, membrane turnover, and vascularity are linked in grade 4 lesions. It is not clear whether there is any relationship between these parameters regions in grade 2 or grade 3 gliomas. While further work is required to optimize the methodology associated with these MR parameters, it seems likely that combining the information from such measurements may be valuable for predicting outcome and tailoring therapy to individual patients.