The Influence of Climatic Factors on the Provocation of Epileptic Seizures.

Background/Objectives: Recent studies provide the first indications of the impact of climate factors on human health, especially with individuals already grappling with internal and neurological conditions being particularly vulnerable. In the face of escalating climate change, our research delves into the specific influence of a spectrum of climatic factors and seasonal variations on the hospital admissions of patients receiving treatment for epileptic seizures at our clinic in Kaiserslautern. Methods: Our study encompassed data from 9366 epilepsy patients who were admitted to hospital due to epileptic seizures. We considered seven climate parameters that Germany's National Meteorological Service made available. We employed the Kruskal-Wallis test to examine the correlation between the frequency of admittance to our hospital in the mentioned patient group and seasons. Furthermore, we used conditional Poisson regression and distributed lag linear models (DLMs) to scrutinize the coherence of the frequency of patient admittance and the investigated climate parameters. The mentioned parameters were also analyzed in a subgroup analysis regarding the gender and age of patients and the classification of seizures according to ILAE 2017. Results: Our results demonstrate that climatic factors, such as precipitation and air pressure, can increase the frequency of hospital admissions for seizures in patients with general-onset epilepsy. In contrast, patients with focal seizures are less prone to climatic changes. Consequently, admittance to the hospital for seizures is less affected by climatic factors in the latter patient group. Conclusions: The present study demonstrated that climatic factors are possible trigger factors for the provocation of seizures, particularly in patients with generalized seizures. This was determined indirectly by analyzing the frequency of seizure-related emergency admissions and their relation to prevailing climate factors. Our study is consistent with other studies showing that climate factors, such as cerebral infarcts or cerebral hemorrhages, influence patients' health.

Multilobar Resections for 3T MRI-Negative Epilepsy: Worth the Trouble?

OBJECTIVE: Multilobar resection in magnetic resonance imaging (MRI)-negative drug-resistant epilepsy warrants attention because they account for up to one third of MRI-negative epilepsy surgery. Despite their high prevalence, data are sparse, and the risk/benefit ratio continues to be debated. The present study investigated the postoperative seizure outcomes in this especially challenging subgroup. METHODS: We retrospectively analyzed the data of 4 consecutive patients with 3T MRI-negative findings and drug-resistant focal epilepsy who had undergone multilobar epilepsy surgery at our institution. RESULTS: The mean age at first surgery was 28.5 years (range, 14-48); 1 patient required 2 consecutive reoperations. The final resection was in the frontotemporal and temporo-parieto-occipital regions in 2 patients each. Histopathological examination revealed mild malformations of cortical development in 2 patients and focal cortical dysplasia type Ia and type IIa in 1 patient each. At the last follow-up examination (median, 3.3 years; range, 1-11), 2 patients were completely seizure free (Engel class Ia), 1 patient had experienced some disabling seizures after surgery but had been free of disabling seizures for 2 years at the last follow-up examination (Engel class Ic), and 1 patient had experienced worthwhile improvement (Engel class IIb) and had been seizure free for 1 year at the last follow-up examination. No surgical complications developed. CONCLUSIONS: Our results have demonstrated that multilobar epilepsy surgery is effective for lasting seizure control for selected 3T MRI-negative candidates, leading to favorable outcomes for all 4 of our patients. Comprehensive multimodal preoperative evaluation is a prerequisite for postoperative success. Reevaluation should be considered for patients with seizure recurrence, because reoperation could be especially beneficial for selected patients who have not responded to an initially limited resection.

Functional hemispherectomy is safe and effective in adult patients with epilepsy.

INTRODUCTION: Functional hemispherectomy (FH) is a well-established therapeutic option for children with epilepsy with parenchymal damage confined to one hemisphere, yet its application in adults remains rare. The intention of our study was to investigate postoperative clinical and epileptological outcome in adults who received FH for intractable epilepsy. MATERIALS AND METHODS: We retrospectively analyzed 12 adult patients (18-56years) with intractable epilepsy due to unihemispheric pathology. All patients underwent FH. Postoperative neurological and cognitive outcome as well as seizure status were evaluated with a mean follow-up period of 4.9years. RESULTS: Ten patients (83%) were seizure-free (Engel I), and two (17%) had recurrent seizures at last follow-up. Apart from one patient requiring operative revision for bone flap infection, no perioperative morbidity or mortality occurred. Postoperative functional assessment revealed deterioration of motor function in 7 patients, whereas 5 remained unchanged. Language was unchanged in 8 patients. The absence of background slowing in preoperative electroencephalogram (EEG) as well as ictal and interictal EEG patterns located ipsilateral to the side of surgery was associated with favorable seizure outcome. CONCLUSION: Favorable seizure control and acceptable functional outcome can be achieved by FH in adults with intractable epilepsy. The risk of postoperative deficits is moderate and even older patients are able to manage postoperative motor impairment. Therefore, FH should be considered in case of unihemispheric lesions also in adults.

Physiological effects of cigarette smoking in the limbic system revealed by 3 tesla magnetic resonance spectroscopy.

Several studies and recent models of effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (p = 0.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.

Magnetic resonance fiber density mapping of age-related white matter changes.

OBJECTIVES: To introduce fiber density mapping (FDM) for investigation of age-related white matter (WM) changes and to compare its capabilities with conventional diffusion tensor imaging (DTI) post-processing. METHODS: DTI data with 1.9 mm(3) isotropic voxels were acquired from 44 healthy volunteers (18-88 years) at 3T. FDM is a 3-step approach which includes diagonalization of the diffusion tensor, fiber reconstruction for the whole brain, and calculation of fiber density (FD) values. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were additionally calculated. Voxel-based analyses were performed to determine volume clusters of significant correlation with age. Bivariate linear regression models and Hotelling-Williams tests were used to detect significant differences between correlations. RESULTS: FDM detected a larger WM volume affected by age-related changes concomitant with fewer significant clusters compared to FA and MD. This indicates that WM alterations due to normal aging occur rather globally than locally. FD values showed a significant stronger correlation with age in frontal lobes (prefrontal and precentral gyrus), limbic lobes (cingulate and parahippocampal gyrus), the corpus callosum (genu) and temporal lobes. CONCLUSIONS: FDM shows higher sensitivity for detection of age-related WM changes because it includes all surrounding fiber structures into the evaluation of each DTI data voxel.

Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial.

To elucidate, in a pilot-study, whether noninvasive transcutaneous vagus nerve stimulation (t-VNS) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy. t-VNS was applied to 10 patients with pharmacoresistant epilepsies. Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months. Subjective documentation of stimulation effects was obtained from patients' seizure diaries. For a more reliable assessment of seizure frequency, we carried out prolonged outpatient video-electroencephalography (EEG) monitoring. In addition, computerized testing of cognitive, affective, and emotional functions was performed. Three patients aborted the study. Of the remaining seven patients, an overall reduction of seizure frequency was observed in five patients after 9 months of t-VNS. The noninvasive t-VNS stimulation is a safe and well-tolerated method for relatively long periods, and might be an alternative treatment option for patients with epilepsy.

Differences in metabolism of fiber tract alterations in gliomas: a combined fiber density mapping and magnetic resonance spectroscopic imaging study.

BACKGROUND: Gliomas propagate diffusely throughout and along white matter structures. Glioma-related changes in structural integrity and metabolism are not detectable by standard magnetic resonance (MR) imaging. OBJECTIVE: To investigate differences in the metabolism of fiber tract alterations between gliomas grade II to IV by correlation of fiber density values with metabolite concentrations measured by fiber density mapping and MR spectroscopic imaging. METHODS: Fiber density mapping and MR spectroscopic imaging were performed in 48 patients with gliomas WHO grade II to IV. Fiber density mapping data were used to define fiber tracts in tumoral and peritumoral areas. Structural integrity of fiber tracts was assessed as fiber density ipsilateral-to-contralateral ratio (FD ICR). Metabolite concentrations for choline-containing compounds and N-acetyl-aspartate were computed and correlated to FD ICR values after coregistration with anatomic MR imaging. RESULTS: In tumoral areas, choline-containing compound concentrations of altered fiber tracts were significantly different between low- and high-grade glioma and showed different courses for the correlations of FD ICR and choline-containing czeompounds. In high-grade glioma, increasing fiber destruction was associated with a massive progression in cell membrane proliferation. Peritumoral fiber structures showed significantly decreased N-acetyl-aspartate concentrations for all patients, but only patients with glioblastoma multiforme had significantly decreased fiber density compared with the contralateral side. Glioma grades II and III had significantly higher peritumoral FD ICR than glioblastoma multiforme. CONCLUSION: A multiparametric MR imaging strategy providing information about both structural integrity and metabolism of the tumor is required for detailed assessment of glioma-related fiber tract alterations, which in turn is essential for treatment planning.

Association of N-acetylaspartate and cerebrospinal fluid Aß42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-ß42 (Aß42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aß42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aß42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.

Classification of peritumoral fiber tract alterations in gliomas using metabolic and structural neuroimaging.

UNLABELLED: The aims of this study were to investigate and categorize peritumoral fiber tract alterations while considering changes in metabolism and integrity of fiber structures using multimodal neuroimaging-that is, PET with O-(2-(18)F-fluoroethyl)-l-tyrosine and diffusion tensor imaging evaluated by fiber density mapping-and to correlate categories of fiber alterations with preoperative neurologic deficits and postoperative course. METHODS: We examined 26 patients with cerebral gliomas. Fiber density data were used to segment peritumoral fiber structures and were coregistered to anatomic MR images and PET data. Fiber density and O-(2-(18)F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-(18)F-fluoroethyl)-l-tyrosine values: tumor-infiltrated tissue, reactive tissue (astrogliosis and microglial activation), normal brain tissue, and tissue with attenuated amino acid metabolism. Fiber density values were grouped in 3 categories for structural integrity: compressed, normal, and attenuated fibers. RESULTS: We evaluated and classified 103 peritumoral fiber structures with 10 patterns of fiber tract alterations. Fiber structures in tumor-infiltrated, reactive, and normal brain tissue showed compressed fibers, displaced fibers, and (partly) destroyed fibers, respectively. Attenuated amino acid metabolism was associated only with attenuated fiber density. Thirteen patients showed white matter-related neurologic deficits (paresis, hypoesthesia, aphasia, or anopia) as initial symptoms. Three patients showed tumor infiltration in the corresponding fiber tracts; all the others had reactive or normal brain tissue. Fiber structures were compressed or attenuated but not normal. The 3 patients with tumor infiltration in the corresponding fiber tracts and 1 with compressed fibers in normal brain showed no improvements or worsening of the deficits in the postoperative course. Eight patients with the corresponding fiber tracts in reactive or normal brain areas showed improvement of deficits. One patient underwent biopsy only. CONCLUSION: Our multimodal neuroimaging approach provides complementary information and more detailed understanding of peritumoral fiber tract alterations in gliomas which are more complex as described so far. We presented a classification model for systematic assessment of these alterations that may be helpful for treatment planning and prediction of patients' prognoses.

18Fluoroethyl-L-tyrosine-PET in long-term epilepsy associated glioneuronal tumors.

PURPOSE: Long-term epilepsy associated tumors (LEATs) are a frequent cause of drug-resistant partial epilepsy. A reliable tumor diagnosis has an important impact on therapeutic strategies and prognosis in patients with epilepsy, but often is difficult by magnetic resonance imaging (MRI) only. Herein we analyzed a large LEAT cohort investigated by 18fluoroethyl-L-tyrosine-positron emission tomography (FET-PET). METHODS: Thirty-six patients with chronic partial epilepsy and a LEAT-suspect MRI lesion were analyzed by FET-PET using visual inspection and quantitative analysis of standard uptake values (SUV). PET results were correlated with clinical and histopathologic data. RESULTS: FET-PET study was positive in 22 of 36 analyzed lesions and in 14 of 22 histologically verified LEAT lesions. The precise World Health Organization (WHO) tumoral entity was not predicted by FET-PET. Notably, FET uptake correlated strikingly with age at epilepsy onset (p = 0.001). Further correlations were seen for age at surgery (p = 0.007) and gadolinium-contrast enhancement on MRI (p < 0.05). DISCUSSION: FET-PET is a helpful tool for LEAT diagnosis, particularly when MRI readings are ambiguous. FET uptake, which is likely mediated by the l-amino acid transporter (LAT) family, might indicate a principally important biologic property of certain LEATs, since LAT molecules also are involved in cell growth regulation.

Multi-voxel magnetic resonance spectroscopy at 3 T in patients with idiopathic generalised epilepsy.

PURPOSE: The objective of our study was to gain further insight into the extent of local metabolic alterations in patients with idiopathic generalised epilepsy (IGE), respectively, the subgroup with generalised tonic-clonic seizures (GTCS). The extent of regional metabolic involvement perhaps indicates the key structures in generation of seizures and involvement of specific network of dysfunction. METHODS: Using the multi-voxel technique at a 3 T MRI Scanner metabolite levels of 25 age-matched healthy controls and 18 patients with GTCS were obtained from the basal ganglia, insular cortex, cingulum, hippocampus and along both hemispheres in the fronto-parietal white and grey matter. RESULTS: Group analysis of GTCS patients versus healthy controls revealed significant (p < 0.05) decrease of tNAA in the cortex of the central region and cingulum, but also in the thalami. Glx was elevated broadly in both hemispheres, in particular in central region, cingulum, insular cortex and left putamen, yet also in the right thalamus. Cho and mI demonstrated a significant coincidental decrease pronounced in the grey and white matter of the central region. Significant metabolic correlation (p ≤ 0.05) based on tNAA, respectively, Glx occurred between the thalamus and the central region, cingulum, putamen and medial frontal cortex. In patients with > 2 tonic-clonic seizures in the last 12 months a trend towards higher Glx and lower tNAA levels was observed. DISCUSSION: Our results demonstrate the altered metabolic interconnection of cerebral anatomic regions in patients with GTCS, in particular the major role of basal ganglia-central region relay in seizure generation.

Alterations of intracerebral γ-aminobutyric acid (GABA) levels by titration with levetiracetam in patients with focal epilepsies.

PURPOSE: The objective of this study was to determine if levetiracetam (LEV) modulates brain γ-aminobutyric acid (GABA) in patients with epilepsy. METHODS: Occipital GABA was assessed by protein magnetic resonance spectroscopy (¹H-MRS) in 16 patients with focal epilepsy at baseline and following the initiation of oral administration of LEV as monotherapy. Responder profiles were calculated as percentage of baseline seizure frequency. Alterations of GABA/Cr (creatine) of baseline measurements compared to GABA/Cr under LEV therapy were analyzed by Student's t-test for paired samples. RESULTS: After administration of LEV, partial seizure reduction (> 50%) was noticed in 5 of 16 patients (31%; 7 of 16 (44%) patients turned out to be free of seizures. Patients with 50-100% seizure reduction under LEV titration were referred to as LEV responders. Of the 32 GABA spectra, only 22 (approximately 70%) yielded a result that met the criteria for spectral quality; therefore, GABA/Cr data from only seven patients were paired. A significant increase of GABA/Cr during titration with LEV was noted in patients responding to LEV (n = 5; p = 0.007). No differences in baseline GABA/Cr levels were detected between patients with and without previous antiepileptic treatment (p = 0.74). DISCUSSION: The increasing GABA/Cr levels under drug titration only in LEV-responding epilepsy patients suggest a more complex and indirect influence of LEV on the GABAergic system.

Multi-voxel magnetic resonance spectroscopy of cerebral metabolites in healthy adults at 3 Tesla.

RATIONALE AND OBJECTIVES: The objective of this study was to determine how metabolite values (total N-acetyl aspartate [tNAA], glutamate plus glutamine [Glx], total choline [tCho], myoinositol [mI], and total creatine [tCr]) vary across brain regions in healthy subjects. This study was implemented to create an internal reference database for patients with psychiatric disorders and epilepsy. MATERIALS AND METHODS: Using the multivoxel technique with a voxelwise phantom calibration on a 3-T magnetic resonance imaging scanner, metabolite levels of 29 healthy controls (13 men, 16 women; average age, 29 years) were obtained from the hippocampi, basal ganglia, insula cortex, cingulum, and precuneus. Additionally, gray and white matter metabolite values were obtained from the frontal and parietal lobes. RESULTS: No significant effect of gender was noticed. The total magnitude of variation was greatest for Glx, followed by tNAA, mI, tCho, and tCr. Glx/tCr, Glx, and tCr were increased in gray matter, while tNAA/tCr, tCho/tCr, respectively tNAA and tCho, were elevated in white matter. These findings indicate (1) anterior-to-posterior increases of tNAA/tCr and Glx/tCr, respectively tNAA and Glx, along the midline in gray matter (cingulum); (2) increased tNAA/tCr, respectively tNAA, in white matter in the fiber tracts of the precentral region; (3) an accentuated anterior-to-posterior increase of tCr in the insula cortex; and (4) an anterior-to-posterior decrease of tCho/tCr and tCho in white matter. CONCLUSIONS: There are significant metabolic differences within tissue types and within tissue types at different locations; therefore, the spectra and metabolite values presented should provide a useful internal reference for both clinical and research studies.

Age-related degradation in the central nervous system: assessment with diffusion-tensor imaging and quantitative fiber tracking.

PURPOSE: To prospectively quantify differences in age-related changes in the diffusivity parameters and fiber characteristics between association, callosal, and projection fibers. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained. Diffusion-tensor imaging data with an isotropic voxel size of 1.9 mm(3) were acquired at 3 T in 38 healthy volunteers (age range, 18-88 years; 18 women). Quantitative fiber tracking was used to calculate fractional anisotropy (FA) and mean diffusivity values, eigenvalues (lambda(1), lambda(2), and lambda(3)), the number of fiber projections, and the number of fiber projections per voxel for three-dimensional reconstructed association, callosal, projection, and total brain fibers. Bivariate linear regression models were used to analyze correlations. Significant differences between correlations were assessed with the Hotelling-Williams test. RESULTS: For FA, the strongest degradation in association fibers and no significant changes in projection fibers were observed. The difference in correlation was significant (P = .002). The number of fiber projections and the number of fiber projections per voxel showed strong to moderate negative correlations that were dependent on age (P < .001) in the three fiber structures and total brain fibers, with the exception of the number of fiber projections per voxel in projection fibers, which showed no significant correlation. The decrease in the number of fiber projections was significantly greater (P = .043) in projection fibers than in total brain fibers, whereas the decrease in the number of fiber projections per voxel was significantly weaker (P = .005). Association fibers showed the largest changes per decade of age for FA (-1.13%) and for the number of fiber projections per voxel (-4.7%), whereas callosal fibers showed the largest changes per decade of age for the number of fiber projections (-10.4%). CONCLUSION: Quantitative fiber tracking enables identification of differences in diffusivity and fiber characteristics due to normal aging.

Quantitative diffusion tensor fiber tracking of age-related changes in the limbic system.

Cerebral white matter is known to undergo degradation with aging, and diffusion tensor imaging (DTI) is capable of revealing the white matter integrity. We assessed age-related changes of quantitative diffusivity parameters and fiber characteristics within the fornix and the cingulum. Thirty-eight healthy subjects aged 18-88 years were examined at 3 Tesla using a 1.9-mm isotropic DTI sequence. Quantitative fiber tracking was performed for 3D-segmentation of the fornix and the cingulum to determine fractional anisotropy (FA), mean diffusivity (MD), eigenvalues (lambda1, lambda2, and lambda3), number of fibers (NoF), and mean NoF/voxel (FpV). In the fornix, all diffusivity parameters (FA, MD, and eigenvalues) were moderately correlated with age. Strong and moderate negative correlations for NoF and FpV were found, respectively. In the cingulum, no correlation was observed between FA and age, and only weak correlations for the other quantitative parameters. Differences in correlations between the fornix and the cingulum were significant for all diffusivity parameters and for NoF, but not for FpV. The strongest relative changes per decade of age were found in the fornix: FA -2.1%, MD 4.2%, NoF -10.6%, and FpV -4.6%. Our quantitative 3D fiber tracking approach shows that the cingulum is resistant to aging while the fornix is not.

Non-invasive detection of hippocampal sclerosis: correlation between metabolite alterations detected by (1)H-MRS and neuropathology.

We assessed (1)H-MRS as a screening tool for detection of hippocampal sclerosis in patients with temporal lobe epilepsy (TLE). (1)H-MRS was carried out in the hippocampus of 23 patients with unilateral TLE. Metabolite alterations detected by (1)H-MRS correlated with degree of segmental neuronal cell loss and amount of astrogliosis. Positive correlation was found between total N-Acetylaspartate (tNAA) reduction and neuronal density in hippocampal CA1 (P < 0.001), CA3 (P = 0.015), and CA4 subfields (P = 0.031) and the dentate gyrus (P = 0.006). Neuronal cell loss in CA1 turned out to be the most predictive and only significant variable for tNAA reduction (P = 0.027). The association between myo-inositol (m-Ins) and astroglial glial fibrillary acidic protein (GFAP) expression revealed significantly increased m-Ins concentrations associated with diffuse astrogliosis (m-Ins = 6.4 +/- 1.1 institutional units) compared with gliosis restricted to isolated sectors of the hippocampus (i.e. hilus) (m-Ins = 5.2 +/- 1.2 institutional units) (P = 0.039). A negative correlation was found between m-Ins and neuronal loss in the CA4 subfield of the hippocampus (P = 0.028). Our results support (1)H-MRS as a suitable non-invasive method for preoperative identification of hippocampal sclerosis in patients with TLE. The extent of tNAA reduction correlates with hippocampal neuronal cell density. Furthermore, m-Ins is associated with the extent of hippocampal astrogliosis.

Proton magnetic resonance spectroscopic imaging in the border zone of gliomas: correlation of metabolic and histological changes at low tumor infiltration--initial results.

PURPOSE: We sought to retrospectively investigate differences in correlation of absolute metabolites concentrations and metabolite ratios with histopathologic parameters of stereotactic biopsies from the border zone of gliomas. MATERIALS AND METHODS: Proton magnetic resonance spectroscopic imaging (H-MRSI) with high spatial resolution was performed in 10 glioma patients at 1.5 T. Magnetic resonance spectroscopic imaging (MRSI) data were coregistered to a 3D MR data set used for stereotactic procedures. Metabolite concentrations of choline-containing compounds (Cho), creatine (Cr), and total N-acetyl-aspartate (tNAA) in addition to metabolite ratios of Cho/Cr, tNAA/Cr, and Cho/tNAA were calculated for voxel positions at biopsy loci with low tumor cell infiltration. Metabolite values were correlated with histopathologic findings expressed as a relative (% tumor infiltration, %TI) and an absolute parameter (tumor cell number, TCN). RESULTS: We found a strong negative linear correlation for tNAA with %TI (R = -0.773, P < 0.001) and TCN (R = -0.769, P < 0.001) but no correlation for Cho (P > 0.05). On the other hand, the metabolite ratio of Cho/Cr showed a moderate positive linear correlation with %TI (R = 0.523, P = 0.012) and TCN (R = 0.486, P = 0.019), but no correlation was obtained for tNAA/Cr (P > 0.05). Differences in correlation between tNAA and Cho as well as tNAA/Cr and Cho/Cr were significant for both %TI (P = 0.012 and P = 0.024) and TCN (P = 0.016 and P = 0.040) using a t test. CONCLUSIONS: We conclude that absolute values of tNAA are more significant than Cho in the detection of low tumor cell infiltration. On the basis of absolute metabolite values, neuronal damage seems to be more distinct than cell membrane proliferation in the border zone of gliomas. Furthermore, the calculation of metabolite ratios versus Cr for the border zone may yield to misleading results because Cr is not constant in this area.

1H-MR spectroscopy indicates severity markers in temporal lobe epilepsy: correlations between metabolic alterations, seizures, and epileptic discharges in EEG.

PURPOSE: In this study, hippocampal metabolite alterations in (1)H-MR spectroscopy ((1)H-MRS) were correlated to the findings of intensive video-EEG monitoring and duration of seizure symptoms in patients with temporal lobe epilepsy (TLE). METHODS: The 14 patients with mesial TLE and no pathological findings in imaging were investigated by (1)H-MRS. Seizures were analyzed by: number of clinical seizures in 24 h, exact duration of clinical symptoms in 24 h, frequency of interictal epileptiform discharges (IEDs) and ictal activity, duration of ictal activity, and IEDs occurring within 24 h in intensive EEG monitoring. Pearson Correlation Coefficient (PCC) was calculated between spectral metabolite alterations and the parameters mentioned above. RESULTS: In the analysis, a negative correlation was found between total (t) NAA values and degree of IEDs in EEG (p = 0.04); a positive correlation was found between Cr levels and duration of seizure symptoms registered by video monitoring (p = 0.01). CONCLUSIONS: Our study shows that, in some patients, (1)H-MRS is able to refer the severity of TLE. The degree of tNAA reduction in (1)H-MRS, probably indicating neuronal dysfunction, is associated with interictal spiking in intensive EEG monitoring. Duration of seizure symptoms associated with increased Cr peaks probably reflects increased gliosis.