Proton magnetic resonance spectroscopy in focal cortical dysplasia at 3T.

PURPOSE: Focal cortical dysplasia (FCD) type II is a frequent cause of medically intractable epilepsy. On conventional MRI diagnosis may be difficult. The purpose of our study was to assess the metabolic characteristics of MRI-typical or neuropathologically confirmed FCD II lesions at 3T. METHODS: In a prospective study, 13 patients with drug-resistant epilepsy and MRI diagnosis of FCD II (seven neuropathologically confirmed) were investigated by single-volume proton magnetic resonance spectroscopy ((1)H MRS). We performed an intra-individual comparison placing spectroscopic volumes of interest in the lesion and in the apparently normal contralateral hemisphere. Spectroscopic results were correlated with clinical data. RESULTS: Matched pair analysis revealed a significant increase in absolute choline (Cho) concentration in the lesion volume (+32%, p=0.015) compared to the control volume. This increase was associated with a significant decrease in N-acetyl-aspartate (NAA) concentration (-13%; p=0.008). Mean myo-inositol (Ins) levels were distinctly (+36%) but not significantly (p=0.051) elevated. Lesional creatine (Cr) concentration correlated significantly with the frequency of seizures (Spearman-Rho r=0.898; p=0.002), while concentrations of NAA, Cho and Ins did not correlate with clinical or imaging parameters. CONCLUSION: MR spectroscopy revealed a characteristic metabolic pattern in FCD II lesions that helps to distinguish normal from epileptogenic tissue.

Magnetic resonance imaging of focal cortical dysplasia: Comparison of 3D and 2D fluid attenuated inversion recovery sequences at 3T.

PURPOSE: Focal cortical dysplasia (FCD) is a frequent finding in drug resistant epilepsy. The aim of our study was to evaluate an isotropic high-resolution 3-dimensional Fluid-attenuated inversion recovery sequence (3D FLAIR) at 3T in comparison to standard 2D FLAIR in the diagnosis of FCD. MATERIALS AND METHODS: In a prospective study, 19 epilepsy patients with the MR diagnosis of FCD were examined with a sagittal 3D FLAIR sequence with modulated refocusing flip angle (slice thickness 1.10mm) and a 2D FLAIR in the coronal (thk. 3mm) and axial planes (thk. 2mm). Manually placed regions of interest were used for quantitative analysis. Qualitative image analysis was performed by two neuroradiologists in consensus. RESULTS: Contrast between gray and white matter (p ≤ 0.02), the lesion (p ≤ 0.031) or hyperintense extension to the ventricle (p ≤ 0.021) and white matter was significantly higher in 2D than in 3D FLAIR sequences. In the visual analysis there was no difference between 2D and 3D sequences. CONCLUSION: Conventional 2D FLAIR sequences yield a higher image contrast compared to the employed 3D FLAIR sequence in patients with FCDs. Potential advantages of 3D imaging using surface rendering or automated techniques for lesion detection have to be further elucidated.

Outcome after epilepsy surgery in patients with MRI features of bilateral ammon's horn sclerosis.

In refractory temporal lobe epilepsy with unilateral ammon's horn sclerosis (uAHS) resective epilepsy surgery is an established treatment option whereas little evidence exists about the consequences of unilateral hippocampal resection in patients with bilateral ammon's horn sclerosis (bAHS). The aim of this study was to evaluate the post-surgical outcome of patients with bAHS after selective amygdalo-hippocampectomy (SAH) in comparison to uAHS patients. For this purpose, all bAHS and uAHS patients, identified at our center between 2003 and 2009 were analyzed retrospectively. Thirty-one bAHS patients and 291 uAHS patients were identified. Only 55% of the bAHS, but 80% of the uAHS patients were referred for formal pre-surgical diagnostics (p=0.001). Eleven bAHS and 127 uAHS patients underwent SAH. There was no difference in seizure-free outcome (Engel IA) at 12 months (bAHS 82% vs. 69%, p=0.40) and 24 months follow up (bAHS 57% vs. 60%, p=0.80). None of the bAHS patients became globally amnesic post-surgically. The favorable outcome in these highly selected bAHS patients suggests that bAHS patients may have a fair chance of becoming seizure-free after SAH. However, due to the large number of bAHS patients not undergoing formal presurgical evaluation, the results cannot be extrapolated to bAHS patients in general.

Neuroimaging characteristics in mitochondrial encephalopathies associated with the m.3243A>G MTTL1 mutation.

Stroke-like lesions (SLL) are common radiological findings in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (SLE; MELAS) harboring the m.3243A>G MTTL1 mutation. Imaging patterns in the m.3243A>G mutation carriers with encephalopathies lacking SLE have not been systematically examined to date. The aim of this study was to analyze brain imaging findings in encephalopathies associated with the m.3243A>G mutation irrespective of the presence or absence of SLE. Brain MRI and cranial CT scans from 11 m.3243A>G mutation carriers with encephalopathies were analyzed by two neuroradiologists in consensus. We evaluated stroke-like lesions (SLL), deep grey matter (DGM) changes on T1- and T2-weighted MR images, calcification on CT, brain atrophy, and white matter (WM) changes. SLL were present in all patients showing the full MELAS phenotype with SLE (4/11). Seven patients did not show SLE. DGM changes with T1 hyperintensity and T2 hypointensity were a distinctive finding in most patients (7/11) and present in the majority of m.3243A>G mutation carriers lacking SLE (5/7). DGM changes were also seen in half of our MELAS patients with SLL (2/4), though less pronounced. Brain atrophy was a prominent finding in general and accentuated in the cerebellum. In contrast, WM changes were rather mild and more prevalent and pronounced in MELAS. Our data stress that the distinction between MELAS with SLE and m.3243A>G mutation carriers lacking SLE is rather artificial. In clinical practice, mitochondrial disorders associated with the m.3243A>G mutation should be taken into consideration in encephalopathies with DGM changes, even when SLE and SLL are lacking.

Thalamus lesions in chronic and acute seizure disorders.

INTRODUCTION: Transient signal changes in the pulvinar have been described following status epilepticus. However, we observed persistent thalamus changes after seizures. The purpose of this study was to characterize thalamus changes in patients with seizure disorders and to correlate imaging findings with clinical features. METHODS: We searched among 5,500 magnetic resonance imaging (MRI) exams performed in patients with seizures and identified 43 patients. The MRI scans of these patients were reviewed and correlated with clinical data. RESULTS: We identified four patterns of thalamus lesions: (a) fluid attenuated inversion recovery-hyperintense pulvinar lesions (20 patients), as known from status epilepticus. Ten patients in this group had a status epilepticus. Among the remaining patients, three had frequent seizures and seven had sporadic seizures. Twelve patients had follow-up exams for a median of 11 months. The lesions had persisted in 11/12 cases in the last available exam and were reversible in one case only. In seven cases, cone-shaped thalamus atrophy resulted, (b) linear defects in the medial and anterior thalamus (five patients), accompanied by atrophy of the mamillary body and the fornix in patients with chronic epilepsy, (c) extensive bilateral thalamus lesions in two patients with a syndrome caused by mutation in the mitochondrial polymerase gamma, and (d) other thalamus lesions not associated with the seizure disorder (16 patients). CONCLUSION: The spectrum of thalamus lesions in patients with seizure disorders is wider than previously reported. Postictal pulvinar lesions can persist and may result in thalamic atrophy. Linear defects in the anterior thalamus are associated with limbic system atrophy.

[A 25-year-old patient with colonic pseudo-obstruction, hyponatremia, hypertension, and diffuse pain]. / Eine 25-jährige Patientin mit Pseudoobstruktion des Kolons, Hyponatriämie, hypertensiver Entgleisung und diffusem Schmerzsyndrom.

CASE REPORT: A 25-year-old hypertensive patient presented to the Emergency Department with constipation and diffuse pain which had been increasing for 10 days. She had consulted several doctors before, but neither various analgesics nor metoclopramide had been beneficial. Blood analysis showed hyponatremia. A megacolon and polyneuropathy were found. Shortly after admission, she developed generalized seizures while hyponatremia increased compatible with SIADH (syndrome of inadequate ADH secretion). Urine examination revealed a markedly elevated excretion of porphyrins. Since porphobilinogen deaminase activity was clearly decreased, diagnosis of acute intermittent porphyria could be confirmed. CONCLUSION: This case shows how definite diagnosis of this illness is often delayed because of its rarity and the variety of its possible symptoms and signs. This delay leads to a high risk of aggravating the disease by prescribing porphyrinogenic drugs.

Radiological assessment of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease is a rare fatal neurodegenerative disorder, characterized by rapidly progressive dementia and neurological signs. There is a need for early and accurate clinical diagnosis in order to exclude any treatable disorder. Additionally, it is of public interest to differentiate the sporadic form of the disease from the variant CJD type (vCJD), which is probably transmitted from cattle infected with bovine spongiform encephalopathy (BSE). High signal in the striatum on T2-weighted, FLAIR and diffusion weighted (DW) MRI as well as cortical high signal in FLAIR and DW MRI are the classical findings in sCJD. The "pulvinar sign", defined as high signal in the pulvinar thalami that is brighter than potential additional high signal in the basal ganglia, is considered pathognomonic for vCJD.

Brain tumors: full- and half-dose contrast-enhanced MR imaging at 3.0 T compared with 1.5 T--Initial Experience.

PURPOSE: To prospectively and intraindividually compare the effect of magnetic resonance (MR) imaging at a higher magnetic field strength (3.0 T) on contrast-to-noise ratio (CNR) at different doses of a T1-shortening contrast agent in patients with contrast-enhancing brain lesions, with 1.5-T MR imaging as a reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for all patient and volunteer studies. Twelve patients (six women, six men; mean age, 58 years; range, 29-76 years) with 12 enhancing brain lesions (11 patients with primary brain tumors and one with a solitary cerebral metastasis) underwent contrast material-enhanced MR imaging three times, on three separate days: once at 1.5 T with a full dose of 0.10 mmol/kg gadopentetate dimeglumine, once at 3.0 T with a full dose, and once at 3.0 T with half that dose, 0.05 mmol/kg. The same contrast-enhanced T1-weighted spin-echo images (repetition time msec/echo time msec, 500/12; section thickness, 5 mm; matrix, 256 x 205) were obtained at both 3.0 T and 1.5 T after prior optimization of parameters at 3.0 T. The number and conspicuity of enhancing brain lesions were assessed with blinded clinical image reading. Signal-to-noise ratio and CNR were determined with region of interest analysis of enhancing lesions and normal contralateral white matter. For 3.0 T with half the standard dose and with the full dose, CNR of lesions was intraindividually compared with CNR at 1.5 T with the full dose by using the Wilcoxon matched-pairs signed rank test. RESULTS: At 3.0 T and full dose, CNR was 2.8-fold higher than that at 1.5 T and full dose (P < .001). At the same time, higher lesion conspicuity at clinical image reading was observed. With only half the standard dose, MR imaging at 3.0 T still yielded higher CNR (1.3-fold higher) than that with full dose at 1.5 T (P < .01). CONCLUSION: With the same amount of contrast agent, MR imaging at 3.0 T offered a significantly higher CNR of enhancing cerebral lesions, compared with that at 1.5 T; even with the dose reduced by half, CNR was still higher at 3.0 T.

MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: a study on inter-observer agreement.

According to the current WHO criteria, technical investigations included in the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) are electroencephalogram (EEG) and CSF-analysis for 14-3-3 proteins. MRI is not a criterion for the diagnosis of sCJD, although typical changes have been described. We investigated the reliability of MRI in the sCJD diagnosis, evaluated MRI sequences and compared MRI with EEG and 14-3-3. This study includes 193 consecutive suspected sCJD patients who had been referred to the German CJD Surveillance Unit from 2001 to 2003. Three observers independently analysed MRI scans, blinded to clinical data. MRI was rated as 'typical for sCJD' if increased signal intensity was detected in the caudate nucleus and putamen. We analysed 442 MRI scans [184 T2-weighted sequences, 132 fluid attenuated inversion recovery (FLAIR) sequences, 75 diffusion-weighted sequences and 51 proton-density weighted sequences]. Inter-observer agreement was 123 of 193 patients or 63.7% (overall kappa = 0.53). Sensitivity of MRI in clinically probable or autopsy-proven sCJD was 59.7% for Observer 1, 58.3% for Observer 2 and 70.8% for Observer 3; specificity was high (84.2, 89.5 and 81.6%, respectively). Diffusion-weighted sequences best showed the pathologic changes, followed by FLAIR. Periodic sharp and slow wave complexes were detected in the EEG in 32% (sensitivity), the 14-3-3 proteins in CSF were elevated in 91%. We conclude that the detection of hyperintense basal ganglia in MRI helps to improve the clinical diagnosis, and therefore, we propose to incorporate MRI in the diagnostic criteria for sCJD.

Time-of-flight MR angiography: comparison of 3.0-T imaging and 1.5-T imaging--initial experience.

Intracranial three-dimensional time-of-flight (TOF) magnetic resonance (MR) angiography was performed in seven healthy volunteers and eight patients with both 1.5-T and 3.0-T MR systems with standard and high spatial resolutions (true voxel sizes, 0.48 x 0.75 x 2.00 mm and 0.30 x 0.44 x 1.00 mm, respectively). Superior image quality and significantly better depiction of small vessel segments and vascular disease were observed at high-spatial-resolution 3.0-T TOF MR angiography but not at standard 1.5-T or standard 3.0-T TOF MR angiography (P <.01, respectively). Intracranial high-spatial-resolution TOF MR angiography at 3.0-T imaging provides diagnostic improvement in studies of cerebrovascular disease.

Thalamic involvement in sporadic Creutzfeldt-Jakob disease: a diffusion-weighted MR imaging study.

BACKGROUND AND PURPOSE: Recent neuropathologic research suggests thalamic involvement in sporadic Creutzfeldt-Jakob disease (sCJD), which has been disregarded in imaging studies. Diffusion-weighted (DW) MR imaging has the highest sensitivity for the detection of signal intensity (SI) abnormalities in CJD. We hypothesized that pathologic changes in the thalamus in sCJD can be detected by using a subtle analysis of DW MR imaging. METHODS: Six sCJD patients and nine healthy controls were examined with a 1.5-T system by using DW single-shot spin-echo echo planar (b = 0, 1000 s/mm(2)), T2-weighted turbo spin-echo, and fluid-attenuated inversion recovery sequences. One patient was examined serially (3, 4, and 8 months after onset of symptoms). MR images were reviewed for SI changes in the striatum, hippocampus, mediodorsal thalamic nucleus (MD), and pulvinar thalami. Apparent diffusion coefficients (ADCs) were measured in these areas. RESULTS: All sCJD patients showed increased SI on DW images in the striatum bilaterally. ADCs in these areas were significantly reduced. Four of six sCJD patients showed increased SI on DW images in the pulvinar thalami, whereas ADCs were significantly reduced in all patients (mean ADC +/- SEM: in patients with SI changes, 701 +/- 38; in patients without SI changes, 684 +/- 37; in controls, 853 +/- 15 [P <.0001]). No patient showed SI changes in the MD on DW images, whereas ADCs were significantly reduced in all (664 +/- 28 as compared with 800 +/- 24 in controls [P =.0011]). Serial measurements in one sCJD patient showed ADC reduction in the pulvinar thalami preceding the SI changes on DW images. CONCLUSION: A quantitative analysis of DW images with ADC measurements shows slight MR imaging changes in the thalamus in sCJD when abnormal SI may not be present.

Clinical findings in sporadic Creutzfeldt-Jakob disease correlate with thalamic pathology.

The pathogenesis underlying the typical findings in Creutzfeldt-Jakob disease (CJD) such as periodic EEG changes or myoclonus is not fully understood. The thalamus possesses a high density of inhibitory neurones and serves as a crucial pacemaker of rhythmic EEG activity. As inhibitory neurones expressing parvalbumin (PV) are reduced in the cerebral cortex and hippocampus in sporadic CJD (sCJD), we studied the distribution and number of PV-immunoreactive neurones in sCJD thalami in order to determine whether damage to them could account for certain clinical findings. Immuno histochemical analysis was performed on the thalami from 21 sCJD patients and five controls. The number of PV+ neurones was counted in the thalamic nuclei and compared with clinical and molecular findings. In sCJD patients, PV+ neurones were significantly reduced in the ventrolateral posterior (VLp), ventrolateral anterior (VLa), anteroventral (AV), lateral dorsal (LD), mediodorsal (MD) and reticular (Re) thalamic nuclei (P < 0.05). The VLp was especially damaged in sCJD patients with homozygosity for methionine at codon 129 and scrapie prion protein (PrP(Sc)) type 1. Patients with typical EEG changes [periodic sharp wave complexes (PSWCs)] and myoclonus had a predominant loss of PV+ cells in the reticular thalamic nucleus. In conclusion, our data support the hypothesis that the damage to PV-immunoreactive neurones determines the generation of certain typical clinical features of CJD, i.e. PSWCs associated with myoclonus.

Positron emission tomography with [(18)F]FDG in the diagnosis of Creutzfeldt-Jakob disease (CJD).

The aim of this study was to explore the sites of metabolic changes with [(18)F]2-fluoro-2-desoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with Creutzfeldt-Jakob disease and to correlate the findings with clinical symptoms. Static [(18)F]FDG-PET studies of eight patients with the diagnosis of confirmed or probable CJD were retrospectively analysed by two physicians from departments of nuclear medicine independently with a strong interrater agreement (kappa=0,98). The clinical data of the patients, based on a standardized evaluation by physicians from the German Creutzfeldt-Jakob disease surveillance study, was correlated with the PET findings. [(18)F]FDG-PET shows widespread hypometabolism in CJD. All patients had a reduction of cerebral glucose metabolism in at least one temporal or parietal region. Additionally in 7 of our own 8 cases and 3 of 4 cases from the literature the occipital lobe, the cerebellum or the basal ganglia were involved. These findings differ from typical patterns of hypometabolism in Alzheimer's disease and other neurodegenerative disorders. In two thirds of the cases the distribution was markedly asymmetric. Myoclonus was present in five out of our eight own cases. Our data suggest that myoclonus might correlate with metabolic impairment of contralateral parietal and temporal lobes. In three of four patients with visual symptoms FDG uptake was reduced in the visual cortex bilaterally. Typical hyperintensities on MRI were only found in two of the eight cases at the time of PET-studies. Our results demonstrate that [(18)F]FDG-PET appears to be a sensitive investigation in CJD and could be useful to differentiate CJD from other neurodegenerative disorders.