Body mass index as a predictor of MS activity and progression among participants in BENEFIT.

BACKGROUND: There is a lack of studies on the association between obesity and conversion from a clinically isolated syndrome (CIS) to multiple sclerosis (MS). OBJECTIVE: The aim of this study was to determine whether obesity predicts disease activity and prognosis in patients with CIS. METHODS: Body mass index (BMI) at baseline was available for 464 patients with CIS in BENEFIT. Obesity was defined as BMI ⩾ 30 kg/m2 and normal weight as 18.5 ⩽ BMI < 25. Patients were followed up for 5 years clinically and by magnetic resonance imaging. Hazard of conversion to clinically definite (CDMS) or to 2001 McDonald criteria (MDMS) MS, annual rate of relapse, sustained progression on Expanded Disability Status Scale (EDSS), change in brain and lesion volume, and development of new brain lesions were evaluated. RESULTS: Obese individuals were 39% more likely to convert to MDMS (95% CI: 1.02-1.91, p = 0.04) and had a 59% (95% CI: 1.01-2.31, p = 0.03) higher rate of relapse than individuals with normal weight. No associations were observed between obesity and conversion to CDMS, sustained progression on EDSS or magnetic resonance imaging (MRI) outcomes, except for a larger reduction of brain volume in obese smokers as compared to normal weight smokers (-0.82%; 95% CI: -1.51 to -0.12, p = 0.02). CONCLUSION: Obesity was associated with faster conversion to MS (MDMS) and a higher relapse rate.

[Prediction of psychosis by stepwise multilevel assessment--the Basel FePsy (Early Recognition of Psychosis)-Project]. / Vorhersage von Psychosen durch stufenweise Mehrebenenabklärung--Das Basler FePsy(Früherkennung von Psychosen)-Projekt.

BACKGROUND: We have conducted various studies in Basel with the aim of improving the methods for the early detection of psychosis (Früherkennung von Psychosen, FePsy). METHODS: From 1.3.2000 to 29.2.2004 234 individuals were screened using the Basel Screening Instrument for Psychosis (BSIP). 106 patients were identified as at risk for psychosis; out of these 53 remained in follow-up for up to 7 years (mean 5.4 years). The assessments were done with a specifically developed instrument for history taking, various scales for the psychopathology, assessments of neuropsychology and fine motor functioning, clinical and quantitative EEG, MRI of the brain, laboratory etc. RESULTS: Based on the BSIP alone, a relatively reliable prediction was possible: 21 (39.6%) of the individuals identified as at risk developed psychosis within the follow-up time. Post-hoc prediction could be improved to 81% by weighting psychopathology and including neuropsychology. Including the other domains obviously allows further improvements of prediction. CONCLUSIONS: The risk for psychosis should be assessed in a stepwise procedure. In a first step, a clinically oriented screening should be conducted. If an at-risk status is found, further assessments in various domains should be done in a specialised centre.

Cortical reorganization after acute unilateral hearing loss traced by fMRI.

Unilateral acoustic stimulation produces a functional MRI (fMRI)-blood-oxygenation-level-dependent (BOLD) response mainly in the contralateral auditory cortex. In unilateral deaf patients, the BOLD response is bilateral. We studied a subject with sudden hearing loss after cochlear nerve resection before and repeatedly after surgery. During normal bilateral hearing, contralateral cortical BOLD responses were found. Progressing compensatory reorganization with bilateral representation of unilateral stimulation was detected over a period of approximately 1 year.

Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study.

To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose metabolism (CMR-Glu) in 47 MS patients using PET and 18F-fluorodeoxyglucose. Applying the Fatigue Severity Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mumol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the right supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen toward the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the right prefrontal cortex. CMRGlu in the cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS values. Our data suggest that fatigue in MS is associated with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.

Dexamethasone treatment and plasma glucose levels: relevance for fluorine-18-fluorodeoxyglucose uptake measurements in gliomas.

UNLABELLED: Dexamethasone (DEX) is frequently used in brain tumor management. This study investigated the effect of DEX treatment and plasma glucose levels on 18F-fluorodeoxyglucose (FDG) uptake in patients with malignant gliomas (16 glioblastoma, 3 anaplastic astrocytoma). METHODS: Fifteen DEX-treated patients (mean relative dose 0.23 +/- 0.15 mg(-1) x kg(-1) x day(-1), range 0.07-0.53), four patients not treated with DEX and nine healthy subjects were studied using PET and FDG. PET data obtained from tumors and the contralateral cortex were fitted to a standard two-tissue compartment model. The FDG transport and phosphorylation rates, distribution volume (DV), steady-state accumulation (Ki), deoxyglucose metabolism (R), plasma volume as well as standardized uptake values (SUVs) and tumor-to-brain ratios were determined. In addition, the tumor size was estimated from the maximal area of contrast-enhancing tumor on computed cranial tomography (CCT) scans or MRI. RESULTS: FDG uptake was depressed in the contralateral cortex of patients and was related to tumor size. With increasing relative DEX dose, a decrease in the DV of tumors (linear regression p = 0.021) and in the DV (p = 0.109) and plasma volume (p = 0.010) of contralateral cortex was found. R, Ki and SUVs in tumors and contralateral cortex were not related to the relative DEX dose. With increasing plasma glucose levels, differential decreases in Ki and SUVs in tumors (p = 0.057 and p = 0.733, respectively) and contralateral cortex (p = 0.001 and p = 0.029, respectively) were observed. CONCLUSION: The data suggest that DEX affects FDG uptake in malignant gliomas through interaction with cerebral blood vessels and extracellular space, whereas FDG metabolism in tumors is not influenced substantially. This is of practical importance for patients having serial brain tumor imaging for treatment evaluation because patients may receive different DEX doses at different time points in the course of their disease. By contrast, the plasma glucose level must be considered a confounding variable when SUVs, tumor-to-brain ratios or Ki are used for treatment evaluation.

Motor, somatosensory and auditory cortex localization by fMRI and MEG.

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in six subjects during self-paced finger movement performance, tactile somatosensory stimulation and binaural auditory stimulation using identical stimulation paradigms. Both functional imaging modalities localized brain activity in adjacent areas of anatomically correct cortex. The mean distances measured between fMRI activity and the corresponding MEG dipoles were 10.1 mm (motor), 10.7 mm (somatosensory), 13.5 mm (auditory right hemisphere) and 14.3 mm (auditory left hemisphere). The distances found may reflect the correlation between electrophysiological and hemodynamic responses due to the different underlying substrates of neurophysiology measured by fMRI and MEG: BOLD contrast vs neuronal biomagnetic activity.

Pattern shift visual evoked potentials in Charcot-Marie-Tooth disease, HMSN type I.

Pattern shift visual evoked potentials were investigated in 9 subjects with Charcot-Marie-Tooth disease, who were classified as HMSN I on clinical, genetic and electromyographic criteria. The latency of the second positive peak was increased in 7 eyes of 5 subjects. These results suggest that patients with HMSN I the optic nerves may be affected more frequently than suspected on clinical examinations.

Acute infectious disorders of the spinal cord and its roots with gadolinium-DTPA enhancement in magnetic resonance imaging.

We studied three patients with myelomeningoradiculitis caused by Borrelia burgdorferi, herpes zoster virus or cytomegalovirus infection. All patients underwent MRI of the spinal cord with gadolinium-DTPA and showed enhancing lesions of the spinal cord or nerve roots that correlated with clinical signs. Gadolinium-DTPA enhancement may visualize lesions that suggest an inflammation associated with blood-brain-barrier alteration and indicate the diagnosis before serological results are available.

Alteration of blood-brain barrier in human brain tumors: comparison of [18F]fluorodeoxyglucose, [11C]methionine and rubidium-82 using PET.

The influence of the blood-brain barrier (BBB) on tracer uptake was investigated in 21 patients with gliomas and meningiomas using PET, [18F]fluorodeoxyglucose (FDG), [18C]methionine (MET) and the K+ analog rubidium-82 (RUB) whose uptake into brain is largely prevented if the BBB is intact. Tracer uptake was quantitated by (1) multiple time graphical plotting providing tracer distribution volume (VD), unidirectional tracer uptake (Ki), and (2) normalized uptake (NU) which is a measure of net tissue radioactivity related to administered activity and body weight. VD, Ki and NU of MET were higher in meningiomas compared to gliomas and were significantly correlated with NU RUB (Spearman rank: p < 0.005 (VD), p < 0.05 (Ki), p < 0.001 (NU)). NU MET correlated with VD (p < 0.001) and Ki (p < 0.005) of MET. For FDG, tumor VD was in the range of contralateral cortex. Ki and NU values of FDG were highest in glioblastomas. NU of FDG correlated significantly with Ki of FDG (p < 0.005) but not with VD. The results suggest, that alteration of MET uptake in tumors is governed by changes of tracer influx across the BBB, whereas FDG uptake is related to tracer metabolism. This makes FDG the appropriate tracer particularly for the differential diagnosis of contrast enhancing lesions in operated and irradiated patients.

Crossed cerebellar diaschisis and brain tumor biochemistry studied with positron emission tomography, [18F]fluorodeoxyglucose and [11C]methionine.

Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localization, histological grade, size and tumor biochemistry. Cerebellar glucose metabolism was measured in 44 glioma patients and 15 healthy subjects using positron emission tomography and [18F]fluorodeoxyglucose (FDG). CCD was determined by calculating an asymmetry index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and [11C]methionine (MET) was also assessed, and was expressed as ratio of normalized tracer uptake in tumor over contralateral cortex (T/C). Frontal lobe tumors were associated with highest CCD values. For these tumors, CCD was higher in malignant (-11.8+/-9.9%) than in low-grade (-4.3+/-4.1%) gliomas (P=0.010). In addition, frontal lobe tumors showed increasing CCD values with increasing size. In tumors of the parietal or temporal lobe, CCD was less marked or absent. T/C ratios of tumor tracer uptake were higher in malignant than in low-grade gliomas, but were not correlated with CCD. Our data indicate that the magnitude of CCD is mainly determined by tumor localization and size, the latter being associated with tumor grade. These findings raise the question whether CCD provides a measure of expansion or progression particularly in low-grade tumors of the frontal lobe.

Severe head injury: should expected outcome influence resuscitation and first-day decisions?

An early 'prognosis' based on initial findings can influence clinical decisions. To evaluate the quality of first-day outcome prediction based on either clinical or neuroradiological information, we prospectively examined 100 consecutive severely head-injured patients from the surgical intensive care unit. The prognoses were always made by the same experienced neurosurgeon and neuroradiologist according to a contracted Glasgow Outcome Scale (GOS). Every patient's outcome was predicted according to a three-class GOS within 24 h after injury. Correct 'first-day' prognoses were made in 59 and 56% of the cases by the neuroradiologist and neurosurgeon, respectively. In those instances where the prognoses made by the clinician and the radiologist coincided, the prognoses were correct for 73% of the patients. Based on accepted criteria, the neuroradiologist tended to overpredict favorable outcomes and missed many of the unfavorable outcomes (dead or vegetative) whereas the clinician overestimated unfavorable outcomes. Our study showed that outcome prognosis of patients with severe head injury has limited accuracy when made within 24 h after the injury, although an improvement in accuracy occurred when there was agreement between clinical and radiological predictions. Even with sophisticated clinical and radiological technologies, it is not possible to predict outcome on the first day after the accident with sufficient accuracy to guide early management.

Effect of ethanol on BOLD response to acoustic stimulation: implications for neuropharmacological fMRI.

The effects of ethanol on acoustically stimulated blood oxygenation level-dependent (BOLD) signal response in healthy humans was examined with echo planar functional magnetic resonance imaging (fMRI). An acquisition mode minimizing neuronal activation by scanner noise in combination with acoustic excitation by a pulsed 1000-Hz sine tone was used. Paradigms were repeated three times before and after the ingestion of 0.7 g of ethanol/kg(body weight). Linear correlation analyses (r>/=0.40) revealed bilateral BOLD responses in the auditory cortex. Significant voxels covered a cortical volume of approximately 3 ml that was reduced by approximately 40% after ethanol. The BOLD signal change initially reaching approximately 3% was reduced by 12-27%, depending on the definition of the region of interest for signal quantitation. Because ethanol produces vasodilation, the hemodynamic contribution to the BOLD signal change was estimated by modeling the relationship between regional cerebral blood flow (rCBF) and BOLD signal changes. Assuming a baseline flow increase by 10% after ethanol intake, the resulting 'Flow-BOLD-Dependence' (FBD) curve suggested that the ethanol-related BOLD signal reduction was approximately 7-12% greater than the reduction contributed purely by vasodilation. However, simultaneous determination of rCBF and regional cerebral blood volume would be required for an exact quantitation of the neuronally induced BOLD response. Although the FBD model needs empirical validation, its cautious implementation appears to be helpful if fMRI is used in combination with vasoactive drugs.

Analysis of input functions from different arterial branches with gamma variate functions and cluster analysis for quantitative blood volume measurements.

Regional cerebral blood volume (rCBV) provides valuable information about the nature and progress of diseases of the central nervous system. While relative rCBV maps can be derived directly from dynamic susceptibility contrast data, the arterial input function (AIF) has to be measured for absolute rCBV quantification. For determination of the AIF pixels located completely within a feeding artery must be selected. However, by using a region-of-interest (ROI) based selection some confounding effects can occur, especially if single shot echo planar imaging (EPI) with low spatial resolution is used. In this study we analyzed the influence of partial volume effects and spatial misregistration due to frequency shifts induced by paramagnetic contrast agents. We analyzed AIFs from the internal carotid artery (ICA), the vertebral artery (VA) and the middle cerebral artery (MCA) using gamma variate function based parameterization. The concentration time curves (CTC) of several pixels which were selected on the basis of strong signal drop appeared distorted during the bolus passage. Moreover, the amplitudes of input functions derived from the MCA were smaller by a factor of three as compared to those of the ICA and VA. Simulations revealed that these effects can be attributed to a spatial shift of the vessel along phase-encoding direction during the passage of the bolus. We therefore developed a procedure for a pixel selection based on cluster analysis which classifies pixels according to the parameters of the fitted gamma variate functions. This approach accounted for misregistration of the vessel and yielded very consistent results for a group of normal subjects.

[Intracranial lymphoma. Radiologic findings in 40 patients]. / Intrakranielle Lymphome. Radiologische Befunde bei 40 Patienten.

We analysed the radiologically findings of 40 patients with histologically confirmed cerebral lymphoma but without AIDS in a retrospective study; 31 of these had primary cerebral lymphoma without any other manifestation of the disease. All patients had CT, 24 had angiography and in five patients MRT had been performed in addition. CT showed a solitary lesion in 60%, of these 62% had scalloped margins and 38% were nodular, 34% were isodense and 57% were hyperdense. Following contrast injection, there was increased density in 97% of the lesions. The most frequent localisation was in the region of the basal ganglia and the corpus callosum (33%), in the frontal lobes (30%) and in the temporal lobes (20%). Angiographically, 63% showed evidence of a space-occupying lesion, there were vascular irregularities in 33% and tumour contrast in 21%; in 25% of the patients angiography was normal. Early venous filling was not found in any case. T1 weighted sequences during MRT of 5 patients showed the tumour to be isointense or slightly hypointense. T2 weighted images showed the tumour to be hyperintense or with mixed signal intensities.

[Perimesencephalic subarachnoid hemorrhage: clinical and computer tomography aspects]. / Die perimesenzephale Subarachnoidalblutung: klinische und computertomographische Aspekte.

AIM: The blood distribution on CCT and the prognosis of patients with nonaneurysmal subarachnoidal haemorrhage were retrospectively studied and compared to a patient group with aneurysmal haemorrhage. METHODS: The blood distribution on CCT (72 h after bleeding episode) of 26 patients with nonaneurysmal subarachnoidal haemorrhage confirmed by two normal cerebral angiograms was compared to the blood distribution of 76 patients with aneurysmal haemorrhage. The clinical condition of these patients was further analysed, 4-60 months after the bleeding episode. RESULTS: In 62% of patients with nonaneurysmal haemorrhage the blood distribution was perimesencephalic. The aneurysmal blood distribution pattern was more extended and only one patient showed a perimesencephalic pattern. 80% of the patients without aneurysms in angiography had no limitations in daily functional capacity. CONCLUSION: The perimesencephalic pattern is frequently found in patients with nonaneurysmal subarachnoidal haemorrhage, the prognosis of these patients is excellent. Rarely is the perimesencephalic haemorrhage caused by a ruptured aneurysm. It needs thorough angiographic evaluation.

[MRI follow-up in multiple sclerosis. A guideline for quality assurance]. / MRT-Verlaufsuntersuchungen bei multipler Sklerose. Ein Leitfaden für die Qualitätssicherung.

Magnetic resonance imaging (MRI) is highly sensitive to pathological tissue changes in multiple sclerosis (MS) patients. It demonstrates the frequently subclinical disease activity and follow-up examinations regularly show the accumulation of new lesions and the development of atrophy. The increasing importance of follow-up examinations in MS patients makes it necessary to provide comparable MRI data even over long observation periods. This review article focusses on critical variables in this regard and technical issues; practical guidelines for MRI protocols in MS patients are presented. The influence of field strength, MR systems from different manufacturers, and new software releases is described. Guidelines concerning the graphic planning of the examination, sequence protocols, documentation and reporting of cranial MR studies in MS patients are presented.

[Acetazolamide stimulation test in the preoperative assessment of cerebrovascular reserve capacity in unilateral carotid obstruction]. / Acetazolamid-Stimulationstest bei präoperativer Evaluation zerebrovaskulärer Kapazitätsreserve bei einseitiger Karotisobstruktion.

Using the 16-detector 133Xe-NaCl technique (Novo Cerebrograph) quantitative measurements of regional cerebral blood flow (rCBF) were performed in 13 patients with unilateral carotid obstruction before and after stimulation with 1 g acetazolamide. In all patients resting studies showed no significant difference in hemispheric perfusion and a 47% flow increase after acetazolamide on the side with normal carotid artery. On the obstructed side in 8 patients the hemispheric flow increased equally indicating a sufficient and adequate intracerebral collateral circulation and capacity. In 5 patients a significant redistribution of brain flow occurred with diminished increase on the occluded side. This flow pattern indicates an inadequate vasodilator response and insufficient collateral capacity. The rCBF stimulation test identifies patients with a restricted collateral capacity and these patients could benefit from a surgical treatment.

[Cerebral circulation at rest and following CO2 stimulation in patients with unilateral carotid obstruction]. / Zerebrale Durchblutung in Ruhe und nach CO2-Stimulation bei Patienten mit einseitiger Karotisobstruktion.

Using the 16-detector 133Xe-NaCl-technique (Novo Cerebrograph) quantitative measurements of regional cerebral blood flow (rCBF) were performed in 14 patients with unilateral carotis obstruction before and during stimulation with 3% CO2 inhalation. In all patients resting studies did not show any significant differences in hemispheric perfusion. In 11 patients the hemispheric blood flow increased significantly (by more than 6%) during CO2 inhalation on the side without carotis obstruction. The following results were found after 3% CO2-stimulation over the hemisphere with the obstructed carotid artery: 1) rCBF increased significantly on both sides (n = 6) indicating the sufficiency of cerebral collateral circulation; 2) a side-to-side significant difference (n = 4) with the lower perfusion on the pathological side, indicating a decreased or suspended reserve capacity; and 3) bilateral loss of cerebrovascular reactivity (n = 4) as indicator of insufficiency of cerebral collateral circulation. Asymmetry in rCBF or missing cerebrovascular reserve are indications for surgical treatment of the carotis obstruction.

[Effect of thrombus endarterectomy (TEA) on the regional cerebral bloodflow (rCBF) in patients with unilateral internal carotid artery stenosis]. / Einfluss der Thrombendarteriektomie (TEA) auf die regionale Hirnperfusion (rCBF) bei Patienten mit unilateraler Karotis-interna-Stenose.

AIM: In a study of patients with unilateral and symptomatic stenosis of the internal carotid artery (ICA), the effect of endarterectomy (EA) on the regional cerebral blood flow (rCBF) was tested over a postoperative interval of 12 months. METHOD: Xenon-133-rCBF was assessed in 74 patients pre- and post-surgery (one week, six weeks, three months and 12 months after EA). This was done at rest and after stimulation with acetazolamide in order to test the perfusion reserve. RESULTS: Before surgery all 74 patients showed a diminished perfusion ipsilaterally-at rest and/or after stimulation. 38/74 (51%) patients had a significant (> 5%) and 36/74 (49%) patients a non-significant (< 5%) interhemispheric perfusion asymmetry. Twelve months after EA, there were only 23/74 (31%) patients with significant interhemispheric perfusion asymmetry. By stimulation, this decreasing effect became more evident: Before surgery 44/74 (60%) patients had a significant interhemispheric perfusion asymmetry, 12 months after surgery there were only 14/74 (19%) patients. CONCLUSION: In regard to the brain hemisphere distal to the ICA stenosis, our study revealed a significant improvement of brain perfusion after EA. Brain perfusion was stable over an interval of 12 months post-surgery. By EA, especially the perfusion reserve increased, as shown by a normal acetazolamide test. Hence, Xenon-133-rCBF could be shown to be an important method in the evaluation of the indication for surgery and of the result of it. In the intra-individual follow-up after EA, rCBF was able to identify hypoperfusion and may help decide, whether re-angiography is necessary or not.

Auditory system: functional magnetic resonance imaging.

Functional MR imaging (fMRI) is being used increasingly to explore the human central auditory system. The considerable background noise produced by echo-planar imaging (EPI) and other fMRI sequences, however, interferes in an unpredictable way with the experimental stimuli. Several approaches exist to overcome this problem. Each has its advantages and disadvantages. These different approaches allow researchers to tailor the experimental designs to specific research questions. Recent studies have yielded significant information about human auditory function. Compared with other sensory systems such as the visual system, the auditory database still is relatively small. It is expected that novel methodologic approaches will stimulate scientific exploration of auditory processing and eventually lead to clinically meaningful applications of auditory fMRI.