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.

Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy.

OBJECTIVE: Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy. METHODS: This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored. RESULTS: With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed. CONCLUSION: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.

[Gorlin-Goltz syndrome: manifestations in an elderly patient]. / Das Gorlin-Goltz-syndrom: Aspekte im Senium.

Gorlin-Goltz syndrome is a rare inherited genodermatosis with an autosomal dominant trait. We hereby present a case of a 69 year old patient with known Gorlin-Goltz syndrome to emphasize the peculiar syndrome manifestations in the elderly.

Clinical and immune responses correlate in glatiramer acetate therapy of multiple sclerosis.

Glatiramer acetate (GA) treatment for relapsing remitting multiple sclerosis (RRMS) leads to decreased GA-specific proliferative responses and a Th2 cytokine shift. To study a possible correlation between immunological and clinical responses to GA therapy, we prospectively followed RRMS patients clinically, by magnetic resonance imaging and by primary immunological assays. Fluctuation of GA-specific proliferative responses was significantly lower in treatment responders than in untreated patients, and GA-specific proliferative responses were increased during relapses. These associations suggest a possible causal relationship between immunological and clinical responses to GA therapy. Primary proliferation assays may thus be a useful marker for treatment response.

[Chronic subdural hemorrhage in a patient with suspected schizophrenia prodrome]. / Chronisch subdurales Hämatom bei einem Patienten mit Verdacht auf Prodromalstadium einer Schizophrenie.

A patient showing "prodromal symptoms" of suspected psychosis was referred to our clinic specialized in early recognition of schizophrenia where an MRI brain scan showed a chronic subdural hemorrhage. Based on this case, it will be shown that organic brain disease, in addition to incipient schizophrenia, needs to be considered in patients with marked personality changes, social withdrawal, aggressiveness, and suspiciousness. Diagnosis of the first episode and prodromal stage of schizophrenia should include-apart from the case history as well as the psychopathological and physiological findings-certain obligatory medical examinations (EEG, cCT, or MRI) in order to identify possible organic causes and avoid misdiagnoses.

Prenatal diagnosis of an infratentorial subdural hemorrhage: case report.

We report a case of a prenatally diagnosed infratentorial subdural hemorrhage. The hematoma located in the posterior cerebral fossa was detected by conventional ultrasound at 24 weeks of gestation. Intrauterine magnetic resonance imaging confirmed the diagnosis. Autopsy of the fetus revealed a well-circumscribed subdural hematoma. The prenatal findings of intracranial bleeding located in the posterior fossa and the prognosis of such cases are discussed.

Dynamic patterns of USPIO enhancement can be observed in macrophages after ischemic brain damage.

Cells of the mononuclear phagocytotic system (MPS) are often found near to or within ischemic tissue and can potentially aggravate cellular damage. Hence, visualization of those cells would allow demarcation of putatively affected from intact tissue. Experimental MRI studies have shown that ultrasmall particles of dextran-coated iron oxide (USPIO) are internalized into cells of the MPS. To test if this cell tagging method may be also applied to cerebral infarction, USPIOs were administered to Fisher rats 5.5 h after permanent occlusion of the middle cerebral artery (pMCAO). During the first 2 days USPIO were preferentially found in patches within the lesion and in surrounding areas. On day 4, USPIOs expanded within the core of the lesion. On day 7 they were found predominantly within the boundary area. Histological analysis showed large populations of macrophages containing iron particles in the infarcted tissue. We conclude, therefore, that it is possible to monitor MPS activity after focal cerebral ischemia using USPIOs.

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.

Quantification of blood flow in the middle cerebral artery with phase-contrast MR imaging.

The aim of this study was to assess blood flow in the middle cerebral artery (MCA) according to age, gender, and side. Eighty-eight subjects without carotid obstruction were measured for mean velocity, vessel area, and volume flow rates of both MCA with phase-contrast MR. A high-resolution sequence with a matrix of 300 x 512 and a double oblique localizing strategy was used for measurement. A mean velocity of 33 +/- 6.8 cm/s, a mean vessel area of 6.2 +/- 1.2 mm2 and a mean flow rate of 121 +/- 28 ml/min were measured in the MCA. Lower volume flow rates were seen in subjects aged over 50 years (p < 0.01). When comparing women with men, a lower vessel area (p < 0.05) of the MCA was counterbalanced by a higher velocity, resulting in no significant difference of the volume flow rate. No difference occurred between the right and the left side. Flow reduction occurs in the elderly. A lower vessel area of the MCA in women is compensated by a higher velocity.

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.

Dynamic susceptibility contrast MR imaging of plaque development in multiple sclerosis: application of an extended blood-brain barrier leakage correction.

Since the pathogenesis of multiple sclerosis (MS) lesions is not yet fully understood, we investigated the potential of dynamic susceptibility contrast (DSC) magnetic resonance (MR) perfusion imaging for a better characterization of lesion pathology. Twenty-five MS patients were examined on a 1.5 T scanner. A single dose of gadolinium (Gd)-DOTA contrast agent was injected, and echoplanar images were acquired every 0.5 seconds for 1 minute. From the signal intensity-versus-time curves, the relative cerebral blood volume (rCBV) was evaluated for regions in plaques and in gray and white matter. The rCBV calculated for acute, Gd-enhancing plaques was corrected for the effects of blood-brain barrier leakage, using a new correction algorithm. Acute plaques had significantly higher blood volumes than normal-appearing white matter (P < = 0.01). Chronic plaques that appeared hypointense on T(1)-weighted images had lower rCBV than T(1)-isointense plaques (P < = 0.03). Our results indicate that the acute phase in MS is accompanied by vasodilation. In later stages of gliosis, the perfusion decreases with increasing axonal injury. Although the DSC technique is less sensitive than conventional MR imaging, the information provided is essentially different from that obtained with any other MR method.

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.

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.

Selection of patients for carotid thromboendarterectomy: the role of magnetic resonance angiography.

It has been shown in clinical trials that patients with high grade symptomatic carotid stenosis benefit from carotid thromboendarterectomy. Because of the invasiveness and the costs of intra-arterial digital subtraction angiography, the current standard of reference for the grading of carotid stenosis, magnetic resonance angiography, has become a technique of utmost interest for evaluation of the carotid arteries. The time-of-flight and the newly developed contrast-enhanced magnetic resonance angiography techniques are discussed. At present, we recommend computer enhanced magnetic resonance angiography for screening procedures and for the post-operative follow-up. For pre-operative evaluation we still recommend intra-arterial digital subtraction angiography.

[Area reduction in carotid stenosis of the internal carotid artery]. / Querschnittsflächenreduktion bei A.-carotis-interna-Stenose. Bestimmung mit intensitätsgewichteter farbkodierter Duplexonographie.

AIM: In patients with atherosclerotic extracranial internal carotid artery (ICA-) stenosis the diagnostic value of colour Doppler energy (CDE)-coded duplexsonography was compared to three other methods: continuous wave (cw) Doppler peak systolic frequency (pF), pulsed wave (pw) Doppler peak systolic velocity (pV), and intraarterial digital subtraction angiography. METHODS: In 58 patients who suffered from 60 moderate to severe ICA stenoses, B-mode sonography combined with CDE-coded duplex sonography was applied to measure the extent of the stenosis by determining the residual lumen width. Results were correlated to pF and pV and with various angiographic indices. RESULTS: The determined values of the degree of stenosis were correlated to the measurement of pV (r = 0.441, p < 0.01), but not to pF (r = 0.122, n.s.). The best correlation to angiography was obtained when the linear ICA diameter was compared to the distal common carotid artery (common carotid artery index) (r = 0.214, n.s.). Sensitivity, specificity and diagnostic accuracy were comparable to the different frequency-based measurements, but the positive predictive value was lower. CONCLUSIONS: Determination of the degree of stenosis based on CDE alone is not reliable enough to allow correct diagnosis of severe carotid artery stenosis. In combination with the peak frequency method is's diagnostic value could be improved. This requires verification in a separate study.

[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.