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Biomedical subjects

F Barkhof

Publications and source records attributed to F Barkhof.

At least 217 records · Page 12Linked to original sources

Correlating MRI and clinical disease activity in multiple sclerosis: relevance of hypointense lesions on short-TR/short-TE (T1-weighted) spin-echo images.

Magnetic resonance imaging (MRI) is being used as an outcome criterion in therapeutic trials in multiple sclerosis (MS) on the assumption that it, as a sensitive marker of biologic disease activity, could serve as a surrogate marker of disability. We evaluated the relation between MRI findings and disability in a quantitative follow-up study of 48 MS patients. Median duration of follow-up was 24 months (range, 10 to 42 months). Computer-assisted volume measurements employing a seed-growing technique yielded a standard error of measurement of 0.275 cm2. The median total area of the hyperintense lesions on the initial T2-weighted images was 8.4 cm2. The median increase was 0.76 cm2/yr (9%). In a subgroup (n = 19) with short-TR/short-TE spin-echo (SE) images, we measured the hypointense lesion load. The median total area of the lesions at entry was 0.70 cm2, with a median increase of 0.28 cm2/yr (40%). The total area of the hyperintense lesions on the initial T2-weighted images showed a weak correlation with the Expanded Disability Status Scale score at entry (Spearman rank correlation coefficient [SRCC] = 0.30; 0.02 < p < 0.05). The increase in disability showed a positive correlation (SRCC = 0.19) with the increase in hyperintense lesion load on the T2-weighted SE images, but this correlation did not reach statistical significance (p = 0.09), probably because of lack of clinical progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multiple sclerosis therapy. A practical guide.

A growing amount of evidence suggests that a disturbance of immunological function is of importance in the pathogenesis of multiple sclerosis. This is reflected in the drugs used to slow progression and to treat relapses. Immunosuppressive drugs such as azathioprine, cyclophosphamide and cyclosporin might have some potential to slow down progression of multiple sclerosis, but their use is limited by potentially serious adverse effects. Recently, it was shown that interferon-beta-1b can diminish the exacerbation rate in multiple sclerosis without leading to unacceptable adverse effects. Nevertheless, symptomatic treatment remains of crucial importance in the management of multiple sclerosis patients. Spasticity, depression, fatigue and urinary, paroxysmal and sensory symptoms can all be alleviated to some extent with pharmacological interventions, although rehabilitation procedures and psychosocial consultations are no less important. Further therapeutic approaches to multiple sclerosis will be directed at either the specificity of the immune response or the grade of activation of the immune response. Magnetic resonance imaging techniques will play an important role in the evaluation of efficacy of new therapeutic agents.

Adjuvants, Immunologic↗

Early treatment of multiple sclerosis with Rebif (recombinant human interferon beta): design of the study.

Two recent properly controlled trials performed in patients with relapsing-remitting MS have demonstrated that interferon beta substantially improves the evolution of the disease. The results of the Optic Neuritis Treatment Trials suggest that early treatment of patients with isolated optic neuritis may delay the conversion to clinically definite MS (CDMS). Moreover, clinical trials in MS and in immune-mediated diseases indicate that better results are obtained in patients in the early phases of the disease. We present the design of a multicentre, randomized, double-blind, placebo-controlled study of recombinant interferon beta (Rebif-Serono) in patients with a first attack suggestive of MS. The primary objective of the study is to investigate the efficacy of Rebif, administered subcutaneously at the dose of 8 million international units (MIU) once a week for 2 years, on the risk of developing CDMS.

Adjuvants, Immunologic↗

Limited duration of the effect of methylprednisolone on changes on MRI in multiple sclerosis.

Treatment with methylprednisolone reduces the duration and severity of clinical relapses in multiple sclerosis (MS), while reducing the number of gadolinium-enhancing lesions on T1-weighted MRI. We performed serial MRI imaging after methylprednisolone treatment to see whether suppression of enhancement persists and whether related abnormalities on T2-weighted images disappear at follow-up. Thirteen patients with definite MS received a total of 31 courses of methylprednisolone over an average period of 50 weeks. Gadolinium-enhanced MRI was obtained before and after treatment, then at monthly intervals, using a standardised repositioning and imaging protocol. Two experienced readers in conference defined the number of active (gadolinium-enhancing and new or enlarging nonenhancing) lesions. We detected 609 active lesions on 195 examinations. Directly after treatment the reduction in the number of enhancing lesions was 78%, indicating restoration of the BBB and suppression of inflammation. It was uncommon for a lesion which stopped enhancing to show enhancement on a subsequent examination. No beneficial effect was observed on the rate of disappearance of related abnormalities on T2-weighted images, indicating persistent change such as oedema, cellular infiltration or demyelination. Moreover, in 89% of cases, an increase in the number of active lesions was observed before new clinical activity, if any, was observed (on average 52% earlier). MRI enabled us to demonstrate that the duration of the effect of methylprednisolone treatment is temporary (on average 9.7 weeks).

Adult↗

Radiotherapy response of cerebral metastases quantified by serial MR imaging.

A patient with cerebral metastases, treated with radiotherapy, underwent serial gadolinium-enhanced MR imaging. The MR images were quantified using home developed software to evaluate the changes in volumes of tumor mass and edema after radiotherapy (mean precision of the quantification technique less than 5%). The decrease in tumor volume and edema observed after radiotherapy preceded clinical improvement. The presented technique can be used to accurately assess, more directly than using clinical scales, the effect of putative therapies.

Brain Edema↗

Magnetic resonance imaging in monitoring the treatment of multiple sclerosis patients: statistical power of parallel-groups and crossover designs.

Serial brain magnetic resonance (MR) imaging detects active lesions 5-10 times more frequently than the occurrence of clinical changes in patients with early relapsing-remitting and secondary progressive multiple sclerosis (MS). Based on monthly unenhanced and gadolinium enhanced MR findings in 23 unselected and untreated patients, the power of an MS treatment trial was calculated, using MR imaging activity as the primary measure of outcome. It was shown that a 80% reduction in the number of active lesions (i.e. an efficacy of 80%) should be detected using a placebo-controlled parallel-groups design with a power of 80%, if either 2 x 20 patients are scanned monthly for 4 months, or 2 x 30 patients monthly for 2 months. Short to medium term studies of new experimental treatments in MS, using MR imaging as the primary outcome measure, provide considerable statistical power in small patient populations studied over a short period of time.

Adult↗

[Contribution of morphological imaging in the diagnosis of dementia. I--Alzheimer disease].

In patients with Alzheimer's disease, morphological neuroimaging techniques usually reveal signs of global cerebral atrophy which gradually worsen over time and depends on age and severity of the cognitive decline. Because of the lack of artifacts and of a more appropriate angle, magnetic resonance imaging scans may visualize a prominent atrophy of the medial temporal lobes, including hippocampal structures. Hippocampal atrophy is relatively specific of Alzheimer's disease before 65 and is related to the severity of memory disorders. White matter changes in patients without cerebrovascular risk factors are not more severe in patients with presenile Alzheimer's disease than in age-matched controls. They are, however, more severe in patients with senile onset than in age-matched controls. These findings suggest that white matter changes in patients with senile onset are consistent with a diagnosis of Alzheimer's disease.

Alzheimer Disease↗

Follow-up study of MS patients treated with high-dose intravenous methylprednisolone.

In a longitudinal prospective study, we followed 56 patients (17 men, 29 women) with definite multiple sclerosis (MS), who were treated with high-dose intravenous methylprednisolone (IVMP), 10 consecutive days with 1000 mg IVMP daily. Mean follow-up period after entry was 2.6 years (range 1.7-3.5 yrs). All patients were treated because of a symptomatic deterioration. Independent of the disease courses (RR-relapsing remitting/CP-chronic progressive/CP+RR- mixed course), 65% of the 46 MS patients (30/46) showed a clinical improvement after the first IVMP course, expressed by a decrease in the EDSS rating (1.0 point or more). During the follow-up period 59 additional IVMP courses (range 0-5 courses per patient) were given; 8 patients were treated with a combination of cyclophosphamide and prednisone, because of strong continuous progression. During the follow-up period 19 patients (41%) showed an increase in the EDSS-rating (1.0 point or more) compared with the EDSS level just after the first IVMP; 22 patients (48%) had no changes in the EDSS-rating, and 5 patients (11%) showed a clinical improvement (decrease of 1.0 point or more). In the relapsing MS patients (RR and CP+RR, n = 38) mean relapse rate/patient/year prior to the first IVMP was 2.6, which significantly (p < 0.0001) decreased to 0.8 during the follow-up period. Statistically no significant difference was found between baseline EDSS and EDSS ratings after the follow-up period in relapsing MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence for atrophy of the corpus callosum in Alzheimer's disease.

Patients with late-onset Alzheimer's disease (AD) have more white matter changes on magnetic resonance imaging (MRI) than controls. To test the hypothesis that AD patients might have also atrophy of the corpus callosum (CC), we compared the CC thickness on MRI from 20 AD patients and 21 controls. We found a significant reduction in the CC thickness in AD compared with age-matched controls (p < 0.01). We demonstrated that atrophy of the CC depends mainly on the diagnosis of senile dementia of the Alzheimer type and at a lower degree on the diagnosis of presenile AD but neither on age nor on ventricle enlargement. This result suggests that beside the greater severity of white matter involvement in late-onset AD, atrophy of the CC may also be present.

Aged↗

Magnetic resonance evaluation of disease activity during pregnancy in multiple sclerosis.

We followed two women with MS during pregnancy by means of serial unenhanced MR imaging. On each follow-up image, we assessed the number of new or enlarging lesions. Both women showed a decrease in MR disease activity during the second half of pregnancy and a return of MR disease activity to prepregnancy levels in the first months postpartum. These findings support the view that pregnancy reduces disease activity in MS.

Adult↗

Phase-contrast cine MR imaging of normal aqueductal CSF flow. Effect of aging and relation to CSF void on modulus MR.

Cine phase-contrast MR imaging was used to study pulsatile CSF flow in the aqueduct in 11 young controls (mean age 30 years) and 9 old controls (mean age 69 years). A high-resolution gradient echo technique and an oblique imaging plane, perpendicular to the aqueduct, was used to avoid volume averaging. Phantom studies confirmed that the technique was accurate. Aqueductal velocity and flux in old controls was higher than in young controls, but the differences were not significant. For all controls together, the averaged peak velocity was 4.2 +/- 1.5 cm/s in rostral and -7.8 +/- 4.9 cm/s in caudal direction; for the flux it was 0.16 +/- 0.10 cm3/s in rostral and -0.29 +/- 0.19 cm3/s in caudal direction. Phase-contrast measurements were significantly related to flow-void on modulus MR images, but not with ventricular size or cortical atrophy. The present technique avoids underestimation of aqueductal flow, and therefore reveals higher aqueductal velocity and flux values than previous studies. Factors other than age or atrophy seem to determine aqueductal CSF flow.

Adult↗

Database for serial magnetic resonance imaging in multiple sclerosis.

The unique sensitivity of magnetic resonance imaging (MRI) in detecting disease activity in multiple sclerosis (MS) and the objective nature of the information obtained suggest that MRI will be a useful and reliable way of monitoring treatment trials. There is a need to develop an appropriate database which would provide a standardised means of assessment, not only of MRI, but also of essential clinical information. As part of the program of Concerted Action in Multiple Sclerosis, funded by the Commission of the European Community (CEC), we have developed a database for recording serial brain MRI results. The database consists of core, entry and follow-up sections. Both entry and follow-up parts are subdivided into clinical, MR system and MRI data. We expect that the use of this database will maximise efficiency of MRI monitoring in MS treatment trials, particularly in multicentre studies.

Brain↗

SPECT, CT and MRI in a Turkish family with Huntington's disease.

A Turkish family with Huntington's disease documented on CT, MRI and SPECT is reported. Whereas in clinically definite cases CT and MRI are of limited value and SPECT does not add anything of value, in one asymptomatic subject SPECT showed moderate caudate nucleus hypoperfusion, underlining the hypothesis that SPECT may have a role in predicting Huntington's disease.

Adult↗

Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone.

Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59, P = 0.0084) between serum vitamin B12 and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of vitamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B12 and folate were below the reference medians. We hypothesize that low or reduced vitamin B12/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low vitamin B12/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B12 and folate metabolism in patients with MS.

Adult↗