Collaborative care for major depressive disorder in an occupational healthcare setting.

Randomised controlled trial to evaluate the effectiveness of collaborative care in a Dutch occupational healthcare setting: 126 workers on sick leave with major depressive disorder were randomised to usual care (n = 61) or collaborative care (n = 65). After 3 months, collaborative care was more effective on the primary outcome measure of treatment response (i.e. reduction in symptoms of ≥50%) on the Patient Health Questionnaire-9 (PHQ-9). However, the groups did not differ on the PHQ-9 as a continuous outcome measure. Implications of these results are discussed.

Psychosis in epilepsy patients and other chronic medically ill patients and the role of cerebral pathology in the onset of psychosis: a clinical epidemiological study.

BACKGROUND: In a 3-year epidemiological survey (N=2623) prevalence of psychosis in epilepsy patients as compared with other chronic medically ill patients is assessed. AIM: To explore the role of cerebral pathology as compared to the role of chronic burden of disease in the onset of psychosis. METHOD: One thousand seven hundred fifty two patients with chronic medical disorders admitted to an Academic Hospital and 901 patients with epilepsy admitted to a tertiary care epilepsy clinic were assessed by CIDI, MINI and clinical psychiatric interview in a two stage screening survey. Medical files were searched for MRI scans about cerebral pathology. Poisson regression analysis was performed to estimate the relative risk for psychosis in both groups. RESULTS: In total, 52 patients with prevalent psychosis were found: 49 (5.4%) in the epilepsy clinic and 3 (0.17%) in the Academic Hospital. Age range (18-88), mean age (42) and gender distribution (equal) were similar in both samples. RR is 8.37 (2.74, 25.52). In 16 of the 49 epilepsy patients, cerebral pathology existed with mainly temporal and frontal localisation and of childhood-onset vascular or infectious origin. CONCLUSIONS: This finding suggests that in the onset of psychosis in epilepsy patients, the role of cerebral pathology, especially localized left temporal and frontal, is of strong etiological importance. The following epilepsy endophenotypes should be explored as factors in vulnerability for psychosis as well: frequent and severe epileptic activity; and psychotic reactions to certain AEDs, such as Topiramate and Lamotrigine. Burden of disease does not seem to play an important role.

Patterns of enhancing lesion evolution in multiple sclerosis are uniform within patients.

BACKGROUND: Histopathologic studies suggest that lesion development differs between patients with multiple sclerosis (MS), but that all lesions appear similar within patients. It is unclear whether the same applies to the evolution of lesions on T1-weighted MRI. OBJECTIVE: To evaluate lesion evolution on MRI, comparing variance within and between patients, as well as the relationship between MRI lesion development and clinical characteristics. METHODS: In 48 patients, signal intensity at baseline and at follow-up on T1-weighted MRI of 789 newly enhancing lesions was studied in relationship with clinical data. Patients were included on the basis of showing at least five enhancing lesions that could be followed on monthly scans for 6 months. Variance component analysis and multilevel analysis were used to compare within-patient and between-patient variability. RESULTS: Although various types of lesion evolution could be observed within a single patient, between-patient variance was considerably larger than within-patient variance for MRI parameters used to describe lesion evolution, indicating that lesion evolution is a patient-specific phenomenon. Evolution of lesions in patients with secondary progressive disease more frequently followed a hypointense-hypointense pattern than in patients with relapsing-remitting disease (odds ratio 4.2). Patients with a benign disease course had more persistent isointense lesions at follow-up, whereas patients with aggressive disease had more hypointense lesions. CONCLUSION: Lesion evolution on MRI appears to be a patient-specific phenomenon, although the outcome seems to vary according to the phase and severity of the disease.

Reproducibility of bone mineral density measurement in daily practice.

BACKGROUND: Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. OBJECTIVE: To examine the reproducibility of BMD by dual energy x ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in a group of postmenopausal women. METHODS: Ninety five women, mean age 59.9 years, underwent two subsequent BMD measurements of spine and hip. Reproducibility was expressed as smallest detectable difference (SDD), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Sources of variation were investigated by multilevel analysis. RESULTS: The median interval between measurements was 0 days (range 0-45). The mean difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004 (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The ICC at spine and hip was 0.99. CONCLUSIONS: Reproducibility in the postmenopausal women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical 2CV (%), the least significant change (LSC), or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC (%) because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total hip should be considered significant.

Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.

OBJECTIVE: The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. METHODS: The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. RESULTS: Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. CONCLUSION: Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.

[The importance of equivalence trials in showing the usefulness of treatments]. / Het belang van equivalentieonderzoek om de waarde van behandelingen aan te tonen.

There are different kinds of randomised controlled trials: trials in which the superiority of a treatment can be demonstrated (superiority trials) and trials in which the equal efficacy of two treatments can be shown (equivalence trials). The main reason for performing an equivalence trial is that for many diseases and disorders an effective treatment already exists. Equivalence trials are appropriate when a new treatment offers some advantages over an existing treatment (less cost, greater safety, improved convenience or freedom of choice for the patient), in addition to the expected equal therapeutic effectiveness. The design of equivalence trials is to a large extent comparable to that of superiority trials, but there are some methodological differences. In equivalence trials, the null hypothesis and alternative hypothesis are interchanged, compared to superiority trials. In equivalence trials, an equivalence margin is defined for the different treatments. Clinical professionals decide on the equivalence margin beforehand on the basis of the clinical relevance. To demonstrate equivalence, the confidence interval of the difference between two treatments must lie completely within the equivalence margin. In equivalence trials, there are usually more patients needed: the smaller the equivalence margin, the more patients are needed. In equivalence trials, both per-protocol analyses and intention-to-treat analyses should be used to prove the equal therapeutic effectiveness of the treatments under study.

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis.

OBJECTIVES: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. METHODS: For an open randomized study, patients with preterm labor (N=185) were allocated to groups to receive ritodrine intravenously (N=90) or nifedipine orally (N=95). RESULTS: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65+/-12 vs. 70+/-8, P=0.001) and 48 h (65+/-12 vs. 71+/-8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105+/-17 vs. 86+/-13, P<0.0001) and 48 h (100+/-21 vs. 85+/-12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68+/-2.53 vs. 4.93+/-1.23, P=0.0016), while mean potassium levels were lower (3.52+/-0.84 vs. 3.81+/-0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. CONCLUSIONS: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.

Combined bedtime insulin--daytime sulphonylurea regimen compared with two different daily insulin regimens in type 2 diabetes: effects on HbA1c and hypoglycaemia rate--a randomised trial.

BACKGROUND: Several efficacy studies of insulin-therapy regimens in patients with type 2 diabetes mellitus have shown varying results. Moreover, most studies did not address hypoglycaemia frequency and severity. METHODS: In this multicentre study, we compared the glycaemic efficacy and incidence rate of hypoglycaemic episodes between 3 treatment regimens in obese type 2 diabetic patients with secondary failure to sulphonylurea and metformin. During the run-in phase, patients were treated with glimepiride and metformin. After 3 months, 261 patients with HbA(1c) values >6.5% were randomised to (A) glimepiride + Neutral Protein Hagedorn (NPH) insulin at bedtime, (B) NPH insulin twice daily and (C) 30/70 mixture of short-acting and NPH insulin twice daily. The therapeutic aim was an HbA(1c) level < or =6.5%. RESULTS: Mean HbA(1c) achieved at 9 months was significantly higher in group A: 8.9% versus 8.3% and 8.4% in groups B and C, respectively (P < 0.001). There was no difference in the mild hypoglycaemic event rate, 0.36 versus 0.48 versus 0.53 events per patient month, in groups A, B and C, respectively. Severe hypoglycaemic events, requiring help from others, did not occur throughout the study. The mean weight gain and insulin dose were comparable in all three groups. CONCLUSIONS: The glimepiride + NPH insulin treatment resulted in a higher HbA(1c) level, as compared to the other regimens. In the clinical setting of this multicentre study, good glycaemic control was only achieved in a minority of the patients, irrespective of the applied regimen.

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Multiple sclerosis functional composite: impact of reference population and interpretation of changes.

The Multiple sclerosis functional composite (MSFC) has been recommended as a clinical outcome measure to be used in future MS trials. A specific characteristic of the MSFC is that it is defined as a measure of impairment relative to a reference population. Using different reference populations affects actual MSFC scores. If the selection of a reference population also has an effect on sensitivity to change of the MSFC, comparison of data from clinical trials will be almost impossible when different reference populations are used We studied the effect of the selection of a reference population on the outcome of a trial by simulating 343 intervention trials and comparing results obtained by using three different reference populations: two previously published MS patient populations and a healthy population. Scores of the healthy population were collected in the first part of the study. The effects of sex, age and education level on test scores of healthy subjects were studied as well. In the healthy controls, sex, age and education level had a different impact on individual test scores of MSFC components and overall MSFC score. Our study shows that, with the use of the MSFC, the selection of different reference populations does not affect the trial statistics and significance, but it does affect comparability of results between different trials, and complicates the dinical interpretation of any observed change.

Information processing characteristics in subtypes of multiple sclerosis.

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing-remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing-remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps.

Prevalence of and risk factors for HIV infection in blood donors and various population subgroups in Ethiopia.

The aim was to determine the prevalence of HIV infection and risk factors for HIV infection in various population subgroups in Ethiopia. Serum panels from blood donors (n = 2610), from various population subgroups in Ethiopia were tested for anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs. 155/2610 (5.9%) blood donors were HIV-1 infected. Of pregnant women, 84/797 (10.5%) were HIV-1 infected, and 1/797 (0.1%) was HIV-2 infected. 1/240 (0.4%) individuals from the rural population were HIV-1 infected. 198/480 (41.3%) female attendees, and 106/419 (25.3%) male attendees at sexual transmitted disease (STD) clinics were HIV-1 infected. One (0.2%) male, and 2 (0.4%) female STD patients were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of HIV-1 infection varied from 0.4% among urban residents to 25.3-41.3% among STD attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects. Risky sexual behaviour is significantly associated with HIV-infection in Ethiopia.

Reproducibility and clinical value of 18F-fluorodeoxyglucose positron emission tomography in recurrent melanoma.

The purpose of this study was to assess the reproducibility and clinical impact of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with (suspected) recurrent melanoma. The clinical value of PET was prospectively measured in 58 consecutive patients referred for PET because of unresolved clinical questions after conventional work-up. Diagnostic understanding and therapy choice by referring physicians were evaluated before, directly after, and 6 months after PET. Observer agreement of PET readings was measured with respect to various parameters (interpretation, number and localization of lesions, 'clinically decisive' metastases), using intra-class correlation coefficients. FDG PET improved diagnostic understanding in 33 cases (57%). In six patients (10%), diagnostic understanding was solely based on PET information. According to the attending clinicians, PET contributed to a positive change of planned treatment in 23 patients (40%) and increased confidence in the chosen treatment in 23 (40%). Observer agreement of PET readings was very high (intra-class correlation coefficients were between 0.87 and 0.94). The diagnostic value related especially to the whole-body scan technique and the superior specificity, compared to conventional work-up. It is concluded that, in problematical cases with (suspected) recurrent melanoma, 18F-FDG PET had considerable impact on diagnostic understanding and management. Together with the excellent observer reliability, these results justify further studies to determine the optimal place of PET in routine diagnostic algorithms in recurrent melanoma.

Seasonal variation in immune measurements and MRI markers of disease activity in MS.

BACKGROUND: The exact mechanisms by which T cells contribute to MS progression are not known. Recently, the results of cross-sectional studies suggested seasonal variation of both interferon (IFN)-gamma production and the number of active MRI lesions in MS. OBJECTIVE: To investigate whether seasonal fluctuations of IFN-gamma and active MRI lesions could be confirmed and whether any correlations could be detected. METHODS: Data were analyzed from a group of 28 MS patients in whom detailed longitudinal monitoring of both immune function and MRI measurements had taken place. RESULTS: Significant seasonal variation was observed in T-cell activation as measured by the ability of T cells to secrete the pro-inflammatory cytokines tumor necrosis factor-alpha and IFN-gamma. Maximum values were found in samples obtained during autumn. Even though clear fluctuations were observed, no significant seasonal variation could be detected in the number of active MRI lesions. Fluctuations of in vitro IFN-gamma secretion correlated weakly with changes in active MRI lesions. CONCLUSIONS: The finding of seasonal variation of immune function in serially MRI-monitored MS patients suggests an environmental role in T-cell activation.

Isotropic 3D fast FLAIR imaging of the brain in multiple sclerosis patients: initial experience.

The application of image registration and subtraction to detect change in multiple sclerosis (MS) disease burden on serial MR scans benefits from the use of isotropic voxels. An optimised 3D fast fluid-attenuated inversion recovery (FLAIR) sequence with 1.2- and 1.8-mm cubic voxels was compared with a 2D T2 SE sequence using standard 3-mm slices. Three-dimensional fast FLAIR and T2 SE series were obtained in 20 MS patients and 15 controls. Whole brain acquisition times for the 1.2- and 1.8-mm FLAIR were 21 and 10.5 min, respectively, for the interleaved T2 SE 16 min. Brain lesions were marked in consensus by two radiologists and the CNR was calculated in ten lesions. The mean number of lesions detected with the 1.2-mm FLAIR sequence was 115 +/- 76, compared with 85 +/- 59 for the T2 SE series ( p<0.001). The 1.8-mm FLAIR detected only 73 +/- 46 lesions. The CNR of the 1.2-mm FLAIR was significantly better than the T2 SE ( p<0.01), but not as good as the 1.8-mm FLAIR. In conclusion, isotropic 3D fast FLAIR using 1.2-mm cubic voxels is superior to the 2D T2 SE in the detection of brain lesions in MS patients. The isotropic 1.8-mm FLAIR is faster and has better contrast characteristics but lacks sensitivity.

Insulin-treated diabetes patients with fear of self-injecting or fear of self-testing: psychological comorbidity and general well-being.

OBJECTIVE: To examine psychological functioning and self-management behaviours of Dutch adult patients with insulin-requiring diabetes mellitus suffering from extreme fear of self-injecting (FSI) and/or fear of self-testing (FST). METHODS: A cross-sectional survey was performed in a sample of insulin-treated diabetes patients (n=1275; 51.1% male; age 49.7+/-15.8 years; 58.0% Type 1 diabetes), assessing FSI and FST. Patients completed the questionnaires concerning trait/state anxiety, depression, fear of hypoglycemia, diabetes-related distress, diabetes self-care activities, and general well-being. Comparisons were made on these measures between patients with extremely high scores on FSI and/or FST (> or = 95th percentile) and the other patients. Patients with extreme scores on FSI and/or FST were invited to take part in a second survey to assess the prevalence of major depression, common fears/phobias, and psychoneuroticism. RESULTS: People with extreme FSI/ FST scores, as compared to the other patients, reported higher levels of trait/state anxiety and depression. This group also reported more fear of hypoglycaemia and diabetes-related distress, had lower levels of general well-being, and reported less frequent self-monitoring of blood glucose. The second survey showed 11.1% of patients with extreme FSI/FST reporting scores indicating major depression. Prevalence of scores greater than or equal to the high scores on phobias (38.0-63.3%) and psychoneuroticism (27.8%) were consistently higher than norm group prevalences. DISCUSSION: Extreme levels of FSI and/or FST are associated with high diabetes-related distress, poor general well-being, and psychological comorbidity, as well as poorer adherence to the diabetes treatment regimen. It is concluded that patients with extreme FSI/FST are often burdened with more than this specific phobia.

The oedema-protective effect of Lycra support stockings.

BACKGROUND: Oedema may be an early sign of chronic venous insufficiency (CVI), but swelling of the lower legs is a common phenomenon in many people. The distinction between physiological swelling and CVI is not clear. There is a gradual transition between healthy legs and the early stages of CVI. In case of CVI, medical elastic compression stockings are used in order to prevent oedema completely. In case of healthy people without demonstrable CVI, no medical stockings are required in the prevention of oedema but stockings exerting less compression. OBJECTIVE: The aim of this study was to investigate the effect of mild compression on the development of swelling of the legs and the effect on subjective complaints in healthy subjects. METHODS: The diurnal volume change (DVC) of the lower legs during full working days was monitored with an optical leg volume meter in 118 healthy volunteers (60 males, 58 females) without objective symptoms of CVI. The DVCs after wearing two kinds of class I support stockings (X: average pressure at the ankle of almost 14 mm Hg; Y: almost 18 mm Hg) were compared with the DVC after wearing a control stocking (Z: almost 6 mm Hg). Also, the effect on subjective feelings of the legs was noted. RESULTS: It appeared that healthy people have a mean daily volume increase of the legs of 2.3% in females and 1.6% in males. Mild compression stockings reduced this daily increase with 31 and 18% in males and females, respectively, by stocking X and 37 and 32% by stocking Y. Subjective feelings occurred in 57% of all cases. A beneficial effect on subjective feelings, in particular of tired and swollen legs, was found. A difference in this beneficial effect between stocking X and Y was not obvious. CONCLUSIONS: Mild compression stockings reduce diurnal oedema and unpleasant feelings of the legs in healthy individuals.

Effects of cognitive behavioural group training (CBGT) in adult patients with poorly controlled insulin-dependent (type 1) diabetes: a pilot study.

A substantial group of patients with type 1 diabetes has difficulty adhering to the treatment regimen, and as a consequence is at increased risk of developing microvascular complications. Cognitive behavioural interventions may help these patients to cope more effectively with their diabetes. We developed a 4 weeks cognitive behavioural group training (CBGT) for patients with type 1 (insulin-dependent) diabetes in persistent poor glycaemic control, to help them overcome negative beliefs and attitudes towards diabetes and improve their self-care behaviours. Feasibility and efficacy of CBGT were tested in a non-randomised prospective study in 24 poorly-controlled type 1 diabetes patients (mean age 35.2+/-11.1years; 15 female; mean HbA(1c) 9.3% (+/-1.2)), with assessments at 3 and 6 months follow-up. The programme was delivered in small groups (n=6-8), by a team of a diabetes nurse specialist and a psychologist. Primary outcome measures were glycosylated haemoglobin (HbA(1c)), diabetes-related emotional distress (PAID) and psychological well-being (WBQ-12). Changes in diabetes self-care activities (DSCI) were documented, along with perceived barriers in diabetes questionniare (BDQ) and fear of hypoglycaemia survey (HFS). Data were analysed using repeated measures analysis of variance. The CBGT proved to be feasible in this selected group of patients and was well appreciated. Following CBGT, mean HbA(1c) dropped by 0.8% at 6 months from baseline, while emotional well-being was preserved. It is concluded that CBGT is a promising intervention that deserves further evaluation in randomised controlled trials.

Optimizing the association between disability and biological markers in MS.

OBJECTIVE: Axonal damage is an important feature of MS pathology and the likely substrate of development of progressive disability. Brain volume measurement on MRI can be used as an overall marker of tissue damage and axonal loss. The authors studied the relation of brain volume measurements with the MS Functional Composite (MSFC) in an attempt to improve the clinico-radiologic association. METHODS: In 137 patients with MS (80 relapsing-remitting [RR], 36 secondary progressive [SP], and 21 primary progressive [PP]) and 12 healthy controls, a brain MRI scan was obtained. Patients also underwent MSFC and Expanded Disability Status Scale (EDSS) assessments. MRI analysis included determination of hypointense T1- and hyperintense T2-weighted lesion load, and two brain volume measurements: 1) the parenchymal fraction (PF): whole brain parenchyma/intracranial volume; and 2) the ventricular fraction (VF): ventricular volume/whole brain parenchyma. RESULTS: The median PF was smaller and the median VF larger in the patient group (0.81 for PF and 0.029 for VF) than in the control group (0.87 for PF, p < 0.001; and 0.013 for VF, p < 0.01). For the patient population, moderate correlations were found between brain volume measurements and MSFC (0.36 for PF and -0.40 for VF). Patients with short disease duration showed a correlation of MSFC with both brain and lesion volume measurements on MRI, whereas patients with long disease duration only showed a correlation with brain volume measurements. CONCLUSION: Brain volume measurements are correlated with disability as assessed by the MSFC. Although in the early phase of the disease the amount of focal demyelination is important, the residual brain volume seems to be more relevant in determining disability in later phases of the disease.