[Rotational Laxity of the Knee Joint - In Vivo MRI Study]. / Rotacní laxita kolenního kloubu ­ in vivo NMR studie.

PURPOSE OF THE STUDY The purpose of the study was to evaluate tibio-femoral rotation during a simulated squat and to investigate the relationship between the rotational position of the femur in full extension and the amount of external rotation of the femur on the tibia during flexion. MATERIAL AND METHODS Part 1: MRIs of volunteers Data on healthy knees of 10 volunteers were obtained using 2D MRI measurements. The foot and the ankle were fixed to prevent rotation and adduction/abduction movements. Sagittal MRIs of the knees have been performed in 4 positions of flexion. The amount of longitudinal rotation in each position of flexion was calculated. Part 2: Mathematical model experiment a) The model of the femur has been positioned in the 3D coordinate system in full extension and at 12.8° of internal rotation and then flexed to 90° without longitudinal rotation. The distance between the centre of the femoral head and the sagittal plane passing through the centre of the knee was then measured. b) Subsequently, the femur was flexed and rotation allowed to retain femoral head within the sagittal plane. The amount of femoral rotation was then calculated. RESULTS Part 1: In full extension the femur was on average in 12.8° of IR relative to the tibia. By 90° flexion femur rotated on average 12.2° externally. Part 2: a)From full extension to 90° flexion the femoral head moved 93.1 mm laterally from the sagittal plane. b)Between full extension and 90° flexion the femur rotated 12.8° externally, a degree which corresponds to the amount of initial internal rotation of the femur in full extension. DISCUSSION The most important finding of the presented in vivo study lies in the fact that in normal knees with tibia rotationally fixed flexion is always coupled with femoral external rotation in order to keep the femoral head in the acetabulum. This rotation is obligatory. CONCLUSIONS We have demonstrated that if the tibia is rotationally fixed, the knee flexion is possible only when accompanied by femoral external rotation to keep the femoral head in the acetabulum. A mathematical description of the experiment has been proposed, the results of which confirm the stated premise. This finding can be explained by initial internal rotation of the femur in full extension of the knee and is allowed by the shape of articulating bones and tension of soft tissues Key words: knee, terminal extension, knee rotation, knee movement, MRI, hip joint.

[Anterior Cruciate Ligament Tears - Influence on Terminal Extension]. / Ruptury predního zkrízeného vazu ­ vliv na terminální extenzi.

PURPOSE OF THE STUDY The aim of this paper was to compare terminal extension in normal and anterior cruciate ligament (ACL) deficient knees, and therefore to determine the role of the ACL during this motion. MATERIAL AND METHODS Ten knees with ACL tears (7 knees with recent ACL tears, 3 knees with long-standing tears) and 10 normal contralateral knees have been examined using MRI in passive hyperextension, 20° flexion and 20° flexion with a 9 kg posteriorly directed load on the femur. Movements of the femoral condyles on the tibia were calculated using previously described methods. RESULTS 1. Under the load at 20° flexion, knees with ACL tear showed posterior femoral subluxation (equivalent to a Lachman test), chronic tears being more unstable. Contralateral normal knees were antero-posteriorly stable. In hyperextension, both femoral condyles subluxed posteriorly in ACL tears but not in normal knees. 2. In all knees with ACL tear, the lateral femoral condyle moved posteriorly from hyperextension to 20°, equating to femoral external rotation. 3. The longitudinal rotation axis during terminal extension in normal knees was medial but in ACL tears it was central causing the medial femoral condyle to move forward from hyperextension to 20°. In normal knees, the medial femoral condyle did not move antero-posteriorly from hyperextension to 20° flexion. DISCUSSION Internal rotation of the femur during terminal extension has been recognized for 150 years. The question remains: what causes the usual combination of longitudinal rotation and extension? In the current literature ACL is considered to be responsible for internal rotation of the femur during terminal extension of the knee. So far, as we are aware, the kinematics of terminal extension, including hyperextension, have not been reported after ACL tear in the living knee. CONCLUSIONS Results of this study imply that: 1. The ACL prevents anterior tibial subluxation in hyperextension. 2. The ACL does not cause rotation in terminal extension. 3. The ACL locates the axis of longitudinal rotation in terminal extension. We hope that by studying living knees with and without ACL tear we may not only clarify the nature and mechanism of rotation in terminal extension, and hence the role of the ACL, but do so in a context of direct clinical relevance. Key words: knee, terminal extension, ACL tear, axis of longitudinal rotation, antero-posterior instability, MRI.

Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: Potential differences between primary progressive and relapsing remitting multiple sclerosis are the subject of ongoing controversial discussions. The aim of this work was to determine whether and how primary-progressive and relapsing-remitting multiple sclerosis subtypes differ regarding conventional MR imaging parameters, cerebral iron deposits, and their association with clinical status. MATERIALS AND METHODS: We analyzed 24 patients with primary-progressive MS, 80 with relapsing-remitting MS, and 20 healthy controls with 1.5T MR imaging for assessment of the conventional quantitative parameters: T2 lesion load, T1 lesion load, brain parenchymal fraction, and corpus callosum volume. Quantitative susceptibility mapping was performed to estimate iron concentration in the deep gray matter. RESULTS: Decreased susceptibility within the thalamus in relapsing-remitting MS compared with primary-progressive MS was the only significant MR imaging difference between these MS subtypes. In the relapsing-remitting MS subgroup, the Expanded Disability Status Scale score was positively associated with conventional parameters reflecting white matter lesions and brain atrophy and with iron in the putamen and caudate nucleus. A positive association with putaminal iron and the Expanded Disability Status Scale score was found in primary-progressive MS. CONCLUSIONS: Susceptibility in the thalamus might provide additional support for the differentiation between primary-progressive and relapsing-remitting MS. That the Expanded Disability Status Scale score was associated with conventional MR imaging parameters and iron concentrations in several deep gray matter regions in relapsing-remitting MS, while only a weak association with putaminal iron was observed in primary-progressive MS suggests different driving forces of disability in these MS subtypes.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome.

BACKGROUND AND PURPOSE: The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months. MATERIALS AND METHODS: Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon ß-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period. RESULTS: In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period. CONCLUSIONS: Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.

Early magnetic resonance imaging predictors of clinical progression after 48 months in clinically isolated syndrome patients treated with intramuscular interferon ß-1a.

BACKGROUND AND PURPOSE: Our aim was to identify early imaging surrogate markers of clinical progression in patients after the first demyelinating event suggestive of multiple sclerosis treated with weekly intramuscular interferon ß-1a. In a prospective observational study, the predictive role of baseline and 6-month changes in magnetic resonance imaging outcomes was investigated with respect to relapse activity and development of confirmed disability progression in patients after 48 months. METHODS: This study examined 210 patients. Multivariate Cox proportional hazard models were used to analyse predictors of relapse activity and confirmed disability progression after 48 months. RESULTS: Greater T2 lesion volume [hazard ratio (HR) 1.81; P = 0.005] and the presence of contrast-enhancing lesions (HR 2.13; P < 0.001) at baseline were significantly associated with increased cumulative risk of a second clinical attack over 48 months. A greater decrease of the corpus callosum volume (HR 2.74; P = 0.001) and greater lateral ventricle volume enlargement (HR 2.43; P = 0.002) at 6 months relative to baseline were associated with increased cumulative risk of a second clinical attack between months 6 and 48. In addition, increased risk of confirmed disability progression over 48 months in patients with greater lateral ventricle volume enlargement between baseline and 6 months (HR 4.70; P = 0.001) was detected. CONCLUSIONS: A greater T2 lesion volume, the presence of contrast-enhancing lesions at baseline, decrease of corpus callosum volume and lateral ventricle volume enlargement over the first 6 months in patients after the first demyelinating event treated with weekly intramuscular interferon ß-1a may assist in identification of patients with the highest risk of a second clinical attack and progression of disability.

Evolution of cortical and thalamus atrophy and disability progression in early relapsing-remitting MS during 5 years.

BACKGROUND AND PURPOSE: Pathologic changes in GM have an important role in MS. We investigated the association between SDGM and cortical volume changes and disability progression in early RRMS. MATERIALS AND METHODS: One hundred eighty patients with RRMS had clinical assessment during 5 years and were divided into those with or without SDP at 5 years by the usual definition in treatment trials. The number of available MR imaging scans at various time points was the following: at baseline, 178; and at 6 months, 172; at 12 months, 175; at 24 months, 155; at 36 months, 160; at 48 months, 158; and at 60 months, 162, respectively. Longitudinal changes in cortical, GM, and WM volume were calculated by using the direct method. RESULTS: At 5 years, 90 patients with RRMS experienced SDP and 90 had stable disease. At baseline, patients with SDP had longer disease duration, greater T2-lesion volume, and smaller whole-brain, WM, cortical, and SDGM volume (P < .01). At 5 years, patients with SDP had significantly greater percentage decreases from baseline compared with those without SDP in the volume of the whole brain (P < .0001), cortex (P = .001), GM (P = .003), and thalamus (P = .01). In patients who developed SDP at 5 years and those who did not, mixed-effect models, adjusted for age, disease duration, and change of the treatment status, showed significant interactions between SDP status at 5 years and changes with time in whole-brain, cortical, lateral ventricle (all P < .001), thalamus (P = .006), and total SDGM (P = .0095) volume. CONCLUSIONS: SDP is associated with progression of cortical, central, and thalamic atrophy in early RRMS during 5 years.

Multiple sclerosis susceptibility loci do not alter clinical and MRI outcomes in clinically isolated syndrome.

It has not yet been established whether genetic predictors of multiple sclerosis (MS) susceptibility also influence disease severity and accumulation of disability. Our aim was to evaluate associations between 16 previously validated genetic susceptibility markers and MS phenotype. Patients with clinically isolated syndrome verified by positive magnetic resonance imaging (MRI) and cerebrospinal fluid findings (n=179) were treated with interferon-ß. Disability and volumetric MRI parameters were evaluated regularly for 2 years. Sixteen single-nucleotide polymorphisms (SNPs) previously validated as predictors of MS susceptibility in our cohort and their combined weighted genetic risk score (wGRS) were tested for associations with clinical (conversion to MS, relapses and disability) and MRI disease outcomes (whole brain, grey matter and white matter volumes, corpus callosum cross-sectional area, brain parenchymal fraction, T2 and T1 lesion volumes) 2 years from disease onset using mixed-effect models. We have found no associations between the tested SNPs and the clinical or MRI outcomes. Neither the combined wGRS predicted MS activity and progression over 2-year follow-up period. Power analyses confirmed 90% power to identify clinically relevant changes in all outcome variables. We conclude that the most important MS susceptibility loci do not determine MS phenotype and disease outcomes.

Corpus callosum atrophy--a simple predictor of multiple sclerosis progression: a longitudinal 9-year study.

AIM: To determine whether corpus callosum atrophy predicts future clinical deterioration in multiple sclerosis. METHODS: In 39 multiple sclerosis patients the area of corpus callosum in the sagittal plane, T2 and T1 lesion volumes, brain parenchymal fraction and brain atrophy were determined at baseline and 1 year after treatment initiation. Non-parametric and multiple regression models were built to identify the most reliable predictors of disability and of its changes over 9 years. RESULTS: Corpus callosum atrophy during the first year of treatment was the best predictor of disability (r = -0.56) and of its increase at 9 years (r = 0.65). Corpus callosum atrophy of at least 2% predicted increase in disability with 93% sensitivity and 73% specificity (odds ratio = 35). CONCLUSION: Corpus callosum atrophy is a simple and accurate predictor of future disability accumulation and is feasible for routine clinical practice.

Subcortical and cortical gray matter atrophy in a large sample of patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Recent studies have shown that selective regional, but not global, GM atrophy occurs from clinical onset to conversion to clinically definite MS. Our aim was to investigate the difference in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS and to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes. MATERIALS AND METHODS: Two hundred twelve patients with CIS recruited at the first clinical event (mean age, 29.3 years; median EDSS, 1.5; median disease duration, 3 months) and 177 patients with early RRMS (mean age, 30.7 years; median EDSS, 2.0; median disease duration, 47 months) were imaged on a 1.5T scanner by using a high-resolution 3D T1 spoiled gradient-recalled sequence. Volumetric data for SDGM structures were obtained by using FSL FIRST, while whole-brain, GM, white matter, cortical, and lateral ventricle volumes were estimated by using SIENAX software. Comparisons between the groups were adjusted for age and sex. RESULTS: Patients with early RRMS showed significantly lower SDGM but not cortical volumes compared with patients with CIS. The most apparent SDGM differences were evident in the caudate and thalamus (P < .0001), total SDGM (P = .0001), and globus pallidus (P = .01). Patients with CIS with a median T2 lesion volume >4.49 mL showed lower total SDGM, caudate, thalamus (P < .001), globus pallidus (P = .007), hippocampus (P = .004), and putamen (P = .01) volumes and higher lateral ventricle volume (P = .001) than those with a median T2 lesion volume <4.49 mL. Decreased thalamic volume showed the most consistent relationship with MR imaging outcomes (P < .0001) in patients with CIS. CONCLUSIONS: Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.

Interferon, azathioprine and corticosteroids in multiple sclerosis: 6-year follow-up of the ASA cohort.

OBJECTIVE: To evaluate long-term effects of 2-year treatment with interferon beta combined with low-dose azathioprine and prednisone in multiple sclerosis. METHODS: In the original 2-year ASA study, 181 patients with early relapsing-remitting multiple sclerosis were randomised into 3 treatment arms: those treated with interferon beta (n=60), with interferon beta and low-dose azathioprine (n=58), and interferon beta, azathioprine and low-dose prednisone (n=63). Of these, 172 were included in this 4-year non-study extension. Three monthly clinical controls and annual MRI scans were carried out. The primary endpoint was annual relapse activity. The secondary endpoints were disability and quantitative MRI parameters. RESULTS: Nine patients were lost to follow-up and 172 were included in the analyses. None of relapse activity, disability accumulation or MRI parameters differed significantly between the groups over 6 years. Only 5.5% and 0.6% of patients were free from disease activity at year 2 and year 6 of the treatment initiation. CONCLUSION: The tested combined therapeutic regimen does not improve long-term outcomes in patients with multiple sclerosis. Furthermore, interferon is not able to completely abolish disease activity.

Early predictors of non-response to interferon in multiple sclerosis.

OBJECTIVE: To identify early clinical and MRI predictors of non-response to interferon (IFN) treatment in multiple sclerosis (MS). METHODS: In 172 patients with relapsing-remitting MS treated with IFNß, we evaluated prediction of future treatment non-response. Candidate predictors comprised disability and its sustained progression, relapse score (combining frequency and severity of relapses), brain volume change, brain parenchymal fraction, number of new T2 lesions, and T2 and T1 lesion volume within the initial year of treatment. Treatment non-response was evaluated as confirmed disability progression or overall average annual relapse score exceeding 1 over the following 5 years. Logistic regression model was adjusted for patient age, gender, disease duration and changes in treatment. RESULTS: Ninety patients (52%) reached the status of IFN non-responders in years 2-6. Patients with ≥1 new T2 lesion and relapse score ≥2 (odds ratio ≥5.7) or those with ≥3 new T2 lesions regardless of the relapse score (odds ratio = 3) were in a significantly higher risk of future treatment non-response. CONCLUSIONS: In patients with MS treated with IFNß for 1 year, number of new T2 lesions and annualized relapse score predict individual risk of treatment non-response over the following 5 years.

[Total elbow replacement in patients with rheumatoid arthritis]. / Totální náhrada loketního kloubu v lécbe nemocných s revmatoidní artritidou.

PURPOSE OF THE STUDY: Total elbow arthroplasty is associated with a higher occurrence of complications than is usual for large-joint replacements. Two kinds of prostheses, unconstrained and semi-constrained, are currently used and each has its supporters or opponents. In this study the results of the two techniques used in our patients are evaluated and compared. MATERIAL: Two groups of elbows in patients with rheumatoid arthritis were evaluated. One comprised 58 elbows treated by Souter-Strathclyde total elbow arthroplasty (S-S group). The mean age of the patients at the time of surgery was 53 years (range, 22 to 71) and the mean follow-up was 9.5 years (range, 0.7 to 16.7). The other group included 63 elbows treated by Coonrad-Morrey elbow arthroplasty (C-M group). The mean age of the patients at the time of surgery was 54 years (range, 26 to 75) and the mean follow-up was 4.21 years (range, 0.28 to 7.87). METHODS: The Kaplan-Meier analysis was used to estimate implant survival in each group. Clinical assessment included range of motion and pain experience. The Mayo Elbow Performance Score (MEPS) was used as a clinical rating scale for the whole group. Radiographs were taken in two basic projections. The elbows with an implant removed or re-implanted were excluded from the evaluation. The patients were studied prospectively. The results were statistically analysed, with the level of significance set at 0.05. RESULTS: All patients experienced pain relief after surgery. In the S-S group, 35 elbows were free from pain (77.7 %), in the C-M group this was 53 elbows (88.3 %). The range of motion improved after arthroplasty in both groups. Flexion more than 110° was achieved in twice as many elbows in the C-M group than in the S-S group. Flexion contracture in the S-S group did not improve significantly. MEPS values after surgery improved in both groups, with significantly better results in the C-M group. In the S-S group, four elbow arthroplasties (6.9 %) showed instability, which was treated by replacement with a semi-constrained implant in one case and managed by articulated external fixation of the elbow for 6 weeks in three cases. Radiolucent lines were detected in five replacements (11.1 %) along the whole ulnar component width, in 12 (26.6 %) in the olecranon region and in 14 (31.1 %) in the distal humeral component. In the C-M group no radiolucency was recorded around the component. In the S-S group, revision surgery was carried out in 13 arthroplasties (22.4 %); of these, 10 (17.2%) were due to aseptic loosening, one (1.7 %) due to instability and one (1.7%) because of deep infection. In the C-M group, three elbows required revision (4.8 %), one for periprosthetic fracture (1.6 %) and two for deep infection (3.2 %). The results of survival analysis did not differ between the two groups. DISCUSSION: The weak point of Souter-Strathclyde total elbow arthroplasty is the ulnar component whose impairment and subsequent wear are involved in all cases of aseptic loosening. An insufficient length of the humeral component is another risk factor. Even natural movements of the elbow joint produce concentration of stresses on a small surface; this gradually weakens component fixation in bone and results in aseptic loosening. A higher risk of failure in Coonrad-Morrey elbow arthroplasty is associated with polyethylene lining of the hinge mechanism. CONCLUSIONS: The Coonrad-Morrey total elbow replacement is at present considered the method of choice. It is easier to perform and provides better functional outcomes than the Souter-Strathclyde elbow implant.

Multiple sclerosis and the accumulation of iron in the Basal Ganglia: quantitative assessment of brain iron using MRI t(2) relaxometry.

The aim of this work was to quantify the accumulation of iron in the basal ganglia in multiple sclerosis (MS) patients and in a control group, and to investigate the relationship between iron accumulation and other parameters assessed in MS, i.e. lesion load (LL) and brain parenchymal fraction (BPF). Magnetic resonance imaging T(2) relaxometry was used for the measurement. 970 patients with clinically definite MS and 117 controls were examined. Patients were divided into three subgroups according to LL and BPF. This work provides quantitative evidence of increased iron accumulation in the basal ganglia in MS patients in comparison to healthy controls. We also found that in the subgroup with small LL value, iron accumulation is higher than in the subgroup with large LL value. The hypothesis of a neurodegenerative component of MS is supported by the changes in iron content in the brain.

Apolipoprotein E ε4-positive multiple sclerosis patients develop more gray-matter and whole-brain atrophy: a 15-year disease history model based on a 4-year longitudinal study.

Multiple sclerosis is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. The objective of the study was to evaluate the relationship between apolipoprotein E (APOE) genotype and the evolution of different clinical and MRI parameters. We investigated a group of 150 relapsingremitting patients that completed 4-year follow-up. The mean age was 30.2 years, disease duration 56.8 months, and baseline Expanded Disability Status Scale (EDSS) 1.8. The changes in brain parenchymal volume (BPV), gray matter (GMV), white matter (WMV) and peripheral gray volume (PGMV) were measured by SIENA/X. T2-lesion volume was assessed by semi-automated methods. The mixed-effect model analysis was used to investigate evolution of clinical and MRI parameters in relation to the APOE ε4 genotype considering two different time models: 4-year follow-up and 15-year period from disease onset. We identified 36 APOE ε4-positive patients. Decline of GMV (P = 0.017), and BPV (P = 0.029) were significantly faster in APOE ε4-positive than in APOE ε4-negative patients in the 15-year model. In the 4- year model, a trend for faster decrease of GMV was found in APOE ε4-positive patients (P = 0.067). No differences in other MRI parameters or EDSS were found between the APOE groups. The results of the study suggest that APOE ε4-positive patients experience faster rate of gray matter atrophy.

Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis.

BACKGROUND: Studies evaluating interferon beta (IFNbeta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNbeta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNbeta with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders. OBJECTIVE: The Avonex-Steroids-Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNbeta-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy. METHODS: A total of 181 patients with relapsing-remitting MS (RRMS) were randomized to receive IFNbeta-1a 30 microg intramuscularly (IM) once weekly, IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily, or IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension. RESULTS: At 2 years, adjusted ARR was 1.05 for IFNbeta-1a, 0.91 for IFNbeta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNbeta-1a, 20.7% for IFNbeta-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNbeta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles. CONCLUSION: In IFNbeta-naïve patients with early active RRMS, combination treatment did not show superiority over IFNbeta-1a monotherapy.

Magnetic resonance volumetry of pathological brain foci in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of our study was to determine the volume of pathological foci in the brain tissue of patients suffering from systemic lupus erythematosus (SLE) with or without neuropsychiatric manifestations (NP), and also to find out if that volume depends on the study subjects' data and clinical records. Magnetic resonance (MR) scans of patients with SLE and, in particular, signs of neuropsychiatric involvement, show pathological foci in the cerebral white matter. METHODS: A total of 53 SLE patients, 29 with signs of neuropsychiatric syndromes (NPSLE), 24 without, and 16 healthy controls underwent prospective volumetric magnetic resonance imaging in a flow attenuated inversion recovery (FLAIR) sequence. The disease activity was expressed in terms of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: All the patients in this study were found to have a larger volume of pathological foci in the brain tissue than the healthy controls. The NPSLE subgroup had a larger volume of pathological foci than the SLE patients without NP (p<0.001). The largest volume of such foci was found in the patients with a history of cerebrovascular disease (p<0.05). These were also noted for a correlation between the duration of the disease and the period of time elapsed from the onset of the first signs of neuropsychiatric lupus (p<0.01). Correlation with SLEDAI-rated disease activity was found statistically significant in all the patients (p<0.05) and in those with NPSLE at a level of p<0.01. CONCLUSION: We found that the lesion load was significantly larger in NPSLE than in SLE patients free from NP and controls. Our measurement revealed a positive correlation between the lesion load and SLEDAI in the whole SLE patients group, particularly in the subgroup with NP manifestation. In the future, longitudinal volumetry might conceivably facilitate the therapeutical effect rating.

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.

Amygdalar volume and psychiatric symptoms in Alzheimer's disease: an MRI analysis.

OBJECTIVES: We measured the volumes of the amygdala to test the hypothesis that the reduction of amygdalar volume may be associated with psychiatric symptoms in Alzheimer's disease. MATERIALS AND METHODS: Twenty-seven patients underwent neuropsychological investigation including the assessment of general clinical severity by the Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI). All patients underwent magnetic resonance imaging (MRI) of the head, from which the volumes of the amygdalae were measured. The obtained values were compared with those of controls (n = 15). RESULTS: Patients with Alzheimer's dementia showed significant reduction in MRI volumetric measurements compared with controls. We found a significant correlation of MMSE score and absolute amygdala volume (r = 0.62, P < 0.01). Neither the absolute nor relative volume of the amygdala showed any correlation with NPI scores. CONCLUSIONS: The atrophy of the amygdala does not have a direct association with the existence of neuropsychiatric symptoms. MRI volumetry of the amygdala may be relevant as a marker of dementia severity in Alzheimer's disease.

Is it possible to actively and purposely make use of plasticity and adaptability in the neurorehabilitation treatment of multiple sclerosis patients? A pilot project.

OBJECTIVE: To investigate whether neurorehabilitation is able to influence clinical parameters and brain function measured radiologically. DESIGN: A group of healthy probands was compared with two groups of multiple sclerosis (MS) patients, one of which received rehabilitative therapy. SETTING: Outpatient in a university hospital. SUBJECTS: Twenty-eight patients with multiple sclerosis (MS), 17 of whom received rehabilitative therapy, and 13 healthy controls. INTERVENTIONS: Two months of rehabilitative eclectic therapy based on principles of sensorimotor learning and adaptation. MAIN MEASURES: Multiple Sclerosis Functional Composite, Modified Fatigue Impact Scale, Beck Depression Inventory Score, Barthel Index, Environment Status Scale and Multiple Sclerosis Quality of Life--54, and functional magnetic resonance imaging (fMRI). RESULTS: Patients who underwent neurorehabilitation showed a greater drop in fatigue, depression, impairment, disability and handicap and more improvement in quality of life than those who did not receive therapy. Correlation of brain activity between the right and the left hemisphere is greater in healthy individuals than in MS patients. Neurorehabilitation resulted in a trend for increased correlation between the left and the right hemisphere in patients (approaching the standard). In comparison with control groups, signal amplitudes in anatomical areas did not show any significant changes. CONCLUSION: Clinical changes seen with neurorehabilitation were not associated with any detectable changes in fMRI observations.