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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 β-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. CIS : clinically isolated syndrome CE : contrast-enhancing EDSS : Expanded Disability Status Scale LV : lesion volume SDGM : subcortical deep gray matter

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

Charles University in Prague, First Faculty of Medicine, Department of Radiology of the First Faculty of Medicineand General University Hospital, U Nemocnice 2, Prague 2, 128 08, Czech RepublicReceived 29 January 2010; accepted 20 September 2010ABSTRACT: We report a rare case of oral mass(epignathus) with intracranial extension originallysuspected antenatally at 16 weeks’ gestation becauseof a persistent open mouth. Postmortem MRI andpathologic examination of the fetus confirmed an oralteratoma with bilateral ventricular dilatation, corpuscallosum agenesis, and a neuroepithelial intracranialcyst. The relevant literature regarding this anomalyis reviewed.

We assessed the relationship between gray matter (GM) and white matter (WM) atrophy and clinical status in early relapsing-remitting multiple sclerosis (MS) patients over 5 years. A group of 181 patients who participated in the ASA (Avonex-Steroid-Azathioprine) study and had complete clinical and MRI assessments over 2 and 5 years was investigated. One hundred seventy (170) patients completed the 12-month follow-up, 147 the 24-month, 98 the 36-month, 65 the 48-month and 47 the 60-month. Changes in GM (GMV), WM (WMV) and peripheral GM (PGV) volumes, whole brain volume (percentage brain volume change PBVC), lateral ventricle volume (LVV), third ventricle width (3VW) and T2-lesion volume (T2-LV) were measured. Patients were assigned according to their clinical status to one of two groups: the Stable group, and the Reached Confirmed Sustained Progression (RCSP) group (24-week interval). At 0-6 months PBVC and GMV, at 0-12 months PBVC, GMV and T2-LV, at 0-24 months PBVC and GMV, at 0-36 months PBVC, GMV and T2-LV, and at 0-48 PBVC predicted the differences between the RCSP and Stable groups. PBVC and LVV showed the strongest ability to differentiate patients who presented 0 or >or=3 relapses in the Stable group. Decline in PBVC and GMV were predictive markers of disability deterioration. Correlation of T2-LV with clinical status was weaker and decreased over time. Higher number of relapses was associated with faster decline in whole brain volume.

Background Studies evaluating interferon beta (IFNβ) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNβ does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNβ 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 IFNβ-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 IFNβ-1a 30 μg intramuscularly (IM) once weekly, IFNβ-1a 30 μg IM once weekly plus AZA 50 mg orally once daily, or IFNβ-1a 30 μg 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 IFNβ-1a, 0.91 for IFNβ-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNβ-1a, 20.7% for IFNβ-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 IFNβ-1a alone (+30.3%, P Conclusion In IFNβ-naïve patients with early active RRMS, combination treatment did not show superiority over IFNβ-1a monotherapy.

Dissolved organic matter in soils can be predicted from forest floor C:N ratio, which in turn is related to foliar chemistry. Little is known about the linkages between foliar constituents such as chlorophylls, lignin, and cellulose and the concentrations of water-extractable forest floor dissolved organic carbon and dissolved organic nitrogen. Lignin and cellulose are not mobile in foliage and thus may be indicative of growing conditions during prior years, while chlorophylls respond more rapidly to the current physiological status of a tree and reflect nutrient availability. The aim of this study was to examine potential links among spectral foliar data, and the organic C and N of forest soils. Two coniferous species (red spruce and balsam fir) were studied in the White Mountains of New Hampshire, USA. Six trees of each species were sampled at 5 watersheds (2 in the Hubbard Brook Experimental Forest, 3 in the Bartlett Experimental Forest). We hypothesized that in a coniferous forest, chemistry of old foliage would better predict the chemical composition of the forest floor litter layer than younger foliage, which is the more physiologically active and the most likely to be captured by remote sensing of the canopy. Contrary to our expectations, chlorophyll concentration of young needles proved to be most tightly linked to soil properties, in particular water-extractable dissolved organic carbon. Spectral indices related to the chlorophyll content of needles could be used to predict variation in forest floor dissolved organic carbon and dissolved organic nitrogen. Strong correlations were found between optical spectral indices based on chlorophyll absorption and forest floor dissolved organic carbon, with higher foliage chlorophyll content corresponding to lower forest floor dissolved organic carbon. The mechanisms behind these correlations are uncertain and need further investigation. However, the direction of the linkage from soil to tree via nutrient availability is hypothetized based on negative correlations found between foliar N and forest floor dissolved organic carbon.

Objectives The aim of this study was to explore the evolution of MRI related gender differences in patients with relapsing–remitting (RR) multiple sclerosis (MS) who participated in a clinical trial over the 5 years. Methods 181 patients (39 males and 142 females) were assessed for clinical and neuroradiological disease activity over a period of 5 years. Clinical and MRI examination were performed at the baseline, 6, 12, 24, 36, 48 and 60 months. Longitudinal percentage volume changes in whole brain (PBVC), gray matter (PGMVC) white matter (PWMVC) cortex (PCVC), and lateral ventricles (PLVVC) were calculated by using direct methods (SIENA and SIENAX-multitimepoint). Absolute tissue volume changes of subcortical deep GM structures including caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala and nucleus accumbens were estimated using FIRST, a model based segmentation/registration tool. T2 lesion volume (T2-LV) and lesion activity analyses were performed, using a contouring-threshold and subtraction techniques. All clinical and MRI variables were analyzed between males and females. Results Global (PBVC) and tissue specific (PGMVC, PWMVC, PCVC, PLVVC) brain volume changes showed no significant gender differences over the 5-year follow-up period. Although total subcortical deep GM, caudate, putamen, globus palidus, thalamus and nucleus accumbens normalized volumes were significantly larger in male subjects at baseline, the follow-up analysis showed no differences over the 5 years. There were no gender differences in lesion activity or T2-LV changes over the 5 years. Conclusion No MRI lesion, global, tissue specific or regional brain volume gender change differences were found over the 5-year follow-up.

We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years,n=37), while patients with DD > 24 months were classified in the late group (DD of 7.1 years,n=99). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) (P<0.001), cortical volume (CV) (P<0.001), and in T2-LV (P<0.001) were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P<0.01). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P=0.01). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.

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 IFNβ, 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 IFNβ for 1 year, number of new T2 lesions and annualized relapse score predict individual risk of treatment non-response over the following 5 years.

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.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are disorders frequently associated with serum osmotic imbalance. The prognosis is very variable from complete regression of clinical symptomatology to signs of significant quadruparesis, a vegetative state and death. We report the case of a 25-year-old man with a diagnosis of osmotic demyelination syndrome. The patient was young healthy man with no history of chronic alcoholism or malnutrition. He underwent head trauma associated with consumption of alcohol, being diagnosed with cerebral commotion. Four days later he presented with generalised epileptic convulsions with unconsciousness. Laboratory findings showed significant hyponatremia and hypochlorinemia. Following the rapid correction of osmotic conditions of serum, spastic quadruparesis and coma developed. MRI of the brain showed finding of CPM and EPM, cortical laminar necrosis (CLN) and coagulative necrosis in the putamina. Our case is suggestive in the rare MRI appearance of myelinolysis in addition to CLN and coagulative necrosis in the basal ganglia following the rapid correction of serum osmolarity. We suggest that this finding is prognostically very unfavourable. In the reported patient clinically initial neurological deficit progressed to a vegetative state within one month.

We report on a meningioma of the cervical spine in a 12-year-old boy with atypical clinical presentation. Meningiomas are relatively rare neoplasms in childhood, representing only 1 to 2% of all pediatric intracranial tumors. The distinction between the meningioma and another extramedullary, intradural tumors like schwannoma might pose difficulties. This case report points out that although a very rare tumor in children, it must be taken into account in differential diagnostics.

Between 1996 and 2006, 17 patients with intracranial lipomas underwent MR imaging examination. Of these, two patients also had CT examination. Lipoma is not a typical tumor and could instead be called intracranial lipoma hamartoma or cerebral malformation. The predominant localization of the lipomas was close to midline structures, such as the area around the corpus callosum, quadrigeminal cisterns, etc. Interpreting the MRI it is necessary to differentiate epidermoid, dermoid and hemorrhage in the metahemoglobin stage from lipoma. Clinically, 47% of patients complained of headache, two presented with epileptic seizures and the remainder had different symptoms. The lipoma was just an incidental finding not related to the clinical symptomatology.

This case report describes a finding of vascular malformation of an aborted foetus of gestational age of the 22nd week. This concerns meningocerebral angiodysplasia, located in the posterior fossa and around the thalami. This disease is rare and is often accompanied by renal agenesis. The finding was complicated by hydrocephalus. Our report compares all three diagnostic methods (prenatal ultrasonography, post-mortem MR and autopsy). Prenatal ultrasonography described only hydrocephalus and reduction of cerebral parenchyma. MR displayed the extent of the malformation, the exact diagnosis was however determined by histological examination. MR described agenesis of structures of midbrain, which was confirmed by autopsy.