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Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 127 records · Page 7Linked to original sources

T(1) hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment.

Recently, the clinical efficacy of interferon beta-1b (IFNbeta-1b) was demonstrated for secondary progressive (SP) multiple sclerosis in a European multicentre study. We evaluated the effect of IFNbeta-1b treatment on the rate of development of hypointense T(1) MRI lesions, a putative marker of axonal damage. Unenhanced T(1)-weighted images were obtained in a subgroup of 95 multiple sclerosis patients from five centres at 6-month intervals; this subgroup was similar to the total study population for all demographic, clinical and MRI parameters. An experienced observer blinded to the clinical data and treatment allocation measured volumes. The median baseline lesion load for hypointense T(1) lesions was 5.1 cm(3) for placebo-treated and 4.9 cm(3) for IFNbeta-1b-treated patients (P = 0.56). Placebo-treated patients showed an increase in T(1) lesion load by a median of 14% per year (P = 0.0002 compared with baseline); this was reduced to 7.7% per year in the IFNbeta-1b-treated patients (P = 0.003 versus placebo). In the IFNbeta-1b arm there was a statistically significant correlation between absolute change in Expanded Disability Status Scale scores and T(1) lesion load by month 36 (r = 0.38, P = 0.0015). In patients with SP multiple sclerosis, IFNbeta-1b treatment reduces the development of hypointense T(1) lesions, suggesting that reduced axonal damage in lesions may play a part in the beneficial effect that is observed clinically.

Adult↗

Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications.

The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.

Adult↗

Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis.

OBJECTIVE: To assess the feasibility of a new technique based on diffusion anisotropy to segment white and grey matter of the brain. To use this technique to measure the mean diffusivity () and magnetisation transfer ratio (MTR) of normal appearing white matter (NAWM) and grey matter (NAGM) from patients with multiple sclerosis. METHODS: Dual echo turbo spin echo, MT, and diffusion weighted scans of the brain were obtained from 30 patients with multiple sclerosis and 18 sex and age matched healthy controls. After image coregistration and removal of T2 visible lesions, white and grey matter were segmented from 10 supratentorial slices using diffusion anisotropy thresholds. Histograms of the average MTR and were created for normal white and grey matter of controls and NAWM and NAGM of patients with multiple sclerosis. RESULTS: All the MTR histogram derived metrics of the NAWM from patients with multiple sclerosis were significantly lower than those of white matter from controls. The peak height of the histogram of NAWM from patients with multiple sclerosis was also significantly different from that of normal white matter. The average MTR, the peak location of the MTR histogram, and peak height of the histogram of the NAGM of patients with multiple sclerosis were significantly lower than the corresponding quantities of grey matter from controls. CONCLUSIONS: A technique was developed for segmenting white and grey matter with the potential for improving the understanding of the pathophysiology of many neurological conditions. Its application to the study of multiple sclerosis confirms the presence of a diffuse tissue damage in the NAWM of these patients and suggests that subtle changes also occur in the NAGM.

Adult↗

Magnetic resonance imaging, magnetisation transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber's hereditary optic neuropathy.

OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to bilateral loss of central vision and severe optic nerve atrophy. A subtype of LHON presents additional clinical and MRI aspects indistinguishable from those of multiple sclerosis (MS) (LHON-MS). In patients with LHON or LHON-MS, an assessment was made of (a) the severity of optic nerve damage, using MRI and magnetisation transfer imaging (MTI), and (b) the presence and extent of macroscopic and microscopic pathology in the brain and cervical cord, using MRI and MT ratio (MTR) and mean diffusivity (D) histogram analysis. METHODS: Ten patients with LHON, four with LHON-MS, and 20 age and sex matched healthy controls were studied. For the optic nerve and the brain, dual-echo turbo spin echo (TSE), T1 weighted spin echo, and MT images were obtained. For the brain, fast fluid attenuated inversion recovery (fast FLAIR) and diffusion weighted images were also obtained. For the cervical cord, fast short tau inversion recovery (STIR) and MT images were obtained. The volume and the average MTR value of both the optic nerves were measured. MTR and histograms of the normal appearing brain tissue (NABT) and MTR histograms of the whole cervical cord tissue were created. RESULTS: The mean values of optic nerve volumes and MTR were significantly lower in patients with LHON than in healthy controls. Mean NABT-MTR histogram peak height was significantly lower in patients with LHON than in controls, whereas no significant difference was found for any of the cervical cord MTR histogram derived measures. Average diffusivity (D) was higher in patients with LHON than in controls. Optic nerve volume and MTR value and mean NABT-MTR were lower in patients with LHON-MS than in those with LHON. CONCLUSIONS: The severity of optic nerve pathology in LHON is measurable in vivo using MRI and MTI. MTR and histogram analysis suggests that microscopic brain damage occurs in LHON and that it is more severe in the MS-like form of the disease.

Adult↗

Clinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets.

OBJECTIVE: A new parametric simulation procedure based on the negative binomial (NB) model was used to evaluate the sample sizes needed to achieve optimal statistical powers for parallel groups (with (PGB) and without (PG) a baseline correction scan). It was also used for baseline versus treatment (BVT) design clinical trials in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), when using the number of new enhancing lesions seen on monthly MRI of the brain as the measure of outcome. METHODS: MRI data obtained from 120 untreated patients with RRMS selected for the presence of MRI activity at baseline, 66 untreated and unselected patients with RRMS, and 81 untreated and unselected patients with SPMS were fitted using an NB distribution. All these patients were scanned monthly for at least 6 months and were all from the placebo arms of three large scale clinical trials and one natural history study. The statistical powers were calculated for durations of follow up of 3 and 6 months. RESULTS: The frequency of new enhancing lesions in patients with SPMS was lower, but not significantly different, from that seen in unselected patients with RRMS. As expected, enhancement was more frequent in patients with RRMS selected for MRI activity at baseline than in the other two patient groups. As a consequence, the estimated sample sizes needed to detect treatment efficacy in selected patients with RRMS were smaller than those of unselected patients with RRMS and those with SPMS. Baseline correction was also seen to reduce the sample sizes of PG design trials. An increased number of scans reduced the sample sizes needed to perform BVT trials, whereas the gain in power was less evident in PG and PGB trials. CONCLUSION: This study provides reliable estimates of the sample sizes needed to perform MRI monitored clinical trials in the major MS clinical phenotypes, which should be useful for planning future studies.

Adult↗

Correlations between clinical findings and magnetization transfer imaging metrics of tissue damage in individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND AND PURPOSE: We obtained magnetization transfer imaging (MTI) scans from individuals with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1) to investigate the presence, extent, and nature of pathology in white and gray matter outside proton density (PD)-visible lesions; (2) to quantify the degree of tissue damage occurring in lesions seen on PD-weighted scans; and (3) to correlate MTI-derived measures of disease burden with age, physical disability, and cognitive performance. METHODS: Dual-echo, T1-weighted, and MTI scans of the brain were obtained from 33 individuals with CADASIL and 12 control subjects. Magnetization transfer ratio (MTR) values from PD-visible lesions, normal-appearing white matter (NAWM), and normal-appearing gray matter (NAGM) were measured. Histograms of MTR from the whole brain and normal-appearing brain tissue were also produced. RESULTS: All MTR values from NAWM and NAGM regions studied were significantly lower for individuals with CADASIL than for control subjects, with the exception of those obtained from the NAWM of the infratentorial structures and the NAGM of the occipital cortex. The average MTR from PD lesions in individuals with CADASIL was significantly lower than that from all the NAWM regions. Average MTR and peak location from whole-brain and normal-appearing brain tissue histograms were significantly lower for individuals with CADASIL than for control subjects. MTR values from NAWM were strongly correlated with the extent of macroscopic lesions and their average MTR. Apart from NAGM, average MTR from all other tissues studied significantly decreased with increasing age, physical disability, and cognitive impairment. CONCLUSIONS: PD lesions of individuals with CADASIL have variable degrees of tissue damage. Brain tissue outside PD abnormalities is also damaged. This study suggests that the extent and the severity of the brain tissue damage are critical factors in determining clinical status in CADASIL.

Age Factors↗

Intra-observer, inter-observer and inter-scanner variations in brain MRI volume measurements in multiple sclerosis.

INTRODUCTION: Measurement of brain volume on magnetic resonance imaging (MRI) scans is regarded as an objective marker of multiple sclerosis (MS) severity with the potential to monitor treatment efficacy accurately. This study was performed to assess the variability of brain MRI volume measurements. PATIENTS AND METHODS: We studied nine patients with relapsing-remitting MS, who were imaged on two occasions (separated by an interval of 24 h) using two different MR scanners and fast fluid-attenuated inversion recovery (fast-FLAIR) sequences. The whole brain volume computed from each image was measured three times by three observers using a seed-growing technique based on signal intensity thresholding. Intra-observer, inter-observer and inter-scanner variabilities were expressed as coefficients of variations (COVs). The inter-scanner variability included not only the intra-observer variation but also the repositioning variability and the variation in observed brain volume caused by different scanner hardware and sequence implementations. RESULTS: There was no statistically significant difference in patients' brain volume values between observers (P=0.82) or between scanners (P=0.30). The mean intra-observer COV was 1.2% (s.e.=0.4%), the mean inter-observer COV was 1.8% (s.e.=0.8%) and the mean inter-scanner COV was 2.4% (s.e.=1.2%). The intra-observer variance was not statistically different from those found between observers (P=0.83) or scanners (P=0.44). CONCLUSION: The intra-observer variability in brain volume measurements found in this study was within the range of intra-observer variability found in previous studies. This study shows that the use of different observers and MR scanners has only a small influence on the measured brain volume and does not affect the reproducibility of this measurement greatly.

Adult↗

European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging--measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group.

Two prior double-blind, placebo-controlled, randomized trials demonstrated that glatiramer acetate (GA) reduces relapse rates in patients with relapsing remitting multiple sclerosis (RRMS). This study was designed to determine the effect, onset, and durability of any effect of GA on disease activity monitored with magnetic resonance imaging (MRI) in patients with RRMS. Two hundred thirty-nine eligible patients were randomized to receive either 20 mg GA (n = 119) or placebo (n = 120) by daily subcutaneous injection. Eligibility required one or more relapses in the 2 years before entry and at least one enhancing lesion on a screening MRI. The study was a randomized, double-blind, placebo-controlled phase during which all patients studied underwent monthly MRI scans and clinical assessments over 9 months. The primary outcome measure was the total number of enhancing lesions on T1-weighted images. Secondary outcome measures included the proportion of patients with enhancing lesions, the number of new enhancing lesions and change in their volume; the number of new lesions detected on T2-weighted images and change in their volume, and the change in volume of hypointense lesions seen on unenhanced T1-weighted images. Clinical measures of disease activity were also evaluated. The active treatment and placebo groups were comparable at entry for all demographic, clinical, and MRI variables. Treatment with GA showed a significant reduction in the total number of enhancing lesions compared with placebo (-10.8, 95% confidence interval -18.0 to -3.7; p = 0.003). Consistent differences favoring treatment with GA were seen for almost all secondary end points examined: number of new enhancing lesions (p < 0.003), monthly change in the volume of enhancing lesions (p = 0.01), and change in volume (p = 0.006) and number of new lesions seen on T2-weighted images (p < 0.003). The relapse rate was also significantly reduced by 33% for GA-treated patients (p = 0.012). All effects increased over time. Glatiramer acetate significantly reduced MRI-measured disease activity and burden.

Adult↗

Scan-rescan variation of measures derived from brain magnetization transfer ratio histograms obtained in healthy volunteers by use of a semi-interleaved magnetization transfer sequence.

SUMMARY: A novel semiinterleaved gradient-echo (GE) sequence for quantitative measurement of magnetization transfer ratio (MTR) is described. With this sequence, several lines of k-space are collected for the non-MT image then several lines are collected for the MT image, thus building up the entire k-space in distinct acquisition blocks, with a good trade-off between motion-induced misregistration and degree of MT effect. The scan-rescan coefficients of variation for several MTR histogram-derived measures from 10 healthy volunteers scanned serially with this semiinterleaved sequence proved to be lower than those achieved using a conventional GE sequence. This sequence may be useful in a clinical environment to measure MTR changes over time more reliably than when acquiring the non-MT and MT images sequentially, which inevitably are affected by patient motion.

Adult↗

Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Compared with conventional T2-weighted MR imaging, diffusion tensor MR imaging provides quantitative indices with increased specificity to the most destructive aspects of multiple sclerosis. In this study, we obtained brain mean diffusivity (_D) and fractional anisotropy histograms of patients with multiple sclerosis to compare them with those of healthy volunteers and to investigate the correlation between diffusion tensor MR imaging histogram-derived measures and the level of disability and quantities derived from conventional MR imaging. METHODS: Dual-echo and diffusion tensor MR images were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive multiple sclerosis and from 20 healthy control volunteers. After obtaining mean diffusivity (_D) and fractional anisotropy images and image coregistration, _D and fractional anisotropy histograms were created. From each histogram, the following measures were derived: the average _D and fractional anisotropy, the histogram peak heights, and the histogram peak locations. RESULTS: All the _D and fractional anisotropy histogram-derived measures were different between patients and controls at a significance level of P <.001. No differences were found in any of the considered quantities among the three multiple sclerosis phenotypes. In patients with relapsing-remitting multiple sclerosis, disability was correlated with histogram average_D (r = 0.4, P =.01) and peak height (r = -0.4, P =.01). In patients with secondary progressive multiple sclerosis, disability was correlated with fractional anisotropy histogram peak position (r = -0.6, P =.01). Significant correlations were also found between T2 lesion load and various diffusion tensor MR quantities. CONCLUSION: This study shows that brain _D and fractional anisotropy histograms are different for patients with multiple sclerosis compared with control volunteers. This study also shows that quantities derived from diffusion tensor MR imaging are correlated with disability in patients with relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, suggesting that they might serve as additional measures of outcome when monitoring multiple sclerosis evolution in these patients.

Adult↗

Correlation of multiple sclerosis measures derived from T2-weighted, T1-weighted, magnetization transfer, and diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), the severity of tissue damage can vary from edema and inflammation to irreversible demyelination and axonal loss. Compared with conventional T2-weighted MR imaging, magnetization transfer (MT) and diffusion tensor (DT) MR imaging provide quantitative indices with increased specificity to the most destructive aspects of MS. To increase our understanding of the pathophysiologic processes of MS, we assessed the correlations between MT and DT MR imaging-derived metrics and the correlations between these quantities and measures derived from conventional MR in patients with MS. METHODS: T2-weighted, T1-weighted, MT, and DT MR images of the brain were obtained from 34 patients with relapsing-remitting MS (RRMS) and 15 age-matched control subjects. T2 and T1 lesion volumes (LV) and brain volume were measured. MT ratio (MTR), mean diffusivity (D macro), and fractional anisotropy (FA) histograms from the overall brain tissue (BT) and the normal-appearing brain tissue (NABT) were obtained. Average lesion MTR, D macro, and FA were also calculated. The correlations between T2 and T1 LV, brain volume, MT-, and DT-derived metrics were assessed with the Spearman rank correlation coefficient. RESULTS: No significant correlations were found between MT and FA histogram-derived metrics and quantities derived from conventional MR scans (T2 and T1 LV and brain volume). On the contrary, T2 and T1 LV (but not brain volume) were significantly correlated with the average D macro values of BT and NABT (r values ranging from 0.52 to 0.78). No significant correlation was found between MT- and DT-derived metrics. CONCLUSION: These results suggest that MT and DT MR imaging provide, at least partially, independent measures of lesion burden in patients with RRMS. This suggests that a multiparametric MR approach has the potential for increasing our ability to monitor MS evolution.

Adult↗

[Laparoscopic or open appendectomy. Critical review of the literature and personal experience].

UNLABELLED: In the era of video-laparoscopic surgery there are a lot of surgeons that still continue to perform open appendectomy. This choice is the consequence of the good results of open appendectomy (clinical, cosmetic, hospital stays and hospital costs). Published trials on laparoscopic appendectomy don't show that it is superior to the open approach. The aim of this study is to critically review the literature on laparoscopic and traditional appendectomies and to report a clinical experience on 86 consecutive patients that underwent open appendectomy. PATIENTS AND METHODS: From September 2000 to March 2001, in the Department of Emergency Surgery of Villa Scassi Hospital in Genoa, 86 patients underwent open appendectomy (32 men; mean age 29.8 years; range 15-54 years/54 women; mean age 22.4 years; range 13-80 years). All the patients underwent blood examinations, abdomino-pelvic ultrasonographys and the women gynecological evaluation. The Authors used, almost always, the Stropeni way of access (cutaneous Mac Burney and right para-rectal incision of the muscles). Discharge has been done as soon as possible. Removed appendices were submitted to histological examination and were classified as normal or pathologic according to the severity of the lesion. Review of articles has been done on Medline. RESULTS: Suspected appendicitis have been confirmed by histological examination that documented 1 normal appendix, 7 chronic appendicitis, 45 acute catharralis, 22 acute suppurative and 11 gangrenous or perforated appendicitis. The specificity of open appendectomy has been 97.6% (100% for men). Post-operative complications were: 2 wound infections and 1 recurrence of an abscess (2.58%). Open appendectomy did carry an hospital bill of 2,500,000 IT liras (1,200 USA dollars) for non complicated appendicitis and 2,000 USA dollars for perforated appendicitis. The early discharge allowed us to spend 119 millions IT liras less in 7 months (99,600 USA dollars in a year). DISCUSSION: The role of laparoscopic appendectomy isn't still established. After a critical review of the literature we can suggest that: 1) laparoscopic appendectomy increase operative time (63 vs 43 minutes: p < 0.0001); 2) laparoscopic approach can reduce the length of post-operative stay in hospital; 3) hospital bill is strongly reduced by open appendectomy (4,274 vs 7,923 USA dollars). On our experience the cost of the hospital for uncomplicated appendicitis is 2,500,000 IT liras (1,200 USA dollars). Otherwise it has been suggested that laparoscopic appendectomy has a better diagnostic accuracy respect to open appendectomy. Some Authors report a percentage of "negative" appendices of 16-50%. In Authors experience the percentage of "negative" appendices is 1.3% and so the diagnostic accuracy is 96% in women and 100% in men, probably because we systematically performed a preoperative abdomino-pelvic ultrasonography and, for the women, a gynecological evaluation. In conclusion, laparoscopic appendectomy should be done in case of suspected appendicitis in women. In the other cases, when there is a strong clinical suspect of appendicitis and, in particular, in case of suppurative appendicitis, the Authors recommend to perform an open appendectomy using the Stropeni approach. In case of perforated appendicitis with abdominal abscess they recommend to perform an open appendectomy using the right para-rectal approach or the median umbilical-pubis approach.

Acute Disease↗

Cladribine. Ortho Biotech Inc.

Cladribine, an adenosine deaminase inhibitor, has been developed and launched by Ortho Biotech in collaboration with The Scripps Research Institute for the treatment of several neoplasms, including acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, cutaneos T-cell lymphoma, hairy-cell leukemia and non-Hodgkin's lymphoma. It was first launched in the US in February 1993. Ortho Biotech and The Scripps Research Institute have since been developing the compound for its potential use in multiple sclerosis (MS). In 1997, Ortho filed air NDA in the US for the use of cladribine in the treatment of relapsing-remitting and secondary progressive MS. An FDA drug advisory committee was planning to meet in January 1999 to discuss the NDA. However, Ortho cancelled the meeting. Following an FDA inspection during December 1998 and January 1999, the Scripps Clinic received a warning letter from the FDA in April 1999 regarding violations in the clinical studies of cladribine for MS, and Ortho withdrew the NDA after concluding that further clinical studies would be necessary. Cladribine has been known since the 1960s as an intermediate for the synthesis of 2-deoxynucleotides and its potential for the treatment of leukemia was disclosed in 1984. The Scripps Research Institute and the Johnson & Johnson group hold several patents claiming preparation methods (US 05208327), and additional indications, such as multiple sclerosis (WO-09316706) and rheumatoid arthritis (US-05310732). The associated patent, WO-09323508, is the only one among those patents that claims the use of unmodified cladribine for the treatment of leukemia, but it focuses particularly on a specific form of the disease, chronic myelogenous leukemia. Analysts at UBS Warburg predicted in October 2001, that the product would make US sales of $50 million in 2004 for its MS indication.

Adenosine Deaminase Inhibitors↗

Whole brain volume changes in patients with progressive MS treated with cladribine.

OBJECTIVE: To compare changes in whole brain volume measured using MRI scans in patients with progressive MS enrolled in a double-blind, placebo-controlled trial assessing the efficacy of two doses of cladribine (0.7 and 2.1 mg/kg) and to assess the correlations between change in whole brain volume and change in other conventional MRI measures. BACKGROUND: Measuring brain parenchymal volumes is an objective and reliable surrogate for the destructive pathologic process in MS. The dynamics and the mechanisms of tissue loss in progressive MS are unclear. METHODS: Whole brain volumes were measured using postcontrast T1-weighted scans with 3 mm slice thickness from 159 patients with progressive MS (70% secondary progressive and 30% primary progressive) enrolled in a double-blind, placebo-controlled trial of 12-month duration. RESULTS: Whole brain volumes were similar in the placebo and cladribine-treated patients on the baseline scans. A significant decrease of brain volume over time was observed both in the entire population of patients (p = 0.001) and in the placebo patients in isolation (p = 0.04). No significant treatment effect of either dose of cladribine on brain volume changes over time was found. In the 54 patients who received placebo, the change in brain volume was not significantly correlated with other MRI measures at baseline (enhancing lesion number and volume and T2-hyperintense and T1-hypointense lesion volumes) or at follow-up (cumulative number of enhancing lesions and absolute and percentage changes of enhancing T2- and T1-hypointense lesion volumes). CONCLUSIONS: This study shows in a large cohort of patients that brain parenchymal loss occurs, even over a short period of time, in progressive MS and that cladribine is not able to alter this process significantly. It also suggests that MRI-visible inflammation and new lesion formation has a marginal role in the development of brain atrophy in patients with progressive MS.

Brain↗

Magnetization transfer imaging to monitor the evolution of MS: a 1-year follow-up study.

OBJECTIVES: To assess the sensitivities of magnetization transfer imaging (MTI)-derived measures in detecting changes over time of macro- and microscopic lesion burdens in different MS phenotypes and to compare them with those of T2-weighted and T1-weighted lesion volumes. METHODS: A total of 96 patients were studied: 39 with relapsing-remitting MS (RRMS), 19 with secondary progressive MS (SPMS), nine with primary progressive MS, and nine with benign MS; 20 with clinically isolated syndromes suggestive of MS at presentation; and 20 healthy subjects. Brain T2-weighted, T1-weighted, and MTI scans were obtained at baseline and after 12 months. The authors measured T2-weighted and T1-weighted lesion volumes and average lesion MT ratio (MTR). The authors also derived MTR histograms from whole brain tissue (WBT) and normal-appearing brain tissue (NABT). RESULTS: In healthy control subjects, there was no significant change of any of the MTR histogram parameters. At follow-up, in the entire patient group, T2-weighted lesion volume significantly increased and average lesion MTR, WBT-MTR, NABT-MTR, and histogram peak positions significantly decreased. Patients with RRMS and SPMS had significantly higher changes in T2-weighted lesion volume and all the MTI-derived metrics compared with the other subgroups. MTI changes were more prominent (and significantly different) in patients with SPMS than in those with RRMS. Compared with patients with benign MS, patients with RRMS had significantly greater changes in T2-weighted lesion volume and WBT- and NABT-MTR metrics. Compared with patients with SPMS, patients with primary progressive MS had similar changes of T1-weighted and T2-weighted lesion volumes, but significantly lower changes of MTI-derived measures. CONCLUSIONS: MTI-derived measures are sensitive for detecting MS-related changes and might provide valuable outcome measures when assessing treatment effects in clinical trials of patients with MS.

Adult↗

Weekly diffusion-weighted imaging of normal-appearing white matter in MS.

To elucidate the dynamics and the nature of normal-appearing white matter (NAWM) changes preceding new lesion formation in MS, the authors obtained weekly diffusion-weighted images for 12 weeks from 6 patients. NAWM areas subsequently involved by enhancement had a significant increase in mean diffusivity values starting 6 weeks before the appearance of enhancement (p values ranging between < 0.0001 and 0.04). This suggests that focal edema and demyelination play a part in the NAWM changes preceding new lesion formation in MS.

Adult↗

Magnetization transfer and diffusion-weighted imaging in nocturnal frontal lobe epilepsy.

The authors assessed the presence of brain abnormalities in 21 patients with nocturnal frontal lobe epilepsy (NFLE), using magnetization transfer ratio (MTR) and mean diffusivity (;D) histograms. Compared with healthy volunteers and patients with idiopathic generalized epilepsy, patients with NFLE had lower MTR (p = 0.002 and 0.01) and;D (p = 0.03 and 0.04) histogram peak heights. Subtle and widespread abnormalities related to intra- and extracellular distribution and motion of water are detectable in the brains of patients with NFLE.

Adolescent↗