Di Legge S, Piattella MC, Pozzilli C, Pantano P, Caramia F, Pestalozza IF, Paolillo A, Lenzi GL
Mult Scler 2003 Jun;9(3):302-6
University of Rome La Sapienza, Department of Neurological Sciences, Rome, Italy
We investigated the relationship between emotional changes, Brain lesion burden and development of Multiple Sclerosis (MS).
Thirty-seven consecutive patients with Clinically Isolated Syndrome (CIS) were prospectively assessed with the Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) and Gadolinium enhanced (Gd+) MRI scans.
BDI and STAI were also administered to 36 age-matched controls. Conversion to MS was defined as the occurrence of a clinical relapse. CIS patients were more likely to endorse symptoms of Anxiety and Depression than controls.
Baseline scores for Depression and Anxiety did not correlate with the Total Lesion Load (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd++ lesions during the first six months of follow-up.
A positive correlation was found between severity of Depressive Scores and the lesion load in the Right Temporal region (P = 0.005).
After 33+/-6 months of the study entry, patients who had a clinical relapse were more frequently Depressed (P = 0.001) than those relapse free.
Emotional disturbances are frequently observed in CIS patients and show a tendency towards a normalization in relapse-free patients.
The increased rate of Depressive Symptoms observed in patients who developed MS seems to result from a combination of Psychological and organic features.
The Lesion Load in the Right Temporal region is confirmed as a key area for developing Depressive Symptoms, even in the early phase of the disease.
Conventional And Magnetization Transfer MRI Predictors Of Clinical Multiple Sclerosis Evolution: A Medium-Term Follow-Up Study
Rovaris M, Agosta F, Sormani MP, Inglese M, Martinelli V, Comi G, Filippi M
Brain 2003 Oct;126(Pt 10):2323-32
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of NeuroScience, Milan, Italy
The correlation between conventional MRI lesion load accumulation and Multiple Sclerosis clinical evolution is only modest.
The assessment of Brain Parenchymal Volume and of its changes over time may provide adjunctive MRI markers reflecting the more disabling aspects of Multiple Sclerosis pathology.
Magnetization Transfer (MT) MRI is sensitive to 'occult' Multiple Sclerosis-related Brain damage and might also contribute to overcome the clinical/MRI paradox.
In this study, we assessed the value of conventional and MT MRI-derived metrics in predicting the medium-term clinical evolution of patients with different Multiple Sclerosis phenotypes.
We studied 73 patients, with Relapsing/Remitting Multiple Sclerosis (n = 34), Secondary/Progressive Multiple Sclerosis (n = 19) and Clinically Isolated Syndromes suggestive of Multiple Sclerosis (n = 20), and 16 healthy subjects.
Brain dual-echo, T1-weighted (only in patients) and MT MRI scans were obtained at baseline and after 12 months.
T2-HyperIntense and T1-HypoIntense lesion volumes, normalized Brain Volume and average lesion MT Ratio (MTR) were measured.
MTR Histograms from the Whole Brain Tissue were also obtained. Clinical Multiple Sclerosis evolution and Neurological disability were re-assessed in all patients after a median follow-up of 4.5 years.
A multivariate analysis was performed to establish which clinical and MRI-derived variables were significant predictors of Neurological deterioration at the end of the study period. At the end of follow-up, 34 patients showed significant Neurological deterioration.
The final multivariable model included average Brain MTR percentage change after one year [P = 0.02, odds ratio (OR) = 0.86] and baseline T2-HyperIntense lesion volume (P = 0.04, OR=1.04) as independent predictors of medium-term disability accumulation (r2 = 0.23).
In this cohort of patients, abnormal values of average Brain MTR changes showed a relatively high specificity (76.9%) and positive predictive value (59.1%) for Expanded Disability Status Scale score deterioration in individual cases.
In patients with Multiple Sclerosis, a comprehensive estimation of the short-term changes of both conventional and MT MRI-detectable lesion burden might provide useful prognostic information for the medium-term clinical disease evolution.
McDonald WI; Ron MA
Philos Trans R Soc Lond B Biol Sci, 1999 Oct, 354:1390, 1615-22
Royal College of Physicians, London, UK
PMID# 10603614; UI# 20071269
Multiple Sclerosis is an Immune-mediated Inflammatory DeMyelinating Disease of the Central Nervous System clinically characterized by relapses and remissions of Neurological Disturbance.
A typical relapse, exemplified by Optic Neuritis, increases in severity over a week or two and after approximately one month begins to remit. Resolution takes place over the course of two to three months.
In the early stages, clinical recovery is virtually complete, though persistent abnormalities of Conduction can usually be detected by Evoked Potential techniques and persistent structural abnormalities can be detected by Magnetic Resonance Imaging (MRI).
These techniques, together with CerebroSpinal Fluid examination for OligoClonal Bands IgG, provide supporting evidence for the diagnosis which, in the absence of a specific test, nevertheless remains primarily clinical.
The course of the disease is very variable, but after a number of years Neurological Deficit begins to accumulate after each relapse.
In most patients, the Relapsing/Remitting phase of the disease is followed by a phase of continuous progression of Disability.
Cognitive Disturbances can be detected in many patients even quite early in the course of the illness.
- Deficits in Attention, Memory and Executive Skills may be prominent and tend to become increasingly prominent as Neurological Deficit increases, although this is not always the case.
There is some correlation between the extent of MRI abnormalities in the Cerebral White Matter and the severity of Cognitive Deficit.
Depression and Anxiety are commonly experienced but are poorly correlated to the Lesion Load seen on MRI.
In contrast, the much rarer Psychotic Symptoms: Euphoria and Emotional Lability are closely linked to the severity of White Matter Disease.
Magnetization Transfer Magnetic Resonance Imaging And Clinical Changes In Patients With Relapsing/Remitting Multiple Sclerosis
Oreja-Guevara C, Charil A, Caputo D, Cavarretta R, Sormani MP, Filippi M
Arch Neurol 2006 May;63(5):736-40
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of Neurology, Via Olgettina 60, 20132 Milan, Italy
Magnetization Transfer (MT) Magnetic Resonance Imaging (MRI) can provide in vivo quantitative estimates of microscopic tissue damage in Normal-Appearing White Matter (NAWM) and Gray Matter (GM) from patients with Multiple Sclerosis (MS).
To determine whether a one-time MT MRI can provide markers of short-term disease evolution in patients with Relapsing/Remitting MS.
Design, Setting, & Patients
Eighteen-month observational study. NeuroImaging Research Unit, Scientific Institute and University Ospedale San Raffaele. Twenty-two patients with untreated Relapsing/Remitting MS.
Main Outcome Measures
Relapse rate; disability according to the Expanded Disability Status Scale (EDSS); dual-echo, 2-dimensional gradient echo with and without a saturation MT pulse and T1-weighted MRIs of the Brain; and MT Ratio (MTR) Histograms for NAWM and GM.
During the study period, 13 patients (59%) experienced 25 relapses. The median EDSS score was 1.25 (range, 0-3.5) at study entry and 1.75 (range, 0-3) at study exit.
Significant, although moderate, correlations were found between average GM MTR values at baseline and EDSS changes during the study period (r = -0.44; P = .04).
A trend was observed for the correlation between NAWM MTR values at baseline and the EDSS changes throughout 18 months (r = -0.42; P = .05).
For the relation between EDSS changes and baseline GM MTR, the slope of the regression line was -0.5 (95% confidence interval, -1.0 to 0.0), indicating that a decrease in the baseline GM MTR of 1% predicted an increase in the EDSS score of 0.5 point throughout the 18 months.
This study indicates that a "snapshot" MT MRI assessment detects subtle Brain tissue changes that are associated with short-term disability accumulation in patients with Relapsing/Remitting MS.