Locatelli L, Zivadinov R, Grop A, Zorzon M
Mult Scler 2004 Oct;10(5):562-8
University of Trieste, Department of Clinical Medicine and Neurology, Trieste, Italy
The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of Whole and Regional Brain Atrophy correlate better with tests assessing the Cognitive Function than the absolute Brain Atrophy measures.
The NeuroPsychological performances and disability have been assessed in 39 patients with Relapsing/Remitting Multiple Sclerosis (MS).
T1- and T2-lesion load (LL) of total Brain and Frontal Lobes (
The Whole Brain Volume and the Regional Brain Parenchymal Volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes.
Normalized measures of Brain Atrophy, i.e., Brain Parenchymal Fraction (BPF) and Regional Brain Parenchymal Fraction (RBPF) of FLs, were calculated.
The scan-rescan, inter- and intrarater Coefficient Of Variation (COV) and Intraclass Correlation Coefficient (ICC) have been estimated.
The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability.
The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with NeuroPsychological functioning, disability and quantitative MRI lesion measures than RBPV.
These differences were statistically significant: P < 0.001 for Stroop Color Word Interference test, P < 0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P < 0.001 for T1-LL of FLs.
BPF demonstrated significant correlations with tests assessing Cognitive functions, whereas BPAV did not.
The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized Brain Atrophy measures were associated with tests exploring the Cognitive Functions.
These data suggest that RBPF is a reproducible and sensitive method for measuring Frontal Parenchymal Atrophy.
The normalized measures of whole and Regional Brain Parenchymal Atrophy should be preferred to absolute measures in future studies that correlate NeuroPsychological performances and Brain Atrophy measures in patients with MS.
Ghezzi A, Bergamaschi R, Martinelli V, Trojano M, Tola MR, Merelli E, Mancardi L, Gallo P, Filippi M, Zaffaroni M, Comi G; Italian Devic's Study Group (IDESG)
J Neurol 2004 Jan;251(1):47-52
Centro Studi Sclerosi Multipla-Ospedale di Gallarate, Via Pastori 4, 21013 Gallarate, Italy
To evaluate the clinical characteristics, course and prognosis of Devic's NeuroMyelitis Optica (DNO), to evaluate the prognostic role of demographic and clinical features, to evaluate the current DNO diagnostic criteria.
Demographic, clinical, CSF and MRI data of patients affected by DNO were collected from fifteen Italian MS Centres.
Inclusion criteria were:
- Two or more acute episodes of Neurological dysfunction indicating involvement of the Optic Nerve and Spinal Cord, in a simultaneous or subsequent temporal relationship
- No evidence of lesions beyond the Optic Nerve or the Spinal Cord
- Brain MRI at onset negative or non-specific for Multiple Sclerosis (MS) (White Matter lesions < or = 2)
- Disability was scored by means of Kurtzke's Expanded Disability Status Scale (EDSS)
46 patients with Relapsing DNO were included, 37 females and 9 males, with mean age at onset of 40.1 +/- 16.3 years (range 12-77 years).
The follow up duration was 8.8 +/- 3.5 years, the mean annualized relapse rate was 1.3 +/- 1.2.
After 5, 10 and 15 years EDSS 3.0 was reached respectively by 65%, 82 % and 86% of cases, EDSS 6.0 respectively by 42%, 53 % and 69% of cases, EDSS 10 respectively by 8%, 12% and 23% of cases.
The probability of reaching EDSS 3 was statistically correlated with age at onset, interval between the first and 2 nd attack, and relapse rate.
The probability of reaching EDSS 6.0 was correlated with the residual EDSS at onset and to relapse rate. During the follow up, Brain White Matter lesions appeared in 8 subjects.
Spinal Cord MRI showed lesions extending across 3 or more segments in 39 subjects, only 1 lesion involving 1 segment in 4 subjects, and was normal in 3 subjects.
One or more CSF abnormalities were found at least once in 29/44 patients (65.9 %), the most frequent findings being PleoCytosis (38.6 %), OligoClonal Bands (34.1 %), high protein level (25 %), and high Albumin ratio (20.5 %).
DNO has a poor prognosis in most cases. Compared with MS, DNO patients have a higher age at onset, females are more frequently affected, the course is more severe.
Brain and Spinal Cord MRI permit the differentiation of DNO from MS. CSF supports the probability of DNO if it shows increased cells and proteins.
Determination Of Ventricular Diameters In Multiple Sclerosis Patients With TransCranial Sonography (TCS) - A Two Year Follow-Up Study
Kallmann BA, Sauer J, Schliesser M, Warmuth-Metz M, Flachenecker P, Becker Dagger G, Rieckmann P, Maurer M
J Neurol 2004 Jan;251(1):30-4
University of Wurzburg, Department of Neurology, Josef-Schneider-Strasse 11, 97080 Wurzburg, Germany
Brain Atrophy is an indicator of Diffuse Brain Pathology that appears even in the early stages of Multiple Sclerosis (MS).
Magnetic Resonance Imaging (MRI) techniques used in clinical trials suggest a correlation between Ventricular enlargement and Axonal pathology and clinical disability in MS.
To evaluate by TransCranial Sonography (TCS) and MRI Ventricular Diameters in order to assess prospectively the development of Brain Atrophy in MS.
Setting, Patients And Methods
MS outpatient clinic of a University Hospital. 38 MS patients (27 females, 11 males) were followed up for 2 years.
Ventricular Diameters (Third Ventricle, Right and Left Lateral Ventricle) were determined by TCS at baseline, 12 and 24 months.
And correlated with clinical disability (Expanded Disability Status Scale, [EDSS]), and the Multiple Sclerosis Functional Composite Score (MSFC). MRI was performed at study entry and after two years.
Main Outcome Measure
Correlation of Ventricular Diameters measured by TCS and MRI with assessment of clinical disability in MS patients at baseline and after two years.
TCS and MRI measurements especially of Third Ventricle Diameter matched closely at study entry and after two years (r = 0.9; p < 0.0001).
At all time points the width of the Third Ventricle was significantly correlated with clinical disability (EDSS: r = 0.6, p < 0.01; MSFC: r = -0.6, p < 0.02).
In the follow-up over 2 years there was an increase of the width of the Third Ventricle in comparison with study entry (p < 0.002).
Increase of Third Ventricle Width at study entry was associated with higher EDSS levels after 2 years (p = 0.01).
Assessment of Ventricular Diameters by TCS is a reliable tool with which to monitor Brain Atrophy in the longitudinal follow-up of MS patients.
Because TCS is a simple, inexpensive, non-invasive and generally available bedside-test it may be used in clinical practice as well as in therapeutic trials to assess Brain Atrophy.
Benedict RH, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R
Arch Neurol 2004 Feb;61(2):226-30
Buffalo General Hospital, & State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Department of Neurology, NY 14203, USA
Cognition and Magnetic Resonance Imaging correlations are well established in patients with Multiple Sclerosis (MS), but it is unclear whether lesion burden or Atrophy accounts for most of the predictive variance. These indices have been directly compared in only a few studies.
No such study included measurement of the Third Ventricle, which was strongly predictive of NeuroPsychological competence in the early literature. Furthermore, few studies accounted for the influence of age, premorbid intelligence, or Depression.
To determine if conventional measures of lesion burden or Atrophy predict Cognitive Dysfunction in MS while accounting for age, premorbid intelligence, and Depression.
We studied 37 patients with MS and 27 controls matched according to demographic variables.
Correlations between NeuroPsychological tests and the following Magnetic Resonance Imaging indices were considered: T1 HypoIntense lesion volume, Fluid Attenuated Inversion Recovery, HyperIntense lesion volume, Third Ventricle Width, BiCaudate Ratio, and Brain Parenchymal Fraction.
Regression models predicting NeuroPsychological performance controlled for the effects of age, premorbid intelligence, and Depression. We included only those tests discriminating patients with MS from controls.
In each regression model, Third Ventricle Width was the sole Magnetic Resonance Imaging measure retained.
When this variable was removed from consideration, Brain Parenchymal Fraction was retained in all analyzes.
Brain Atrophy accounts for more variance than lesion burden in predicting Cognitive Impairment in MS, and Central Atrophy in particular is strongly associated with NeuroPsychological morbidity.
This finding may be explained in part by Atrophy of the Thalamus, a deep Gray Matter structure that mediates Cognitive function via Cortical and SubCortical Pathways.
Enthusiasm for the clinical utility of Third Ventricle Width is tempered by modest intraobserver and interobserver reliability.