Showing papers by "Alex Rovira published in 2008"

Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis

Abstract: Background: To evaluate whether oligoclonal bands (OB) add information to MRI in predicting both a second attack and development of disability in patients with clinically isolated syndromes (CIS). Methods: From 1995 to 2006, 572 patients with CIS were included in a prospective study. Patients underwent brain MRI and determination of OB within 3 months of first attack. The number and location of lesions and presence of OB were studied. We analyzed time to second attack and to Expanded Disability Status Scale 3.0 according to number of Barkhof criteria (BC) and the presence or absence of OB. Results: We studied 415 (73%) patients with CIS with both baseline MRI and determination of OB. Patients were followed for a mean of 50 months (SD 31). Compared to the reference group with 0 BC at baseline MRI, patients with one to two BC showed a hazard ratio (HR) for conversion to CDMS of 3.8 (2.0 to 7.2) and patients with three to four BC of 8.9 (4.8 to 16.4). Of the total cohort, OB were positive in 61% of the patients. However, broken down by MRI group, OB were positive in 31% of those with no BC; 69% of those with one to two BC; and 85% of those with three or four BC. The presence of OB increased the risk of a second relapse (HR 1.7; 1.1 to −2.7) independently of baseline MRI but did not modify the development of disability. Conclusions: Presence of oligoclonal bands doubles the risk for having a second attack, independently of MRI, but does not seem to influence the development of disability. GLOSSARY: BC = Barkhof criteria; CDMS = clinically definite multiple sclerosis; CIS = clinically isolated syndromes; EDSS = Expanded Disability Status Scale; HR = hazard ratio; MS = multiple sclerosis; OB = oligoclonal bands.

MR imaging findings in hepatic encephalopathy.

Abstract: The term hepatic encephalopathy (HE) includes a spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction. Most cases are associated with cirrhosis and portal hypertension or portal-systemic shunts, but the condition can also be seen in patients with acute liver failure and, rarely, with portal-systemic bypass and no associated intrinsic hepatocellular disease. Although HE is a clinical condition, several neuroimaging techniques, particularly MR imaging, may eventually be useful for the diagnosis because they can identify and measure the consequences of central nervous system (CNS) increase in substances that under normal circumstances, are efficiently metabolized by the liver. Classic MR imaging abnormalities include high signal intensity in the globus pallidum on T1-weighted images, likely a reflection of increased tissue concentrations of manganese, and an elevated glutamine/glutamate peak coupled with decreased myo-inositol and choline signals on proton MR spectroscopy, representing disturbances in cell-volume homeostasis secondary to brain hyperammonemia. Recent data have shown that white matter abnormalities, also related to increased CNS ammonia concentration, can also be detected with several MR imaging techniques such as magnetization transfer ratio measurements, fast fluid-attenuated inversion recovery sequences, and diffusion-weighted images. All these MR imaging abnormalities, which return to normal with restoration of liver function, probably reflect the presence of mild diffuse brain edema, which seems to play an essential role in the pathogenesis of HE. It is likely that MR imaging will be increasingly used to evaluate the mechanisms involved in the pathogenesis of HE and to assess the effects of therapeutic measures focused on correcting brain edema in these patients.

MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics.

Abstract: BACKGROUND AND PURPOSE: Wernicke encephalopathy (WE) is a severe neurologic disorder resulting from dietary vitamin B 1 deficiency This study was undertaken to analyze and compare MR imaging findings and neurologic manifestations at clinical presentations of patients with WE with and without a history of alcohol abuse MATERIALS AND METHODS: WE patients were identified using diagnostic neurologic data bases Fifty-six patients (29 females, 27 males) diagnosed between 1999 and 2008 with WE who improved within 1 month from the onset of thiamine administration were included in the analysis Patients’ records were reviewed for clinical manifestations and imaging studies’ findings MR imaging was performed in the acute phase of the disease at a field strength of 1T (16 patients) and 15T (40 patients) All MR images were of acceptable to good quality and were retrospectively reviewed We compared imaging findings and clinical presentation in the alcoholic (AL) group versus the non-alcoholic (NA) group using the 2-tailed Fisher exact test and the Phi coefficient as appropriate RESULTS: Forty-three percent of the patients were in the AL group, whereas 57% were in the NA group Eighty-nine percent showed changes in consciousness, 75% had ocular manifestations, and 54% had ataxia On MR imaging, 80% of the patients had evidence of symmetric lesions in the medial thalami and in the periventricular region of the third ventricle; 59%, in the periaqueductal area; 45%, in the mamillary bodies; 36%, in the tectal plate; and 7%, in the periventricular gray matter located anteriorly to the fourth ventricle Signal-intensity alterations in areas considered atypical for the disease were noted only in the NA group and always in association with the typical findings Contrast enhancement of the thalamus and mamillary bodies was significantly associated with alcohol abuse CONCLUSIONS: Contrast enhancement in the mamillary bodies and thalamus is a typical finding of the disease in AL patients Atypical MR imaging findings characterize NA patients

Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging†

Abstract: Objective The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis. Methods In this retrospective multicenter study, prospectively collected data from 645 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours ( 100ml; n = 56) DWI lesions. Results In total, 44 (6.8%) patients experienced development of sICH. The sICH rate was significantly different between subgroups: 2.8, 7.8, and 16.1% in patients with small, moderate, and large DWI lesions, respectively (p < 0.05). This translates to a 5.8 (2.8)-fold greater sICH risk for patients with large DWI lesions as compared with patients with small (or moderate) DWI lesions. The results were similar in the large subgroup (n = 536) of patients treated with intravenous tissue plasminogen activator. DWI lesion size remained an independent risk factor when including National Institutes of Health Stroke Scale, age, time to thrombolysis, and leukoariosis in a logistic regression analysis. Interpretation This multicenter study provides estimates of sICH risk in potential candidates for thrombolysis. The sICH risk increases gradually with increasing DWI lesion size, indicating that the potential benefit of therapy needs to be balanced carefully against the risk for sICH, especially in patients with large DWI lesions. Ann Neurol 2007

Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study.

Abstract: Rates of progression vary widely in primary progressive multiple sclerosis. This multicenter study aimed to identify predictors of progression over 10 years. A total of 101 patients who had been imaged at baseline and 2 years were scored on the expanded disability status scale after 10 years. Ordinal logistic regression identified the following independent variables that predicted progression: male sex, shorter disease duration, and slower timed walk test at baseline (best overall predictor), and deterioration in expanded disability status scale score and reduction in brain volume over 2 years. These predictors of long-term disability provide some insight into disease progression.

The basal ganglia: a substrate for fatigue in multiple sclerosis.

Abstract: The origin of fatigue in multiple sclerosis (MS) remains uncertain. However, the use of nonconventional magnetic resonance techniques has increased our understanding of this problem. We aimed to study the relationship between fatigue in MS and the presence of focal dysfunction in the basal ganglia and frontal white matter. Included in the study were 41 patients with relapsing–remitting MS with mild disability and 20 healthy controls. Fatigue was assessed by the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Patients were classified as “fatigued” when they expressed a subjective feeling of fatigue, and the FSS score was ≥5.0 and/or the MFIS score was >38. Patients with no subjective fatigue were classified as “nonfatigued” when the FSS score was <4.0. Proton magnetic resonance spectra were obtained from two different regions: the frontal white matter and the lentiform nucleus. The relationships between fatigue and NAA/Cr, NAA/Cho and Cho/Cr ratios were analysed. A significant decrease in NAA/Cr in the lentiform nucleus region in patients with fatigue was observed. No differences between the groups were found in the frontal white matter. Although confirmatory studies are needed, our results would support the idea that a specific dysfunction or involvement of the basal ganglia might partly contribute to the development of MS-related fatigue.

Will Rogers phenomenon in multiple sclerosis.

Abstract: Objective Using different criteria for classifying patients into various stages of a disease can modify the stage-specific prognosis, even though the overall disease course remains unchanged. This is known as the “Will Rogers phenomenon,” precluding the use of historical controls for treatment trials. We assessed whether the Will Rogers phenomenon may affect multiple sclerosis (MS) prognosis when applying different diagnostic criteria. Methods Patients with a clinically isolated syndrome (CIS) suggestive of MS were studied. After 1 year, each patient was classified as CIS or evolved to MS according to two diagnostic criteria (Poser and McDonald). The outcome for prognosis was the time to reach an Expanded Disability Status Scale score ≥ 3.0. Results 309 patients were studied for a median period of 84 months. After 1 year, 16% of patients had MS according to Poser and 44% according to McDonald criteria. The probability to reach Expanded Disability Status Scale score ≥ 3.0 at median follow-up was 11% in CIS patients according to Poser and 7% according to McDonald criteria; it was 46% in MS patients according to Poser and 27% acccording to McDonald criteria. The group with a discordant diagnosis had a worse prognosis than that of CIS patients according to both criteria (p = 0.01), but better than that of MS patients according to both criteria (p = 0.01). Interpretation The use of different diagnostic criteria may generate spurious improvements in the medium-term prognosis of MS. This calls for caution in using historical controls for MS trials. Ann Neurol 2008

Progression of Symptomatic Intracranial Large Artery Atherosclerosis Is Associated With a Proinflammatory State and Impaired Fibrinolysis

Abstract: Background and Purpose— The molecular pathways involved in the progression of intracranial large artery atherosclerosis (ILA) are largely unknown. Our objective was to prospectively study the relationship between circulating levels of inflammatory markers and fibrinolysis inhibitors, and the risk of progression of symptomatic ILA. Methods— Seventy-five consecutive patients with first-ever symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13, plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3 months after the qualifying stroke or transient ischemic attack. Thereafter, patients underwent long-term transcranial Doppler follow-up to detect progression of ILA. Results— During a median follow-up time of 23 months, 25 (33%) patients showed ILA progression. Multivariable adjusted Cox regression models and Kaplan...

A three-year, multi-parametric MRI study in patients at presentation with CIS

Abstract: To define the extent of overall brain damage in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to identify non-conventional magnetic resonance (MR) metrics predictive of evolution to definite MS. Brain conventional and magnetization transfer (MT) MRI scans were obtained from 208 CIS patients and 55 matched healthy controls, recruited in four centres. Patients were assessed clinically at the time of MRI acquisition and after a median period of 3.1 years from disease onset. The following measures were derived: T2, T1 and gadolinium (Gd)- enhancing lesion volumes (LV), normalized brain volume (NBV), MTR histogram-derived quantities of the normal-appearing white matter (NAWM) and grey matter (GM). During the follow-up, 43 % of the patients converted to definite MS. At baseline, a significant inter-centre heterogeneity was detected for T2 LV (p = 0.003), T1 LV (p = 0.006), NBV (p < 0.001) and MTR histogram-derived metrics (p < 0.001). Pooled average MTR values differed between CIS patients and controls for NAWM (p = 0.003) and GM (p = 0.01). Gdactivity and positivity of International Panel (IP) criteria for disease dissemination in space (DIS), but not NAWM and GM MTR and NBV, were associated with evolution to definite MS. The final multivariable model retained only MRI IP criteria for DIS (p = 0.05; HR = 1.66, 95 % CI = 1.00–2.77) as an independent predictor of evolution to definite MS. Although irreversible tissue injury is present from the earliest clinical stages of MS, macroscopic focal lesions but not "diffuse" brain damage measured by MTR are associated to an increased risk of subsequent development of definite MS in CIS patients.

MRI findings in aphasic status epilepticus.

Abstract: Ictal-MRI studies including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and MR-angiography (MRA) in patients with aphasic status epilepticus (ASE) are lacking. In this report, we aim to describe the consequences of the ASE on DWIs and its impact on cerebral circulation. We retrospectively studied eight patients with ASE confirmed by ictal-EEG, who underwent ictal-MRI shortly after well-documented onset (mean time delay 3 h). ASE consisted in fluctuating aphasia, mostly associated with other subtle contralateral neurological signs such as hemiparesia, hemianopia, or slight clonic jerks. In MRI, six patients showed cortical temporoparietal hyperintensity in DWI and four of them had also ipsilateral pulvinar lesions. Five patients showed close spatial hyperperfusion areas matching the DWI lesions and an enhanced blow flow in the middle cerebral artery. Parenchymal lesions and hemodynamic abnormalities were not associated with seizure duration or severity in any case. The resolution of DWI lesions at follow-up MRI depended on the length of the MRIs interval. In patients with ASE, lesions on DWI in the temporo-parietal cortex and pulvinar nucleus combined with local hyperperfusion can be observed, even when they appear distant from the epileptic focus or the language areas.

Lack of Evidence for Arterial Ischemia in Transient Global Amnesia

Abstract: Background and Purpose— Lesions in diffusion-weighted imaging (DWI-L) have been commonly described in transient global amnesia (TGA). We investigated a possible relationship between brain ischemia and TGA. Methods— Twenty-eight patients underwent transcranial and carotid Doppler ultrasonography (including microembolus detection) and MRI within 24 hours of TGA onset (including DWI, perfusion-weighted imaging and angio-MRI). MRI was repeated at 48 to 96 hours (21 patients) and 30 days (18 patients). Results— Punctate DWI-L were observed in 16 patients (57%) and were not attributable to perfusion abnormalities, arterial stenoses or underlying cardioembolic disease. MRIs performed between 12 and 72 hours showed the highest frequency of DWI-L (88%; P<0.001). No pathological findings were observed at 30 days. Conclusions— These results suggest that TGA is not related to cerebral arterial ischemia.

Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis.

Abstract: Although the mechanisms underlying the accumulation of disability in primary progressive (PP) multiple sclerosis (MS) are still unclear, a major role seems to be played by 'occult' tissue damage. We investigated whether conventional and magnetization transfer (MT) MRI may provide complementary information for the assessment of PPMS severity. Conventional and MT MRI scans from 226 PPMS patients and 84 healthy controls were collected for centralized analysis. The expanded disability status scale (EDSS) score was rated at the time of MRI acquisition. T2 lesion volume, normalized brain volume (NBV) and cervical cord cross-sectional area (CSA) were measured. Magnetization transfer ratio (MTR) histograms from whole brain tissue, normal-appearing white matter and grey matter (NAGM) were also obtained. Mean NBV, CSA and MTR histogram-derived metrics showed significant inter-centre heterogeneity. After correcting for the acquisition centre, pooled average MTR and histogram peak height values were different between PPMS patients and controls for all tissue classes (P-values between 0.03 and 0.0001). More severe brain and cord atrophy and MT MRI-detectable NAGM damage were found in patients who required walking aids than in those who did not (P-values: 0.03, 0.001 and 0.016). A composite score of NBV, CSA, whole brain and NAGM MTR histogram peak height z-scores was correlated with patients' EDSS (r = 0.37, P 0.001). Magnetization transfer MRI might provide information complementary to that given by conventional MRI when assessing PPMS severity. Sequence-related variability of measurements makes the standardization of MT MRI acquisition essential for the design of multicentre studies.

Very early scans for demonstrating dissemination in time in multiple sclerosis.

Abstract: ObjectiveTo evaluate the clinical significance of the 2005 modified imaging criteria for dissemination in time in multiple sclerosis stating that detection of a new T2 lesion appearing at any time compared with a reference scan done at least 30 days after the onset of a clinically isolated syndrome implies dissemination in time.MethodsWe included consecutive patients younger than 50 years examined at our center within 3 months of a clinical syndrome suggestive of central nervous system demyelination of the type seen in multiple sclerosis and followed for at least 3 years. We classified patients into one of two groups, according to the timing when reference scan was performed: less than 30 days and at least 30 days after symptom onset. We analyzed the interaction in time to relapse between timing of reference scan and new T2 lesion effect.ResultsA total of 218 patients were included. The hazard ratio (95% confidence interval) of this interaction was 0.90 (0.31–2.62) (or 1.02 (0.27–3.91) in patients with di...