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J Sastre-Garriga

Publications and source records attributed to J Sastre-Garriga.

At least 19 recordsLinked to original sources
PubMed2006

Baseline MRI predicts future attacks and disability in clinically isolated syndromes.

OBJECTIVE: To determine the relation between baseline MRI and both conversion to multiple sclerosis (MS) and development of disability in a cohort of patients with clinically isolated syndromes (CIS). METHODS: From 1995 to 1998, 175 consecutive patients with CIS underwent brain MRI within 3 months of their first attack and again 12 months and 5 years later. We studied the number and location of lesions at baseline and development of new T2 lesions. We also analyzed conversion to MS and development of disability (Expanded Disability Status Scale [EDSS] > or = 3.0). RESULTS: We included 156 patients with CIS followed for a median of 7 years. Compared to the reference group with 0 Barkhof criteria at baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low, medium, and high conversion risk. EDSS at year 5 correlated with baseline number of Barkhof criteria (r = 0.46, p < 0.0001). When categorizing by number of baseline lesions, similar results were seen. Patients with a baseline MRI with three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for reaching EDSS > or = 3.0. Only 10% of the latter had disability at year 5, but 40% reached this at 8 years. CONCLUSIONS: Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.

Adult↗
PubMed2006

Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis.

BACKGROUND AND OBJECTIVE: The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. METHODS: Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. RESULTS: Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. CONCLUSION: Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.

Adult↗
PubMed2006

Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study.

BACKGROUND: Patients with primary progressive multiple sclerosis (PPMS) often develop severe disability despite low levels of abnormality on conventional magnetic resonance imaging (MRI). This may relate to diffuse pathological processes occurring in normal appearing brain tissue (NABT) involving both white matter (NAWM) and grey matter (NAGM). Magnetisation transfer imaging (MTI) is capable of identifying these processes and may be particularly informative when applied to patients with early PPMS. AIM: To assess the relationship between abnormalities in NABT identified by MTI and disability and other radiological data in patients with early PPMS. METHODS: We studied 43 patients within 5 years of disease onset and 43 controls. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) were scored. Magnetisation transfer ratios (MTR) of NABT, NAWM, and NAGM were calculated and the following MTR parameters were measured: mean, peak height, peak location, and MTR value at the 25th, 50th, and 75th percentiles. Proton density, T2, T1, and gadolinium enhancing lesion loads were also calculated. RESULTS: Differences were found between patients and controls in mean, peak height, and peak location of NAWM and NAGM (p < or = 0.001). Weak to moderate correlations were found between MTR parameters and disability in both NAWM and NAGM. Strong correlations between MTR parameters and lesion loads were found, particularly in NAWM. CONCLUSION: MTR abnormalities are seen in NAWM and NAGM in early PPMS and both are associated with disability. NAWM MTR abnormalities are more closely related to conventional MRI measures than those seen in NAGM.

Adult↗
PubMed2006

Variations in chemokine receptor and cytokine expression during pregnancy in multiple sclerosis patients.

Although several T cell-mediated autoimmune diseases have shown a reduction in their clinical disease activity during pregnancy, the underlying mechanisms by which pregnancy causes such a beneficial effect on the disease activity are not fully understood. We performed a longitudinal study of chemokine receptors (CCR3, CCR4, CCRS, CXCR3, CXCR4) by flow cytometry in different subsets of peripheral blood mononuclear cells (PBMC) during pregnancy in multiple sclerosis (MS) patients. The levels of cytokine mRNA expression (IL-10, IFN-gamma) were also investigated by real-time quantitative reverse transcription polymerase chain reaction. The expression of CXCR3 by CD4 and CD8 positive T cells was decreased to a statistically significant extent during the second trimester of pregnancy. CD4 and CD8 T cells showed a statistically significant increase in the expression of CXCR4 during the third trimester of pregnancy. At the mRNA expression level, an increase in the IL-10/IFN-gamma ratio was observed during pregnancy, especially during the third trimester. These findings indicate immunomodulatory effects of pregnancy on the expression of chemokine receptors and cytokines, which may be related to changes in the clinical disease activity of T cell-mediated autoimmune diseases, such as MS.

Adult↗
PubMed2005

Metabolite changes in early relapsing-remitting multiple sclerosis. A two year follow-up study.

Previous in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by (1)H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent (1)H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7%, p = 0.003), as well as in the CGM (-8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial (1)H-MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.

Adult↗
PubMed2005

Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data.

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.

Atrophy↗
PubMed2005

Gray and white matter volume changes in early RRMS: a 2-year longitudinal study.

BACKGROUND: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray matter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. OBJECTIVES: To characterize the evolution of GM and WM volumes over 2 years, and their associations with lesion loads in a cohort of patients with clinically early RRMS. METHODS: Twenty-one patients with RRMS (mean age 37.5 years, mean disease duration from symptom onset 2.1 years) and 10 healthy control subjects (mean age 37.1 years) were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1- and 2-year follow-up. Brain parenchymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated. In subjects with MS, brain lesion loads were determined on conventional T2-weighted along with pre- and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. RESULTS: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1% vs -1.0%, p = 0.044), while no change was seen in WMF over the same period (mean -0.09% vs +0.09%, p = 0.812). However, when the MS cohort was divided in half, dependent upon change in Gd-enhancing lesion load over 2 years (n = 20), a decrease in WMF was seen in the group (n = 10) with the largest decline in Gd volume, whereas WMF increased in the other half (n = 10) concurrent with a net increase in volume of Gd-enhancing lesions (difference between groups: p = 0.034). CONCLUSIONS: Increasing gray matter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM lesions appear to be related to volume changes in WM over this time period.

Adult↗
PubMed2005

Metabolite changes in normal-appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis.

BACKGROUND: Abnormalities in normal-appearing brain tissues may contribute to disability in primary progressive multiple sclerosis (PPMS), where few lesions are seen on conventional imaging. OBJECTIVES: To evaluate the mechanisms underlying disease progression in the early phase of PPMS by measuring metabolite concentrations in normal-appearing white matter (NAWM) and cortical gray matter (CGM) and to assess their relationship with clinical outcomes. DESIGN: Case-control study. SETTING: Tertiary referral hospital. Patients Forty-three consecutive patients within 5 years of onset of PPMS and 44 healthy control subjects. MAIN OUTCOME MEASURES: Concentrations of choline-containing compounds, phosphocreatine, myo-inositol, total N-acetyl-aspartate (tNAA), and glutamate-glutamine were estimated using proton magnetic resonance spectroscopic imaging. Brain parenchymal, white matter and gray matter fractions and proton density and gadolinium-enhancing lesion loads were calculated. The Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores were recorded. RESULTS: In CGM, concentrations of the tNAA (P<.001) and glutamate-glutamine (P = .005) were lower in patients with PPMS than in controls. In NAWM, myo-inositol levels were higher (P = .002) and tNAA levels were lower (P = .005) in patients with PPMS than in controls. The Expanded Disability Status Scale score correlated with the tNAA concentration in CGM (r = -0.44; P = .03) and with myo-inositol (r = 0.41; P = .01) and glutamate-glutamine concentrations (r = 0.41; P = .01) in NAWM. Proton density lesion load correlated negatively with CGM tNAA concentration and positively with NAWM myo-inositol concentration. CONCLUSION: Metabolite changes, which differ in CGM and NAWM, occur in early PPMS and are linked with disability.

Adult↗
PubMed2005

Is inflammation important in early PPMS? a longitudinal MRI study.

BACKGROUND: Magnetic resonance imaging (MRI) studies in primary progressive multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with relapsing-remitting multiple sclerosis (RRMS), and it has been suggested that there may be a less important role for inflammation in its pathogenesis. However, the earliest clinical stages of PPMS have not been studied and thus it has not been possible to exclude the existence of an early inflammatory phase. OBJECTIVE: To study the presence, characteristics, and implications of inflammation in early PPMS. METHODS: 45 patients with a mean disease duration of 3.3 years had triple dose Gd enhanced MRI, expanded disability status scale (EDSS), and multiple sclerosis functional composite (MSFC) assessments at baseline. Repeat MRI was done at 1 and 2 months in 24 patients, and at 6 months in 38. RESULTS: Enhancing brain lesions were present in 42% of patients at baseline but enhancing cord lesions were uncommon (7%); 85% of enhancing lesions enhanced for one month or less. Patients with enhancing lesions had greater disability (EDSS, p = 0.027; MSFC, p = 0.026) and more MRI abnormalities (greater T2 load, p = 0.008; greater T1 hypointensity load, p = 0.001; and reduced partial brain volume, p = 0.012) than those without enhancement. Enhancement at 6 months was seen in 32% of patients and was restricted to a subset of patients who enhanced at baseline. CONCLUSIONS: Enhancement is present in some cases of early PPMS and is associated with greater disease impact in terms of both clinical and MRI measures.

Adult↗
PubMed2005

[Neurorehabilitation in multiple sclerosis].

Neurorehabilitation is predominantly an educational, dynamic process based on the adaptation of the individual and his environment to the actual neurological impairment and focuses on decreasing the impact of disabling neurological conditions on the individual in order to achieve optimum quality of life. It has been suggested by some that neurorehabilitation is the only approach available to us which can improve the limitations in activity and restrictions in social participation of people with multiple sclerosis. The neurorehabilitation approach is a holistic one and is a fundamental part of neurological care; it should not be forgotten by neurologists, especially when dealing with people with chronic disabling conditions such as multiple sclerosis. Together with the social model of disability, the concept of restorative neurology, as a scientific and therapeutic attempt to minimize those impairments directly responsible for the disability presented by the person, is recently gaining ground among neuroscientists and clinicians. In this review the conceptual basis for neurorehabilitation will be presented together with a review of the literature concerning the biological aspects of neurorehabilitative therapy (neuroplasticity) and the clinical trials evaluating the effectiveness of neurorehabilitation in people with multiple sclerosis. Finally, we will consider the practical aspects of neurorehabilitation.

Adaptation, Psychological↗
PubMed2004

Decreased MMP-9 production in primary progressive multiple sclerosis patients.

BACKGROUND: An increase in MMP-9 levels has been found in relapsing-remitting (RR) multiple sclerosis (MS) showing correlation with magnetic resonance (MR) parameters mainly during relapses. However, data regarding primary progressive (PP) MS is scarce. OBJECTIVES: To determine both the pro and active forms of MMP-9 in PPMS and transitional progressive (TP) MS, RRMS and healthy controls (HC), and to assess the relationship between MMP-9 levels and clinical and radiological variables in PP/TPMS. METHODS: 73 patients with PP/TPMS, 50 RRMS and 43 HC were studied. Levels of pro and active forms of MMP-9 in serum were measured with ELISA. EDSS and MSFC scores were recorded and T2- and T1-weighted MR scans were obtained at the time of blood sampling and one and two years later for PP/TP MS cases. RESULTS: MMP-9 levels were 202.27 ng/ml for PP/TPMS, 242.20 ng/ml for RRMS and 274.49 ng/ml for HC. MMP-9 levels were significantly lower in PP/TPMS compared to RRMS (P= 0.026) and HC (P= 0.001). No significant correlations were found between MMP-9 levels and clinical scores or radiological parameters. CONCLUSIONS: These results point to different regulatory mechanisms of MMP-9 production and/or activity between PP/TPMS and RRMS.

Adult↗
PubMed2003

New diagnostic criteria for multiple sclerosis: application in first demyelinating episode.

BACKGROUND: Recently developed diagnostic criteria for MS (McDonald criteria) indicate that in patients with a single demyelinating episode (clinically isolated syndromes [CIS]), evidence for dissemination in space and time, essential for diagnosis, may be provided by MRI. OBJECTIVE: To assess the usefulness of these new criteria in patients with CIS suggestive of MS. METHODS: A total of 139 patients with CIS followed for a median of 3 years underwent brain MRI within 3 months of their first attack and again 12 months later. The number and location of lesions at baseline, the development of new lesions at follow-up, and the results of CSF examination (which, if positive, requires fewer MR abnormalities for diagnosis) were analyzed. The new McDonald criteria (incorporating MRI) were compared to the existing Poser diagnostic criteria and their accuracy was evaluated. RESULTS: At 12 months, 11% had clinically definite MS according to the Poser criteria compared to 37% with the McDonald criteria. Eighty percent of patients fulfilling these new criteria developed a second clinical episode within a mean follow-up of 49 months. The new criteria showed a sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to clinically definite MS. CONCLUSION: One year after symptom onset, more than three times as many patients with CIS were diagnosed with MS using new diagnostic criteria incorporating MRI results compared to older criteria. However, the proposed MRI criteria require further prospective studies to optimize sensitivity and specificity.

Adolescent↗
PubMed2003

APS and the brain.

Antiphospholipid antibody syndrome (APS) may present with neurological syndromes. Cerebrovascular disease, chorea/ballismus, epileptic seizures, headache, cognitive impairment, transverse myelopathy, Devic's syndrome and multiple sclerosis-like presentations feature among others. Cerebrovascular disease is one of the most common presenting symptoms of APS, second only to deep vein thrombosis, and accounts for half of neurological manifestations in patients with APS; accelerated atherogenesis and cardioembolism are the most likely mechanisms implicated. Though infrequent, chorea is consistently associated with APS; the pathogenetic role of antiphospholipid antibodies (APLab) in this case might be routed through cerebrovascular disease in some cases and through purely immunological pathways in others. Both ischemic and immunological mechanisms have been demonstrated in the pathogenesis of epileptic seizures, which may account for 7% of neurological manifestations in APS. Although frequent in APS, a causative link between APLab and most common types of headache (migraine and tension-type headache) is more than dubious. Cognitive impairment may derive from a well-defined clinical tableau of multi-infarct dementia. Nevertheless, (highly frequent) less severe cognitive impairment has also been associated with the presence of APLab in the absence of magnetic resonance findings. A relationship between APS and transverse myelopathy seems likely but small numbers in the studies published to date preclude definite statements; routinely testing for APLab patients with neurological manifestations suggestive of multiple sclerosis seems to be unrecommended at the present time.

Antibodies, Antiphospholipid↗
PubMed2003

Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging, cerebrospinal fluid and neurophysiological findings.

BACKGROUND AND AIM: Conversion to multiple sclerosis (MS) after optic neuritis and myelitis has been thoroughly studied; however, limited data are available regarding conversion to MS after a clinically isolated syndrome of the brainstem (CISB). The aim of this study was to investigate conversion to MS in patients with CISB. METHODS: Fifty-one patients with CISB were prospectively studied. Cranial magnetic resonance imaging (MRI), determination of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and evoked potentials (EPs) were performed. Based on conversion to MS at follow-up, the sensitivity, specificity, accuracy and positive and negative predictive values of these tests were calculated. RESULTS: Clinically definite MS developed in 18 (35%) patients after a mean follow-up of 37 months. Paty's MRI criteria showed a sensitivity of 89%, a specificity of 52% and an accuracy of 65%; Fazekas' criteria showed a sensitivity of 89%, a specificity of 48% and an accuracy of 63%; Barkhof's criteria showed a sensitivity of 78%, a specificity of 61% and an accuracy of 67%. The presence of OBs in the CSF showed a sensitivity of 100%, a specificity of 42% and an accuracy of 63%. No differences for neurophysiological parameters were found between patients who did and those who did not convert to MS. CONCLUSION: Fulfilling Paty's, Fazekas' or Barkhof's MRI criteria and the presence of OBs in the CSF are associated with a higher risk of conversion to MS in patients with CISB. Determination of OBs in the CSF has the greatest sensitivity of all tests. Barkhof's MRI criteria have greater specificity (although less than previously published for mixed cohorts of clinically isolated syndromes) in predicting conversion to MS for CISB than either Paty's or Fazekas' criteria.

Adolescent↗
PubMed2003

Myelopathy in seronegative Sjögren syndrome and/or primary progressive multiple sclerosis.

OBJECTIVE: The relationship between multiple sclerosis (MS) and Sjögren syndrome (SS) is controversial. Nine patients, previously diagnosed with primary progressive MS (PPMS) and who fulfilled the diagnostic criteria for SS, are described. METHODS: The European classification criteria for SS were used to study nine PPMS patients that complained of sicca complex symptoms. The following tests were performed: Schirmer test, rose bengal staining, salivary scintigraphy, minor salivary gland biopsy and serologic tests (antibodies Ro/SS-A, La/SS-B and antinuclear antibodies). RESULTS: The nine patients met criteria to be diagnosed with SS (at least four criteria). All patients were women with a mean age of 46.6 years at symptom onset. Spastic paraparesis was the presenting symptom in all patients, and spinal cord magnetic resonance imaging (MRI) showed abnormalities in most; anti-Ro and anti-La antibodies were mostly negative. CONCLUSIONS: Some MS patients, predominantly women over 45 years of age, with progressive spastic paraparesis, antiextractable nuclear antigen antibodies (Ro/SS-A or La/SS-B) negative and with abnormalities in spinal cord MRI, may have SS as an additional or alternative diagnosis.

Adult↗
PubMed2002

[Descriptive study of first visits in a multiple sclerosis specialised unit].

BACKGROUND: The need for optimal care has led to implementation of multiple sclerosis care units, specialised in diagnosis and follow-up of multiple sclerosis patients. Since information on multiple sclerosis prognosis is crucial, accurate diagnosis is one of their major roles. METHOD: Prospective analysis of first visits during a year (origin and diagnosis) at the Unidad de Neuroinmunología Clínica of Hospital Vall d'Hebron. RESULTS: A total of 437 first visits were analysed; a moderate agreement (kappa = 0.468) between referral diagnoses and diagnosis at follow-up was obtained; agreement was very good (kappa = 0.844) between diagnosis at first visit and diagnosis at follow-up. In the subgroup of 200 patients with a demyelinating disease on follow-up after one year, 37.6% of referrals came from other non-specialised centers and 40.6% from our own center. CONCLUSION: Specialised care units enhance diagnostic precision; direct influence zone and non-specialised centers referrals are their more important sources of patients.

Adolescent↗