[show abstract][hide abstract] ABSTRACT: In 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IATM.
Eighty-seven patients diagnosed with IATM between 1989 and 2011 were retrospectively reviewed. Two patients with positive neuromyelitis optica IgG serum antibodies were excluded. Epidemiological, clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85 patients were analyzed.
Eleven (13%) patients converted to MS after a median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of symptoms was related to conversion to MS. Only 9.4% of patients with IATM were unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38-45.00) were associated with a poorer outcome (Rankin >= 2).
At least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.
[show abstract][hide abstract] ABSTRACT: Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy.
Revista de neurologia 04/2013; 56(7):375-90. · 1.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neurosarcoidosis accounts for approximately 5% of cases of sarcoidosis.
To determine the frequency of Neurosarcoidosis in our setting and analyze the clinical-radiological findings and evolution of 30 patients consecutively diagnosed.
The medical records of patients with a diagnosis of Neurosarcoidosis were reviewed, and data regarding the clinical features, ancillary tests performed, treatment, and outcome were recorded. We revised the literature to summarize and discuss the previous clinical series of Neurosarcoidosis.
It accounted for 6.7% of all cases of sarcoidosis. Seven patients had definite diagnosis and 23 had probable diagnosis. The mean age at onset of Neurosarcoidosis was 48.3 years and 66.7% of patients were women. Neurologic clinical features were the first manifestation of Neurosarcoidosis in 70% of cases. Cranial neuropathy was present in 17 patients and 14 of them had facial palsy. The central nervous system was affected in 10 patients and the peripheral nervous system in 5. Chest disease, the most common extraneurologic manifestation, was present in 20 patients. All patients were treated with corticosteroids, and all those with central nervous system involvement had poor outcome.
Neurosarcoidosis requires a high degree of suspicion to establish the diagnosis. Central nervous system involvement is associated with a poor prognosis.
European Journal of Internal Medicine 12/2011; 22(6):e125-32. · 2.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: IntroductionWernicke's encephalopathy (WE) is an underdiagnosed condition, usually associated with alcoholism, and has a worse prognosis if there is a delay in diagnosis. A series of 8 non-alcoholic patients with WE is presented and an assessment is made on whether a delay in diagnosis leads to a worse prognosis.
[show abstract][hide abstract] ABSTRACT: The term rhombencephalitis refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum). Rhombencephalitis has a wide variety of etiologies, some of them potentially severe and life threatening without proper early treatment. In this retrospective observational study, we reviewed the records of consecutively hospitalized patients at University Hospital of Bellvitge (Barcelona, Spain) from January 1990 to December 2008. Rhombencephalitis was defined as a brainstem and/or cerebellar condition demonstrated clinically or by neuroimaging, with pleocytosis (>4 cells/mm) in cerebrospinal fluid. Ninety-seven patients (48 female; mean age, 37 yr; range, 14-79 yr) fulfilled these criteria. We reviewed their clinical, cerebrospinal fluid, and radiologic characteristics. The mean follow-up was 5 years (range, 0-20 yr). The etiologies of rhombencephalitis were as follows: unknown cause (n = 31), multiple sclerosis (n = 28), Behçet disease (n = 10), Listeria monocytogenes infection (n = 9), paraneoplastic syndrome (n = 6) (3 cases associated with anti-Yo antibodies and 3 with anti-Tr antibodies), Epstein-Barr virus (n = 4), tuberculosis (n = 2), pneumococcal infection (n = 2), systemic lupus erythematosus (n = 1), lymphoma (n = 1), Brucella species infection (n = 1), JC virus (n = 1), and relapsing polychondritis (n = 1). Certain clinical, cerebrospinal fluid, and radiologic characteristics that are commonly seen in some of these etiologies can guide us in the first approach to the etiologic diagnosis of rhombencephalitis.
Medicine 06/2011; 90(4):256-61. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Electrodiagnostic studies play a key role in the evaluation of patients with Guillain-Barré syndrome (GBS). However, at early stages patients may not meet current neurophysiologic criteria. We report electrodiagnostic findings for 18 patients with suspected GBS within 4 days of clinical onset. Fifteen patients (83%) showed abnormality in the motor nerve conduction study. Prolonged distal motor latency (DML) was the most frequent demyelinating parameter (seen in 55% of patients). Abnormal late responses were noted in 14 patients (77%). Electrodiagnostic study of cranial nerves was abnormal in eight (44%), and motor nerve conduction velocity was abnormal in only six patients (23%). The study shows a predominant motor neuropathy pattern followed by a sural-sparing pattern; no patients showed a strictly normal electrodiagnostic study. Reduced distal compound muscle action potential and prolonged DML in the demyelinating range were associated with severity of GBS on admission. After the electrodiagnostic study, 5 patients (27%) already fulfilled electrodiagnostic criteria for acute inflammatory demyelinating polyneuropathy (AIDP), 1 (5%) for the axonal variant of GBS, and 13 (72%) were classified as equivocal. We conclude that exhaustive electrodiagnostic studies of patients with suspected GBS in very early stages are useful in the diagnosis and management of the condition.
Journal of the Peripheral Nervous System 06/2011; 16(2):136-42. · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Wernicke's encephalopathy (WE) is an underdiagnosed condition, usually associated with alcoholism, and has a worse prognosis if there is a delay in diagnosis. A series of 8 non-alcoholic patients with WE is presented and an assessment is made on whether a delay in diagnosis leads to a worse prognosis.
The clinical records of patients admitted to 2 university hospitals between 2004 and 2009 with the diagnosis of WE, excluding those with a history of alcoholism, were retrospectively reviewed.
The study included 4 men and 4 women aged 35-82 of whom 7 had a history of gastrointestinal pathology, and persistent vomiting was the precipitating factor in 7. Encephalopathy was the most frequent onset symptom (4). The classical triad was present in seven patients. Thiamine levels were low in 3/6 and normal in 3/6 cases. MRI was abnormal in seven patients, with high signal intensity in the diencephalon and mammillary bodies (7), periaqueductal grey matter (6), cortex (3) and cerebellum (1). Seven improved with thiamine. Sequelae were mild in 6, and severe in 2 after 6-12 months of follow-up. All patients with a diagnostic delay less than 18 days had mild sequelae.
Non-alcoholic WE frequently occurs after gastrointestinal disturbances that could result in lower thiamine absorption. Whereas thiamine levels can be normal in many cases, in almost all cases the MRI shows signal alterations in typical locations. A delay in the diagnosis, and therefore, in treatment leads to a worse prognosis.
[show abstract][hide abstract] ABSTRACT: The HLA-DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA-DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS.
The HLA-DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA-DRB1 allelic frequencies were compared between OCB-positive and OCB-negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA-DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB.
We found 206 OCB-positive and 62 OCB-negative patients. The HLA-DRB1*15 allele in OCB-positive patients had a higher frequency when compared with OCB-negative patients (39.3% in OCB-positive vs. 16.1% in OCB-negative, OR = 1.38 95% CI = 1.18-1.61, P < 0.001). The other alleles did not show differences. When we compared with controls, the HLA-DRB1*15 allele was associated with the disease only in the OCB-positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB.
HLA-DRB1*15 allele is associated with OCB-positive patients with MS when studying a Spanish MS population.
European Journal of Neurology 03/2011; 18(10):1258-62. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The association of HLA-DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA-DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population.
HLA-DRB1 typing was performed by PCR-SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS.
The HLA-DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR)=2.07, 95% CI=1.64-2.60, P<0.001). In the univariate analysis, the DRB1*01 and DRB1*04 alleles were associated with a worse prognosis when considering the time to reach an EDSS of 6, whereas the DRB1*03 was correlated with a better outcome. In the multivariate analysis, the alleles*01 and *04 were demonstrated to be independent factors to have a worse prognosis.
HLA-DRB1*15 is associated with MS when comparing patients with unrelated healthy controls in a Spanish population. The HLA-DRB1*01 and HLA-DRB1*04 alleles are related to a worse prognosis when considering the time taken to reach severe disability.
European Journal of Neurology 02/2011; 18(2):337-42. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: To describe the clinical characteristics and evolution of a series of adult patients hospitalized for neuro-Behçet disease (NBD).
Consecutive patients admitted for NBD in a teaching hospital were retrospectively selected. Disability at discharge and during follow-up was graded with the modified Rankin Scale, and outcome classified as good or poor (grades 3-6).
Twenty patients were included (M/F, 13/7). Mean age at NBD diagnosis was 36.3 years. Nineteen patients had other manifestations of Behçet disease (BD) before NBD developed, but only 7 met the complete diagnostic criteria for BD. Fever, headache, motor weakness, and cranial nerve palsy were each present in approximately 60% of patients. There was a low prevalence of behavioral changes (5%), seizures (5%), and sphincter incontinence (0%), and a relatively high prevalence of meningism (25%). Non-neurologic manifestations of BD were concurrently detected in 15 patients (75%). 80% had parenchymal involvement. Brain biopsies during 5 attacks showed perivascular lymphocytic infiltration with reactive astrocytosis, but no frank vasculitis. During a mean follow-up of 6.3 years per patient, 12 had at least one relapse. In total, there were 22 relapses; all but two were in the same location and were symptomatically similar in each patient. At the end of follow-up, 7 patients (35%) had a poor outcome, including 4 who died.
Recording of previous manifestations of BD and a physical examination to detect concomitant systemic manifestations of BD may help establish an early diagnosis of NBD. Relapses frequently occurred in the same location. No frank vasculitis was present in brain biopsies.
European Journal of Internal Medicine 12/2010; 21(6):536-41. · 2.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: Multiple sclerosis (MS) has been consistently associated with the HLA-DR2 haplotype and particularly with the HLA-DRB1*15 allele. Epistatic interactions between both parental alleles in the DRB1 loci have been shown to modify the MS susceptibility risk. This study investigated the frequencies of various HLA-DRB1 genotypes, their impact on MS susceptibility and their correlation with the clinical severity in a Spanish population.
A genotype was considered as the combination of the two parental DRB1 alleles. We compared the frequencies of the genotypes in a sporadic MS population (n=380) with those of an unrelated healthy control cohort (n=1088). We correlated the different genotypes with the age at onset, gender distribution, symptoms at onset, course of the disease and progression severity by means of the time to reach the progressive phase and EDSS scores of 3 and 6.
We found 81 different genotypes. There were four different MS-predisposing genotypes. Three of them contained the DRB1*15 allele (DRB1*03/15, DRB1*04/15, and DRB1*08/15) and the fourth was homozygote for the DRB1*03 allele. The highest odds ratio was found with the genotype DRB1*08/15 (OR=3.88, 95% CI=1.83-8.26, p<0.01), followed by DRB1*03/03 (OR=3.15, 95% CI=1.93-5.14, p<0.01), DRB1*03/15 (OR=2.72, 95% CI=1.88-3.94, p<0.01) and DRB1*04/15 (OR=2.54, 95% CI=1.64-3.98, p<0.01). The DRB1*01/04 and the DRB1*15/15 genotypes were associated with a shorter time to reach an EDSS score of 6.
Our results show the importance of epistatic interactions among the HLA-DRB1 alleles, modifying the risk for MS as well as its clinical severity.
Journal of the neurological sciences 11/2010; 298(1-2):96-100. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time.
The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method.
Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found.
Anticipation of age at onset is undetectable when adjusted for follow-up time.