NFL during acute spinal cord lesions in MS: a hurdle for the detection of inflammatory activity.

INTRODUCTION: Levels of neuro-filament light chain (NFL) correlate with clinical and radiological activity in multiple sclerosis (MS) and have been used as a surrogate biomarker of axonal destruction related to inflammatory activity. The main objective of this work is to explore the specific contribution of acute inflammation within the spinal cord to the elevation of NFL levels. PATIENTS AND METHODS: MS patients with a baseline study of NFL at diagnosis of the disease and a brain and spinal cord MRI scan were selected. Patients were classified according to the presence, number and location of gadolinium enhancing lesion (GEL) and the relationship between NFL levels and both brain and spinal cord GEL were explored. RESULTS: Seventy-seven patients were selected. NFL levels were significantly higher in patients with only one GEL restricted to the brain than those without GEL (1702 pg/ml vs 722.7 pg/mL, p = 0.03) and correlated with number. However, no differences were seen among patients with GEL limited to the spinal cord and those without GEL (735.2 pg/ml vs 722.7 pg/mL). CONCLUSION: Our study reaffirms the value of NFL levels in monitoring asymptomatic inflammatory activity in the brain measured by GEL. However, NFL concentration is not as useful when only inflammatory activity occurs in the spinal cord.

[Prevalence of Neisseria gonorrhoeae, amongst inmates of the Preventive Reclusion Center in Arica]. / Prevalencia de Neisseria gonorrhoeae, en reclusos del Centro de Detención Preventiva de Arica.

BACKGROUND: Sex workers, people with drug addiction, early onset of sexual activity population, and criminal population, are considered the groups most at risk of contracting sexually transmitted infections (STIs). AIM: To determine the prevalence of infection by Neisseria gonorrhoeae in inmates of the Preventive Detention Center (CDP) at Arica and Parinacota Region, Chile. The Scientific Ethical Committee of Universidad de Tarapacá approved this study. METHOD: 140 inmates participated, who voluntarily agreed to be part of the study and signed an informed consent. A sample of urethral meatus was taken to investigate N. gonorrhoeae, and an epidemiological survey was applied, which included age, drug use, overcrowding, among others. RESULTS: The prevalence of the agent was 16.4% in inmates of the Arica CDP, a result lower than that reported in other similar studies. CONCLUSION: Knowing the reality of the prevalence of this STI and some risk factors associated with the situation of deprivation of freedom in a tri-border area of northern Chile, contributes to the proposals for prevention programs in this vulnerable and at-risk population.

Prevalencia de Neisseria gonorrhoeae, en reclusos del Centro de Detención Preventiva de Arica / Prevalence of Neisseria gonorrhoeae, amongst inmates of the Preventive Reclusion Center in Arica

Resumen Introducción: Los/as trabajadores/as sexuales, personas con adicción a drogas, población de inicio sexual precoz y población penal son considerados los grupos de mayor riesgo de contraer infecciones de transmisión sexual (ITS). Objetivo: Determinar prevalencia de infección por Neisseria gonorrhoeae, en reclusos del Centro de Detención Preventiva (CDP) de la Región de Arica y Parinacota, Chile. Este estudio contó con la aprobación del Cómité Ético Científico de la Universidad de Tarapacá. Material y Método: Participaron 140 reclusos, que aceptaron ser parte del estudio en forma voluntaria y firmaron un consentimiento informado. Se tomó una muestra del meato uretral para pesquisa de N. gonorrhoeae y se aplicó una encuesta epidemiológica que consignó edad, consumo de drogas, hacinamiento, entre otros. Resultados: La prevalencia del agente fue de 16,4% en reclusos del CDP de Arica, resultado menor a lo reportado en otros estudios similares. Conclusiones: Conocer la realidad de la prevalencia de esta ITS y algunos factores de riesgo asociados a la situación de privación de la libertad en una zona tri-fronteriza del norte de Chile, contribuye a las propuestas de programas de prevención en esta población vulnerable y de riesgo.

Abstract Background: Sex workers, people with drug addiction, early onset of sexual activity population, and criminal population, are considered the groups most at risk of contracting sexually transmitted infections (STIs). Aim: To determine the prevalence of infection by Neisseria gonorrhoeae in inmates of the Preventive Detention Center (CDP) at Arica and Parinacota Region, Chile. The Scientific Ethical Committee of Universidad de Tarapacá approved this study. Method: 140 inmates participated, who voluntarily agreed to be part of the study and signed an informed consent. A sample of urethral meatus was taken to investigate N. gonorrhoeae, and an epidemiological survey was applied, which included age, drug use, overcrowding, among others. Results: The prevalence of the agent was 16.4% in inmates of the Arica CDP, a result lower than that reported in other similar studies. Conclusion: Knowing the reality of the prevalence of this STI and some risk factors associated with the situation of deprivation of freedom in a tri-border area of northern Chile, contributes to the proposals for prevention programs in this vulnerable and at-risk population.

Treatment with alemtuzumab or rituximab after fingolimod withdrawal in relapsing-remitting multiple sclerosis is effective and safe.

BACKGROUND: It has been described that treating relapsing-remitting multiple sclerosis (RRMS) patients with alemtuzumab following fingolimod could be less effective due to the different dynamics of lymphocyte repopulation. Effectiveness and safety of alemtuzumab compared to rituximab after fingolimod withdrawal were analyzed. PATIENTS AND METHODS: A follow-up of a cohort of RRMS patients treated with alemtuzumab or rituximab after fingolimod withdrawal was accomplished. Effectiveness, measured by the percentage of patients with no evidence of disease activity (NEDA), and the presence of side effects (SE) were registered. RESULTS: Fifty-five patients, 28 with alemtuzumab and 27 with rituximab, were analyzed. No differences in the washout period or in the baseline lymphocytes counts were observed. After a mean follow-up period of 28.8 months, the annualized relapsing rate was significantly reduced in the alemtuzumab group from 1.29 to 0.004 (p < 0.001) and in the rituximab group from 1.24 to 0.02 (p < 0.001), without differences. A significant reduction of the median EDSS from 2.8 to 2.0 in the alemtuzumab group and from 3.5 to 2.5 (p < 0.01) in the rituximab group was observed, without differences. Eighty-two per cent (n = 28) of patients in alemtuzumab group and 69.2% (n = 26) in rituximab group achieved NEDA criteria, without differences (p = 0.3). Symptoms related to the infusion were the most frequent SE in both groups. No serious SE were registered. CONCLUSION: Treating RRMS patients with alemtuzumab or rituximab after fingolimod withdrawal is effective and safe, without significant differences between both groups in our series.

Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study.

INTRODUCTION: Rituximab is considered as a potential therapeutic option in relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in MS. PATIENTS AND METHODS: Observational study of effectiveness (clinical and radiological) and safety of rituximab in RRMS and PMS. RESULTS: A total of 90 rituximab-treated patients were collected: 31 RRMS and 59 PMS All patients had an active disease despite standard treatment. The annualized relapse rate (ARR) the year before rituximab was 0.86, 53.3% of patients had gadolinium enhanced lesion, and mean Expanded Disability Status Scale (EDSS) had increased from 4.2 to 4.9. During treatment, the ARR was reduced an 88.4% (p < 0.001). A significant decrease of EDSS to 4.6 was observed (p = 0.01) after 1 year of treatment, which remained stable during the second year in both groups. There was no evidence of disease activity in 70% of total sample, 74.2% of RRMS, and 67% of the PMS patients. Infusion-related symptoms were the most prevalent side effect (18.8%) and most were mild. Three thrombotic events were detected. CONCLUSION: Rituximab could be an effective and safe treatment in aggressive RRMS. Some selected PMS patients could also benefit from this treatment.

Autologous hematopoietic stem cell transplantation for pediatric multiple sclerosis: a registry-based study of the Autoimmune Diseases Working Party (ADWP) and Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.

Strategy of total synthesis based on the use of Rh-catalyzed stereoselective 1,4-addition.

In 1998, Hayashi and Miyaura reported the first asymmetric conjugate addition of aryl- and alkenyl-boronic acids to α,ß-unsaturated ketones using chiral rhodium complexes as catalysts. During the last decade, this reaction has been developed quickly and the enantioselectivity was significantly improved with the emergence of new phosphine ligands. In addition to the methodological work, this reaction was applied as a key step in the total synthesis of natural compounds. The purpose of this paper focuses on examples of the use of this reaction to prepare elaborated chiral molecules with high diastereoselectivies and/or enantioselectivities.

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

Estudio del efecto del tratamiento con inmunoglobulinas por vía intravenosa en la neuromielitis óptica / The effect of intravenous immunoglobulin on neuromyelitis optica

Objetivo: Evaluar la seguridad y tolerancia de las inmunoglobulinas por vía intravenosa (IgIV) para el tratamiento de la neuromielitis óptica (NMO). Métodos: Ocho pacientes que cumplían los criterios diagnósticos revisados de Wingerchuk fueron tratados con IgIV cada 2 meses (0,7 g por kg de peso y día durante 3 días). Las medidas deresultado principales fueron los eventos adversos graves, definidos de acuerdo con las directrices NIH para los ensayos clínicos. Las medidas de resultado secundarias fueron los cambios en la tasa anualizada de brotes y la discapacidad neurológica medida con la Expanded Disability Status Scale (EDSS). Resultados: Ocho pacientes fueron tratados: 5 con episodios recidivantes de neuritis óptica y/o mielitis y 3 pacientes con mielitis transversa longitudinal extensa recurrente. La edad media de inicio fue de 20,5 a˜nos (rango 7-31), el 87,5% mujeres. El tiempo medio de duración de la enfermedad al inicio del tratamiento fue de 9,0 a˜nos (rango 3-17). Tras 83 infusiones (rango 4-21) y na media de seguimiento de 19,3 meses (rango 6-39), hubo eventos adversos menores dolor de cabeza en 3 pacientes y erupción cutánea leve en un paciente). La tasa de recaídas se redujo de 1,8 en el a˜no anterior a 0,006 en el seguimiento (z = —2,5, p = 0,01). La EDSS se redujo de 3,3±1,3 a 2,6±1,5 (z = —2,0, p = 0,04). Conclusiones: El tratamiento con IgIV es seguro y bien tolerado y podría ser una alternativa de tratamiento para los trastornos del espectro de la NMO (AU)

Objective: Evaluate safety and tolerance levels for intravenous immunoglobulins (IVIG) as treatment for neuromyelitis optica (NMO). Methods: Eight patients meeting Wingerchuk’s revised diagnostic criteria were treated withIVIG every 2 months (0.7 g per kg body weight per day for 3 days). The primary outcome measure was the occurrence of serious adverse effects, defined according to NIH guidelines for clinical trials. Secondary outcome measures were changes in the yearly rate of attacks and in the degree of neurological disability measured with the Expanded Disability Status Scale (EDSS). Results: All 8 patients were treated; 5 had relapsing optic neuritis with or without myelitis and 3 had recurrent longitudinally extensive transverse myelitis. The mean age of onset was 20.5 years (range, 7-31 years) and 87,5% were female. The mean duration of the disease before beginning treatment was 9.0 years (range, 3-17 years). Following 83 infusions (range, 4-21 per patient) and a mean follow-up time of 19.3 months ( ange, 6-39 months), minor adverse events had occurred (headache in 3 patients and a mild cutaneous eruption in a single patient). The relapse rate decreased from 1.8 in the previous year to 0.006 during follow-up (z= 2,5, P=.01). The EDSS score fell from 3.3 ± 1.3 to 2.6 ± 1.5 (z = −2.0, P=.04). Conclusions: Treatment with IVIG is safe and well-tolerated, and it may be used as a treatment alternative for NMO spectrum disorders (AU)

Analysis of "task-positive" and "task-negative" functional networks during the performance of the Symbol Digit Modalities Test in patients at presentation with clinically isolated syndrome suggestive of multiple sclerosis.

An abnormal pattern of brain activations has been shown in patients with multiple sclerosis during the performance of several cognitive tasks. The aim of this study is to investigate abnormalities of the patterns of activation/deactivation in the functional networks related to "task-positive" and "task-negative" events during the execution of the Symbol Digit Modalities Test (SDMT) in patients with clinically isolated syndromes (CIS) and preserved cognitive abilities. Eighteen CIS patients within 3 months from their first clinical attack and 15 healthy controls (HC) underwent neuropsychological assessment and performed an adapted functional magnetic resonance imaging (fMRI) version of the SDMT. "Task-positive" responses to task execution and "task-negative" activity of the default mode network were compared between groups. A regression analysis was performed to investigate the correlation between fMRI results and T2 lesion load (T2 LL) and brain atrophy. Neuropsychological performance did not differ between groups. Compared to HC, CIS patients exhibited an enhanced deactivation of the "task-negative" network at the level of the posterior cingulate cortex, whereas no differences between groups were found when the patterns of "task-positive" events were compared. A regression analysis detected a correlation (p < 0.001,r ranging from 0.62 to 0.73) between T2 LL and "task-positive" activations of areas that are part of the attention network, comprising the anterior cingulate gyrus, left prefrontal gyrus and inferior parietal lobe. No correlation was found between patterns of functional modifications and brain atrophy. CIS patients experience an enhanced pattern of brain deactivations during cognitive performances, which might contribute to their normal neuropsychological status.

The effect of intravenous immunoglobulin on neuromyelitis optica.

OBJECTIVE: Evaluate safety and tolerance levels for intravenous immunoglobulins (IVIG) as treatment for neuromyelitis optica (NMO). METHODS: Eight patients meeting Wingerchuk's revised diagnostic criteria were treated with IVIG every 2 months (0.7 g per kg body weight per day for 3 days). The primary outcome measure was the occurrence of serious adverse effects, defined according to NIH guidelines for clinical trials. Secondary outcome measures were changes in the yearly rate of attacks and in the degree of neurological disability measured with the Expanded Disability Status Scale (EDSS). RESULTS: All 8 patients were treated; 5 had relapsing optic neuritis with or without myelitis and 3 had recurrent longitudinally extensive transverse myelitis. The mean age of onset was 20.5 years (range, 7-31 years) and 87,5% were female. The mean duration of the disease before beginning treatment was 9.0 years (range, 3-17 years). Following 83 infusions (range, 4-21 per patient) and a mean follow-up time of 19.3 months (range, 6-39 months), minor adverse events had occurred (headache in 3 patients and a mild cutaneous eruption in a single patient). The relapse rate decreased from 1.8 in the previous year to 0.006 during follow-up (z=2,5, P=.01). The EDSS score fell from 3.3±1.3 to 2.6±1.5 (z=-2.0, P=.04). CONCLUSIONS: Treatment with IVIG is safe and well-tolerated, and it may be used as a treatment alternative for NMO spectrum disorders.

The relationship between inflammatory activity and brain atrophy in natalizumab treated patients.

OBJECTIVE: To assess the evolution of brain atrophy and its relationship with inflammatory activity in RRMS patients treated with natalizumab. METHODS: Eighteen RRMS patients were prospectively followed up for 18 months after starting natalizumab therapy. Patients were monitored monthly and assessed for signs of relapses, adverse events or disability increase. MRI scans were performed before starting natalizumab and every six months. Cross-sectional T2 lesion volume (T2LV) and the normalized brain volume (NBV) at baseline and 18 months MRI scans were calculated using the Steronauta® and SIENAx softwares, respectively. Longitudinal Percentage of Brain Volume Change (PBVC) was estimated with SIENA. Linkage between inflammatory activity and brain atrophy was studied. RESULTS: Natalizumab reduced ARR by 67% and cumulative CEL by 87.5%. T2 lesion volume decreased from 1000 mm3, to 960 mm3 (p=0.006) and NBV decreased from 1.55×10(5) mm3 to 1.42×10(5) mm3 (p=0.025). Global PBVC from baseline to 18 months was -2.5%, predominantly during the first six months (0-6 months PBVC -1.7%; 6-12 months PBVC -0.74%; 12-18 months PBVC -0.50%). The number of relapses before treatment was correlated to the PBVC during the first semester (Pearson's coefficient -0.520, p=0.003), while the number of basal CEL or baseline T2LV did not correlate with brain atrophy rate. During follow-up, nine patients had clinical or radiological inflammatory activity. Their PBVC was significantly higher in the first semester (-2.3% to -1.1%, p=0.002). CONCLUSIONS: Natalizumab reduced relapse rate and CEL in MRI. Brain atrophy predominated in the first semester and was related to previous inflammatory activity.

Functional magnetic resonance imaging correlates of cognitive performance in patients with a clinically isolated syndrome suggestive of multiple sclerosis at presentation: an activation and connectivity study.

BACKGROUND/OBJECTIVE: To assess whether abnormalities on functional magnetic resonance imaging (fMRI) are related to cognitive function in patients at presentation with clinically isolated syndrome (CIS) suggestive of multiple sclerosis. METHODS: Eighteen patients with CIS and 15 healthy controls (HCs) performed an adapted fMRI version of the Paced Auditory Serial Addition Test (PASAT). According to their PASAT performance, CIS patients were divided into two groups: 10 with a low PASAT performance (<1 SD from the mean value of HCs) were considered 'cognitive impairment' (CI); eight patients were defined as 'cognitively preserved' (CP). Between-group differences in the patterns of brain activations and effective connectivity were assessed. RESULTS: During PASAT, compared to HCs, CIS patients showed increased activations of the bilateral inferior parietal lobe (IPL), bilateral precuneus, bilateral middle frontal gyrus (MFG), left anterior cingulate cortex (ACC), left claustrum, right thalamus and right caudate nucleus. When CIS patients were analyzed, the CI group had a more significant activation of the bilateral IPL than HCs and CP patients. Compared to CP patients, they also had more significant recruitment of the right superior parietal lobe, right cerebellum, left MFG and left ACC. The analysis of effective connectivity showed stronger connections between several regions of the right hemisphere involved in working memory function in CI patients versus CP and HC. CONCLUSIONS: During performance of the PASAT, CIS patients show abnormalities in the patterns of cortical recruitment and connectivity related to the level of their cognitive impairment.

Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice.

An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.

Evaluación de la efectividad y la seguridad del natalizumab en el tratamiento de la esclerosis múltiple remitente recidivante / Assessment of the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis

Objetivo Evaluar la efectividad y la seguridad del natalizumab en el tratamiento de la esclerosis múltiple remitente recidivante en un hospital de tercer nivel. Método Estudio observacional, prospectivo, de los pacientes adultos tratados con natalizumab desde mayo de 2007 hasta febrero de 2009. Tratamiento: natalizumab 300mg cada cuatro semanas. Criterio de respuesta: valoración de la progresión de la enfermedad, aparición de brotes y evaluación de imágenes mediante resonancia magnética. Se han recogido las reacciones adversas durante el tratamiento con natalizumab. Resultados Treinta pacientes (el 73% eran mujeres); promedio de edad: 34±8,4 años; escala expandida del estado de discapacidad medio basal: 3,4±1,3, y número de brotes en el último año: 2,1±1,2. Cinco pacientes suspendieron el tratamiento, uno por abandono del tratamiento, dos por ineficacia y dos por reacciones anafilácticas. Catorce pacientes completaron un año de tratamiento con resultados satisfactorios. Se obtuvieron reducciones de la escala expandida del estado de discapacidad del 36, el 47, el 31, el 54 y el 28% a los 3, los 6, los 9, los 12 y los 15 meses de tratamiento, respectivamente. La prevalencia de pacientes libres de recidiva fue del 94, el 76 y el 54% a los 3, los 6 y los 12 meses, respectivamente. Las imágenes de resonancia magnética al año de tratamiento correspondientes a 11 pacientes no mostraron nuevas lesiones. Dos pacientes sufrieron reacciones anafilácticas graves y otro sufrió una reacción urticarial. Un 6,6% de los pacientes presentó anticuerpos neutralizantes que motivaron la suspensión del tratamiento. Conclusiones La efectividad y la seguridad obtenidas en nuestros pacientes sugieren que el natalizumab constituye una alternativa para los pacientes refractarios o con formas agresivas de esclerosis múltiple, aunque falta conocer los efectos a largo plazo y la evolución de la aparición de anticuerpos neutralizantes (AU)

Objective Assessing the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis in a tertiary hospital. Method Observational, prospective study of adult patients treated with natalizumab from May 2007 until February 2009. Treatment: 300mg natalizumab every four weeks. Response criteria: assessment of disease progression, appearance of flare-ups and assessment of magnetic resonance images. Adverse reactions during treatment with natalizumab were recorded. Results Thirty patients (73% female); average age 34±8.4 years; mean baseline EDSS 3.4±1.3; number of flare-ups in the past year 2.1±1.2. Treatment was discontinued in five patients, due to refusal in one case, ineffectiveness in two cases and anaphylaxis in the other two cases. Fourteen patients completed one year of treatment with satisfactory results. A lower EDSS score by 36%, 47%, 31%, 54% and 28% was obtained at 3, 6, 9, 12 and 15 months of treatment respectively. The prevalence of relapse-free patients was 94%, 76% and 54% at 3, 6 and 12 months. MRI imaging studies in 11 patients one year after they began treatment showed no new lesions. Two patients suffered severe anaphylactic shock and another one had an outbreak of urticaria. The presence of neutralising antibodies was the reason for suspending treatment in 6.6% of the patients. Conclusions The treatment's effectiveness and safety in our patient group suggest that natalizumab is a treatment for refractory patients or those with aggressive types of multiple sclerosis, although we do not yet know about its long-term effects and the evolution of the appearance of neutralising antibodies (AU)

Assessment of the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis.

OBJECTIVE: Assessing the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis in a tertiary hospital. METHOD: Observational, prospective study of adult patients treated with natalizumab from May 2007 until February 2009. TREATMENT: 300 mg natalizumab every four weeks. Response criteria: assessment of disease progression, appearance of flare-ups and assessment of magnetic resonance images. Adverse reactions during treatment with natalizumab were recorded. RESULTS: Thirty patients (73% female); average age 34 ± 8.4 years; mean baseline EDSS 3.4 ± 1.3; number of flare-ups in the past year 2.1 ± 1.2. TREATMENT was discontinued in five patients, due to refusal in one case, ineffectiveness in two cases and anaphylaxis in the other two cases. Fourteen patients completed one year of treatment with satisfactory results. A lower EDSS score by 36%, 47%, 31%, 54% and 28% was obtained at 3, 6, 9, 12 and 15 months of treatment respectively. The prevalence of relapse-free patients was 94%, 76% and 54% at 3, 6 and 12 months. MRI imaging studies in 11 patients one year after they began treatment showed no new lesions. Two patients suffered severe anaphylactic shock and another one had an outbreak of urticaria. The presence of neutralising antibodies was the reason for suspending treatment in 6.6% of the patients. CONCLUSIONS: The treatment's effectiveness and safety in our patient group suggest that natalizumab is a treatment for refractory patients or those with aggressive types of multiple sclerosis, although we do not yet know about its long-term effects and the evolution of the appearance of neutralising antibodies.

Early diffuse demyelinating lesion in the cervical spinal cord predicts a worse prognosis in relapsing-remitting multiple sclerosis.

OBJECTIVE: To study the long-term outcome and persistence of two patterns of cervical spinal cord abnormality in early relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients with a spinal cord MRI performed during the first 3 years of the disease, a control MRI 5 years later and who have been followed up at least 10 years were included. Patients were grouped according the T2 spinal cord MRI into: (A) nodular pattern, if one or more focal lesions were present; and (B) diffuse pattern, defined as a poorly demarcated high signal area. The end point was defined as the time to reach an Expanded Disability Status Score (EDSS) of 4.0. RESULTS: Twenty-five patients were included; 12 in group A and 13 in group B. Three patients in group A and 9 in group B reached EDSS 4, in a mean time of 11 years in group A and 7 years in group B (log rank 10.3, p = 0.001). Multivariate Cox regression analysis assessing the risk of EDSS 4.0 including sex, age, number of relapses in the first 2 years, number of T2 brain lesions and spinal cord pattern showed higher risk for the diffuse pattern (hazard ratio 7.2, 95% confidence interval 1.4-36.4). Control MRI showed the persistence of the diffuse pattern in all patients, and the development of diffuse pattern in two patients with basal nodular lesions. CONCLUSIONS: The diffuse abnormality in cervical spinal cord at the beginning of the disease is persistent and predicts a worse prognosis in RRMS patients.

The risk of relapse after a clinically isolated syndrome is related to the pattern of oligoclonal bands.

We prospectively assessed the risk of second relapse in 192 patients with clinically isolated syndromes (CIS) divided into three groups: patients lacking oligoclonal IgG bands (OC-IgG, 25.7%), those showing OC-IgG (52.4%), and those with both OC-IgG and lipid-specific IgM bands (LS-OC-IgM, 22%). OC-IgG increased 9.3-fold the risk compared to lacking OC-IgG; OC-IgG+LS-OC-IgM increased the risk 39.6-fold compared to not having OC-IgG and 4.4-fold compared to having only OC-IgG. Median time to second relapse was 0.7 years for patients with OC-IgG+LS-OC-IgM and 3.3 years for those with only OC-IgG. Therefore, CSF analysis identifies CIS patients at risk of second relapse.

Response to interferon in multiple sclerosis is related to lipid-specific oligoclonal IgM bands.

The objective of this study was to investigate whether the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid (CSF) influences the response to treatment with beta-interferon in relapsing-remitting multiple sclerosis (RRMS) patients. We performed a collaborative prospective study including RRMS patients with brain MRI and LS-OCMB studies performed before starting interferon treatment. The primary endpoint was the risk of having a relapse after treatment initiation. Secondary endpoints included relapse rate, relapse-rate reduction, proportion of relapse-free patients and proportion of patients with sustained disability increase during follow-up. One-hundred and two patients were included. After a mean follow-up of 37.4 months, the risk of suffering a relapse was two-fold higher in patients with LS-OCMB (hazard ratio 2.0, 95% confidence interval 1.1-3.8). LS-OCMB+ patients showed lower reduction in relapse rate (51.8% versus 80.8%; p < 0.0001), higher relapse rate in the first year (0.8 versus 0.2; p = 0.001), lower proportion of relapse-free patients (25% versus 61.3%; p = 0.003), and higher proportion of patients with sustained 1.0 increase in the Expanded Disability Status Score (45% versus 12.9%; p = 0.0003). In conclusion, LS-OCMB can have an influence on the response to interferon treatment in RRMS patients. They could be used as a biological marker to predict high inflammatory activity after treatment.