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.

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)

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.

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.

Effect of relapses over early progression of disability in multiple sclerosis patients treated with beta-interferon.

Observational study designed to explore the effect of demographical variables and number of relapses over the disability progression in the two first years of beta-interferon treatment for multiple sclerosis. One hundred and sixty two patients treated with beta-interferon for at least two years were included, 70.9% females, mean age 33.4 years, mean disease duration 75.1 months, mean EDSS 2.4, previous year relapse rate 1.3. Main end-point was defined as a sustained EDSS increase (1.5 if previous EDSS 0-2.0; 1.0 if previous EDSS 2.5-4.0; 0.5 if previous EDSS 4.5 or higher). 62.3% of patients presented one or more relapses and 32.7% patients reached sustained disability increase. The univariate and multivariate Cox regression analysis only showed statistical significance for the relapses in the two first years after the treatment (HR 1 relapse: 3.4, p = 0.05; HR > or = 2 relapses: 4.3, p < 0.001). The Kaplan-Meier survival analysis showed a higher probability of EDSS progression for patients with one relapse (log rank 10.9, p = 0.02) and with > or = 2 relapses (log rank 17.7, p < 0.001), with no differences between them (p = 0.38). In conclusion, patients with one or more relapses in the first two years of interferon treatment developed an earlier sustained progression of the disability.

Evaluación prospectiva del tratamiento de brotes de sclerosis múltiple con megadosis oral de metilprednisolona: datos de respuesta y seguridad / Prospective assessment of the treatment of multiple sclerosis relapses with oral high-dose methylprednisolone: response and tolerability data

Objetivo. Evaluación de la respuesta y seguridad del tratamiento de brotes de esclerosis múltiple (EM) con dosis altas de metilprednisolona oral (MPO), y análisis de la correlación entre la escala de Kutzke (EDSS) y la escala funcional compuesta (EFC) en la evaluación de los cambios posbrote. Método. Se incluyeron consecutivamente pacientes diagnosticados de EM clínicamente definida con un brote de menos de 3 semanas de evolución. Los pacientes fueron evaluados y tratados con 1.000 mg de MPO en dosis única durante 3 días sin pauta de reducción. De todos disponíamos de una EDSS basal y al menos tres medidas de la EFC. Ambas escalas se completaron el día 0, antes del tratamiento, y las semanas 1, 4 y 12 después del mismo. Consideramos buena respuesta a la mejoría de al menos 1 punto en la EDSS respecto al día 0 o la recuperación de la EDSS basal. Resultados. Se trataron 21 brotes en 20 pacientes. EDSS basal media, 2,5; z-score de la EFC basal medio, 0,15; tiempo medio de evolución del brote, 6,8 días. Durante el brote la EDSS empeoró a 3,8 y el z-score a -0,57. Hubo buena respuesta en el 33,4 % de los brotes en la semana 1 y en el 85,7% en las semanas 4 y 12. Aunque ambas escalas mejoraron significativamente en la primera semana, la EDSS media no recuperó su valor basal hasta la semana 4 y la EFC lo hizo en la semana 12. Las escalas se correlacionaron en cada evaluación y respecto a los cambios debidos al brote (p<0,01). No se registraron acontecimientos adversos graves. Discusión. La megadosis de MPO es un tratamiento seguro y eficaz de los brotes de EM. EDSS y EFC son sensibles a los cambios posbrote, aunque su dinámica de recuperación es diferente, proporcionándonos cada una información complementaria (AU)

Objective: This study aims to assess the response and safety of the treatment of multiple sclerosis (MS) episodes with high oral doses of methylprednisolone (MP) and to investigate the correlation between expanded disability status scale (EDSS) and MS functional composite (MSFC) during recovery from relapses. Method: Patients consecutively diagnosed of clinically defined MS with an episode of less than three weeks course were included. They were evaluated and treated with a single dose of 1,000 mg of MP for three days without oral tapering. Baseline EDSS and at least three MSFC scale measurements were available. Patients were scored with EDSS and MSFC before the treatment and after 1, 4 and 12 weeks. Adverse events were also recorded. Response to treatment was defined as the recovery of at least 1 point in the EDSS or the return to baseline EDSS. Results: Twenty one episodes in 20 patients were treated. Mean baseline EDSS was, 2.5; mean baseline z-score was, 0.15, and mean relapse duration was, 6.8 days. During relapse, mean EDSS worsened to 3.8 and mean z-score to -0.57. At week 1, 33.4% of relapses had responded to treatment, and at weeks 4 and 12, 85.7% had responded. Although mean EDSS and mean z-score had already improved at week 1, mean EDSS did not reach baseline value until week 4 and mean z-score until week 12. EDSS correlated significantly to MSFC in each evaluation as well as to scale changes related to relapse (p;0.05). No serious adverse events were seen. Discussion: Oral high-dose of MP is a safe and effective therapy for MS relapses. Both EDSS and MSFC were sensitive to changes related to relapses although the dynamics of recovery was different, providing complementary information (AU)

Evaluation of response of multiple sclerosis (MS) relapse to oral high-dose methylprednisolone: usefulness of MS functional composite and Expanded Disability Status Scale.

To compare the usefulness of multiple sclerosis functional composite (MSFC) to the Expanded Disability Status Scale (EDSS) in assessing functional changes related to relapse. A prospective 12-week follow-up study after relapse was conducted among 14 multiple sclerosis (MS) patients treated with oral high-dose (1 g) methylprednisolone for 3 days. MSFC and the EDSS were assessed on day 0, before treatment and, 1, 4 and 12 weeks afterwards. In relapses, EDSS (2.5 +/- 1.2 to 3.8 +/- 1.0) and z-score of the MSFC (0.15 +/- 0.58 to -0.59 +/- 0.70) worsened. After 1 week of treatment, the EDSS improved (3.3 +/- 1.2; P = 0.002) while the MSFC did not change significantly. At week 4, EDSS improvement was maximal (2.8 +/- 1.3; P = 0.001). At week 12, EDSS remained stable whereas z-score continued improving (0.26 +/- 0.74). z-9peg-hole-test was the most sensitive subtest. There was correlation between baseline values of both scales (-0.620, P < 0.05) and between changes due to relapse (-0.535, P < 0.05). 78.5% of patients had improved at week 4 (35.7% at week 1). There were no serious adverse effects. MSFC and the EDSS were sensitive to changes due to relapses, although the dynamics for restoring baseline function were different. Our data support the usefulness of both scales in clinical trials, providing complementary information about outcome of MS patients with relapses.

[Prospective assessment of the treatment of multiple sclerosis relapses with oral high-dose methylprednisolone: response and tolerability data]. / Evaluación prospectiva del tratamiento de brotes de esclerosis múltiple con megadosis oral de metilprednisolona: datos de respuesta y seguridad.

OBJECTIVE: This study aims to assess the response and safety of the treatment of multiple sclerosis (MS) episodes with high oral doses of methylprednisolone (MP) and to investigate the correlation between expanded disability status scale (EDSS) and MS functional composite (MSFC) during recovery from relapses. METHOD: Patients consecutively diagnosed of clinically defined MS with an episode of less than three weeks course were included. They were evaluated and treated with a single dose of 1,000 mg of MP for three days without oral tapering. Baseline EDSS and at least three MSFC scale measurements were available. Patients were scored with EDSS and MSFC before the treatment and after 1, 4 and 12 weeks. Adverse events were also recorded. Response to treatment was defined as the recovery of at least 1 point in the EDSS or the return to baseline EDSS. RESULTS: Twenty one episodes in 20 patients were treated. Mean baseline EDSS was, 2.5; mean baseline z-score was, 0.15, and mean relapse duration was, 6.8 days. During relapse, mean EDSS worsened to 3.8 and mean z-score to -0.57. At week 1, 33.4% of relapses had responded to treatment, and at weeks 4 and 12, 85.7% had responded. Although mean EDSS and mean z-score had already improved at week 1, mean EDSS did not reach baseline value until week 4 and mean z-score until week 12. EDSS correlated significantly to MSFC in each evaluation as well as to scale changes related to relapse (p;0.05). No serious adverse events were seen. DISCUSSION: Oral high-dose of MP is a safe and effective therapy for MS relapses. Both EDSS and MSFC were sensitive to changes related to relapses although the dynamics of recovery was different, providing complementary information.

Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis.

OBJECTIVE: To assess the relationship between the spectroscopically measured axonal damage in the normal-appearing white matter of the brainstem, the total brain T2-hyperintense lesion volume (T2LV), and disability in patients with early relapsing-remitting multiple sclerosis (RRMS). METHODS: Forty-three RRMS patients and 10 sex- and age-matched healthy controls were prospectively studied for 2 years. T2-weighted magnetic resonance (MR) images and proton MR spectroscopy were acquired at the time of recruitment and at year 2. Brainstem was considered, where large tracts join together, as a suitable region to detect early axonal damage. The T2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) resonances areas were integrated with the jMRUI program, and the ratios were calculated for the sum of the volume elements represented at brainstem. RESULTS: The basal NAA/Cho ratio was significantly decreased in patients compared with controls. After 2-year follow-up, there was a decrease in the NAA/Cho (-9%; p = 0.002) and NAA/Cr (-13%; p = 0.001) ratios, and an increase in the T2LV (19%; p = 0.043) in multiple sclerosis patients, whereas control subjects had no significant metabolic changes. Significant NAA/Cr ratio decreases were observed in both patients, with and without relapses, whereas T2LV only increased in patients with relapses. The final Expanded Disability Status Scale (EDSS) score correlated with T2LV at baseline, but no significant correlations were found between metabolic values, T2LV change, or EDSS score over the study period. CONCLUSIONS: Our data reveal an early and progressive axonal damage in relapsing-remitting multiple sclerosis. Axonal loss and T2 lesion volume seem to be at least partly dissociated processes in early stages of the disease.

Accurate quantification methods to evaluate cervical cord atrophy in multiple sclerosis patients.

OBJECT: Automatic accurate measurement techniques are needed to increase reproducibility in the quantification of cervical cord area (CCA) with magnetic resonance (MR) imaging in the assessment of central nervous system (CNS) atrophy in multiple sclerosis (MS) patients. MATERIALS AND METHODS: Two segmentation methods were implemented: (1) spatial mean brightness level estimation (SMBLE), and (2) partial-volume modeling (PVM). These were evaluated with the inclusion of spinal cord inclination and/or partial-volume-effect corrections. An averaged manually segmented set was considered as reference. Thirty MR studies were used to compare the different methods. A set of 15 MS patients and 15 control subjects within a two-year longitudinal study were used to evaluate cord atrophy with the best method. Statistical evaluation was made by using an intraclass correlation coefficient and Bland-Altman comparisons. RESULTS: Partial-volume modeling with spinal cord inclination correction and partial-volume spinal-cord contour contribution estimation was the most accurate method. The longitudinal test showed a 4% decrease in CCA in MS patients with no significant reduction in control subjects. CONCLUSION: The automatic PVM cord-segmentation approach, taking into consideration the spinal-cord inclination and partial-volume treatment, provides reproducibility and increased accuracy in the evaluation of cord atrophy, allowing the monitoring of changes in MS patients.

[Atypical clinicoradiological course in a case panancephalic variant of Creutzfeldt-Jakob]. / Evolución clinicorradiológica atípica en un caso de variante panencefálica de la enfermedad de Creutzfeldt-Jakob.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is the most frequent of the human transmissible spongiform encephalopathies. Pathogenic mechanisms of CJD are still unknown. Sporadic CJD, the most habitual, is clinically characterized by rapidly progressive dementia, myoclonia and ataxia. Panencephalic variant CJD, typically from Japan, is characterized by extensive involvement of the cerebral white and gray matter. International interest has grown from more than one decade ago in relation to the diagnosis of new variant (vCJD). New protocols of MR imaging have contributed to the early diagnosis of CJD with specific signs. CASE REPORT: We report a case of panencephalic CJD, with atypical clinical presentation and unusual MR imaging findings. DISCUSSION: Our patient developed visual and psychiatric symptoms. Brain MR imaging showed extensive white matter lesions in posterior parietal lobe and occipital regions, which disappeared after steroid treatment. The most characteristic radiological sign for sporadic CJD is the high signal intensity of the basal ganglia, for vCJD the pulvinar sign and, for panencephalic CJD the presence of periventricular white matter lesions, with tendency to the spread when the disease progress. In serial MR imaging studies of our patient, we could see how typical signs were appearing. However, the complete and unusual resolution of the original white matter lesions makes us to think about a possible inflammatory component, in some time in the evolution of white matter damage.

Evolución clinicorradiológica atípica en un caso de variante panencefálica de la enfermedad de Creutzfeldt-Jakob / Atypical clinicoradiological course in a case panancephalic variant of Creutzfeldt-Jakob

Introducción. La enfermedad de Creutzfeldt-Jakob (ECJ) es la encefalopatía espongiforme transmisible más frecuente; su fisiopatogenia aún no se conoce con exactitud. La forma esporádica es la más habitual caracterizada por la tríada: demencia rápidamente progresiva, mioclonías y ataxia. La ECJ tipo panencefálico, descrita excepcionalmente fuera de Japón, se caracteriza por la afectación difusa de la sustancia gris y blanca. El interés internacional por esta enfermedad surge hace más de una década con el descubrimiento de la nueva variante. Desde entonces los avances en resonancia magnética (RM) han contribuido al diagnóstico pre mortem de la enfermedad con la descripción de signos específicos. Caso clínico. Presentamos un caso de ECJ tipo panencefálico en nuestro medio con una evolución clinicorradiológica atípica. Discusión. Nuestra paciente comenzó con síntomas visuales y psiquiátricos. La RM cerebral mostró lesiones inespecíficas de sustancia blanca en regiones parietal posterior y occipital bilateral que se resolvieron tras tratamiento esteroideo. El hallazgo radiológico más característico en las formas esporádicas es la hiperintensidad bilateral y simétrica de los ganglios de la base, en la nueva variante del núcleo pulvinar y en la variante panencefálica, la presencia de lesiones de sustancia blanca de distribución periventricular con tendencia a la extensión local a medida que la enfermedad progresa. En los sucesivos estudios de RM de nuestra paciente pudimos ver cómo los signos característicos iban apareciendo; sin embargo, la resolución completa de las lesiones iniciales nos permite plantear la posible implicación de mecanismos inflamatorios en algún momento de la evolución de las lesiones de sustancia blanca (AU)

Introduction: Creutzfeldt-Jakob disease (CJD) is the most frequent of the human transmissible spongiform encephalopathies. Pathogenic mechanisms of CJD are still unknown. Sporadic CJD, the most habitual, is clinically characterized by rapidly progressive dementia, myoclonia and ataxia. Panencephalic variant CJD, typically from Japan, is characterized by extensive involvement of the cerebral white and gray matter. International interest has grown from more than one decade ago in relation to the diagnosis of new variant (vCJD). New protocols of MR imaging have contributed to the early diagnosis of CJD with specific signs. Case report: We report a case of panencephalic CJD, with atypical clinical presentation and unusual MR imaging findings. Discussion: Our patient developed visual and psychiatric symptoms. Brain MR imaging showed extensive white matter lesions in posterior parietal lobe and occipital regions, which disappeared after steroid treatment. The most characteristic radiological sign for sporadic CJD is the high signal intensity of the basal ganglia, for vCJD the pulvinar sign and, for panencephalic CJD the presence of periventricular white matter lesions, with tendency to the spread when the disease progress. In serial MR imaging studies of our patient, we could see how typical signs were appearing. However, the complete and unusual resolution of the original white matter lesions makes us to think about a possible inflammatory component, in some time in the evolution of white matter damage (AU)

CADASIL: estudio de una familia / CADASIL: study of a family

No disponible

Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis: a HMRS study.

OBJECTIVE: Wallerian degeneration in normal appearing white matter in early relapsing-remitting multiple sclerosis (RRMS), and its correlation with the number of relapses and disease duration. Background Recent pathological studies have demonstrated Wallerian degeneration in normal appearing white matter (NAWM) in multiple sclerosis (MS), in established RRMS, and in chronic MS. However, the presence of Wallerian degeneration early in the disease and its correlation with relapse and with disease duration has not been studied. METHODS: We performed proton magnetic resonance spectroscopic imaging in 21 MS patients, and 4 healthy controls, age and gender matched, aged under 45 years, with a maximum of 4 years since first bout, and an EDSS score of less than 3.0. N-acetyl-aspartate (NAA) (an index of axonal integrity) was measured in the NAWM from the pons and the cerebellar peduncles. RESULTS: We observed that the NAA levels were abnormally low in the NAWM in the early RRMS patients (p = 0.04, Student's t-test). The decrease in the NAA concentration correlated with disease duration in the two areas studied (p = 0.03 for pons and p = 0.04 for cerebellar peduncle); and with the number of previous relapses (Pearson's correlation = -0.582, p < 0.002). CONCLUSION: Wallerian degeneration measured by the NAA concentration at pons and cerebellar peduncles is present early in the disease and correlates with the number of relapses and disease duration.