Onset-adjusted incidence of multiple sclerosis in the Girona province (Spain): Evidence of increasing risk in the south of Europe.

BACKGROUND: Recent studies show an increasing incidence of multiple sclerosis (MS) in southern Europe. Although by its geographical location and genetic characteristics Spain is expected to be similar to other southern European regions, data on incidence are scarce. The aim of this study was to determine the onset-adjusted incidence of MS in the Girona province in Catalonia (Spain). METHODS: A prospective incidence study pooling data from the population-based Catalonia MS Registry was performed. Incident cases were defined as patients who had the onset of symptoms compatible with a clinically isolated syndrome (CIS) suggestive of MS in 2009 and fulfilled McDonald-2005 criteria during follow-up. Age- and sex-specific incidence rates were obtained. RESULTS: The Registry included 182 patients residing in Girona that presented a CIS from January 2009 to December 2013. Fifty one patients had the onset of symptoms in 2009, of whom 27 patients fulfilled the diagnostic criteria, giving an incidence of 3.6 per 100,000 (CI 95% 2.4-5.3) inhabitants; 4.3 (CI 95% 2.5-7.1) for women and 2.9 (CI 95% 1.4-5.2) for men. The age-adjusted incidence rate for the European population was 3.29 (CI 95% 3.2-3.3). CONCLUSION: The incidence estimation derived in this study is consistent with recent epidemiological data of MS in southern Europe suggesting an increase in incidence in this region.

[Multiple sclerosis epidemiological situation update: pertinence and set-up of a population based registry of new cases in Catalonia]. / Situación epidemiológica actual de la esclerosis múltiple: pertinencia y puesta en marcha de un registro poblacional de nuevos casos en Cataluña.

INTRODUCTION: The first epidemiological studies on multiple sclerosis (MS) around the world pictured a north to south latitudinal gradient that led to the first genetic and environmental pathogenic hypothesis. MS incidence seems to be increasing during the past 20 years based on recent data from prospective studies performed in Europe, America and Asia. This phenomenon could be explained by a better case ascertainment as well as a change in causal factors. The few prospective studies in our area together with the increase in the disease in other regions, justifies an epidemiological MS project in order to describe the incidence and temporal trends of MS. DEVELOPMENT: A prospective multicenter MS registry has been established according to the actual requirements of an epidemiological surveillance system. Case definition is based on the fulfillment of the McDonald diagnostic criteria. The registry setting is the geographical area of Cataluna (northeastern Spain), using a wide network of hospitals specialized in MS management. CONCLUSION: Recent epidemiological studies have described an increase in MS incidence. In order to contrast this finding in our area, we consider appropriate to set up a population based registry.

Situación epidemiológica actual de la esclerosis múltiple: pertinencia y puesta en marcha de un registro poblacional de nuevos casos en Cataluña / Multiple sclerosis epidemiological situation update: pertinence and set-up of a population based registry of new cases in Catalonia

Introducción. Los primeros estudios epidemiológicos de esclerosis múltiple (EM) de ámbito mundial caracterizaron un patrón geográfico latitudinal, con prevalencias más altas en las zonas más alejadas del ecuador. A raíz de esta distribución, se plantearon hipótesis causales de índole genética y ambiental. Según los datos de estudios prospectivos desarrollados en diversas regiones de Europa, América y Asia, la incidencia de la enfermedad ha aumentado a lo largo de los últimos 30 años, lo cual podría indicar una mejor detección de casos o un cambio en los factores causales subyacentes. Los escasos estudios prospectivos disponibles en nuestro entorno y el aumento de la enfermedad descrito en otras regiones justifican la pertinencia de un proyecto epidemiológico dirigido a conocer las tasas de incidencia y la tendencia temporal de EM. Desarrollo. De acuerdo con los requisitos actuales de un sistema de vigilancia epidemiológica, se ha establecido un registro prospectivo de carácter multicéntrico. Para la definición de nuevo diagnóstico se emplean los criterios establecidos por McDonald. El ámbito de aplicación es el territorio de Cataluña, a través una red de hospitales de referencia especializados en el manejo de EM, que notifican la información mediante un aplicativo informático conectado a internet. Conclusiones. Los estudios epidemiológicos de la EM de las últimas décadas han descrito un incremento de su incidencia. Para dimensionar este fenómeno en nuestro ámbito, creemos pertinente la puesta en marcha de un registro poblacional de la enfermedad en Cataluña (AU)

Introduction. The first epidemiological studies on multiple sclerosis (MS) around the world pictured a north to south latitudinal gradient that led to the first genetic and environmental pathogenic hypothesis. MS incidence seems to be increasing during the past 20 years based on recent data from prospective studies performed in Europe, America and Asia. This phenomenon could be explained by a better case ascertainment as well as a change in causal factors. The few prospective studies in our area together with the increase in the disease in other regions, justifies an epidemiological MS project in order to describe the incidence and temporal trends of MS. Development. A prospective multicenter MS registry has been established according to the actual requirements of an epidemiological surveillance system. Case definition is based on the fulfillment of the McDonald diagnostic criteria. The registry setting is the geographical area of Cataluña (northeastern Spain), using a wide network of hospitals specialized in MS management. Conclusion. Recent epidemiological studies have described an increase in MS incidence. In order to contrast this finding in our area, we consider appropriate to set up a population based registry (AU)

[Mitoxantrone]. / Mitoxantrona.

Mitoxantrone is an antineoplastic agent that exerts a potent immunosuppresive effect, including suppression of B cell immunity and reduction of T cell numbers. Clinical trials have shown that mitoxantrone has a statistically significant impact on reduction of relapse rate and delays disability progression in patients with relapsing remitting (RR) multiple sclerosis (MS) or secondary progressive (SP) MS. Treatment is well tolerated, but the risk of cardiotoxicity at higher cumulative doses is likely to limit the duration of treatment. The maximum cumulative dose recommended is 140 mg/m2. In 2000, the FDA (Food and Drug Administration) approved the use of mitoxantrone for the treatment of active RRMS, SPMS and progressing relapsing (PR) MS.

Mitoxantrona / Mitoxantrone

La mitoxantrona es un agente antineoplásico con un potente efecto inmunosupresor, que suprime la inmunidad mediada por células B y reduce el número de células T. Diversos estudios clínicos han demostrado que la mitoxantrona reduce el número de brotes y la progresión de la discapacidad en pacientes con una esclerosis múltiple remitente recurrente (EMRR) o esclerosis múltiple secundariamente progresiva (EMSP) activas. El tratamiento con mitoxantrona es bien tolerado, pero el riesgo de cardiotoxicidad a altas dosis limita la duración del tratamiento. La dosis máxima acumulada recomendada es de 140 mg/m2. En el año 2000 la FDA (Food and Drug Administration) aprobó el uso de la mitoxantrona para la EMRR activa, EMSP y esclerosis múltiple progresiva recurrente (AU)

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.

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.

[Listeria rhombencephalitis. Neuroradiological findings]. / Rombencefalitis por listeria. Hallazgos neurorradiológicos.

Rhombencephalitis due to listeria monocytogenes is an uncommon and serious form of brainstem infection. The disease has a characteristic biphasic course: a nonspecific prodrome of headache, nausea or vomiting, and fever lasting for a several days is followed by progressive asymmetrical cranial-nerve palsies. We report two cases of Listeria monocytogenes rhombencephalitis. The first case is a previously healthy 20 year-old-man who developed fever, headache, nausea and vomiting, followed by numbness in left trigeminal nerve. The second case is an immunosuppressed 77 year-old-man, who developed sudden left hemiparesis, followed by fever and severe brainstem dysfunction with ophthalmoplegia and dysphagia. In both cases, a brain magnetic resonance imaging (MRI) scan, showed increased intensity on T2-weighted lesions in the brainstem that enhanced after contrast on T1-weighted sequences. Both patients had a favorable outcome with full clinical recovery. We conclude that MRI aids in the early detection of parenchymal infections, therefore, MRI is crucial for early diagnosis and is very useful for follow-up examinations.

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.

Rombencefalitis por listeria. Hallazgos neurorradiológicos / Listeria rhombencephalitis. Neuroradiological findings

La rombencefalitis por listeria monocytogenes es una infección grave e infrecuente del tronco cerebral. Clínicamente se caracteriza por un curso bifásico. Un pródromo inespecífico con fiebre, cefalea, náuseas y vómitos seguido, en días, de una afectación progresiva y asimétrica de pares craneales. Presentamos dos casos de rombencefalitis por listeria. El primer caso es un varón de 20 años, previamente sano, que debutó con fiebre, cefalea, náuseas y vómitos, seguido de una afectación del V nervio craneal. El segundo caso es un varón de 77 años, inmunosuprimido, que presentó de forma brusca una hemiparesia izquierda, seguido de fiebre y afectación de otros nervios craneales con oftalmoplejía y disfagia. La resonancia magnética (RM) craneal, en ambos casos, mostró lesiones hiperintensas en T2 a nivel del tronco cerebral que se realzaban tras la administración de contraste. Ambos casos presentaron una evolución favorable tras el tratamiento antibiótico, con una recuperación clínica completa. Concluimos que la detección con RM de lesiones en tronco encefálico deben hacer sospechar la existencia de una rombencefalitis por listeria. La RM craneal permite demostrar las lesiones a nivel del tronco cerebral de forma temprana y es útil para el seguimiento evolutivo (AU)

Expression of chemokine receptors in the different clinical forms of multiple sclerosis.

Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sderosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS However, a pattem of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.

Esclerosis múltiple

La esclerosis múltiple (EM) es una enfermedad inflamatoria del sistema nervioso central (SNC) que afecta a personas jóvenes predispuestas genéticamente y que estarían expuestas en la infancia a un agente ambiental que ocasionaría una disfunción del sistema inmunológico, con el desarrollo de una acción autolesiva dirigida contra la sustancia blanca que produciría un defecto en la conducción de los impulsos nerviosos. Los síntomas de la enfermedad se caracterizan por su gran variabilidad, al estar las lesiones diseminadas por el SNC. La enfermedad puede iniciarse por alteraciones sensitivas, motoras, visuales, vértigo, trastornos esfinterianos o cognitivos. Cursa en forma de brotes o de forma progresiva. El diagnóstico clínico de la EM se realiza tomando en consideración la existencia de criterios de diseminación espacial (síntomas y signos que indiquen la existencia de dos lesiones independientes en el SNC) y de dispersión temporal (dos o más episodios de disfunción neurológica).La RM cerebral muestra lesiones multifocales de la sustancia blanca en el 95-99 por ciento de los pacientes con EM clínicamente definida. El tratamiento de la EM ha experimentado una revolución gracias a los estudios sobre su patogenia, por lo que se han podido diseñar estrategias con base inmunológica. No obstante, no existe en la actualidad un tratamiento curativo de la enfermedad, por lo que el tratamiento sintomático de la enfermedad es clave. (AU)

[Conversion to clinically definite multiple sclerosis after isolated spinal cord syndrome: value of brain and spinal MRI]. / Conversión a esclerosis múltiple clínicamente definida tras un síndrome medular aislado: valor de la resonancia magnética craneal y medular.

BACKGROUND: Isolated spinal cord syndrome might be due to a first episode of multiple sclerosis. The aim of the study was to determine the clinical usefulness and paraclinical characteristics and of spinal and brain MR imaging predicting conversion to clinically definite multiple sclerosis (CDMS) in patients with an isolated spinal cord syndrome. PATIENTS AND METHODS: We have evaluate thirty-eight patients with isolated spinal cord syndrome. A clinical protocol, lumbar puncture, evoked potential and brain-spinal cord MRI were performed. RESULTS: Twenty two percent of the patients fulfilling brain MRI Paty criteria (p < 0.01), 54.5% Fazekas (p = 0.007) and 80% of patients fulfilling Barkhof criteria (p = 0.009) presented CDMS. The spinal MR imaging from CDMS patients was always abnormal, showing cervical and marginal location with a diameter < 2 cm. CONCLUSION: Brain MRI is strongly predictive of the risk of developing CDMS and spinal cord MRI may increase the sensitivity to detect conversion to CDMS.

Jacob's disease: report of two cases and review of the literature.

Jacob's disease is a rare condition consisting of new joint formation between the coronoid process of the mandible and the inner aspect of the zygomatic arch. Strictly speaking, it was first described by the French anatomist Oscar Jacob in 1899, although in 1853 von Langenbeck had described coronoid process hyperplasia. The pathogenesis of both conditions remains unknown. In this paper we present two new cases and a complete review of the literature on Jacob's disease, of which we have found only 12 cases. Due to the low prevalence of this condition, its diagnosis is not straight forward.

Influencia de la presión arterial en el estudiode la reactividad cerebrovascular en oclusiones carotídeas / The influence of the arterial pressure in the study of cerebrovascular reactivity in carotid obstructions

Introducción. La reactividad cerebrovascular (RCV) es la capacidad de la microcirculación cerebral de incrementar el flujo sanguíneo cerebral ante estímulos vasodilatadores; en pacientes con oclusión carotídea se encuentra disminuida. Los cambios en la presión arterial producidos durante la realización de los distintos tests de estimación de la RCV podrían influir en la cuantificación de la misma por Doppler transcraneal (DTC). Objetivos. Evaluar la concordancia entre los distintos métodos de estimación de la RCV por DTC en pacientes con oclusiones carotídeas y valorar la importancia de la monitorización de la presión arterial durante los tests de RCV. Pacientes y métodos. Se evaluaron 17 pacientes con oclusión de la arteria carótida interna confirmada por arteriografía. Se determinó la RCV mediante tres métodos distintos: test de apnea, Breath-Holding index (BHI) y test de acetazolamida endovenosa. Durante los tests de RCV se monitorizaba la presión arterial. Resultados. Se objetivó una reducción de la velocidad media basal de flujo y del índice de pulsatilidad en el lado ocluido, con una asociación estadísticamente significativa, en relación con el contralateral (p< 0,001). Existe una buena concordancia entre los distintos tests de RCV, objetivándose una disminución de la RCV en el lado ocluido, en comparación con el contralateral (p< 0,001) para los distintos tests; sin embargo, esta correlación no existe en las estenosis <70 por ciento. Durante el test de apnea se producían cambios en la presión arterial, con una tendencia a aumentar la PA sistólica; por el contrario, durante el test de acetazolamida no había variaciones significativas en la presión arterial. Conclusiones. Existe una buena concordancia en la RCV entre el test de apnea, BHI y acetazolamida en oclusiones carotídeas. Se producen cambios en la presión arterial durante los tests de apnea y BHI; sin embargo, el test de acetazolamida no modifica los valores de la presión arterial (AU)

[The influence of the arterial pressure in the study of cerebrovascular reactivity in carotid obstructions]. / Influencia de la presión arterial en el estudio de la reactividad cerebrovascular en oclusiones carotídeas.

INTRODUCTION: Cerebrovascular reactivity (CVR) is the capacity of the cerebral microcirculation to increase cerebral blood flow on vasodilator stimulation. This is reduced in patients with carotid obstruction. The changes in arterial pressure produced whilst carrying out different tests for estimation of the CVR may affect its measurement by transcranial Doppler. OBJECTIVES: To evaluate the concordance between the different methods for estimation of the CVR by transcranial Doppler in patients with carotid obstruction and to evaluate the importance of monitoring the arterial pressure during CVR tests. PATIENTS AND METHODS: We evaluated 17 patients with internal carotid artery obstruction confirmed on arteriography. The CVR was determined by three different methods: apnea test. Breath-Holding Index (BHI) and intravenous acetazolamide test. RESULTS: During the tests of RCV the arterial pressure was monitored. We found that there was a reduction in the average basal rate of flow and of the pulsatile index on the obstructed side, with a statistically significant association in relation to the contralateral side (p < 0.001). There was good concordance between the different tests of CVR, with reduced CVR seen on the obstructed side as compared to the contralateral side (p < 0.001) for the different tests. However, this correlation was not seen in stenosis < 70%. During the apnea test changes in blood pressure occurred, with a tendency to increase in the systolic pressure. However, there were no significant changes in blood pressure during the acetazolamide test. CONCLUSIONS: There is good concordance in the CVR between the apnea, BHI and acetazolamide tests in carotid obstruction. Changes in arterial pressure occurred during the apnea and BHI tests. However, the acetazolamide test caused no change in arterial pressure.