Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple / Nicolau syndrome due to self-injectable drugs in multiple sclerosis

Introducción y objetivos: El síndrome de Nicolau, o embolia cutis medicamentosa, es una complicación cutánea infrecuente de los fármacos inyectados que se ha descrito escasamente en relación con los fármacos empleados en la esclerosis múltiple. Pacientes y métodos: Es un estudio retrospectivo de pacientes afectos de síndrome de Nicolau que reciben fármacos autoinyectables para la esclerosis múltiple desde 2010 hasta octubre de 2022. Resultados: Desde enero de 2010 hasta octubre de 2022 se ha seguido en nuestra consulta de patología desmielinizante a 449 pacientes con fármacos autoinyectables –317 con interferón beta y 132 con acetato de glatiramer (AG)–. En este período de tiempo se han recogido 10 episodios de síndrome de Nicolau en siete pacientes (seis hombres y una mujer) que recibían AG, lo que supone un 5,3% del total de pacientes bajo ese tratamiento. Las zonas más afectadas fueron el glúteo (n = 4) y el brazo (n = 3). Tres pacientes (42,8%) sufrieron un segundo episodio. Conclusión: El síndrome de Nicolau es una complicación exclusiva del AG y más frecuente en hombres en nuestra cohorte de pacientes con esclerosis múltiple. La recurrencia de esta complicación cutánea es frecuente en un mismo paciente, lo que es un factor que hay que tener en cuenta en la decisión de mantener el fármaco o cambiar a otra estrategia terapéutica.(AU)

Introduction and aims: Nicolau syndrome, or embolia cutis medicamentosa, is a rare cutaneous complication of drug injection that has been rarely described in relation to medication used in multiple sclerosis. Patients and methods: We conducted a retrospective study of patients with Nicolau syndrome receiving self-injectable multiple sclerosis medication from 2010 to October 2022. Results: From January 2010 to October 2022, 449 patients were followed up in our demyelinating pathology unit with self-injectable drugs - 317 with beta interferons and 132 with glatiramer acetate (GA). In this period of time, 10 episodes of Nicolau syndrome were recorded in seven patients (six men and one woman) receiving GA, which represents 5.3% of the total number of patients receiving this treatment. The most commonly affected areas were the buttocks (n = 4) and the arms (n = 3). Three patients (42.8%) suffered a second episode. Conclusion: Nicolau syndrome is a complication unique to GA and more frequent in men in our cohort of multiple sclerosis patients. This cutaneous complication frequently recurs in the same patient, which is a factor to be taken into account in the decision to maintain the drug or switch to another therapeutic strategy.(AU)

[Nicolau syndrome due to self-injectable drugs in multiple sclerosis]. / Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple.

INTRODUCTION AND AIMS: Nicolau syndrome, or embolia cutis medicamentosa, is a rare cutaneous complication of drug injection that has been rarely described in relation to medication used in multiple sclerosis. PATIENTS AND METHODS: We conducted a retrospective study of patients with Nicolau syndrome receiving self-injectable multiple sclerosis medication from 2010 to October 2022. RESULTS: From January 2010 to October 2022, 449 patients were followed up in our demyelinating pathology unit with self-injectable drugs - 317 with beta interferons and 132 with glatiramer acetate (GA). In this period of time, 10 episodes of Nicolau syndrome were recorded in seven patients (six men and one woman) receiving GA, which represents 5.3% of the total number of patients receiving this treatment. The most commonly affected areas were the buttocks (n = 4) and the arms (n = 3). Three patients (42.8%) suffered a second episode. CONCLUSION: Nicolau syndrome is a complication unique to GA and more frequent in men in our cohort of multiple sclerosis patients. This cutaneous complication frequently recurs in the same patient, which is a factor to be taken into account in the decision to maintain the drug or switch to another therapeutic strategy.

TITLE: Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple.Introducción y objetivos. El síndrome de Nicolau, o embolia cutis medicamentosa, es una complicación cutánea infrecuente de los fármacos inyectados que se ha descrito escasamente en relación con los fármacos empleados en la esclerosis múltiple. Pacientes y métodos. Es un estudio retrospectivo de pacientes afectos de síndrome de Nicolau que reciben fármacos autoinyectables para la esclerosis múltiple desde 2010 hasta octubre de 2022. Resultados. Desde enero de 2010 hasta octubre de 2022 se ha seguido en nuestra consulta de patología desmielinizante a 449 pacientes con fármacos autoinyectables ­317 con interferón beta y 132 con acetato de glatiramer (AG)­. En este período de tiempo se han recogido 10 episodios de síndrome de Nicolau en siete pacientes (seis hombres y una mujer) que recibían AG, lo que supone un 5,3% del total de pacientes bajo ese tratamiento. Las zonas más afectadas fueron el glúteo (n = 4) y el brazo (n = 3). Tres pacientes (42,8%) sufrieron un segundo episodio. Conclusión. El síndrome de Nicolau es una complicación exclusiva del AG y más frecuente en hombres en nuestra cohorte de pacientes con esclerosis múltiple. La recurrencia de esta complicación cutánea es frecuente en un mismo paciente, lo que es un factor que hay que tener en cuenta en la decisión de mantener el fármaco o cambiar a otra estrategia terapéutica.

[Rituximab: its efficacy, effectiveness and safety in the treatment of multiple sclerosis]. / Rituximab: eficacia, efectividad y seguridad en el tratamiento de la esclerosis multiple.

INTRODUCTION: There is increasing evidence that B cells and humoral immunity play key roles in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, an anti-CD20 monoclonal antibody, has been shown to be effective in controlling the disease and has recently been aproved by the Food and Drug Administration for the treatment of primary progressive and relapsing MS. While awaiting its marketing authorization, the use of rituximab, with a similar mechanism of action, has expanded widely in the area of demyelinating diseases. AIM: To address the main aspects of efficacy, effectiveness and safety of rituximab in the treatment of MS. DEVELOPMENT: PubMed review of placebo-controlled clinical trials, prospective open label studies, retrospective observational studies, and case series using rituximab in adult MS affected populations were performed. Its impact on the clinical and radiological control of the disease was evaluated, as well as any relevant safety issues. CONCLUSIONS: In all of the studies reviewed, rituximab demonstrated a consistent benefit in controlling inflammatory activity, both clinically, reducing the incidence of relapses, and radiologically, avoiding the appearance of new and/or active lesions. On the contrary, with regards to the progression of disability, its effect is more controversial. Safety profile appears acceptable. Rituximab seems to be an effective and safe drug in the treatment of MS.

TITLE: Rituximab: eficacia, efectividad y seguridad en el tratamiento de la esclerosis multiple.Introduccion. Existe evidencia creciente de que las celulas B y la inmunidad humoral tienen un papel fundamental en la fisiopatogenia de la esclerosis multiple (EM). El ocrelizumab, un anticuerpo monoclonal anti-CD20, ha demostrado ser eficaz en el control de la enfermedad y recientemente ha sido aprobado por la Food and Drug Administration estadounidense para el tratamiento de las formas primariamente progresivas y las formas recidivantes de la EM. A la espera de su comercializacion, el uso del rituximab, con un mecanismo de accion similar, se ha expandido ampliamente en el area de las enfermedades desmielinizantes. Objetivo. Abordar los principales aspectos de eficacia, efectividad y seguridad del rituximab en el tratamiento de la EM. Desarrollo. Se realizo una revision bibliografica a traves de PubMed de los ensayos clinicos controlados con placebo, los estudios prospectivos abiertos, los estudios observacionales retrospectivos y las series de casos que utilizaron rituximab en poblaciones adultas afectas de EM. Se valoro su impacto en el control clinico y radiologico de la enfermedad, asi como los aspectos relevantes de seguridad. Conclusiones. En todos los estudios revisados, el rituximab demostro un beneficio consistente en cuanto al control de la actividad inflamatoria, tanto clinica, reduciendo la incidencia de brotes, como radiologica, evitando la aparicion de lesiones nuevas o activas. Por el contrario, respecto a la progresion de la discapacidad, su efecto es mas controvertido. No se hallaron alertas de seguridad destacables. El rituximab parece ser un farmaco eficaz, efectivo y seguro en el tratamiento de la EM.

Netrin-1 and multiple sclerosis: a new biomarker for neuroinflammation?

BACKGROUND AND PURPOSE: Netrin-1, an axon guidance protein, reduces serum levels of pro-inflammatory mediators and stabilizes the blood-brain barrier limiting the entrance of immune cells into the central nervous system. The aim was to investigate its presence in the experimental autoimmune encephalomyelitis (EAE) model and in multiple sclerosis (MS) patients with and without clinical activity. METHODS: Netrin-1 levels were evaluated in EAE mouse tissues. Afterwards, serum netrin-1 was cross-sectionally quantified in 90 patients with different MS phenotypes and 30 control subjects. An additional group of 10 relapsing-remitting MS (RRMS) patients was longitudinally evaluated throughout a relapse (RRMSr) with an interval of 60 days. Tumour necrosis factor α (TNFα), a reference inflammatory cytokine, and netrin-1 were quantified by enzyme-linked immunosorbent assay. RESULTS: Experimental autoimmune encephalomyelitis mice showed significantly lower netrin-1 levels and higher TNFα amounts in sera, spinal cord and cerebella than healthy control mice. MS patients showed significantly lower serum netrin-1 levels than controls (511.62 ± 209.30 and 748.32 ± 103.24 pg/ml, respectively; P ≤ 0.005). The lowest protein levels were found in RRMSr, remaining significantly lower throughout the relapse. TNFα serum concentrations were higher in MS patients compared to controls, and negatively correlated with netrin-1 levels (r = -0.3734, P ≤ 0.0001). CONCLUSIONS: Netrin-1 decreased in EAE and in MS patients, mainly during relapse, suggesting an anti-inflammatory role of netrin-1. Further research should be performed in a larger cohort of patients to validate netrin-1 as a biomarker of MS inflammatory activity.

Aneurisma intracraneal distal con presentación atípica, localización y evolución en una mujer joven / Atypical presentation of a distal cerebral aneurysm: location and outcome in a young woman

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Síndrome HaNDL: correlación entre la topografía del déficit neurológico y las alteraciones en electroencefalograma y SPECT en una serie de 5 nuevos casos / HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases

Introducción: El síndrome de cefalea transitoria y déficits neurológicos con linfocitosis de líquido cefalorraquídeo (LCR), conocido por su acrónimo en inglés, HaNDL, se caracteriza por episodios de cefalea de características migrañosas acompañados por síntomas deficitarios motores, sensitivos o de lenguaje. El electroencefalograma (EEG) o la tomografía por emisión de fotón único (SPECT) pueden mostrar anomalías focales consistentes con los déficits neurológicos. Pretendemos evaluar dicha correlación en una serie de 5 nuevos pacientes. Pacientes: Análisis retrospectivo de pacientes atendidos en un hospital terciario (enero del 2010-mayo del 2014, 5 casos [3 varones, 2 mujeres]), de 30,6 ± 7,7 años (21-39). Presentaron 3,4 ± 2,6 (2-8) episodios de cefalea moderada-severa y déficits neurológicos durante un tiempo no superior a 5 semanas. En todos, pleocitosis de LCR (70 a 312 células/mm3, 96,5-100% linfocitos), con estudio etiológico negativo. Resultados: EEG en 4 pacientes y SPECT en 3. Caso 1: 8 episodios, 4 de hemisferio izquierdo, 3 hemisferio derecho y 1 de tronco, 2 EEG con enlentecimiento temporal izquierdo y bitemporal; SPECT normal. Caso 2: 2 cuadros, hemisférico izquierdo y hemisférico derecho respectivamente y SPECT con flujo disminuido temporal izquierdo. Caso 3: 3 episodios hemisféricos izquierdos; EEG con enlentecimiento temporo-frontal bilateral. Caso 4: 2 cuadros con topografía parieto-occipital derecha y EEG con enlentecimiento frontal derecho. Caso 5: 2 episodios, hemisférico derecho y hemisférico izquierdo, EEG con enlentecimiento temporal derecho; SPECT normal. Conclusiones: Existe gran heterogeneidad clínica en los déficits neurológicos del HaNDL; las alteraciones en SPECT y, sobre todo, en EEG no son infrecuentes y no siempre se relacionan con la topografía clínica

Introduction: Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes accompanied by neurological deficits consisting of motor, sensory, or aphasic symptoms. Electroencephalogram (EEG) and single photon emission computed tomography (SPECT) may show focal abnormalities that correspond to the neurological deficits. We aim to evaluate the correlation between focal deficit topography and EEG or SPECT abnormalities in 5 new cases. Patients: We retrospectively reviewed patients attended in a tertiary hospital (January 2010-May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 ± 7.7 (21-39) years. They presented 3.4 ± 2.6 episodes of headache (range, 2-8) of moderate to severe intensity and transient neurological deficits over a maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312 cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological studies. Results: At least one EEG was performed in 4 patients and SPECT in 3 patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1 brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2 episodes, right hemisphere and left hemisphere, EEG with right temporal slowing; normal SPECT. Conclusion: The neurological deficits accompanying headache in HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of all EEG abnormalities were not uncommon in our series and they did not always correlate to the topography of focal deficits

HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases. / Síndrome HaNDL: correlación entre la topografía del déficit neurológico y las alteraciones en electroencefalograma y SPECT en una serie de 5 nuevos casos.

INTRODUCTION: Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes accompanied by neurological deficits consisting of motor, sensory, or aphasic symptoms. Electroencephalogram (EEG) and single photon emission computed tomography (SPECT) may show focal abnormalities that correspond to the neurological deficits. We aim to evaluate the correlation between focal deficit topography and EEG or SPECT abnormalities in 5 new cases. PATIENTS: We retrospectively reviewed patients attended in a tertiary hospital (January 2010-May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 ± 7.7 (21-39) years. They presented 3.4 ± 2.6 episodes of headache (range, 2-8) of moderate to severe intensity and transient neurological deficits over a maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312 cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological studies. RESULTS: At least one EEG was performed in 4 patients and SPECT in 3 patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1 brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2 episodes, right hemisphere and left hemisphere, EEG with right temporal slowing; normal SPECT. CONCLUSION: The neurological deficits accompanying headache in HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of all EEG abnormalities were not uncommon in our series and they did not always correlate to the topography of focal déficits.

Características de los 2.000 primeros pacientes registrados en una consulta monográfica de cefaleas / Characteristics of the first 2, 000 patients registered in a specialist headache clinic

Objetivos: Analizar las características demográficas de los 2.000 primeros pacientes del registro de una consulta monográfica de cefaleas (CMC), y la incidencia de los diferentes tipos de cefaleas codificadas según los criterios de la clasificación internacional de cefaleas, ii edición (CIC-II) Pacientes y métodos: En enero de 2008 se estableció una CMC en un hospital terciario. Los pacientes podían ser derivados desde atención primaria en formato de alta resolución, la consulta general de neurología u otras especialidades. Se atendieron fuera de agenda a profesionales del centro o familiares. Recogimos prospectivamente en cada paciente la edad, el sexo, la vía de acceso a la consulta y los tratamientos sintomáticos o profilácticos prescritos con anterioridad. Las cefaleas fueron clasificadas de acuerdo a la CIC-II; cuando un paciente cumplía criterios para más de un tipo de cefalea todas eran diagnosticadas y clasificadas. Resultados: En octubre de 2012 2.000 pacientes (ratio mujeres/hombres: 2,59/1) habían sido incluidos. La mediana de edad de estos pacientes era de 42 años (rango: 11-94). El 55,3% fueron derivados desde atención primaria. Un 68,1% no requirió pruebas complementarias. Se codificaron 3.095 cefaleas; 2.222 (71,8%) primarias y 382 (12,3%) secundarias. Ciento diecisiete (3,8%) neuralgias craneales, 136 (4,3%) no clasificables y 238 (7,7%) incluidas en el apéndice de investigación de la CIC-II. El grupo más representado era el 1 (migraña) con un 53% del total de cefaleas. Conclusiones: Las características de nuestro registro son comparables a las descritas previamente en consultas monográficas de cefaleas. La migraña fue el diagnostico más habitual. Las cefaleas secundarias no son frecuentes en nuestra serie. La mayoría de las cefaleas pudieron ser codificadas por la CIC-II

Objectives: Headache is a common cause of medical consultations. We aim to analyze demographic characteristics of first two thousand patients in our register, and the incidence of their different headaches coded according to the International Classification of Headache Disorders, ii edition (ICHD-II). Patients and methods: On January 2008 a headache outpatient clinic was established in a tertiary hospital. Patients could be referred by general practitioners according to previously consensused criteria, as well as by general neurology or other specialities clinics. The following variables were prospectively collected on all patients; age, sex, referral source, complementary tests required, and the previously prescribed symptomatic or prophylactic therapies. All headaches were classified accordingly to ICHD-II. When a patient fulfilled criteria for more than one type of headache, all of them were diagnosed and classified. Results: In October 2012, 2000 patients (ratio women/men 2.59/1) had been seen in our headache clinic. The median age was 42 years (range: 11-94), 55.3% were referred from primary care, and 68.1% did not require complementary tests. A total of 3095 headaches were recorded in these 2000 patients, of which 2222 (71.8%) were considered primary headaches, 382 (12.3%) secondary headaches, with 117 (3.8%) corresponding to cranial neuralgias, 136 (4.3%) were unclassified headaches, and 238 (7.7%) were included in the research Appendix of the ICHD-II. The most represented group was 1 (migraine) with 53% of all headaches. Conclusions: The characteristics of first 2000 patients in our register were comparable to those previously described in other types of headache outpatient clinics. Migraine was the most frequent diagnosis, and secondary headaches were not as frequent in our series. Most headaches could be coded according to ICHD-II criteria

Diferencias entre migraña crónica con y sin uso excesivo de medicación: experiencia en una serie hospitalaria de 434 pacientes / Chronic migraine with and without medication overuse: Experience in a hospital series of 434 patients

Introducción: La migraña crónica (MC) es una evolución de la migraña episódica favorecida por factores de riesgo, entre los que se encuentra el uso excesivo de medicación (UEM). Pretendemos comparar características clínicas y demográficas de una serie de casos de MC, con y sin UEM. Métodos: Pacientes con MC (criterios revisados 2006) atendidos en una consulta monográfica de cefaleas de un hospital terciario entre enero del 2008 y mayo del 2012. Recogimos datos demográficos, evolución, utilización previa de preventivos e impacto de la migraña medido con la escala HIT-6. esultados: Cuatrocientos treinta y cuatro pacientes (357 mujeres, 77 varones) fueron diagnosticados de MC entre un total de 1,868 (23,2%) atendidos en la mencionada consulta durante el periodo de inclusión. Doscientos cincuenta y ocho (72,2%) presentaban UEM. El 59,8% de los casos con UEM recibieron previamente tratamiento preventivo frente al 41,1% sin UEM (p < 0,001). La edad de inicio de la migraña fue menor en los pacientes con UEM (21,2 ± 10,1 vs. 23,8 ± 12,5 años; p = 0,02) y el tiempo de evolución al llegar a nuestra consulta mayor en los pacientes con UEM (23,8 ± 14,1 vs. 18,3 ± 14,8 años; p < 0,001). No encontramos diferencia en la puntuación HIT-6 o el porcentaje de casos con HIT-6 mayor de 55 entre ambos grupos. Conclusiones: La MC con o sin UEM es una afección frecuente y discapacitante en una consulta de cefaleas. En nuestra población, los pacientes con UEM llegan a la consulta tras una evolución más larga, en la que ya recibieron tratamientos preventivos

Introduction: Chronic migraine (CM) is a complication of episodic migraine, favored by risk factors as medication overuse (MO). We intend to compare demographic and clinic characteristics of a series of CM patients, with and without MO. Methods: The study included patients with CM (2006 revised criteria) attended in a headache outpatient office located in a tertiary hospital between January 2008 and May 2012. We recorded demographic characteristics, age at migraine onset, time from onset, previous use of symptomatic or preventive therapy, and headache impact measured with six-item headache impact test (HIT-6). Results: A total of 434 patients (357 women, 77 men) were diagnosed with CM out of the 1868 (23.2%) that attended our clinic. Of these, 258 (72.2%) fulfilled criteria of MO, and 59.8% of those with MO, and 41.1% of cases without MO had previously received preventative treatment (P<.001). Age at onset of migraine was lower in MO patients (21.2 ± 10.1 vs 23.8 ± 12.5 years, P=.02) and time from onset to headache clinic consultation was higher in MO cases (23.8 ± 14.1 vs 18.3 ± 14.8 years, P<.001). We found no difference between both groups in average HIT-6 score and the percentage of patients with a HIT-6 score over 55. Conclusions: CM, with or without MO, is a burdensome group of patients in our headache clinic. Patients with MO are referred later and have more frequently received preventive treatments

Chronic migraine with and without medication overuse: experience in a hospital series of 434 patients.

INTRODUCTION: Chronic migraine (CM) is a complication of episodic migraine, favored by risk factors as medication overuse (MO). We intend to compare demographic and clinic characteristics of a series of CM patients, with and without MO. METHODS: The study included patients with CM (2006 revised criteria) attended in a headache outpatient office located in a tertiary hospital between January 2008 and May 2012. We recorded demographic characteristics, age at migraine onset, time from onset, previous use of symptomatic or preventive therapy, and headache impact measured with six-item headache impact test (HIT-6). RESULTS: A total of 434 patients (357 women, 77 men) were diagnosed with CM out of the 1868 (23.2%) that attended our clinic. Of these, 258 (72.2%) fulfilled criteria of MO, and 59.8% of those with MO, and 41.1% of cases without MO had previously received preventative treatment (P<.001). Age at onset of migraine was lower in MO patients (21.2±10.1 vs 23.8±12.5 years, P=.02) and time from onset to headache clinic consultation was higher in MO cases (23.8±14.1 vs 18.3±14.8 years, P<.001). We found no difference between both groups in average HIT-6 score and the percentage of patients with a HIT-6 score over 55. CONCLUSIONS: CM, with or without MO, is a burdensome group of patients in our headache clinic. Patients with MO are referred later and have more frequently received preventive treatments.

Characteristics of the first 2,000 patients registered in a specialist headache clinic.

OBJECTIVES: Headache is a common cause of medical consultations. We aim to analyze demographic characteristics of first two thousand patients in our register, and the incidence of their different headaches coded according to the International Classification of Headache Disorders, ii edition (ICHD-II). PATIENTS AND METHODS: On January 2008 a headache outpatient clinic was established in a tertiary hospital. Patients could be referred by general practitioners according to previously consensused criteria, as well as by general neurology or other specialities clinics. The following variables were prospectively collected on all patients; age, sex, referral source, complementary tests required, and the previously prescribed symptomatic or prophylactic therapies. All headaches were classified accordingly to ICHD-II. When a patient fulfilled criteria for more than one type of headache, all of them were diagnosed and classified. RESULTS: In October 2012, 2000 patients (ratio women/men 2.59/1) had been seen in our headache clinic. The median age was 42 years (range: 11-94), 55.3% were referred from primary care, and 68.1% did not require complementary tests. A total of 3095 headaches were recorded in these 2000 patients, of which 2222 (71.8%) were considered primary headaches, 382 (12.3%) secondary headaches, with 117 (3.8%) corresponding to cranial neuralgias, 136 (4.3%) were unclassified headaches, and 238 (7.7%) were included in the research Appendix of the ICHD-II. The most represented group was 1 (migraine) with 53% of all headaches. CONCLUSIONS: The characteristics of first 2000 patients in our register were comparable to those previously described in other types of headache outpatient clinics. Migraine was the most frequent diagnosis, and secondary headaches were not as frequent in our series. Most headaches could be coded according to ICHD-II criteria.

Cefaleas en la persona mayor: características de una serie de 262 pacientes / Headache in the elderly: Characteristics in a series of 262 patients

Introducción: Aunque la prevalencia de las cefaleas disminuye en las personas mayores (≥ 65 años), son causa importante de consulta, con particularidades diagnósticas y terapéuticas que es necesario conocer. Analizamos las características de este grupo etario en una consulta de cefaleas. Métodos: Recogimos las variables demográficas y clínicas de los pacientes atendidos en una consulta de cefaleas de un hospital terciario (enero del 2008-mayo del 2012). Las cefaleas se codificaron según la Clasificación Internacional de Cefaleas, 2.ª edición (CIC-2). Resultados: Doscientos sesenta y dos pacientes (189 mujeres, 73 varones) con ≥ 65 años fueron atendidos sobre un total de 1.868 (14%); 99 (68 mujeres, 31 varones, 5,3% del total) superaban los 75 años. Inicio de la cefalea tras los 65 años en 136 casos (51,9%). Se codificaron 362 cefaleas, el 23,8% en el grupo 1 de CIC-2 (migrañas) y el 28,7% en el grupo 2 (cefalea tensional). Se diagnosticaron 59 (16%) cefaleas secundarias; 26 (7,2%) se encuadraron en el grupo 13 (neuralgias) y 23 (6,4%) en el grupo 14 (no clasificables). En 38 casos (14,5%) había sobreúso de medicación sintomática. Entre las cefaleas típicas de esta edad identificamos 41 migrañas crónicas, 6 cefaleas hípnicas, 4 neuralgias del occipital, 2 SUNCT, una cefalea cervicogénica, una cefalea primaria de la tos y 2 arteritis de la temporal. Conclusiones: El porcentaje de personas mayores atendidas en una consulta de cefaleas es elevado. La cefalea tensional es la más frecuente en esta población. Cefaleas típicas de esta edad, como la cefalea hípnica o la neuralgia del occipital, están presentes

Introduction: Although headache prevalence decreases in patients older than 65, headaches are a common complaint and their different clinical and therapeutic features must be understood. This article analyses the clinical characteristics of elderly patients treated in an outpatient headache unit. Methods: We collected demographic and clinical data from patients treated in a tertiary hospital headache unit between January 2008 and May 2013. Headaches were codified according to the International Classification of Headache Disorders, 2nd edition (ICHD-2). Results: Of a total of 1868 patients treated, 262 patients (14%, 189 women and 73 men) were older than 65 years. Ninety-nine (68 women, 31 men, 5.3% of the total) were over 75. Headaches began after the age of 65 in only 136 patients (51.9%). The 362 headaches were codified as follows: 23.8% as Group 1 (Migraine) and 28.7% as Group 2 (Tension-type headache). We diagnosed 58 (16%) secondary headaches; 26 (7.2%) were classified as Group 13 (Cranial neuralgias) and 23 (6.4%) in Group 14 (Other headaches). Symptomatic medication overuse was detected in 38 patients (14.5%). We also identified headaches considered typical in the elderly, including chronic migraine (41 cases), hypnic headache (6), occipital neuralgia (4), SUNCT (2), cervicogenic headache (1), primary cough headache (1), and giant cell arteritis (2). Conclusions: Elderly patients were frequently treated in our outpatient headache unit. Tension-type headache was the most common diagnosis in this population. Geriatric headache syndromes such as hypnic headache or occipital neuralgia were also represented in our series

Immune reconstitution inflammatory syndrome and natalizumab-Is it possible before removing the drug?

Multiple sclerosis (MS) patients treated with natalizumab have a significant reduction in annualized relapse rate; in these patients, a relapse is uncommon but not unexpected. In contrast, the appearance of a severe exacerbation is striking and requires the differential diagnosis with progressive multifocal leukoencephalopathy. Here, we describe a case of a 22-year-old woman with relapsing-remitting MS who developed an unexpected response after the patient׳s fifth natalizumab infusion with an aggressive radiological and clinical evolution. Changing the patient׳s treatment to fingolimod resulted in the absence of new clinical relapses and the absence of active lesions on brain magnetic resonance images (MRI) during the first 12 months of follow-up. We hypothesize that the appearance of natalizumab antibodies in this patient triggered lymphocyte migration to the central nervous system in a rebound phenomenon; this is similar to what occurs during immune reconstitution inflammatory syndrome (IRIS) after removal of natalizumab.

Headache in the elderly: characteristics in a series of 262 patients.

INTRODUCTION: Although headache prevalence decreases in patients older than 65, headaches are a common complaint and their different clinical and therapeutic features must be understood. This article analyses the clinical characteristics of elderly patients treated in an outpatient headache unit. METHODS: We collected demographic and clinical data from patients treated in a tertiary hospital headache unit between January 2008 and May 2013. Headaches were codified according to the International Classification of Headache Disorders, 2nd edition (ICHD-2). RESULTS: Of a total of 1868 patients treated, 262 patients (14%, 189 women and 73 men) were older than 65 years. Ninety-nine (68 women, 31 men, 5.3% of the total) were over 75. Headaches began after the age of 65 in only 136 patients (51.9%). The 362 headaches were codified as follows: 23.8% as Group 1 (Migraine) and 28.7% as Group 2 (Tension-type headache). We diagnosed 58 (16%) secondary headaches; 26 (7.2%) were classified as Group 13 (Cranial neuralgias) and 23 (6.4%) in Group 14 (Other headaches). Symptomatic medication overuse was detected in 38 patients (14.5%). We also identified headaches considered typical in the elderly, including chronic migraine (41 cases), hypnic headache (6), occipital neuralgia (4), SUNCT (2), cervicogenic headache (1), primary cough headache (1), and giant cell arteritis (2). CONCLUSIONS: Elderly patients were frequently treated in our outpatient headache unit. Tension-type headache was the most common diagnosis in this population. Geriatric headache syndromes such as hypnic headache or occipital neuralgia were also represented in our series.

Abordaje terapéutico de los síntomas no motores de la enfermedad de Parkinson / Therapeutic management of the non-motor symptoms in Parkinson's disease

Introducción. La enfermedad de Parkinson (EP) es una entidad compleja con una sintomatología diversa que presenta, además de los clásicos síntomas motores, un amplio número de síntomas no motores. Estos síntomas son muy prevalentes desde el inicio de la enfermedad e incluso pueden preceder en el tiempo a los síntomas motores (estreñimiento, alteración del olfato, trastorno de conducta del sueño REM) actuando como marcadores precoces de la enfermedad. Causan importante impacto en la calidad de vida de los enfermos con EP. Pueden ser los síntomas más incapacitantes para el paciente. Por todo ello, precisan de un manejo adecuado que mejore el bienestar de nuestros pacientes. Objetivo. Dar una visión actualizada del tratamiento de los síntomas no motores más prevalentes de la EP. Desarrollo. Se describen los síntomas no motores (vegetativos, trastornos del sueño, apatía) más prevalentes y discapacitantes de la enfermedad de Parkinson y se hace una revisión actualizada de su tratamiento. Conclusión: La alteración que la enfermedad produce en otros sistemas distintos al dopaminérgico causa un amplio número de síntomas distintos a los motores. Su mejor conocimiento permitirá diagnosticar y optimizar el tratamiento de estos síntomas, reforzando el bienestar de nuestros pacientes (AU)

Introduction. Parkinson's disease (PD) is a complex condition with a variety of symptoms, including a large number of nonmotor symptoms, in addition to the classic motor symptoms. These symptoms are highly prevalent from the onset of the disease and may even appear earlier than the motor symptoms (constipation, altered sense of smell, REM sleep behaviour disorder) and act as early markers of the disease. They have a significant impact on the quality of life of patients with PD and can be the most disabling symptoms for the patient. As a result, they need adequate management that improves our patients’ welfare. Aims. The objective of this study is to offer an updated view of the most prevalent non-motor symptoms of PD. Development. We describe the most prevalent and disabling non-motor symptoms (vegetative, sleep disorders, apathy) of Parkinson's disease and we also conduct a review of the state-of-the-art in its treatment. Conclusions. The alterations that the illness produces in systems other than the dopaminergic system cause a large number of symptoms in addition to the motor ones. A better understanding of them will make it possible to diagnose and optimise the treatment of these symptoms, thereby boosting our patients' welfare (AU)

Degeneración corticobasal / Corticobasal degeneration

La degeneración corticobasal (DCB) es un proceso neurodegenerativo lentamente progresivo, de inicio en la edad adulta que se presenta típicamente con parkinsonismo asimétrico y disfunción cognitiva. Actualmente, se clasifica como una taupatía. Los hallazgos neuropatológicos muestran una importante pérdida neuronal cortical que hasta fases muy avanzadas de la enfermedad es de predominio asimétrico y multifocal, más a menudo en las regiones frontalesparietales. Es un síndrome de una gran diversidad clínica cuya evolución estará marcada por la asimetría de los principales síntomas. El trastorno cognitivo puede ser una forma habitual de presentación identificándose un espectro de fenotipos clínicos dependiendo de la topografía del área degenerativa. Típicamente, se caracteriza por marcada rigidez e hipocinesia, distonía de predominio en una extremidad, mioclonías corticales reflejas, piramidalismo y temblor grosero postural o de acción. También destacan los déficits apráxicos, el déficit sensitivo cortical y el denominado fenómeno del miembro ajeno que aunque menos habitual cuando aparece es característico. El diagnóstico es fundamentalmente clínico, en base a los criterios diagnósticos del síndrome corticobasal propuestos en el año 2003 y con el apoyo de las pruebas las complementarias. El diagnóstico diferencial debería considerarse con los Parkinson-Plus así como con las demencias degenerativas primarias con predominio de síntomas frontales y/o temporales, en especial, con la PSP y la demencia fronto-temporal .La DCB progresa en 3-15 años hacia la muerte del individuo, normalmente como consecuencia de complicaciones derivadas de la inmovilidad (AU)

Corticobasal degeneration (CBD) is a slowly progressive neurodegenerative process, which begins in adulthood and typically presents with asymmetrical parkinsonism and cognitive dysfunction. It is currently classified as a tauopathy. Neuropathological findings show an important loss of cortical neurons that is predominantly asymmetrical and multifocal until very advanced phases of the disease, more often in the frontal-parietal regions. It is a syndrome with a wide clinical diversity and a progression that will be marked by the asymmetry of the main symptoms. Cognitive disorder may be a common presenting symptom and a range of clinical phenomena have been identified, depending on the topography of the degenerative area. It is typically characterised by a marked rigidity and hypokinesia, dystonia with predominance in one extremity, cortical reflex myoclonus, pyramidal signs and postural or action coarse tremor. Also prominent are apraxic deficits, cortical sensory deficit and the so-called alien limb phenomenon, which, although less frequent, is considered characteristic when it does appear. Diagnosis is fundamentally clinical and based on the diagnostic criteria of corticobasal syndrome put forward in the year 2003 and with the support of complementary tests. Differential diagnosis should be considered with Parkinson-Plus as well as with the primary degenerative dementias with predominance of frontal and/or temporal symptoms, more especially with PSP and fronto-temporal dementia. CBD progresses in 3-15 years towards the death of the individual, normally as a consequence of complications deriving from immobility (AU)

Epicrania fugax: características clínicas de una serie de 18 pacientes / Epicrania fugax: the clinical characteristics of a series of 18 patients

Introducción. La epicrania fugax es una entidad de reciente descripción, consistente en breves paroxismos dolorosos iniciados en regiones cefálicas posteriores, con irradiación hacia ojo, nariz o sien ipsilaterales. Objetivo. Presentar 18 casos de epicrania fugax de una consulta monográfica de cefaleas de un hospital terciario y analizar sus características demográficas y clínicas, así como la indicación y respuesta al tratamiento profiláctico. Pacientes y métodos. Entre marzo de 2008, momento en el que se describe la epicrania fugax y marzo de 2011, 18 pacientes (12 mujeres y 6 hombres), de entre 1.210 atendidos en dicha consulta (1,48%), recibieron dicho diagnóstico. Seis de estos casos se habían publicado con anterioridad. Resultados. Edad media al inicio de 42,5 ± 17,7 años (rango: 23-82 años). Presentaban paroxismos dolorosos iniciados en la región occipital (n = 11; 61,1%), parietal (n = 6; 33,3%) o parietooccipital (n = 1; 5,6%), e irradiados hacia el ojo (n = 12; 66,6%) o la sien (n = 6; 33,3%) ipsilaterales; todo el proceso duraba menos de 15 segundos. La mayoría describía su dolor como lancinante o punzante. En 10 casos (55,5%) persistía un dolor en la zona de origen de los paroxismos, que en 6 (33,3%) estaba circunscrito a una zona circular bien delimitada y reunía criterios de cefalea numular. En 12 casos (66,6%) se utilizó tratamiento profiláctico, sobre todo lamotrigina y gabapentina con respuesta variable. Conclusión. Pretendemos reforzar la propuesta de la epicrania fugax como un nuevo síndrome con un espectro clínico bien caracterizado. No parece una entidad excepcional, y su conocimiento dará lugar probablemente a la descripción de nuevas series. Con frecuencia es necesario tratamiento y, aunque se requiere mayor experiencia, la gabapentina y la lamotrigina tienen un papel prometedor (AU)

Introduction. Epicrania fugax is a recently reported condition consisting in brief painful paroxysms that begin in the posterior regions of the brain and irradiate towards the ipsilateral eye, nose or temple. Aims. To present 18 cases of epicrania fugax from a monographic headache centre in a tertiary hospital and to analyse their demographic and clinical features, as well as the indication and response to prophylactic treatment. Patients and methods. Between March 2008, when epicrania fugax was first reported, and March 2011, of a total of 1210 patients who were attended in that service (1.48%), 18 (12 females and 6 males) were diagnosed as suffering from this condition. Six of these cases had been published earlier. Results. The mean age at onset was 42.5 ± 17.7 years (range: 23-82 years). They presented painful paroxysms that began in the occipital (n = 11; 61.1%), parietal (n = 6; 33.3%) or parieto-occipital (n = 1; 5.6%) regions and irradiated towards the ipsilateral eye (n = 12; 66.6%) or temple (n = 6; 33.3%); the whole process lasted less than 15 seconds. Most of them described the pain as lancinating or stabbing. In 10 cases (55.5%) a pain remained in the area where the paroxysms began, which in 6 cases (33.3%) was limited to a well-defined circular area and met the criteria for classification as nummular headache. In 12 cases (66.6%), prophylactic treatment was used, above all lamotrigine and gabapentin, with varying results. Conclusion. Our aim is to back the proposal of epicrania fugax as a new syndrome with a well-defined clinical spectrum. It does not appear to be an exceptional condition and further knowledge about it will probably give rise to the description of new series. Treatment is often necessary and, although further information and experience are needed, gabapentin and lamotrigine both play a promising role (AU)

[Nummular headache: clinical features and therapeutic experience in a series of 30 new cases]. / Cefalea numular: caracteristicas clinicas y experiencia terapeutica en una serie de 30 nuevos casos.

INTRODUCTION: Nummular headache (NH) is a mild or moderate pain, located in a small, well circumscribed, rounded or elliptical area. Temporal pattern is variable and pain exacerbations have been described. AIM. To analyze clinical characteristics and therapy requirement and response in a series of patients attended due to NH in a headache outpatient office. PATIENTS AND METHODS: 30 patients (18 females, 12 males) diagnosed as NH. We considered demographic and nosological characteristics, temporal pattern, presence and intensity of exacerbations, and requirement of symptomatic or preventive therapies. RESULTS: Age at onset 49.2 ± 18.1 years (range: 21-79 years). Two of the patients presented a bifocal NH and we analyzed 32 areas, 28 rounded and 4 elliptical. Diameter: 4.7 ± 1.1 cm. Regarding locations occipital (10 areas, 31.3%), parietal (9 areas, 28.1%) and frontal (6 areas, 18.8%). Pain intensity of 5.2 ± 1.8 on a ten-point visual analogical scale. Regarding temporal profile, in 18 areas (56.3%) was chronic, in 5 (15.6%) episodic and undefined due to a scarce time from onset in 9 (28.1%). In 16 areas (50%) pain exacerbations lasting from 3 seconds to 15 minutes occurred. Nine (30%) patients did not improve with symptomatic drugs, and at least one preventative was prescribed in 23 (76.6%) patients without consistent effectiveness. CONCLUSIONS: NH is not an uncommon diagnosis in an outpatient headache office. In our series, basal pain intensity is moderate and symptomatic drugs commonly provide no relief. So, patients frequently need a preventive therapy.

Incidence and influence on referral of primary stabbing headache in an outpatient headache clinic.

Primary stabbing headache (PSH) is a pain, as brief, sharp, jabbing stabs, predominantly felt in the first division of trigeminal nerve. Population studies have shown that PSH is a common headache. However, most people suffer attacks of low frequency or intensity and seldom seek for medical assistance. There are few clinic-based studies of PSH, and its real influence as a primary cause for referral to neurology outpatient offices is to be determined. We aim to investigate the burden of PSH as main complaint in an outpatient headache clinic. We reviewed all patients with PSH (ICHD-II criteria), attended in an outpatient headache clinic in a tertiary hospital during a 2.5-year period (January 2008-June 2010). We considered demographic and nosological characteristics and if PSH was main cause of submission. 36 patients (26 females, 10 males) out of 725 (5%) were diagnosed of PSH. Mean age at onset 34.1 ± 2.9 years (range 10-72). Mean time from onset to diagnosis 68.8 ± 18.3 months. Twenty-four patients fulfilled ICHD-II criteria for other headaches (14 migraine, 6 tension-type headache, 2 hemicrania continua, 1 primary cough headache and 1 primary exertional headache). 77.7% of patients were submitted from primary care. In 14 patients (39%), PSH was main reason for submission, its intensity or frequency in 5 (35.7%) and fear of malignancy in 9 (74.3%). Only two patients of those who associated other headaches were submitted due to PSH. In conclusion, PSH is not an uncommon diagnosis in an outpatient headache office. However, and according to our data, it is not usually the main cause of submission to a headache clinic.