G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus.

G protein-coupled estrogen receptor (GPER) in the amygdala and the dorsal hippocampus mediates actions of estradiol on anxiety, social recognition and spatial memory. In addition, GPER participates in the estrogenic regulation of synaptic function in the amygdala and in the process of adult neurogenesis in the dentate gyrus. While the distribution of the canonical estrogen receptors α and ß in the amygdala and dorsal hippocampus are well characterized, little is known about the regional distribution of GPER in these brain regions and whether this distribution is affected by sex or the stages of the estrous cycle. In this study we performed a morphometric analysis of GPER immunoreactivity in the posterodorsal medial, anteroventral medial, basolateral, basomedial and central subdivisions of the amygdala and in all the histological layers of CA1 and the dentate gyrus of the dorsal hippocampal formation. The number of GPER immunoreactive cells was estimated in these different structures. GPER immunoreactivity was detected in all the assessed subdivisions of the amygdaloid nucleus and dorsal hippocampal formation. The number of GPER immunoreactive cells was higher in males than in estrus females in the central (P = 0.001) and the posterodorsal medial amygdala (P < 0.05); higher in males than in diestrus females in the strata orients (P < 0.01) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer of the dentate gyrus (P < 0.01); higher in diestrus females than in males in the basolateral amygdala (P < 0.05); higher in diestrus females than in estrus females in the central (P < 0.01), posterodorsal medial (P < 0.01) and basolateral amygdala (P < 0.01) and higher in estrus females than in diestrus females in the strata oriens (P < 0.05) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer (P < 0.05) and the hilus of the dentate gyrus (P < 0.05). The findings suggest that estrogenic regulation of the amygdala and hippocampus through GPER may be different in males and in females and may fluctuate during the estrous cycle.

Toxina botulínica tipo A en la migraña crónica refractaria: experiencia en uso compasivo preautorización / Botulinum toxin A in chronic refractory migraine: premarketing experience

Introducción. La migraña crónica es frecuentemente incapacitante y se asocia a abuso de analgésicos. La reciente aprobación de la toxina botulínica tipo A -OnabotulinumtoxinA (OnabotA)- supone un avance considerable. Objetivo. Describir la casuística en el uso compasivo preautorización. Pacientes y métodos. Son 35 casos con migraña crónica de una consulta de cefaleas, tratados entre julio de 2009 y diciembre de 2011. Se inyectaron 100 U de OnabotA en 21 puntos de la musculatura facial y craneal, según el protocolo modificado del ensayo PREEMPT. Para el análisis se determinaron, antes y después del tratamiento, los episodios y días de migraña, la intensidad de dolor y los días de incapacidad (Migraine Dissability Assessment Scale), y los datos cuantitativos de la medicación. En el seguimiento se repitieron las dosis en los respondedores, en un intervalo terapéutico individualizado de respuesta. Se consideró respuesta: caída de la intensidad del dolor a la mitad o ≥ 4 puntos en la escala visual analógica (VAS), y descenso de días de dolor en ≥ 7/mes o conversión a no abuso de fármacos. Resultados. Observamos respuesta en 27 casos (80%). En ellos apreciamos: disminución de la intensidad de la cefalea, tanto en intensidad del dolor (VAS < 0,001) como en días mensuales de incapacidad (3,2 frente a 0,4; p < 0,001); mejoría en el número de días mensuales de dolor (19,8 frente a 13,8; p < 0,05); y reducción significativa de casos de abuso de analgésicos (69% frente a 13%; p < 0,01). La duración media del efecto fue de 15 semanas; el seguimiento medio, de 9,8 meses. Encontramos efectos adversos (ptosis palpebral o dolor local) en cinco casos (14%). Conclusiones. La OnabotA demostró eficacia en el tratamiento preventivo de la migraña crónica. Observamos mejoría, con especial significado clínico, en la intensidad de la cefalea. Se redujo también el abuso de analgésicos. Los efectos adversos fueron escasos (AU)

Introduction. Chronic migraine is very disabling, with medication overuse commonly associated. The recent approval of botulinum toxin-A -OnabotulinumtoxinA (OnabotA)- means a hallmark. Aim. To describe our experience in compassionate use before approval Patients and methods. 35 cases with chronic migraine assessed between July 2009-December 2011 in a specialized headache consultation. 100 U of OnabotA were injected in 21 points over the facial and pericranial muscles, according to a modified PREEMPT protocol. We determined before and after treatment: number of episodes and migraine days; pain intensity and days of disability extracted from MIDAS score, and data regarding drug intake. After follow-up, new injections were given at intervals dictated by individualized response timing. Therapeutic response was considered when: intensity of pain was reduced to a half o ≥ 4 VAS points, or the number of monthly days of pain descended ≥ 7/month, or the case converted to non-drug overuser. Results. In 27 cases (80%) it was proved clinical improvement. This effect was confirmed by: a reduction in headacheseverity, reflected as much in pain intensity (VAS scale < 0.001) as in the number of days with disability (3.2 vs 0.4, p < 0.001); an improvement in the number of monthly days of pain (19.8 vs 13.8, p < 0.05; a significant decrease in the number of cases of medication overuse (69% vs 13%, p < 0.01). Mean duration of effect was 15 weeks and mean follow-up 9.8 months. Conclusions. OnabotA disclosed efficacy as prophylactic treatment of chronic migraine. It is mainly expressed as a reduction of pain intensity. Medication overuse also descended. Adverse events were sparse (AU)

[Botulinum toxin A in chronic refractory migraine: premarketing experience]. / Toxina botulinica tipo A en la migraña crónica refractaria: experiencia en uso compasivo preautorización.

INTRODUCTION: Chronic migraine is very disabling, with medication overuse commonly associated. The recent approval of botulinum toxin-A -OnabotulinumtoxinA (OnabotA)- means a hallmark. AIM: To describe our experience in compassionate use before approval. PATIENTS AND METHODS: 35 cases with chronic migraine assessed between July 2009-December 2011 in a specialized headache consultation. 100 U of OnabotA were injected in 21 points over the facial and pericranial muscles, according to a modified PREEMPT protocol. We determined before and after treatment: number of episodes and migraine days; pain intensity and days of disability extracted from MIDAS score, and data regarding drug intake. After follow-up, new injections were given at intervals dictated by individualized response timing. Therapeutic response was considered when: intensity of pain was reduced to a half o ≥ 4 VAS points, or the number of monthly days of pain descended ≥ 7/month, or the case converted to non-drug overuser. RESULTS: In 27 cases (80%) it was proved clinical improvement. This effect was confirmed by: a reduction in headache severity, reflected as much in pain intensity (VAS scale < 0.001) as in the number of days with disability (3.2 vs 0.4, p < 0.001); an improvement in the number of monthly days of pain (19.8 vs 13.8, p < 0.05; a significant decrease in the number of cases of medication overuse (69% vs 13%, p < 0.01). Mean duration of effect was 15 weeks and mean follow-up 9.8 months. CONCLUSIONS: OnabotA disclosed efficacy as prophylactic treatment of chronic migraine. It is mainly expressed as a reduction of pain intensity. Medication overuse also descended. Adverse events were sparse.

[Cardiac cephalgia: an underdiagnosed condition? ]. / Cefalea cardíaca: 'una entidad infradiagnosticada?

Cardiac cephalgia, or headache occurring as manifestation of myocardial ischemia, has only recently been recognized as a distinct entity. In patients with known ischemic cardiopathy, its diagnosis depends on the presence of severe headache that is accompanied by nausea, worsened by physical exercise, and only ceases with nitrate administration. We report on two patients who met diagnostic criteria for this entity. In both, headache was the only symptom of coronary ischemia, and delayed its diagnosis. Headache occurred both at rest and during exertion, and resolved only after the administration of nitrates. Cardiac cephalgia should be suspected in patients with a history of ischemic cardiopathy who present with de novo headache, even when thoracic pain is absent, especially if the headache improves with nitrates. Differential diagnosis with migraine is crucial to avoid the administration of vasoconstrictors.

Cefalea cardíaca: ¿una entidad infradiagnosticada? / Cardiac cephalgia: an underdiagnosed condition?

La cefalea cardíaca, o cefalea como manifestación de isquemia miocárdica, es una entidad individualizada recientemente. Su diagnóstico en un paciente con cardiopatía isquémica requiere una cefalea intensa, acompañada de náuseas y empeorada por el ejercicio, que cede tras la administración de nitratos. Presentamos los casos de 2 pacientes que cumplían estos criterios diagnósticos. En ambos, esta cefalea fue el único síntoma de isquemia coronaria, lo que retrasó el diagnóstico, aconteció con esfuerzos y en reposo, y sólo cedió tras la administración de nitratos. La cefalea cardíaca ha de sospecharse en pacientes con cardiopatía isquémica que consultan por cefalea de reciente comienzo, aunque no presenten dolor torácico, sobre todo si mejoran con nitratos. El diagnóstico diferencial con la migraña es crucial de cara a evitar medicaciones vasoconstrictoras

Cardiac cephalgia, or headache occurring as manifestation of myocardial ischemia, has only recently been recognized as a distinct entity. In patients with known ischemic cardiopathy, its diagnosis depends on the presence of severe headache that is accompanied by nausea, worsened by physical exercise, and only ceases with nitrate administration. We report on two patients who met diagnostic criteria for this entity. In both, headache was the only symptom of coronary ischemia, and delayed its diagnosis. Headache occurred both at rest and during exertion, and resolved only after the administration of nitrates. Cardiac cephalgia should be suspected in patients with a history of ischemic cardiopathy who present with de novo headache, even when thoracic pain is absent, especially if the headache improves with nitrates. Differential diagnosis with migraine is crucial to avoid the administration of vasoconstrictors