Evaluation of structural changes in orbitofrontal cortex in relation to medication overuse in migraine patients: a diffusion tensor imaging study / Avaliação das mudanças estruturais no córtex orbitofrontal em relação ao uso excessivo de medicamentos em pacientes com migrânea: um estudo de imagem por tensor de difusão

Abstract Background: Migraine is a prevalent neurological disease that leads to severe headaches. Moreover, it is the commonest among the primary headaches that cause medication overuse headache (MOH). The orbitofrontal cortex (OFC) is one of the structures most associated with medication overuse. Objective: To determine microstructural changes in the OFC among migraine patients who developed MOH, through the diffusion tensor imaging (DTI) technique. Methods: Fifty-eight patients who had been diagnosed with migraine based on the Classification of Headache Disorders (ICHD-III-B) were included in the study. Patients were sub-classified into two groups, with and without MOH, based on the MOH criteria of ICHD-III-B. DTI was applied to each patient. The OFC fractional anisotropy (FA), and apparent diffusion coefficient (ADC) values of the two groups were compared. Results: The mean age of all the patients was 35.98±7.92 years (range: 18-65), and 84.5% (n=49) of them were female. The two groups, with MOH (n=25) and without (n=33), were alike in terms of age, gender, family history, migraine with or without aura and duration of illness. It was found that there was a significant difference in FA values of the left OFC between the two groups (0.32±0.01 versus 0.29±0.01; p=0.04). Conclusions: An association was found between MOH and changes to OFC microstructure. Determination of neuropathology and factors associated with medication overuse among migraine patients is crucial in terms of identifying the at-risk patient population and improving proper treatment strategies specific to these patients.

RESUMO Introdução: A migrânea é uma doença neurológica prevalente que causa fortes dores de cabeça. Além disso, é a mais comum entre as cefaleias primárias que causam cefaleia por uso excessivo de medicamentos (CUEM). O córtex orbitofrontal (OF) é uma das estruturas mais associadas ao uso excessivo de medicamentos. Objetivo: Determinar alterações microestruturais no córtex OF em pacientes com migrânea que desenvolveram CUEM, por meio da técnica de imagem por tensor de difusão (ITD). Métodos: Cinquenta e oito pacientes com diagnóstico de migrânea, com base na Classificação das Cefaleias (ICHD-III-B), foram incluídos no estudo. Os pacientes foram subclassificados em dois grupos, com e sem CUEM, com base nos critérios de CUEM da ICHD-III-B. A ITD foi aplicada a cada paciente. Os valores de anisotropia fracionada OFC (AF) e coeficiente de difusão aparente (CDA) dos dois grupos foram comparados. Resultados: A média de idade de todos os pacientes foi de 35,98±7,92 anos (variação: 18‒65), sendo 84,5% (n=49) do sexo feminino. Os dois grupos, com CUEM (n=25) e sem (n=33), são semelhantes em termos de idade, sexo, história familiar, migrânea com ou sem aura e duração da doença. Verificou-se que houve diferença significativa nos valores de AF do córtex OF esquerdo entre os dois grupos (0,32±0,01 versus 0,29±0,01; p=0,04). Conclusões: Foi encontrada associação entre o CUEM e as alterações na microestrutura do córtex OF. A determinação da neuropatologia e dos fatores associados ao uso excessivo de medicamentos entre pacientes com migrânea é crucial para identificar a população de pacientes em risco e melhorar as estratégias de tratamento adequadas específicas para esses pacientes.

Secondary Headaches in Children and Adolescents: What Not to Miss.

INTRODUCTION: Headaches are a common occurrence in childhood and adolescence. Most children presenting with a chief complaint of headache have a self-limited infectious disorder or primary headache syndrome that should not require extensive workup. PURPOSE OF REVIEW: Differentiating these conditions from other more serious causes of headache in children can sometimes be difficult. This article aims to provide information regarding "red flags" that should indicate a need for concern for disorders that require more urgent evaluation. RECENT FINDINGS: Long-held beliefs about specific "red flags" that have been analyzed in recent years as to their validity and new criteria for the diagnosis of idiopathic intracranial hypertension have been elaborated based on study. These publications are reviewed in this article. Knowledge of past and current literature on secondary headache in children, combined with thorough history taking and examination, should help determine when there is concern for a serious secondary cause for headache in children and adolescents and direct workup.

Longitudinal assessment of gray matter volumes and white matter integrity in patients with medication-overuse headache.

Background Medication-overuse headache is a common clinical entity, but neuroimaging studies investigating volumetric and microstructural alterations of the brain in medication-overuse headache are rare. Therefore, in the current longitidunal study we evaluated gray matter volume and white matter integrity in patients with medication-overuse headache before and after drug withdrawal. Methods A prospective study evaluated 27 patients with medication-overuse headache and 27 age-, sex-, and education-matched healthy adults. High-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging were obtained from the control group and medication-overuse headache patients before and six months after drug withdrawal. Tract-based spatial statistics of multiple diffusivity indices and voxel-based morphometry were employed to investigate white and gray matter abnormalities. Results No correlation was found between age, gender, education and smoking status in both groups. The most commonly overused medications were simple analgesics (96.3%) and combined analgesics (3.7%). The mean duration of the history of medication overuse and headaches was 56.7 ± 63.5 months. White matter diffusional and gray matter morphological alterations including volume, fractional anisotropy, radial diffusivity, and axial diffusivity analyses showed no significant relationship in the patients before and six months after withdrawal of analgesics. Also no difference was observed between the patients versus controls. Conclusion Our data demonstrated no structural alterations within the brain in medication-overuse headache.

Volume gain of periaqueductal gray in medication-overuse headache.

BACKGROUND: Periaqueductal gray (PAG) is a substantial descending pain modulatory center, and previous voxel-based morphometry study confirmed the clusters with increased volume in PAG region in medication-overuse headache (MOH). The aim of this study is to investigate altered PAG volume in MOH using an automated PAG segment method to measure the true PAG volume. METHODS: High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 22 patients with MOH and 22 normal controls (NC). PAG template was created based on ICBM 152 gray template, and the individual PAG was generated by applying the deformation field from structural image segment to the PAG template, and individual PAG volume was calculated. RESULTS: There was a significant increased volume of PAG in MOH (0.366 ± 0.005 ml) than that in NC (0.341 ± 0.005 ml)(P < 0.05). There was no significant correlation between the PAG volume and the clinical variables in MOH patients (P > 0.05). The area of receiver operating characteristic (ROC) curve was 0.845, and the cut-off of PAG volume was 0.341 ml with sensitivity 95.5% and specificity 63.6%. CONCLUSION: The present study demonstrated that the PAG volume gain was confirmed in MOH patients, and the automated individual PAG volume measure may be considered as a simple and effective imaging biomarker in MOH diagnosis.

Cefalea... ¿y algo más?: Neuroimágenes en el estudio de la cefalea / Headache and something else? Neuroimaging in the study of headaches

Se revisa la iconografía de los hallazgos por tomografía computada (TC) y resonancia magnética (RM) de la cefalea, según nuestra experiencia. De acuerdo con la base MESH, esta entidad se define como un dolor craneano, que puede ser de ocurrencia benigna o la manifestación de una amplia gama de desórdenes. Las cefaleas se clasifican por su evolución temporal (aguda o crónica), presentación (en estallido, gravativa, etc.) o coexistencia de síntomas asociados, como auras, convulsiones o déficits focales. También se dividen en primarias o secundarias, según la existencia o no de una patología subyacente. Las primarias pueden tener manifestaciones clínicas definidas, pero en las secundarias ciertos signos y síntomas deben alertar sobre la presencia de una patología estructural. En este caso, las neuroimágenes tienen un rol esencial al detectar las causantes del cuadro. Nuestros hallazgos correspondieron a cefaleas primarias (p. ej: infarto migrañoso) y a etiologías orgánicas, entre las que se destacaron causas vasculares, como patología venosa (trombosis), vasoespasmo y leucoencefalopatía posterior reversible; hemorragias intraparen-quimatosas y extraaxiales; cefaleas postraumáticas y posquirúrgicas; y causas infecciosas y tumorales (apoplejía hipofisaria e hipertensión endocraneana). Además, hubo malformaciones (Arnold-Chiari, p.ej.) y otras como hipotensión endocraneana. En algunos casos inicialmente se realizó una TC y luego una RM, mientras que en otros la RM fue el método de elección. Las neuroimágenes facilitan el estudio de la cefalea, caracterizando la afección en primaria o secundaria. En el segundo caso permiten, a su vez, clasificar los hallazgos

A review is presented of the radiological findings (computed tomography -CT- and magnetic resonance imaging -MRI-) of headache, according to our experience. According to MESH database this entity is a skull based pain that can have a benign cause or be an expression of a wide spectrum of disorders. Headaches can be classified according to their temporal evolution (acute or chronic), presentation (blow up, aura, rapidly evolutionary, etc.), or according to associated symptoms, such as seizures or focal deficits. They could also be classified into primary or secondary, depending on the presence or absence of demonstrable disease. The primary headaches can have known symptoms (i.e. migraine), but in secondary ones certain symptoms and signs should alert on the existence of structural disease. At this point imaging methods have an outstanding role, as they allow detecting and identifying structural causes in patients with headache. Our findings corresponded to primary headaches (i.e.: migraine infarction) and organic aetiologies, such as vascular causes (venous thrombosis, vasospasm and posterior reversible leukoencephalopathy); intracerebral and extra-axial haemorrhage; post-surgical and post- traumatic headaches; and those due to infections and tumours (pituitary apoplexy or intracranial hypertension). Malformations, such as Arnold-Chiari's, and intracranial hypotension have also been found. In some cases a CT is initially performed and then an MR, whilst in others MR is the method of choice. Neuroimaging facilitates the study of headache, helping to characterise them into primary or secondary. In the latter case, the imaging also enables the findings to be classified