Evaluation of headache in patients with cancer.

Headache is a common complaint and is often benign. When patients with cancer describe new headaches, it is important to ensure that there are no emergent or concerning etiologies, including metastatic disease. This review article details primary and secondary headaches. Red flags-the do-not-miss warning signs-are described. An initial approach to the evaluation, including suggestions for imaging, features to look for in a targeted examination, and when to request a consultation, is outlined. An overview of headache etiologies is described with a particular emphasis on the most common types: migraine and tension. The classification of headaches, based on criteria from the International Classification of Headache Disorders (3rd edition; beta version), is reviewed. Medications used for treatment, including newer biological agents, are described, and there are details about both abortive and preventive medication therapies. Suggestions for complementary and integrative therapies, some of which may be synergistic in treating other cancer symptoms, are outlined; they include mindfulness therapies, which are gaining traction in treating a variety of medical conditions. Readers should have an understanding of headache evaluation in patients with cancer and should know how to formulate a plan for a diagnosis. In addition, readers will gain familiarity with common treatments, both pharmacological and complementary/integrative.

The migraine eye: distinct rod-driven retinal pathways' response to dim light challenges the visual cortex hyperexcitability theory.

Migraine-type photophobia, most commonly described as exacerbation of headache by light, affects nearly 90% of the patients. It is the most bothersome symptom accompanying an attack. Using subjective psychophysical assessments, we showed that migraine patients are more sensitive to all colors of light during ictal than during interictal phase and that control subjects do not experience pain when exposed to different colors of light. Based on these findings, we suggested that color preference is unique to migraineurs (as it was not found in control subjects) rather than migraine phase (as it was found in both phases). To identify the origin of this photophobia in migraineurs, we compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual-evoked potential paradigms. Unexpectedly, it was the amplitude of the retinal rod-driven b wave, which was consistently larger (by 14%-19% in the light-adapted and 18%-34% in the dark-adapted flash ERG) in the migraineurs than in the controls, rather than the retinal cone-driven a wave or the visual-evoked potentials that differs most strikingly between the 2 groups. Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex. Clinically, the findings may explain why migraineurs complain that the light is too bright even when it is dim to the extent that nonmigraineurs feel as if they are in a cave.

Color-selective photophobia in ictal vs interictal migraineurs and in healthy controls.

Aversion to light is common among migraineurs undergoing acute attacks. Using psychophysical assessments in patients with episodic migraine, we reported that white, blue, amber, and red lights exacerbate migraine headache in a significantly larger percentage of patients and to a greater extent compared with green light. This study aimed at determining whether these findings are phase-dependent-namely, manifested exclusively during migraine (ictally) but not in its absence (interictally), or condition-dependent-ie, expressed uniquely in migraineurs but not in healthy controls. To determine whether the color preference of migraine-type photophobia is phase- or condition-dependent, we compared the effects of each color of light in each intensity between migraineurs during and in-between attacks and healthy controls. During the ictal and interictal phases, the proportion of migraineurs reporting changes in headache severity when exposed to the different colors of light increased in accordance with elevated light intensities. During the ictal phase, white, blue, amber, and red lights exacerbated headaches in ∼80% of the patients; however, during the interictal phase, light initiated headache in only 16% to 19%. Notably, green light exacerbated headaches in 40% and triggered headaches in 3% of the patients studied during the ictal and interictal phases, respectively. With one exception (highest red light intensity), no control subject reported headache in response to the light stimuli. These findings suggest that color preference is unique to migraineurs-as it was not found in control subjects-and that it is independent of whether or not the patients are in their ictal or interictal phase.

Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine.

Migraineurs avoid light because it intensifies their headache. However, this is not the only reason for their aversion to light. Studying migraineurs and control subjects, we found that lights triggered more changes in autonomic functions and negative emotions during, rather than in the absence of, migraine or in control subjects, and that the association between light and positive emotions was stronger in control subjects than migraineurs. Seeking to define a neuroanatomical substrate for these findings, we showed that, in rats, axons of retinal ganglion cells converge on hypothalamic neurons that project directly to nuclei in the brainstem and spinal cord that regulate parasympathetic and sympathetic functions and contain dopamine, histamine, orexin, melanin-concentrating hormone, oxytocin, and vasopressin. Although the rat studies define frameworks for conceptualizing how light triggers the symptoms described by patients, the human studies suggest that the aversive nature of light is more complex than its association with headache intensification.

Migraine photophobia originating in cone-driven retinal pathways.

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

Posttraumatic stress disorder and intimate partner violence in a women's headache center.

BACKGROUND: Posttraumatic stress disorder has been linked to women's ill health, including headaches. Intimate partner violence, which may result in posttraumatic stress disorder, is often reported by women with headaches. Prior studies of intimate partner violence and headache have estimated lifetime but not 12-month prevalence. The researchers in this study examined the relationship between headache and posttraumatic stress disorder in a novel population, and estimated 12-month and lifetime prevalence rates of intimate partner violence. METHODS: Patients were recruited from a women's headache center (n = 92) during 2006-07 and completed the Migraine Disability Assessment measure of headache severity. Posttraumatic stress disorder was measured using a modified Breslau scale. Twelve-month and lifetime physical intimate partner violence were measured with the Partner Violence Screen and the STaT ("slapped, threatened and throw") measure. Multivariable regression determined factors independently associated with headache severity. RESULTS: Among all participants, 28.3% screened positive for posttraumatic stress disorder; 9.8% and 36.9% of women endorsed recent and lifetime intimate partner violence. Posttraumatic stress disorder was strongly associated with headache severity (ß = 34.12, p = 0.01). Patients reporting lifetime intimate partner violence exhibited a trend of nine additional days of disability due to headache over 90 days. CONCLUSIONS: Posttraumatic stress disorder and intimate partner violence occur among a sizable proportion of women referred for headache. The authors' findings reaffirm that clinicians treating women with headaches must be aware of the possibility of posttraumatic stress disorder and intimate partner violence in such patients.