Some children have visual disturbances that occur in the absence of, or are out of proportion to, their objective ophthalmological findings. These symptoms reflect a wide range of processes that may be benign or a sign of neurological, systemic, or psychiatric disease. This chapter deals with the neuro-ophthalmologic detection of organic and psychogenic disorders that may manifest as transient or unexplained visual loss of the same episodic visual disturbances that occur in childhood, but several formidable problems confront the physician who is trying to reach the correct diagnosis. The descriptions of episodic visual disturbances and hallucinations in children are less complex in detail than those of the adult population because children have limited vocabulary and limited experiential basis of sensory phenomenon to draw upon.

The field of migraine genetics has seen an explosion of information over the last year. In a recent breakthrough, missense mutations in a chromosome 1q23 gene, ATP1A2, encoding a Na⁺, K⁺-ATPase, have been identified in four distinct pedigrees with a rare form of familial hemiplegic migraine (FHM). ATP1A2 is expressed in the brain, like the voltage gated calcium channel gene, CACNA1A, previously identified as the first hemiplegic migraine gene (FHM1). The shared hemiplegic migraine phenotype of mutations in ATP1A2 and CACNA1A raises the possibility that they coordinately regulate ion homeostasis that determines susceptibility to the initiation of both migraine aura and the pain phase of migraine. For the more common and genetically complex forms of migraine, genome-wide screens have identified several new loci on 4q24, 6p12.2–21.1, 11q24, and 14q21.2-q22.3, suggesting additional migraine genes in these regions. In addition, a recent large case-control association study has linked single nucleotide polymorphisms in the insulin receptor/INSR gene with migraine. However, these polymorphisms do not result in detectable changes in receptor function. The continuing genetic identification of key proteins involved in migraine will refine our understanding of this common and sometimes debilitating disorder, which can strike during the most productive years of a person’s life. Given the co-morbidity of migraine with depression and bipolar disorder, our knowledge of the causes of migraine may also contribute to our understanding of these disorders.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease.

The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.

Key Chapter Points

One in five women experiences migraine during her reproductive years.

Cycling estradiol levels predict migraine changes throughout a woman’s reproductive years. Migraine is typically aggravated by low estradiol (e.g., premenstrual exacerbation) and improved with high estradiol (e.g., pregnancy).

Migraine improves during pregnancy for about half of women. If improvement is going to occur, it usually does so before the end of the first trimester.

Migraines typically reoccur after delivery, although breastfeeding may delay headache recurrence.

After menarche, women have an increased prevalence of migraine compared to men. There is significant variability in the frequency and severity of migraine throughout the menstrual cycle. Women report migraines occur more frequently during menses, and that those are more severe than other migraines. This creates a unique challenge of effectively treating menstrually related and pure menstrual migraines. As with treatment of other migraines, both abortive and prophylactic treatment regimens are used. Triptans demonstrate efficacy in the abortive management of menstrually related and pure menstrual migraines. For migraines that occur primarily during menses or that are particularly resistant to other therapies, intermittent prophylactic therapies can be used. Naproxen and estrogens have been studied for this use. More recently, triptans have been examined and have shown efficacy for intermittent prophylaxis of menstrual migraine.

Menstrual migraine is commonly encountered in women who are experiencing attacks of migraine without aura. It remains controversial whether attacks of menstrually associated migraine are more severe and have a longer duration than non-menstrually associated attacks. The pathogenesis of menstrual migraine is not understood completely, but it may be related to estrogen withdrawal or prostaglandin release. Preventative therapies may be considered in those who have failed abortive medications or have attacks lasting longer than 2 days. They can be administered short-term during the perimenstrual time period or continuously throughout the menstrual cycle. Short-term prophylactics should be tried first because menstrual migraines generally last for 1 to 4 days only. Continuous prophylactics may be considered in those with attacks refractory to short-term therapies.

Migraine is often comorbid with psychiatric disorders such as major depression, bipolar disorder, and anxiety disorders. Although most of the research on psychiatric comorbidities and migraine is of an epidemiologic nature, a growing body of literature has investigated possible mechanisms underlying this relationship, such as medication overuse, serotonergic dysfunction, ovarian hormone fluctuations, and central sensitization. The present article overviews this growing literature and notes strategies for the clinical management of migraine patients with psychiatric comorbidities.

The understanding of migraine pathophysiology has evolved from the belief that migraine is a vascular disorder, to evidence that better defines migraine as a neurogenic disorder associated with secondary changes in brain perfusion. There is evidence to suggest that the early phase of migraine pain results from neurogenic infiammation affecting cranial blood vessels and dura. Allodynia, hyperalgesia, and expansion of nociceptive fields occur during most well-established migraine attacks. These clinical features of migraine are evocative of those traditionally associated with neuropathic pain. A hypothesis that defines migraine pain as a unique neuropathic pain disorder can imply the potential for neural plasticity and may provide insight into the mechanisms that underlie the transformation of episodic to chronic forms of migraine. The neuropathic pain model of migraine pathophysiology not only paves the way for mechanism-based treatment strategies that can improve the acute and preventive management of migraine attacks, but also opens the door for the discovery of novel therapeutic targets. It also lends momentum to an understanding of clinically intriguing topics such as opiate-induced hyperalgesia and medication-overuse headache (rebound headache), opioid resistance in the treatment of chronic headache, and disease modification in defending against the potential for migraine transformation.

The objective of this study is to estimate the prevalence of gastroesophageal reflux disease (GERD) and heartburn in migraine patients and examine their use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin-containing medications when treating acute migraine attacks. Responses from a web-based survey of migraine patients were matched to the same patient’s responses on a general health survey. A total of 1,832 migraineurs (92.0%) were successfully matched. A total of 403 migraineurs (22.0%) reported having diagnosed GERD, 212 (11.6%) reported diagnosed heartburn, and 290 (15.8%) reported reflux symptoms but were undiagnosed. The most common prescription drugs used to treat migraines were triptans. First-line NSAID/aspirin medication use was 10.0% among diagnosed GERD and heartburn patients, 17.8% among undiagnosed patients, and 11.8% among GERD/heartburn-free migraineurs. In conclusion, almost half of migraineurs reported physician-diagnosed GERD and heartburn or symptoms of these conditions. Use of NSAID medications for migraine is fairly common among diagnosed GERD patients and more so for those with undiagnosed GERD symptoms. Physicians should minimize prescribing NSAIDs or NSAID-containing acute migraine medications in this population.