severe headaches

2 Types of Severe Headaches Connected to Body’s Internal Clock

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Researchers say they have found links between two types of headaches and the body’s internal clock, which could lead to better treatments.

Cluster headaches more commonly happen at night, and migraines occur more often during the day, according to a meta-analysis published in Neurology, the medical journal of the American Academy of Neurology.

Cluster headaches bring pain around the eyes in bursts that can last for 15 minutes; an attack can last up to three hours. These headaches are rare and more common in men than in women.

Migraines, meanwhile, are three times more common among women.

“Cluster headache is known to be circadian, but it was surprising how circadian migraine is,” Mark Burish, MD, the study’s lead author and director of the Will Erwin Headache Research Center at UTHealth Houston, told NBC News.

The meta-analysis looked at 72 studies that examined how the body’s internal clock, or circadian rhythm, is involved with headache disorders. Combined, the two headache types affect more than 40 million Americans.

Cluster headaches were more closely tied to circadian cycles during seasonal changes in the spring and fall. More than 70% of people in 16 studies said they had more attacks during these seasons and said they usually happen between late night and early morning.

Researchers were surprised that migraines came in cycles throughout the day and the year. Migraine headaches were reported less often from 11 p.m. to 7 a.m., with more frequent and worse migraines from spring through fall.

“Medications that target the circadian cycle might be a new type of treatment we can offer these patients,” Burish said. “We weren’t sure if looking at circadian targets of therapy for migraine would actually do anything but after putting all of this together, we are more confident that it could be,” he said. 

Migraine, severe headache history associated with hypertension risk

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U.S. adults who reported a history of migraine or severe headache were 25% more likely to develop hypertension compared with those with no migraine history, with a higher risk for women vs. men, researchers reported.

“Elevated blood pressure is more frequently detected in patients with headaches during admission to the emergency department than in those without headaches,” Jing Zhang, MBBS, PhD, of the department of cardiology at the First Affiliated Hospital of Nanjing Medical University, China, and colleagues wrote in the study background. “Migraineurs also tend to have a higher risk of cardio-cerebrovascular diseases. In addition, several BP-lowering drugs, including beta-blockers, ACE inhibitors and angiotensin II receptor blockers, have been demonstrated to be effective in the prophylactic treatment of migraine. Collectively, these findings provide a rationale for elucidating the association between migraine and hypertension.”

Graphical depiction of data presented in article
U.S. adults who reported a history of migraine or severe headache were 25% more likely to develop hypertension vs. those with no migraine history, with a higher risk for women vs. men.
Data were derived from Zhang J, et al. Nutr Metab Cardiovasc Dis. 2022;doi:10.1016/j.numecd.2022.11.014.

In a cross-sectional study, Zhang and colleagues analyzed data from 5,716 adults who completed the National Health and Nutrition Examination Survey between 1999 and 2004. Self-reported migraine was identified from yes/no responses to the question, “Has a doctor ever said that you suffer or have suffered from migraine or severe headache?” Researchers assessed the association between migraines, severe headaches and hypertension.

Within the cohort, 19.8% of respondents reported migraine or severe headaches. Participants with migraine were predominantly younger women and had a higher BMI, lower education level and lower dietary intake of potassium and calcium compared with participants without migraine. Those reporting migraines also had lower serum levels of total cholesterol, creatinine and hemoglobin, as well as a higher estimated glomerular filtration rate (P for all < .05).

After adjustment for potential confounders, a history of migraine or severe headaches was positively associated with hypertension (OR = 1.25; 95% CI, 1.03-1.53).

In subgroup analyses, positive associations between migraine or severe headache and hypertension were detected in women (OR = 1.39; 95% CI, 1.07-1.82), those with a lower BMI, defined as 25 kg/m2 or less (OR = 1.51; 95% CI, 1.09-2.08) and those without diabetes (OR = 1.27; 95% CI, 1.05-1.55). However, there was no statistically significant association among migraine, severe headache and hypertension across all subgroup characteristics.

The researchers noted that the association of migraine with hypertension may differ between patients with or without aura and between patients with different headache frequencies.

“Further prospective and mechanistic studies are needed to elucidate the causality of these associations,” the researchers wrote.

A Chilly Fever

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A 30-year-old graduate student presented with fevers associated with shaking chills and severe headaches. He had been well until 1 week before presentation, when he began to have daily fevers, with temperatures as high as 39.4°C. Any fever in a patient who has had possible exposure to malaria should prompt consideration of this diagnosis.

Clinical Pearls

•What is the annual incidence of malaria in the United States?

In the United States, the annual incidence of malaria is approximately 1500 cases. In 2010, a total of 1691 cases were reported to the Centers for Disease Control and Prevention (CDC), the largest number reported since 1980; P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 58%, 19%, 2%, and 2% of cases, respectively.

•How do malaria and babesiosis differ in appearance on a peripheral blood smear?

Intraerythrocytic parasites are seen in both malaria and babesiosis. Plasmodia metabolize heme to form an intracellular crystallized pigment, hemozoin. Although hemozoin is not invariably identified in cases of malaria, its presence reliably distinguishes malaria infection from babesia infection. Malaria parasites can be distinguished from B. [Babesia] microti by the presence of recognizable gametocytes (characteristically banana-shaped in Plasmodium falciparum and round, with a granular appearance, in nonfalciparum species). In addition, intracellular vacuoles and extracellular merozoites are unusual in malaria but common in babesiosis, and the classic “Maltese cross” (a tetrad of parasites budding at right angles) is unique to babesia species.  Morning Report Questions

Q: Which malaria species can remain dormant in the liver?

A: In the case of P. vivax and P. ovale, some sporozoites (immature malaria parasites) do not replicate immediately when they invade hepatocytes but remain dormant (as hypnozoites) for prolonged periods. The average time to relapse is approximately 9 months, but it can range from weeks to years. The interval to relapse depends on the strain (earlier with tropical strains and later with temperate strains), the initial inoculum, and host factors (e.g., febrile illnesses can trigger relapse associated with P. vivax). None of the commonly used prophylactic agents (chloroquine, mefloquine, doxycycline, or atovaquone-proguanil) eliminate hypnozoites. Primaquine, the only effective drug against dormant hypnozoites, has not been approved by the Food and Drug Administration for primary prophylaxis, but the CDC endorses its use for prophylaxis in Latin American countries where P. vivax predominates, because the drug can prevent both primary attacks and relapses caused by all species that are a source of malarial infection.

Q: How is acute or recurrent P. vivax infection treated?

A: In patients with acute or recurrent malaria infection, treatment depends on the species and the resistance status in the area where the infection was acquired. P. falciparum is resistant to chloroquine in most regions in which it is endemic and resistant to mefloquine in parts of Southeast Asia. In contrast, nonfalciparum malaria parasites do not have substantial resistance to mefloquine, and the distribution of chloroquine-resistant P. vivax malaria is limited, occurring primarily in Indonesia and Papua New Guinea. After treatment is initiated, peripheral-blood smears should be obtained daily for 4 days (parasitemia is typically eliminated by day 4), on days 7 and 28 to confirm eradication, and at any time symptoms recur, suggesting treatment failure. In areas other than those with known chloroquine resistance, chloroquine, followed by a 14-day course of primaquine to prevent subsequent relapses, remains the standard treatment for P. vivax parasitemia. Given the risk of hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency who receive treatment with primaquine, potential recipients should be tested for G6PD deficiency. Among patients with a contraindication to primaquine therapy, treatment with chloroquine alone carries a 20% risk of relapse; extended chloroquine prophylaxis can be offered to patients who have frequent relapses.