Primary Cough Headache.

PURPOSE OF REVIEW: In this review article, we summarize the most recent findings and observations in patients experiencing primary cough headache. RECENT FINDINGS: Recent studies draw attention to further characterization of patients with primary cough headache in a pulmonology clinic. There have also been recent case studies describing new therapy considerations, including noninvasive vagus nerve stimulation and lumbar punctures. Primary cough headache has been a recognized entity since as early as 1932. Patients generally report a sudden onset, sharp headache lasting a few hours that is precipitated by Valsalva maneuver or coughing. It remains an uncommon diagnosis, and secondary causes are crucial to rule out with imaging studies. Additionally, there can be an overlap with other primary headache disorders such as primary exercise headache and headache associated with sexual activity, thus requiring a detailed history. Many hypotheses exist regarding the pathophysiology including relative pressure gradients and a crowded posterior fossa. Generally, patients are responsive to indomethacin, but more recent case reports have suggested benefits of other medications and procedures that may offer patients an alternative option, including vagus nerve stimulation, lumbar punctures, and beta blockers. Future case series and studies should focus on management of these patients, with a specific focus on individuals who do not tolerate indomethacin.

Hemiplegic Migraine.

PURPOSE OF REVIEW: In this article, we review recent updates to the epidemiology, diagnostic testing, genetics, pathophysiology, and management of hemiplegic migraine. RECENT FINDINGS: While three genes have been historically associated with hemiplegic migraine, recent studies suggest two additional genes may also be implicated including PPRT2 and SLC1A3. Hemiplegic migraine is a severe subset of migraine with aura with symptoms including reversible hemiparesis in addition to other aura symptoms such as visual, sensory, or speech. The exact pathophysiology of hemiplegic migraine is not clear, but it is thought that this phenomenon is due to neuronal and glial depolarization causing cortical spreading depression. Due to the severity of presentation as well as the numerous mimickers, it is important to know a comprehensive differential and work-up. Given the low prevalence of the disease, most studies regarding treatment are limited to case studies. There is still an important need for further and larger studies regarding management of these cases.

Dermatologic Symptoms and Syndromes Associated with Headache.

PURPOSE OF REVIEW: Headache disorders are often accompanied by associated symptoms involving organ systems other than the central and peripheral nervous system, including the integumentary, cardiovascular, and musculoskeletal system. However, skin changes or conditions are not commonly associated with headache disorders. Recognition of possible etiologies of headache in patients with bruising, rash, or neurocutaneous disorders can help guide workup and management. The purpose of this article is to review the various dermatologic presentations associated with headache. RECENT FINDINGS: Multiple review articles and retrospective studies have noted the association between head pain with dermatologic changes including ecchymoses, inflammatory skin conditions, and neurocutaneous disorders. Postulated mechanisms include activation of the trigeminal autonomic system and involvement of similar pro-inflammatory molecules. In this review, we discuss three different classes of rashes including ecchymoses, inflammatory skin conditions, and neurocutaneous disorders, all of which have been associated with migraine and/or headache. We discuss the possible underlying pathophysiology and treatment options.

A retrospective evaluation of the combination of erenumab and onabotulinum toxin A for the prevention of chronic migraine.

OBJECTIVE: Prior to the approval of erenumab, onabotulinum toxin A (onabot A) was the only Food and Drug Administration-approved chronic migraine preventive treatment. In this study, we assess the safety and efficacy of the combination of erenumab and onabot A for chronic migraine prevention. METHODS: This is a retrospective cohort study of patients with a diagnosis of chronic migraine receiving onabot A, who were additionally started on erenumab. Primary endpoint was a decrease in number of migraine days while on the combination treatment as compared to onabot A alone. Secondary endpoints included a decrease in headache days and reported side effects. RESULTS: When erenumab was added to onabot A, participants (n = 50) experienced significantly lower number of monthly migraine days (11.3 ± 9.3 vs. 14.9 ± 9.4, p < 0.001). The treatment of onabot A and erenumab also significantly lowered the number of monthly headache days (18.2 ± 10.3 vs. 20.7 ± 9.1, p = 0.042). There were no "severe" adverse effects reported in the combined treatment group. CONCLUSION: This retrospective case series showed a reduction in monthly migraine and headache days with the treatment combination of erenumab and onabot A compared to onabot A alone in patients with chronic migraine.

Primary Exercise Headache.

PURPOSE OF REVIEW: Primary exercise headache has gone through many descriptors in the past but generally is a headache that is precipitated by strenuous exercise without significant intracranial pathology. Its presentation can remain vague, often confused with other primary and secondary headache disorders and thus undertreated. This review aims to discuss primary exercise headache in the context of epidemiology, presentation, pathophysiology, differential diagnosis, and treatment. RECENT FINDINGS: Two large epidemiological studies in Iran and Japan have further characterized a predilection for female patients, comorbidity with migraine, and frequent bilateral nature of headache. While large-scale epidemiological studies have aided in further characterization and determining varying prevalence, a lack of randomized clinical trials in the treatment of primary exercise headache remains. Indomethacin and beta-blocker use remain the mainstays of treatment based on case series with several case reports that urge caution when diagnosing said headache.

An Analysis of Whether Health Literacy and Numeracy Are Associated with Diabetes Medication Adherence.

Many people with type 2 diabetes do not take medications as prescribed, resulting in suboptimal glycemic control and a greater risk of diabetes complications. Taking medications regularly requires adequate health literacy and numeracy skills, but associations between health literacy and numeracy skills and medication taking are mixed. We used validated, reliable, and widely accepted measures to examine the relationship between health literacy, numeracy, and medication adherence among a sample of patients with T2D. We analyzed cross-sectional data using non-parametric Mann-Whitney U-tests and unadjusted and adjusted logistic regression models. For every one point increase on the Brief Health Literacy Screen and Subjective Numeracy Scale, participants were 1.8 and 2.7 times more likely to optimally take medications (p < 0.05). Health literacy and numeracy skills should be considered in the design of education materials for medication management and adherence among people with T2D.

Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration.

PURPOSE: Oxidative stress in the RPE is widely accepted as a contributing factor to AMD. We have previously shown that ribozyme-mediated reduction in the antioxidant enzyme manganese superoxide dismutase (MnSOD) leads to some of the features of geographic atrophy in mice. To develop a mouse model independent of viral injection, we used a conditional knockout of the Sod2 gene in the RPE to elevate mitochondrial oxidative stress in that cell layer. METHODS: Experimental mice in which exon 3 of Sod2 was flanked by loxP sites were also transgenic for PVMD2-rtTA and tetO-PhCMV cre, so that cre recombinase was expressed only in the RPE. Pups of this genotype (Sod2(flox/flox)VMD2cre) were induced to express cre recombinase by feeding doxycycline-laced chow to nursing dams. Controls included mice of this genotype not treated with doxycycline and doxycycline-treated Sod2(flox/flox) mice lacking the cre transgene. Expression of cre in the RPE was verified by immunohistochemistry, and deletion of Sod2 exon 3 in the RPE was confirmed by PCR. Mice were followed up over a period of 9 months by spectral-domain optical coherence tomography (SD-OCT), digital fundus imaging, and full-field ERG. Following euthanasia, retinas were examined by light and electron microscopy or by immunohistochemistry. Contour length of rod outer segments and thickness of the RPE layer were measured by unbiased stereology. RESULTS: Following doxycycline induction of cre, Sod2(flox/flox) cre mice demonstrated increased signs of oxidative stress in the RPE and accumulation of autofluorescent material by age 2 months. They showed a gradual decline in the ERG response and thinning of the outer nuclear layer (by SD-OCT), which were statistically significant by 6 months. In addition, OCT and electron microscopy revealed increased porosity of the choroid. At the same interval, hypopigmented foci appeared in fundus micrographs, and vascular abnormalities were detected by fluorescein angiography. By 9 months, the RPE layer in Sod2(flox/flox) cre mice was thicker than in nontransgenic littermates, and the rod outer segments were significantly longer over most of the retina, although localized atrophy of photoreceptors was also obvious in some eyes. CONCLUSIONS: Conditional tissue-specific reduction in MnSOD induced oxidative stress in mouse RPE, leading to RPE dysfunction, damage to the choroid, and death of photoreceptor cells. The RPE oxidative stress did not cause drusen-like deposits, but the model recapitulated certain key aspects of the pathology of dry AMD and may be useful in testing therapies.