Comparison of migraine with left- versus right-sided headache: A cross-sectional study.

OBJECTIVE: The goal of this study was to clarify whether clinical differences exist between patients with migraine who experience headache that is typically left-sided ("left-migraine") versus right-sided ("right-migraine") during attacks. BACKGROUND: Migraine has been associated with unilateral headache for millennia and remains a supportive trait for the clinical diagnosis of migraine of the International Classification of Headache Disorders. It is currently unknown why headache in migraine is commonly unilateral, and whether headache-sidedness is associated with other clinical features. METHODS: This is a cross-sectional study comparing left- versus right-migraine using all available intake questionnaires of new patients evaluated at an academic tertiary headache center over a 20-year period. Eligibility was based on patient written responses indicating the typical location of headache during attacks. In our analyses, the side of headache (left or right) was the predictor variable. The outcomes included various migraine characteristics and psychiatric comorbidities. RESULTS: We identified 6527 patients with migraine, of which 340 met study eligibility criteria. Of these, 48.8% (166/340) had left migraine, and 51.2% (174/340) had right migraine. When comparing patients with left- versus right-migraine, patients with left migraine experienced 3.6 fewer headache-free days (95% confidence interval [CI] 1.3-5.9; p = 0.002) and 2.4 more severe headache days (95% CI 0.8-4.1; p = 0.004) in the previous 4 weeks. No significant differences in age, sex, handedness, migraine characteristics, or psychiatric comorbidities were identified between the two groups. CONCLUSIONS: Patients with migraine with typically left-sided headache during attacks reported a higher burden of headache frequency and severity than those with typically right-sided headache during attacks. These findings may have implications for our understanding of migraine pathophysiology, treatment, and clinical trial design.

Left- vs right-sided migraine: a scoping review.

BACKGROUND: Migraine is a historically unilateral head pain condition, the cause of which is not currently known. A growing body of literature suggests individuals who experience migraine with left-sided headache ("left-sided migraine") may be distinguished from those who experience migraine with right-sided headache ("right-sided migraine"). OBJECTIVE: In this scoping review, we explore migraine unilaterality by summarizing what is currently known about left- and right-sided migraine. METHODS: Two senior medical librarians worked with the lead authors to construct and refine a set of search terms to identify studies of subjects with left- or right-sided migraine published between 1988, which is the year of publication of the first edition of the International Classification of Headache Disorders (ICHD), and December 8, 2021 (the date the searches were conducted). The following databases were searched: Medline, Embase, PsycINFO, PubMed, Cochrane Library, and Web of Science. Abstracts were loaded into Covidence review software, deduplicated, then screened by two authors to determine study eligibility. Eligible studies were those involving subjects diagnosed with migraine (according to ICHD criteria) in which the authors either: a) compared left- to right-sided migraine; or b) described (with analysis) a characteristic that differentiated the two. Data were extracted by the lead author, including ICHD version, the definition of unilateral migraine used by the authors, sample size, whether the findings were collected during or between attacks, and their key findings. The key findings were grouped into the following themes: handedness, symptoms, psychiatric assessments, cognitive testing, autonomic function, and imaging. RESULTS: After deduplication, the search yielded 5428 abstracts for screening. Of these, 179 met eligibility criteria and underwent full text review. 26 articles were included in the final analysis. All of the studies were observational. One study was performed during attack, nineteen between attacks, and six both during and between attacks. Left- and right-sided migraine were found to differ across multiple domains. In several cases, reciprocal findings were reported in left- and right-migraine. For example, both left- and right-sided migraine were associated with ipsilateral handedness, tinnitus, onset of first Parkinson's symptoms, changes in blood flow across the face, white matter hyperintensities on MRI, activation of the dorsal pons, hippocampal sclerosis, and thalamic NAA/Cho and NAA/Cr concentrations. In other cases, however, the findings were specific to one migraine laterality. For example, left-sided migraine was associated with worse quality of life, anxiety, bipolar disorder, PTSD, lower sympathetic activity, and higher parasympathetic activity. Whereas right-sided migraine was associated with poorer performance on multiple cognitive tests, a greater degree of anisocoria, changes in skin temperature, higher diastolic blood pressure, changes in blood flow through the middle cerebral and basilar arteries, and changes on EEG. CONCLUSION: Left- and right-sided migraine differed across a wide range of domains, raising the possibility that the pathophysiology of left- and right-migraine may not be identical.

Imaging of large volume subcutaneous deposition using MRI: exploratory clinical study results.

Subcutaneous (SC) delivery is a preferred route of administration for biotherapeutics but has predominantly been limited to volumes below 3 mL. With higher volume drug formulations emerging, understanding large volume SC (LVSC) depot localization, dispersion, and impact on the SC environment has become more critical. The aim of this exploratory clinical imaging study was to assess the feasibility of magnetic resonance imaging (MRI) to identify and characterize LVSC injections and their effect on SC tissue as a function of delivery site and volume. Healthy adult subjects received incremental injections of normal saline up to 5 mL total volume in the arm and up to 10 mL in the abdomen and thigh. MRI images were acquired after each incremental SC injection. Post-image analysis was performed to correct imaging artifacts, identify depot tissue location, create 3-dimensional (3D) SC depot rendering, and estimate in vivo bolus volumes and SC tissue distention. LVSC saline depots were readily achieved, imaged using MRI, and quantified via subsequent image reconstructions. Imaging artifacts occurred under some conditions, necessitating corrections applied during image analysis. 3D renderings were created for both the depot alone and in relation to the SC tissue boundaries. LVSC depots remained predominantly within the SC tissue and expanded with increasing injection volume. Depot geometry varied across injection sites and localized physiological structure changes were observed to accommodate LVSC injection volumes. MRI is an effective means to clinically visualize LVSC depots and SC architecture allowing assessment of deposition and dispersion of injected formulations.Trial Registration: Not applicable for this exploratory clinical imaging study.

The current state of headache medicine education in the United States and Canada: An observational, survey-based study of neurology clerkship directors and curriculum deans.

OBJECTIVE: To investigate the current headache medicine education paradigm in allopathic and osteopathic medical schools in the United States and Canada. BACKGROUND: There is a disparity in the number of clinicians specially trained to treat patients with headache disorders and the number of people who have them. Early education and exposure to headache medicine is crucial to address this disparity. However, the current state of headache education within medical schools across the United States and Canada is unknown. METHODS: The authors created a medical student headache education survey, which is a 20-question REDCap survey that was distributed via email to the neurology clerkship director, curriculum dean, or similar role at each US and Canadian MD or DO conferring medical school. The email listserv was created using the American Academy of Neurology Clerkship Directory, the Association of American Medical Colleges Organization Directory, the American Association of College of Osteopathic Medicine Organization Directory, manual searches of the institutions' websites, and phone calls and emails to administrators as needed. RESULTS: Of the 249 individuals contacted, 78 completed the survey, yielding a response rate of 31.3%. Of those responses, 84.6% of respondents (66/78) reported that their institution has at least one mandatory session on headache disorders. Many of these sessions (72.7% (48/78)) occurred during preclinical training, and 74.2% (49/78) occurred as part of the clinical curricula. Of respondents, 44.9% (39/78) reported that their institutions coordinate headache education across training levels (i.e., from preclinical to clinical), and only 17.9% (14/78) coordinate across clinical rotations. The most common topics covered were headache red flags, migraine, pharmacologic management, and differentiating primary versus secondary headache. 65.4% of respondents (51/78) felt that the preclinical headache curriculum prepares their students for the clinical experience, and 55.1% (43/78) felt that medical students were learning enough about headache medicine at their institution. Barriers to educating medical students about headache included insufficient time during courses, lack of administrative support in curricula development, lack of available resources, and lack of student interest. Case-based learning modules and online lectures were the most desired educational materials to improve medical student headache education at their institution. CONCLUSIONS: The majority of medical schools report incorporating headache medicine education into preclinical or clinical curricula and cover a range of topics in headache medicine. Yet there remains a lack of consistency, with some reporting limited headache education, citing barriers such as lack of administrative support and available educational resources. There is also variation in what is being taught at the medical student level. Future projects should aim to address said barriers, with the goal of providing a standardized headache medicine curriculum for use across medical schools.

Familial "Diplegic" Migraine - Description of a Family With a Novel CACNA1A Mutation.

OBJECTIVE: To characterize phenotypes of a novel CACNA1A mutation causing familial hemiplegic migraine type 1. BACKGROUND: Familial hemiplegic migraine is a rare monogenic form of migraine associated with attacks of fully reversible unilateral motor weakness. We now report a novel CACNA1A gene mutation associated with fully reversible bilateral motor weakness (diplegia). METHODS: The proband underwent genotyping which identified a novel CACNA1A missense mutation (c.622 [isoform 1] G > A [p.Gly208Arg]). To characterize phenotypes associated with this novel mutation, the proband and 8 of her similarly affected family members underwent a semi-structured interview. RESULTS: All 9 subjects who were interviewed met ICHD-3 phenotypic diagnostic criteria for FHM, including reporting attacks with reversible unilateral motor weakness. Additionally, 7 of 9 subjects reported attacks including reversible motor weakness affecting both sides of the body simultaneously. CONCLUSIONS: We describe a novel CACNA1A mutation associated with migraine attacks including reversible diplegia.

No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine.

OBJECTIVE: To determine whether transgenic mouse models of migraine exhibit upper gastrointestinal dysmotility comparable to those observed in migraine patients. BACKGROUND: There is considerable evidence supporting the comorbidity of gastrointestinal dysmotility and migraine. Gastrointestinal motility, however, has never been investigated in transgenic mouse models of migraine. METHODS: Three transgenic mouse strains that express pathogenic gene mutations linked to monogenic migraine-relevant phenotypes were studied: CADASIL (Notch3-Tg88), FASP (CSNK1D-T44A), and FHM1 (CACNA1A-S218L). Upper gastrointestinal motility was quantified by measuring gastric emptying and small intestinal transit in mutant and control animals. Gastrointestinal motility was measured at baseline and after pretreatment with 10 mg/kg nitroglycerin (NTG). RESULTS: No significant differences were observed for gastric emptying or small intestinal transit at baseline for any of the 3 transgenic strains when compared to appropriate controls or after pretreatment with NTG when compared to vehicle. CONCLUSIONS: We detected no evidence of upper gastrointestinal dysmotility in mice that express mutations in genes linked to monogenic migraine-relevant phenotypes. Future studies seeking to understand why humans with migraine experience delayed gastric emptying may benefit from pursuing other modifiers of gastrointestinal motility, such as epigenetic or microbiome-related factors.

Randomized controlled trial: targeted neck cooling in the treatment of the migraine patient.

Cold therapy has long been the number one self-care treatment employed for migraine without aura and the second most common for migraine with aura, yet its mechanism remains elusive. In this study, a mechanism by which this time-tested therapy works is proposed (by cooling the blood passing through intracranial vessels) in an attempt to further elucidate its beneficial effects. The study is designed as a randomized, controlled, crossover clinical trial utilizing an adjustable wrap containing two freezable ice packs targeting the carotid arteries at the neck, where they come close to the skin surface. Fifty-five participants successfully completed the study. Pain at onset, as recorded on a visual analog scale, was similar between the two treatment arms. Maximum pain reduction was observed at the 30 minute time point with a 31.8% ± 15.2% decrease in pain in the treatment arm compared to a 31.5% ± 20.0% increase in pain at the same time interval in the control arm. These findings confirm the application of a frozen neck wrap at onset of migraine headache targeting the carotid arteries at the neck significantly reduced recorded pain in participants with migraine headaches (P<.001).

Combined preoperative use of celecoxib and gabapentin in the management of postoperative pain.

BACKGROUND: In 2005 we reported a study on the efficacy of the preoperative use of the selective COX-2 inhibitor celecoxib (Celebrex) for reducing both postoperative pain and opioid requirements in patients undergoing bilateral subpectoral breast augmentation. Our findings showed that patients who received 400 mg of celecoxib 30 min before surgery required significantly less postoperative opioid analgesics compared with those given a placebo. Gabapentin (Neurontin) is an agent commonly used to control neuropathic pain. Here we describe a prospective study assessing the efficacy of preoperative gabapentin in combination with celecoxib for reducing postoperative pain and opioid requirements in elective subpectoral breast augmentation. METHODS: One hundred eighteen patients were given 1200 mg of gabapentin and 400 mg of celecoxib 30-60 min before surgery. From the day of surgery until postoperative day 5, patients documented any use of analgesics and recorded their degree of pain. Results were then compared with those of our previous study in which only celecoxib was used. RESULTS: The combination of gabapentin and celecoxib was found to be significantly superior (p < 0.001) in reducing postoperative pain and opioid requirements than celecoxib alone in the management of postoperative pain and opioid requirements. CONCLUSION: To decrease postoperative opioid requirements, we recommend 400 mg of celecoxib and 1200 mg of gabapentin taken 30-60 min before surgery by patients undergoing subpectoral breast augmentation or a comparable plastic surgery procedure.

Selective arterial embolization for control of lower gastrointestinal bleeding: recommendations for a clinical management pathway.

PURPOSE: Angiography remains as the modality of choice in the diagnosis of lower gastrointestinal bleeding. Traditionally, angiography is used for localization of a bleeding source for surgical resection. Advances in transcatheter techniques have allowed for hemorrhage control through embolization of bleeding points, without the need for emergent laparotomy. METHODS: A series of 10 consecutive patients who underwent angiographic embolization for lower gastrointestinal hemorrhage was retrospectively reviewed. Success and complication rates, as well as post-embolization follow-up methods, were recorded. RESULTS: Over a 3-year period, 10 angiographic embolizations were performed for lower gastrointestinal hemorrhage. Average age of the patients was 75 years. Source of hemorrhage included diverticular disease in 4 patients, cancer in 2, polyps in 2, angiodysplasia in 1, and anastomotic bleeding in 1. Six patients required no further therapy. Four patients went on to have surgery: Three secondary to recurrent hemorrhage, 1 due to sepsis from ischemic bowel necrosis. There were no deaths. Four patients had an abdominal and pelvic computed tomography (CT) scan within 48 hours of embolization. Four patients had a colonoscopy within 48 hours of the procedure. CONCLUSIONS: Angiography remains an important diagnostic tool in the management of lower gastrointestinal bleeding. In addition, it is a safe and effective treatment option, especially in patients with high surgical risk. Hemorrhage control obtained in the angiography suite may allow for patient stabilization and resuscitation with staging and bowel preparation for surgery. Patients need to be carefully monitored for evidence of bowel ischemia through the use of colonoscopy or computed tomography.