Faculty Bibliography

BACKGROUND:Migraine treatment may mitigate migraine and associated pain in the perioperative period. OBJECTIVE:The aim of the study was to estimate the effect of perioperative acute and prophylactic migraine treatment on the risk of postoperative 30-day hospital readmission with an admitting diagnosis specifying any pain complaints among migraine patients. DESIGN/METHODS:Electronic health records were analysed for 21,932 adult migraine patients undergoing surgery between 2005 and 2017 at Beth Israel Deaconess Medical Center and Massachusetts General Hospital in Boston, Massachusetts, USA. METHODS:Perioperative abortive migraine treatment was defined as guideline-recommended medication (triptan, ergotamine, acetaminophen, nonsteroidal anti-inflammatory drug) prescription after surgery, within 30 days after discharge and prior readmission. Perioperatively continued prophylactic migraine treatment was defined as prescription both prior to surgery and perioperatively for recommended medications (beta-blockers, antidepressants, antiepileptics, onabotulinumtoxin A). RESULTS:Overall, 10,921 (49.8%) patients received a prescription for abortive migraine drugs. Of these, 1.2% and 1.5% of patients with and without such prescription were readmitted for pain, respectively. Patients with abortive treatment had lower odds of pain-related readmission (adjusted odds ratio 0.63 [95% confidence interval 0.49-0.81]). Prophylactic migraine treatment showed no effect on pain-related readmission independently of acute treatment (adjusted odds ratio 0.97 [95% confidence interval 0.72-1.32]). CONCLUSIONS:Migraine patients undergoing surgery with a perioperative prescription for abortive migraine drugs were at decreased risk of pain-related hospital readmission.

OBJECTIVE:To investigate the role of calcitonin gene-related peptide (CGRP) in persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). METHODS:A total of 100 individuals with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls were enrolled between July 2018 and June 2019. Blood was drawn from the antecubital vein and subsequently analyzed using a validated radioimmunoassay for human CGRP. Measurements were performed on coded samples by a board-certified laboratory technician who was blind to clinical information. RESULTS: = 0.85). CONCLUSIONS:CGRP plasma measurements are unlikely a feasible blood-based biomarker of persistent PTH. Future studies should assess whether CGRP plasma measurements can be used to predict development of persistent PTH.

OBJECTIVE:To assess the proportion of pediatric patients who develop post-traumatic stress disorder (PTSD) attributed to traumatic brain injury (TBI). METHODS:PubMed and Embase were searched from database inception until January 26, 2019. Two independent investigators screened titles, abstracts, and subsequently, full-text articles. Following this, the same investigators also extracted data relevant for the scope of this review. RESULTS:Ten articles were included in this review. In these, six unique cohorts were described, with relative frequencies of PTSD attributed TBI ranging from 3.3% to 48.5%. Two studies also found that PTSD was more common in children after TBI compared to pediatric orthopedic controls. Study quality was determined as high or very high for all six included cohorts, although the studies differed considerably in terms of methodology. CONCLUSIONS:Methodological variations confound comparisons of relative frequency assessments of PTSD attributed to TBI. However, PTSD is associated with considerable long-term disability and undetected PTSD in children should raise public concern. Thus, large scale, prospective studies are needed to ascertain the clinical course of PTSD attributed to TBI in children and adolescence.

OBJECTIVE:To systematically identify risk factors for the development of post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) as defined in the International Classification of Headache Disorders (ICHD). BACKGROUND:PTH is a common sequela of TBI and a leading cause of injury-related disability worldwide. However, little is known about risk factors for the development of PTH attributed to TBI. METHODS:We searched PubMed and Embase for literature on risk factors for the development of acute and/or persistent PTH attributed to TBI in accordance with any version of the ICHD. Original studies published in English and of prospective, cross-sectional or retrospective design were considered for the review. Data extraction was performed independently by 2 investigators. RESULTS:Of 1993 potentially relevant articles identified, 3 articles met the inclusion criteria. The following risk factors were assessed for the development of acute PTH: age, sex, type of injury, loss of consciousness, previous TBIs, history of primary headache disorders, history of chronic pain condition other than headache, current treatment for depression/anxiety, attention or learning disorders, body mass index, and other diseases (not further specified). None of the included studies assessed risk factors for the development of persistent PTH. CONCLUSIONS:We found that there is little evidence for any risk factors involved in the development of acute PTH, whereas no study had assessed risk factors for the development of persistent PTH. Further studies are warranted and should be powered to examine possible risk factors for the development of PTH. Rigorous methodology and standardized monitoring should be prioritized to support high-quality research and validate potential findings.

Neck pain and headache are two of the most common complications of whiplash injury. Therefore, we performed a systematic literature search on PubMed and Embase for publications reporting on the prevalence of neck pain and headache following whiplash injury. The literature search identified 2,709 citations of which 44 contained relevant original data. Of these, 27 studies provided data for the quantitative analysis. For non-population-based studies, the present meta-analysis showed that a pooled relative frequency of neck pain was 84% CI (68-95%) and a pooled relative frequency of headache was 60% (46-73%), within 7 days following whiplash injury. At 12 months post-injury, 38% (32-45%) of patients with whiplash still experienced neck pain, while 38% (18-60%) of whiplash patients reported headache at the same time interval post-injury. However, we also found considerable heterogeneity among studies with I-values ranging from 89-98% for the aforementioned meta-analyses. We believe that the considerable heterogeneity among studies underscores the need for clear-cut definitions of whiplash injury and standardized reporting guidelines for post-whiplash sequelae such as neck pain and headache. Future studies should seek to optimize these aspects paving the way for a better understanding of the clinical characteristics and natural course of whiplash-associated sequelae.

Non-steroidal anti-inflammatory drugs (NSAIDs), commonly known as COX-1/COX-2 inhibitors, can be effective in treating mild to moderate migraine headache. However, the mechanism by which these drugs act in migraine is not known, nor is the specific contribution of COX-1 versus COX-2 known. We sought to investigate these unknowns using celecoxib, which selectively inhibits the enzymatic activity of COX-2, by determining its effects on several migraine-associated vascular and inflammatory events. Using in vivo two-photon microscopy, we determined intraperitoneal celecoxib effects on CSD-induced blood vessel responses, plasma protein extravasation, and immune cell activation in the dura and pia of mice and rats. Compared to vehicle (control group), celecoxib reduced significantly CSD-induced dilatation of dural arteries and activation of dural and pial macrophages but not dilatation or constriction of pial arteries and veins, or the occurrence of plasma protein extravasation. Collectively, these findings suggest that a mechanism by which celecoxib-mediated COX-2 inhibition might ease the intensity of migraine headache and potentially terminate an attack is by attenuating dural macrophages activation and arterial dilatation outside the blood brain barrier (BBB), and pial macrophages activation inside the BBB.

OBJECTIVE:To assess the proportion of individuals who report dizziness and/or vertigo during the prodromal phase or headache phase of migraine. METHODS:The databases of MEDLINE and EMBASE were searched for studies on dizziness and/or vertigo during the prodromal phase or headache phase of migraine. Pooled relative frequencies were estimated using a random-effects meta-analysis. RESULTS: = 87%). Study quality was rated 5/9 or below for seven studies and 6/9 or above for two studies. CONCLUSION/CONCLUSIONS:We found that there is a scarcity of literature on dizziness and vertigo as prodromal- and headache-associated symptoms in individuals with migraine. Methodological variations confound comparisons of epidemiological patterns, although it appears that dizziness and vertigo are more frequent during the headache phase of migraine, compared with the prodromal phase. Future studies should ensure use of standardized definitions and rigorous methodology to enable accurate measurements of dizziness and vertigo in migraine.

BACKGROUND:Status migrainosus is a condition with limited epidemiological knowledge, and no evidence-based treatment guideline or rational-driven assessment of successful treatment outcome. To fill this gap, we performed a prospective observational study in which we documented effectiveness of treatment approaches commonly used in a tertiary headache clinic. MATERIAL AND METHODS/METHODS:Patients with episodic and chronic migraine who experienced continuous and prolonged attacks for more than 72 hours were treated with dexamethasone (4 mg orally twice daily for 3 days), ketorolac (60 mg intramuscularly), bilateral nerve blocks (1-2% lidocaine, 0.1-0.2 ml for both supraorbital and supratrochlear nerves, 1 ml for both auriculotemporal nerves, and 1 ml for both greater occipital nerves), or naratriptan (2.5 mg twice daily for 5 days). Hourly (for the first 24 hours) and daily (for first 30 days) change in headache intensity was documented using appropriate headache diaries. RESULTS:Fifty-four patients provided eligible data for 60 treatment attempts. The success rate of rendering patients pain free within 24 hours and maintaining the pain-free status for 48 hours was 4/13 (31%) for dexamethasone, 7/29 (24%) for nerve blocks, 1/9 (11%) for ketorolac and 1/9 (11%) for naratriptan. These success rates depended on time to remission, as the longer we allowed the treatments to begin to work and patients to become pain free (i.e. 2, 12, 24, 48, 72, or 96 hours), the more likely patients were to achieve and maintain a pain-free status for at least 48 hours. DISCUSSION/CONCLUSIONS:These findings suggest that current treatment approaches to terminating status migrainosus are not satisfactory and call attention to the need to develop a more scientific approach to define a treatment response for status migrainosus.

OBJECTIVE:To investigate clinical characteristics and treatment patterns in persistent post-traumatic headache attributed to mild traumatic brain injury. METHODS:A total of 100 individuals with persistent post-traumatic headache attributed to mild traumatic brain injury were enrolled between July 2018 and June 2019. Deep phenotyping was performed using a semi-structured interview while allodynia was assessed using the 12-item Allodynia Symptom Checklist. RESULTS:In 100 subjects with persistent post-traumatic headache, the mean headache frequency was 25.4 ± 7.1 days per month. The most common headache phenotype was chronic migraine-like headache (n = 61) followed by combined episodic migraine-like and tension-type-like headache (n = 29) while nine subjects reported "pure" chronic tension-type-like headache. The most frequent trigger factors were stress, lack of sleep, and bright lights. A history of preventive medication use was reported by 63 subjects, of which 79% reported failure of at least one preventive drug, while 19% reported failure of at least four preventive drugs. Cutaneous allodynia was absent in 54% of the subjects, mild in 23%, moderate in 17%, and severe in 6%. CONCLUSIONS:The headache profile of individuals with persistent post-traumatic headache most often resembled a chronic migraine-like phenotype or a combined episodic migraine-like and tension-type-like headache phenotype. Migraine-specific preventive medications were largely reported to be ineffective. Therefore, there is a pressing need for pathophysiological insights and disease-specific therapies.

OBJECTIVE:To report a case of petrous apicitis that manifested as chronic migraine without aura and to discuss the pathophysiological mechanisms behind this presentation. BACKGROUND:Petrous apicitis is a rare complication of acute otitis media with varied clinical presentations that stem from the close proximity of the petrous apex to numerous neurovascular structures. Headache is among the common symptoms of petrous apicitis. METHODS:A case of new onset headache in the setting of petrous apicitis with symptomatic response to antibiotic therapy was reported. We provided a brief review of peripheral pathophysiological mechanisms of migraine and correlated to mechanism of headache in petrous apicitis. RESULTS:A 65-year-old man with chronic otitis externa/media presented with ongoing headache fulfilling International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for chronic migraine without aura that persisted despite undergoing right mastoidectomy and tympanoplasty with multiple courses of oral antibiotic therapy for his chronic otitis. MRI brain revealed petrous apicitis, otomastoiditis, and clival osteomyelitis. His imaging findings improved and his migraine-like headache completely resolved after treatment with a prolonged course of antibiotics. CONCLUSIONS:Petrous apicitis can present as a headache with features of migraine, and in this case in particular, as chronic migraine without aura. The pathophysiological mechanisms that may underlie the generation of migraine-like headache in petrous apicitis may include the activation of nociceptive fibers within the periosteum of the petrous apex and clivus whose cell bodies originate in the trigeminal ganglion and upper cervical dorsal root ganglia. By treating the peripheral pathology, resolution of the headache may be achieved.