Hypersensitivity to CGRP as a predictive biomarker of migraine prevention with erenumab.

BACKGROUND: The present study aimed to investigate the predictive value of calcitonin gene-related peptide (CGRP)-induced migraine attacks for effectiveness to erenumab treatment in people with migraine. METHODS: In total, 139 participants with migraine underwent a single experimental day involving a 20-min infusion with CGRP. Following this, the participants entered a 24-week treatment period with erenumab. The primary endpoints were the predictive value of CGRP-induced migraine attacks on the effectiveness of erenumab, defined as ≥50% reduction in monthly migraine days, or ≥ 50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity. RESULTS: Among participants with CGRP-induced migraine attacks, 60 of 99 (61%) achieved ≥50% reduction in monthly migraine days during weeks 13-24 with erenumab. Conversely, 13 of 25 (52%) where CGRP infusion did not induce a migraine achieved the same endpoint (p = 0.498). There were no significant differences between the ≥50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity between CGRP-sensitive and non-sensitive participants (p = 0.625). CONCLUSIONS: Our findings suggest that the CGRP-provocation model cannot be used to predict erenumab's effectiveness. It remains uncertain whether this finding extends to other monoclonal antibodies targeting the CGRP ligand or to gepants.Trial Registration: The study was registered at ClinicalTrials.gov (NCT04592952).

An exploratory analysis of clinical and sociodemographic factors in CGRP-induced migraine attacks: A REFORM study.

OBJECTIVE: To investigate whether clinical and sociodemographic factors are associated with calcitonin gene-related peptide (CGRP) induced migraine attacks. METHODS: A total of 139 participants with migraine received a 20-minute intravenous infusion of CGRP (1.5 µg/min) on a single experiment day. The incidence of CGRP-induced migraine attacks was recorded using a headache diary during the 12-hour observational period post-infusion. Univariable and multivariable regression analyses were conducted to examine potential predictors' relationship with CGRP-induced migraine attacks. RESULTS: CGRP-induced migraine attacks were reported in 110 (79%) of 139 participants. Univariable analysis revealed that participants with cutaneous allodynia had higher odds of developing CGRP-induced migraine attacks, compared with those without allodynia (OR, 2.97, 95% CI, 1.28 to 7.43). The subsequent multivariable analysis confirmed this association (OR, 3.26, 95% CI, 1.32 to 8.69) and also found that participants with migraine with aura had lower odds of developing CGRP-induced migraine attacks (OR, 0.32, 95% CI, 0.12 to 0.84). CONCLUSION: Our results suggest that cutaneous allodynia and aura play a role in CGRP-induced migraine attacks, while other clinical and sociodemographic factors do not seem to have any noticeable impact. This indicates that the CGRP provocation model is robust, as the CGRP hypersensitivity remained unaffected despite differences among a heterogeneous migraine population.Trial Registration: ClinicalTrials.gov Identifier: NCT04592952.

White matter hyperintensities and cerebral microbleeds in persistent post-traumatic headache attributed to mild traumatic brain injury: a magnetic resonance imaging study.

OBJECTIVE: To examine whether white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs) are more prevalent in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI), compared with healthy controls. METHODS: A magnetic resonance imaging (MRI) study of adults with persistent post-traumatic headache attributed to mild TBI and age- and gender-matched healthy controls. A semi-structured interview and validated self-report instruments were used to record data on demographics, clinical characteristics, and comorbidities. Imaging data were obtained on a 3T MRI Scanner using a 32-channel head coil. Participants and controls underwent a single MRI session, in which fluid-attenuated inversion recovery was used to visualize WMHs, and susceptibility-weighted imaging was used to detect CMBs. The primary outcomes were (I) the difference in the mean number of WMHs between participants with persistent post-traumatic headache and healthy controls and (II) the difference in the mean number of CMBs between participants with persistent post-traumatic headache and healthy controls. All images were examined by a certified neuroradiologist who was blinded to the group status of the participants and controls. RESULTS: A total of 97 participants with persistent post-traumatic headache and 96 age- and gender-matched healthy controls provided imaging data eligible for analyses. Among 97 participants with persistent post-traumatic headache, 43 (44.3%) participants presented with ≥ 1 WMH, and 3 (3.1%) participants presented with ≥ 1 CMB. Compared with controls, no differences were found in the mean number of WMHs (2.7 vs. 2.1, P = 0.58) and the mean number of CMBs (0.03 vs. 0.04, P = 0.98). CONCLUSIONS: WMHs and CMBs were not more prevalent in people with persistent post-traumatic headache than observed in healthy controls. Future studies should focus on other MRI techniques to identify radiologic biomarkers of post-traumatic headache.

CGRP-induced migraine-like headache in persistent post-traumatic headache attributed to mild traumatic brain injury.

OBJECTIVE: To ascertain whether intravenous infusion of calcitonin gene-related peptide (CGRP) can induce migraine-like headache in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) and no pre-existing migraine. METHODS: A non-randomized, single-arm, open-label study at a single site in Denmark. Eligible participants were aged 18 to 65 years and had a known history of persistent post-traumatic headache attributed to mild TBI for ≥ 12 months. All participants received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min. A headache diary was used to collect outcome data until 12 h after the start of CGRP infusion. The primary end point was the incidence of migraine-like headache during 12-hour observational period. RESULTS: A total of 60 participants completed the study protocol and provided data for the analysis of the primary end point. The median age was 32.5 (IQR, 25.5-43.0) years; 43 participants (72%) were female. Following CGRP infusion, 43 (72%) of 60 participants developed migraine-like headache during the 12-hour observational period. The median time to peak headache intensity was 40 min (IQR, 20-60), and the median peak headache intensity was 6 (IQR, 5-8) on the 11-point numeric rating scale. CONCLUSION: Intravenous infusion of CGRP is a potent inducer of migraine-like headache in people with persistent post-traumatic headache attributed to mild TBI. This observation underscores the importance of CGRP in the genesis of migraine-like headache that is often experienced by individuals who are afflicted by persistent post-traumatic headache. Further research is warranted to ascertain whether other signaling molecules also contribute to the disease mechanisms underlying post-traumatic headache.

Psychiatric Sequelae Following Whiplash Injury: A Systematic Review.

Background: Anxiety, depression, post-traumatic stress disorder (PTSD), and sleep disturbance are reported following whiplash injury. However, the prevalence of these condition varies among studies. In this review, anxiety, depression, PTSD, and sleep disturbance will be referred as psychiatric outcomes. Methods: We performed a systematic literature search on PubMed and Embase (from database inception until March 20, 2021) to identify studies reporting on the relative frequency of these psychiatric outcomes. Three independent investigators screened titles, abstracts and full-texts. Studies including patients with whiplash injury and where the number of patients with whiplash and anxiety, depression, PTSD, or sleep disturbances could be extrapolated, were included. Furthermore, to be included, studies had to defined psychiatric outcomes in accordance with diagnostic criteria [i.e., Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD)] or by use of a validated instrument with cut-off scores for assessing psychiatric symptoms. Quality rating was done using the Newcastle-Ottawa Scale (NOS) on the included studies. A protocol was registered with PROSPERO (CRD42021232037). Results: The literature search identified 5,068 citations, of which five articles were eligible for inclusion. The relative frequency of depressive symptoms following whiplash injury was 32.8% at 6 months, and 34.0% at 6-12 months. The relative frequency of PTSD symptoms after whiplash injury was 9.0-22.3% at 3 months, 15.8% at 6 months and 14.6-17.1% at 12 months. No studies evaluating the relative frequency of anxiety and sleep disturbances were eligible for inclusion. Discussion and Conclusion: Our results suggest that there are persistent psychiatric outcomes following whiplash trauma. However, we found considerable heterogeneity among the studies. Thus, we have focused on the most notable limitations of the included studies: 1) small sample sizes, 2) differences in enrollment criteria, 3) lack of control groups, 4) considerable variation in the method used for outcome assessment, 5) directionality of association is difficult to determine and 6) incomplete assessment of compensation factors. We highlight these methodological limitations and outline recommendations for future research. Since psychiatric outcomes are potentially modifiable, future studies should optimize and address the identified methodological limitations so psychiatric sequelae following whiplash injury may be prevented.

Airplane flights triggering spontaneous intracranial hypotension: Observations from the Danish headache centre.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) manifests as orthostatic headache, which can be confirmed by radiological signs of low intracranial pressure on magnetic resonance imaging of the brain. The most common mechanisms of SIH are ruptured meningeal diverticula, ventral dural tears and CSF-venous fistulas. SIH is associated with connective tissue disorders, and cases of SIH onset after trivial trauma have been reported. As SIH is often underdiagnosed, the aim of this study is to identify possible new risk factors of SIH onset in a case series of SIH patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 36 patients diagnosed with SIH. We reviewed and identified potential factors that led to or presented at headache onset in SIH patients. RESULTS: We identified 4/36 (11%) patients that had a close temporal relationship between the onset of SIH symptoms and airplane travel. In all four patients, the clinical and imaging features confirmed the diagnosis of SIH. CONCLUSION: This is the first report of a case series of four patients with SIH that could be related to airplane travel. Describing four cases (11%) is not proof but should alert us to a possible causal relationship, which calls for further research. We suggest that when taking medical history, thorough details about the patient's activities, such as headache onset, should be documented because of their importance in correctly diagnosing SIH, which is a debilitating, yet treatable, disease.

Transorbital sonography: A non-invasive bedside screening tool for detection of pseudotumor cerebri syndrome.

BACKGROUND: Our objective was to assess optic nerve sheath diameter (a marker of elevated intracranial pressure) and optic disc elevation (a marker of papilledema) in pseudotumor cerebri syndrome using transorbital sonography. METHODS: The study was a prospective case-control study. We included patients with new-onset pseudotumor cerebri syndrome and matched healthy controls. All had fundoscopy, lumbar puncture with opening pressure and transorbital sonography. Sonography was assessed by a blinded observer. RESULTS: We evaluated 45 patients and included 23 cases. We recruited 35 controls. Optic nerve sheath diameter was larger in pseudotumor cerebri syndrome compared to controls (6.3 ± 0.9 mm versus 5.0 ± 0.5 mm, p < 0.001) and so was optic disc elevation (0.9 ± 0.4 mm versus 0.4 ± 0.1 mm, p < 0.001). The optimal cut-off point for optic nerve sheath diameter was 6 mm with a sensitivity of 74% for prediction of pseudotumor cerebri syndrome and 68% for prediction of elevated opening pressure. Specificity was 94%. The optimal cut-off point for optic disc elevation was 0.6 mm. Sensitivity was 100% and specificity 83% for prediction of pseudotumor cerebri syndrome. CONCLUSION: Optic disc elevation and optic nerve sheath diameter are increased in new-onset pseudotumor cerebri syndrome. Optic disc elevation achieved high specificity and excellent sensitivity for diagnosis of pseudotumor cerebri syndrome. Transorbital sonography (TOS) is a potential, non-invasive screening tool for pseudotumor cerebri syndrome in headache clinics.

Prevalence of neck pain in migraine: A systematic review and meta-analysis.

BACKGROUND: Neck pain is a frequent complaint among patients with migraine and seems to be correlated with the headache frequency. Neck pain is more common in patients with chronic migraine compared to episodic migraine. However, prevalence of neck pain in patients with migraine varies among studies. OBJECTIVE: To estimate the prevalence of neck pain in patients with migraine and non-headache controls in observational studies. METHODS: A systematic literature search on PubMed and Embase was conducted to identify studies reporting prevalence of neck pain in migraine patients. This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data was extracted by two independent investigators and results were pooled using random-effects meta-analysis. The protocol was registered with PROSPERO (CRD42021264898). RESULTS: The search identified 2490 citations of which 30 contained relevant original population based and clinic-based data. Among these, 24 studies provided data eligible for the analysis. The meta-analysis for clinic-based studies demonstrated that the pooled relative frequency of neck pain was 77.0% (95% CI: 69.0-86.4) in the migraine group and 23.2% (95% CI:18.6-28.5) in the non-headache control group. Neck pain was more frequent in patients with chronic migraine (87.0%, 95% CI: 77.0-93.0) compared to episodic migraine (77.0%, 95% CI: 69.0-84.0). Neck pain was 12 times more prevalent in migraine patients compared to non-headache controls and two times more prevalent in patients with chronic migraine compared to episodic migraine. The calculated heterogeneity (I2 values) ranged from 61.3% to 72.0%. CONCLUSION: Neck pain is a frequent complaint among patients with migraine. The heterogeneity among the studies emphasize important aspects to consider in future research of neck pain in migraine to improve our understanding of the driving mechanisms of neck pain in a major group of migraine patients.

Validation of the Temporomandibular Disorder Pain Screener in a Specialized Headache Center.

AIMS: To investigate the sensitivity and specificity of the TMD pain screener in a headache population. METHODS: A cross-sectional study was conducted at the Danish Headache Center (DHC). Patients were included if they had primary or secondary headache, trigeminal neuralgia, or facial pain. The pain screener was compared to the outcome of a full Diagnostic Criteria for TMD (DC/TMD) examination. RESULTS: A total of 62 headache patients were included (77% women). The sensitivity of the pain screener short version (three questions) was 85% (95% CI: 70% to 94%), and the specificity was 64% (95% CI: 41% to 83%). In the full version (six questions), the sensitivity was 83% (95% CI: 67% to 93%), and the specificity was 82% (95% CI: 60% to 95%). CONCLUSION: The TMD pain screener seems to be a valid tool to accurately screen for the presence of TMD to provide the most optimal treatment for headache patients. These findings should however be confirmed in a larger sample with migraine, tension-type headache, and trigeminal neuralgia.

Diagnosis and management of migraine in ten steps.

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.

Post-traumatic headache attributed to traumatic brain injury: classification, clinical characteristics, and treatment.

Post-traumatic headache is a common sequela of traumatic brain injury and is classified as a secondary headache disorder. In the past 10 years, considerable progress has been made to better understand the clinical features of this disorder, generating momentum to identify effective therapies. Post-traumatic headache is increasingly being recognised as a heterogeneous headache disorder, with patients often classified into subphenotypes that might be more responsive to specific therapies. Such considerations are not accounted for in three iterations of diagnostic criteria published by the International Headache Society. The scarcity of evidence-based approaches has left clinicians to choose therapies on the basis of the primary headache phenotype (eg, migraine and tension-type headache) and that are most compatible with the clinical picture. A concerted effort is needed to address these shortcomings and should include large prospective cohort studies as well as randomised controlled trials. This approach, in turn, will result in better disease characterisation and availability of evidence-based treatment options.

Reference programme: diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 3rd edition, 2020.

Headache and facial pain are among the most common, disabling and costly diseases in Europe, which demands for high quality health care on all levels within the health system. The role of the Danish Headache Society is to educate and advocate for the needs of patients with headache and facial pain. Therefore, the Danish Headache Society has launched a third version of the guideline for the diagnosis, organization and treatment of the most common types of headaches and facial pain in Denmark. The second edition was published in Danish in 2010 and has been a great success, but as new knowledge and treatments have emerged it was timely to revise the guideline. The recommendations for the primary headaches and facial pain are largely in accordance with the European guidelines produced by the European Academy of Neurology. The guideline should be used a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organized in Denmark. This description is followed by sections on the characteristics, diagnosis and treatment of each of the most common primary and secondary headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular challenges regarding migraine and female hormones as well as headache in children are addressed.

Interrelations between migraine-like headache and persistent post-traumatic headache attributed to mild traumatic brain injury: a prospective diary study.

BACKGROUND: Persistent post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) and retrospective assessments have found a migraine-like phenotype to be very frequent. This has raised a discussion of shared underlying mechanisms and whether persistent PTH is simply trauma-triggered migraine. METHODS: A 28-day prospective diary study with daily entries and acquisition of data on headache characteristics, associated symptoms, and acute medication use. A total of 64 patients with persistent PTH were enrolled from April 2019 to August 2019. Outcomes were the proportion of monthly headache days of any intensity that met the criteria for a migraine-like day or TTH-like day, as well as the corresponding figures for monthly headache days of moderate to severe intensity. Headache phenotypes were initially assigned based on diagnostic evaluation by semi-structured interview, whilst final headache phenotypes were assigned by diary review. RESULTS: After diary review, we found that monthly headache days were exclusively migraine-like in 24 of 64 patients (38%) and exclusively TTH-like days in 8 of 64 patients (13%). Considering only monthly headache days of moderate to severe intensity, the corresponding figures were 35 of 64 patients (55%) for migraine-like days and 8 of 64 patients (13%) for TTH-like days. The following headache phenotypes were assigned based on diary review: chronic migraine-like (n = 47, 73%), combined episodic migraine-like and chronic TTH-like (n = 9, 13%), and 'pure' chronic TTH-like (n = 8, 13%). CONCLUSIONS: A migraine-like phenotype is common in patients most adversely affected by persistent PTH, although some patients did have a pure chronic TTH-like phenotype. At minimum, these findings suggest that persistent PTH is - at least in some - not 'trauma-triggered migraine'.

Hypersensitivity to Calcitonin Gene-Related Peptide in Post-Traumatic Headache.

OBJECTIVE: To demonstrate that calcitonin gene-related peptide (CGRP) induces headache exacerbation with migraine-like features in patients with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). METHODS: A randomized, double-blind, placebo-controlled, two-way crossover study was conducted. Analyses were intention-to-treat. Eligible patients were aged 18 to 65 years and had a history of persistent PTH after mild TBI for at least 12 months. Patients were randomized to receive an intravenous infusion of 1.5µg/min of CGRP or placebo (isotonic saline) over 20 minutes on two separate experimental days. A 12-hour observational period was used to evaluate the following outcomes: (1) difference in incidence of headache exacerbation with migraine-like features and (2) difference in area under the curve for headache intensity scores. RESULTS: Thirty patients (mean age = 37 years, 25 women [83%]) were randomized and completed the study. During the 12-hour observational period, 21 of 30 patients (70%) developed headache exacerbation with migraine-like features after CGRP, compared with 6 patients (20%) after placebo (p < 0.001). The baseline-corrected area under the curve for headache intensity scores was significantly larger after CGRP, compared with placebo (p < 0.001). INTERPRETATION: Patients with persistent PTH are hypersensitive to CGRP, which underscores its pathophysiological importance. Furthermore, CGRP-targeted therapies might provide a novel mechanism-based treatment option for patients with persistent PTH. ANN NEUROL 2020;88:1220-1228.

Post-Traumatic Stress Disorder After Traumatic Brain Injury-A Systematic Review and Meta-Analysis.

OBJECTIVE: To estimate the relative frequency and relative risk of post-traumatic stress disorder (PTSD) attributed to traumatic brain injury (TBI). DATA SOURCES: PubMed and Embase were searched from database inception until January 26, 2019. STUDY SELECTION: Two independent investigators screened titles, abstracts, and full texts. We selected studies that included subjects presenting with TBI, and where the number of subjects with TBI and PTSD could be extrapolated. There were no restrictions on study design. DATA EXTRACTION AND SYNTHESIS: Data were extracted by two independent investigators and results were pooled using random-effects meta-analysis. RESULTS: In civilian populations, relative frequency of PTSD following TBI was 12.2% after 3 months (CI-95 (7.6 to 16.8%) I2 = 83.1%), 16.3% after 6 months (CI-95 (10.2 to 22.4%), I2 = 88.4%), 18.6% after 12 months (CI-95 (10.2 to 26.9%), I2 = 91.5%), and 11.0% after 24 months (CI-95 (0.0 to 25.8%), I2 = 92.0%). Relative risk was 1.67 after 3 months (CI-95 (1.17 to 2.38), P = 0.011, I2 = 49%), 1.36 after 6 months (CI-95 (0.81 to 2.30), P = 0.189, I2 = 34%), and 1.70 after 12 months (CI-95 (1.16-2.50), P = 0.014, I2 = 89%). In military populations, the relative frequency of associated PTSD was 48.2% (CI-95 (44.3 to 52.1%), I2 = 100%) with a relative risk of 2.33 (CI-95 (2.00 to 2.72), P < 0.0001, I2 = 99.9%). CONCLUSIONS AND RELEVANCE: TBI is a risk factor for PTSD in clinic-based civilian populations. There are insufficient data to assess the relative frequency or relative risk of PTSD in moderate to severe TBI. Due to significant between-study heterogeneity, the findings of our study should be interpreted with caution.

Dizziness and vertigo during the prodromal phase and headache phase of migraine: A systematic review and meta-analysis.

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: We identified nine articles eligible for inclusion. Of these, one study reported results for the prodromal phase, seven studies for the headache phase and one study for both the prodromal and headache phase. In the prodromal phase, 9.0% of individuals with migraine reported dizziness, while 3.3% reported vertigo. During the headache phase, relative frequency of dizziness ranged from 6.7% to 59.6%, while vertigo ranged from 6.4% to 44.7%. The meta-analysis showed a relative frequency of 35.7% for dizziness (95% CI = 13.7-61.5%, I2 = 99%) and 33.9% for vertigo (95% CI = 26.7-41.5%, I2 = 87%). Study quality was rated 5/9 or below for seven studies and 6/9 or above for two studies. CONCLUSION: 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.

Risk Factors for the Development of Post-Traumatic Headache Attributed to Traumatic Brain Injury: A Systematic Review.

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 after whiplash injury: a systematic review and meta-analysis.

Neck pain and headache are 2 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 after whiplash injury. The literature search identified 2709 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% confidence interval (68%-95%) and a pooled relative frequency of headache was 60% (46%-73%), within 7 days after whiplash injury. At 12 months after 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 after injury. However, we also found considerable heterogeneity among studies with I-values ranging from 89% to 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 postwhiplash 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-invasive methods for measuring vascular changes in neurovascular headaches.

Vascular changes during spontaneous headache attacks have been studied over the last 30 years. The interest in cerebral vessels in headache research was initially due to the hypothesis of cerebral vessels as the pain source. Here, we review the knowledge gained by measuring the cerebral vasculature during spontaneous primary headache attacks with the use of single photon emission tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRA) and transcranial Doppler (TCD). Furthermore, the use of near-infrared spectroscopy in headache research is reviewed. Existing TCD studies of migraine and other headache disorders do not provide solid evidence for cerebral blood flow velocity changes during spontaneous attacks of migraine headache. SPECT studies have clearly shown cortical vascular changes following migraine aura and the differences between migraine with aura compared to migraine without aura. PET studies have shown focal activation in brain structures related to headache, but whether the changes are specific to different primary headaches have yet to be demonstrated. MR angiography has shown precise changes in large cerebral vessels during spontaneous migraine without aura attacks. Future development in more precise imaging methods may further elucidate the pathophysiological mechanisms in primary headaches.