Acute Headache Research Articles

The association between neuropathic pain features and central sensitization with acute headache associated to a whiplash injury

BackgroundHeadache is one of the most common symptoms after a whiplash injury, although the pathophysiology remains under discussion. This study aimed to evaluate differences in neuropathic pain and central sensitization features between those who present with whiplash-associated headache (WAH) soon after a whiplash injury and those who do not. MethodsThis case-control study evaluated differences on the self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Pain Detect Questionnaire (PDQ) and the Central Sensitization Inventory (CSI) between those who present with WAH in the acute phase after a whiplash injury (n = 46) and those who do not (n = 36). Moreover, the association of these variables in addition to neck pain intensity and the Neck Disability Index (NDI) score, with the presence of WAH was examined through logistic regression. ResultsWhile differences between groups were found for both neuropathic and central sensitization features, only the presence of neuropathic pain features was associated with the presence of headache, with 27 scores for the S-LANSS and 23 for the PDQ from 46 people with headache (58.6% and 50.0%, respectively). The NDI and the S-LANSS partially explained (R2 = 0.68) the presence of WAH according to a logistic regression model. ConclusionSignificant differences were found between people with whiplash with and without WAH when the S-LANSS, the PDQ and the CSI were assessed. S-LANSS and NDI were the variables most associated with the presence of WAH. These findings suggest that neuropathic pain features may be associated with the presence of acute WAH.

The potential to prevent unnecessary emergency department visits by timely diagnosis of migraine-A prospective observational study.

Successful acute migraine treatment potentially prevents emergency room (ER) consultations but requires that the diagnosis of migraine was given earlier. The aim of this study is to quantify the problem of missed migraine diagnosis prior to ER visits. Inclusion criterion for this single-center prospective study was the presentation at the ER for acute headache. Patients with acute migraine attacks were assessed for previous migraine attacks, and whether they were given a diagnosis of migraine in the past. Of 137 patients with migraine diagnosis at discharge, 108 (79%) had previous headache attacks fulfilling the criteria for migraine according to The International Classification of Headache Disorders 3rd edition (ICHD-3). Of those, 54 (50%) received the diagnosis for the first time. Half of the migraine patients (50%) presenting in the ER for headache could have been diagnosed earlier. This highlights the need for better detection and treatment of migraine by pre-hospital healthcare providers, as earlier diagnosis and specific acute treatment could have prevented the ER visit.

Understanding Experiences of Headache-Sufferers Attending Emergency Departments Through Photovoice.

Our aim was to explore the experiences of individuals receiving emergency department (ED) care for acute headaches. Patients with headache exacerbations commonly present to EDs. This study explored the experiences of adult patients during the exacerbation period, specifically using photovoice. Recruited from two urban EDs in Alberta, Canada, participants with primary headaches took photographs over 3-4 weeks and subsequently completed a 60-90 minute, one-on-one, in-person photo-elicitation interview. Interviews were audio recorded, transcribed and thematically analyzed alongside photographs. Eight participants (six women) completed the study. The average age was 42 years (standard deviation: 16). Five themes emerged: (1) the struggle for legitimacy in light of the invisibility of their condition; (2) the importance of hope, hopelessness and fear in the day-to-day life of participants; (3) the importance of agency and becoming "your own advocate"; (4) the struggle to be and be seen as themselves despite the encroachment of their headaches; and (5) the realities of "good" and "bad" care in the ED. Participants highlighted examples of good care, specifically when they felt seen and believed. Additionally, some expressed the acute care space itself being a beacon of hope in the midst of their crisis. Others felt dismissed because providers "know it's not life or death." This study highlighted the substantial emotional impact that primary headaches have on the lives of participants, particularly during times of exacerbation and while seeking acute care. This provides insight for acute care settings and practitioners on how to effectively engage with this population.

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case.

High-grade astrocytoma with piloid features (HGAP) is a novel condition introduced in the 2021 World Health Organization classification. Given that it has been recently classified, reports clarifying its clinical features or diagnostic criteria are lacking, especially in cases of atypical presentation. Herein, the authors present a rare case of HGAP with repeated symptomatic hemorrhages. A woman in her 20s presented with an acute headache and vertigo. Computed tomography and magnetic resonance imaging revealed a 2.5 × 2.8 × 2.3-cm hemorrhagic cerebellar mass with calcifications. After moderate improvement of her symptoms, she developed recurrent hemorrhage, and the tumor size increased (3.0 × 3.6 × 4.0 cm) 18 days later, necessitating resection. Pathological and molecular analyses confirmed the diagnosis of HGAP with an FGFR1-TACC1 fusion, MTAP/CDKN2A/B deletion, and SETD2 rearrangement. Radiologically, the presence of calcification and cystic components and the absence of perilesional edema were atypical features of previously reported HGAP. Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

8319 Pituitary Apoplexy Leads to the Spontaneous Resolution of Hypercortisolism Secondary to Cushing Disease: A Clinical Case

Abstract Disclosure: N. Sweis: None. J. Sanchez Perez: None. M. Fariduddin: None. R.M. Sargis: None. D.J. Toft: None. S. Reutrakul: None. Background: Pituitary apoplexy is a potentially fatal condition involving the infarction or hemorrhage of the pituitary gland. Rarely, it can occur in the setting of an ACTH-secreting pituitary adenoma. Clinical Case: A 27-year-old female with a past medical history of obesity, spontaneous miscarriages, and amenorrhea presented to the ER with an acute onset frontal headache of throbbing quality, associated with nausea and vomiting. The headache began two days prior, rapidly intensified, and did not improve with oral acetaminophen. CT of the head revealed an enlarged pituitary gland, while neurovascular imaging showed no abnormalities. Her neurologic examination was normal. She denied visual changes, photophobia, neck rigidity, fevers, chills, or recent infections. Furthermore, she endorsed a weight gain of about 40 pounds over the past year despite no change in dietary habits. This was accompanied by amenorrhea, hair thinning, itchy comedonal acne, hirsutism, and a loss of libido. Her physical examination was remarkable for the presence of cushingoid features including violaceous abdominal striae, facial acne, moon facies, a dorsal fat pad, and acanthosis nigricans around the neck and axillae. Pituitary MRI with and without contrast showed an enlarged sellar and suprasellar macroadenoma measuring approximately 2.1x1.4x1.2 cm abutting the optic chiasm. The visualized lesion contained hemorrhagic products, suggesting pituitary apoplexy. Biochemical testing on admission included a low morning plasma cortisol of 6.5 ug/dL (ref. range: 6.7-22.6 ug/dL), a 24-hour urine free cortisol of 12.0 (<=45.0 ug/24 hour), and an elevated ACTH of 145.0 pg/mL (7.2 - 63.3 pg/mL). A1c was 5.8% (<5.7%). Serum levels of prolactin, IGF1, GH, LH, FSH, TSH, Free T4, estradiol, total and bioavailable testosterone were within normal limits. She was evaluated with an ACTH stimulation test, which showed a morning cortisol level of 1.2 ug/dL at baseline, lower from prior. Cortisol levels were adequately increased at 19.6 ug/dL and 22.6 ug/dL, 30 and 60 minutes after the administration of Cosyntropin 250 mcg, respectively (>=18 ug/dL after 30-60 mins). The level of ACTH at the time was also decreased to 76.6 pg/mL. The patient was therefore started on steroid replacement therapy with hydrocortisone and later underwent transsphenoidal resection of the pituitary mass without complications. Histopathological examination of the resected mass showed pituitary adenoma cells with diffuse weak to moderate ACTH staining, most consistent with a sparsely granulated corticotroph pituitary adenoma. Conclusion: We report an interesting case of Cushing disease that spontaneously resolved after pituitary apoplexy. Our case underlines the importance of close monitoring of such patients who may rapidly undergo a period of adrenal insufficiency after hypercortisolism. Presentation: 6/3/2024

Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.

Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences. A cohort study spanning 10years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits. Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304days, IQR 1433-3274) indicated favorable outcomes in both groups. This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

7422 Adipsic Diabetes Insipidus Following Pituitary Macroadenoma Resection

Abstract Disclosure: J. Chippior: None. L. Ghalib: None. A 44 year-old female with a PMH of primary hypothyroidism, and a pituitary macroadenoma that was lost to follow up, presented to the ED with a chief complaint of an acute headache and decreased visual acuity involving the right eye over the past year. Patient was found to have a large, homogenous suprasellar mass with the largest dimension measuring 6.3 cm in size, and causing displacement of the optic chiasm. Initial hormonal workup was most notable for elevated prolactin at 128 ng/ml (3.3-26.7 ng/ml), which was slightly lower than when it was previously measured 10 years ago. The patient was taken to the OR for transsphenoidal endoscopic partial resection, but within 24 hours of post-op, she developed hypernatremia at 153 mmol/dL (135-145 mmol/dL) that was suspected to be secondary to diabetes insipidus (DI). In addition, she also suffered several small strokes involving her right midbrain and basal ganglia. She required multiple doses of DDAVP throughout her stay and this was ultimately continued upon discharge. Unfortunately, as follow up MRI had shown residual tumor within the third ventricle, she returned for a 2nd resection but once again suffered additional post-operative complications. The patient experienced additional strokes involving the right frontal and parietal lobes, and her DI became more labile than before, with her serum sodium peaking at 172 mmol/dL. Despite such a high degree of hypernatremia, she did not demonstrate any signs of thirst or any desire to access free water, even after her post-stroke encephalopathy had largely resolved. With less than 100 severe cases documented over the past four decades, it was suspected that the patient had a rare form of DI known as “adipsic DI”. Osmoreceptors within the hypothalamus can trigger the release of ADH or stimulate thirst, with the former requiring a smaller change in serum osmolality to generate such a response. Pituitary surgery involves manipulation of the infundibulum and any inadvertent severing can prevent ADH’s ability to travel from the hypothalamus to the posterior pituitary, subsequently leading to DI. The majority of patients with post-op DI increase their free water intake and subsequently do not develop hypernatremia. Those with adipsic DI lack this compensatory mechanism which leads to the electrolyte disturbance, and carries a higher risk of morbidity and mortality than those with typical DI. Following her second surgery, our patient was discharged with DDAVP once again but this time with a higher dose and frequency. She’s had numerous hospital readmissions since then for altered mental status in the setting of hypernatremia as she still struggles to meet her free water intake and continuously relies on her family for reminders. Though her case is certainly not typical, it highlights the added complexity of managing adipsic DI as it relies not only on DDAVP replacement, but replicating what is supposed to be an innate behavior. Presentation: 6/3/2024

The effectiveness of parenteral agents to mitigate relapses after severe acute migraine headache presentations: A systematic review and network analysis.

To compare the effectiveness of parenteral agents to reduce relapse in patients with acute migraine and identify factors that predict relapse. Following discharge from emergency settings, many patients with acute migraine will experience a relapse in pain; severe relapses may result in re-visits to emergency settings. A comprehensive literature search, updated to 2023, was conducted to identify randomized controlled trials assessing the effectiveness of parenteral agents on relapse outcomes in patients with acute migraine discharged from emergency settings. Two independent reviewers completed study selection, quality assessment, and data extraction. A traditional meta-analysis compared parenteral corticosteroids to placebo; a frequentist network analysis assessed direct and indirect comparisons. Results are reported as risk ratios (RRs) and 95% confidence intervals (CIs). The review protocol was registered with the International Prospective Register of Systematic Reviews (identifier: CRD42018099493). From 8949 citations, a total of 53 unique studies were included involving 6167 patients. Most studies had a high or unclear risk of bias. Corticosteroids significantly reduced relapses compared to placebo (RR 0.67, 95% CI 0.52-0.88; I2 = 0%). Patients receiving lidocaine (RR 0.10, 95% CI 0.01-0.82), sedatives/hypnotics (RR 0.33, 95% CI 0.14-0.75), ergot agents (RR 0.44, 95% CI 0.25-0.75), neuroleptics (RR 0.47, 95% CI 0.31-0.71), opioids (RR 0.58; 95% CI 0.35-0.94), or corticosteroids (RR 0.64, 95% CI 0.47-0.86) were significantly less likely to relapse. Lidocaine (RR 0.09, 95% CI 0.01-0.71), combination therapy (RR 0.12, 95% CI 0.02-0.74), or adding corticosteroids (RR 0.61, 95% CI 0.44-0.84) were more likely to reduce severe relapses. Longer duration of headache and residual pain at discharge were significantly associated with higher relapses. Corticosteroids remain the recommended first-line option to reduce relapse outcomes. Some parenteral agents typically provided for pain relief including ergot agents, neuroleptics, or combination therapy may effectively reduce relapse; however, opioids are not recommended due to safety concerns. Additional research is needed for some lesser studied, albeit promising, agents including lidocaine and propofol. Effective pain control in emergency settings prior to discharge and duration of headache may play a role in the success of such treatments and further investigations could provide further insight regarding how and why some parenteral agents are effective in mitigating relapse events.

IIH, SIH and headache: Diagnosis and treatment update

Idiopathic intracranial hypertension (IIH) and spontaneous intracranial hypotension (SIH) are two major secondary headache disorders resulting from abnormal intracranial pressure (ICP). This short communication outlines the pathophysiology, diagnostic criteria, and management strategies for IIH and SIH. IIH predominantly affects obese women of childbearing age and presents with daily headaches, visual disturbances, and papilledema. It is characterized by elevated cerebrospinal fluid (CSF) pressure, with diagnosis supported by imaging and lumbar puncture. Treatment includes weight reduction, medications, and surgical interventions in refractory cases. SIH, conversely, is caused by spontaneous spinal CSF leaks and presents with acute orthostatic headaches. Diagnosis is supported by neuroimaging and lumbar puncture, revealing low CSF pressure. Treatment includes supported care, (targeted) epidural blood patch, with surgical repair considered in refractory cases. Advances in imaging and treatment have significantly improved outcomes for both conditions.

Assessment of prolonged safety and tolerability of erenumab in migraine patients in a long-term open-label study (APOLLON)

BackgroundEfficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab’s tolerability and safety profile in individuals experiencing episodic and chronic migraines.MethodsThe study population consisted of adult patients with episodic or chronic migraine, who had successfully completed the HER-MES study (NCT03828539). Patients were treated with erenumab for 128 weeks at a flexible dose of either 70 mg or 140 mg. Treatment discontinuation attempts were allowed as voluntary single treatment interruption (‘drug holiday’) of up to 24 weeks.Results701 patients were enrolled in APOLLON. The exposure associated incidence rate (EAIR) of adverse events (AEs) (N = 601) per 100 subject years was 101.71 (95% CI [92.28; 111.14]) meaning a patient could expect having about one adverse event per each year of treatment. EAIR was higher in females (n = 524, EAIR: 104.40, 95% CI [93.93; 114.86]) than in males (n = 77, EAIR: 86.55, 95% CI [65.39; 107.71]) and increased with initial monthly migraine days (MMD) and prior prophylactic treatment failures. A total of 155 patients discontinued erenumab treatment during open-label treatment phase. Of these, 29 were due to AEs (4.1% of total cohort) and out of these 65.5% (N = 19) were considered treatment-related. Safety parameters were in line with HER-MES data and did not reveal new safety signals. Drug holidays were realized by 108 patients (15.4%), of which 64.8% (N = 70) returned to treatment. The mean number of monthly headache days (MHDs), MMDs, and days with acute headache medication significantly increased during drug holiday. After resumption of erenumab treatment, a rapid reduction of the migraine parameters was observed.ConclusionsAPOLLON provides long-term safety and tolerability data confirming the beneficial safety profile of erenumab over a period of 128 weeks. In addition, reversibility of migraine deterioration during drug holiday was shown and most patients returned to their treatment with similar response rates compared to initial treatment.Trial registrationClinicalTrials.gov ID: NCT04084314 (https://clinicaltrials.gov/study/NCT04084314), First submitted: 2019-09-06.

Efficacy and Safety of Erenumab for Nonopioid Medication Overuse Headache in Chronic Migraine

Patients with chronic migraine and medication overuse headaches (CM-MOH) represent a particularly burdened subpopulation. This trial provides first, to our knowledge, American Academy of Neurology class I evidence for a preventive therapy in CM-MOH. To assess erenumab efficacy and safety in patients with nonopioid CM-MOH. This randomized, double-blind, parallel-group, placebo-controlled trial took place at 67 centers in North America, Europe, and Australia from October 7, 2019, to November 2, 2022. This report reflects the primary analysis conducted in January 2023, using a database snapshot from December 1, 2022, which contains the complete dataset of the double-blind treatment period (DBTP). Participants included adults with CM-MOH who had 1 or more preventive treatment failure(s). There were 992 participants screened and 620 participants enrolled (584 in nonopioid cohort and 36 in opioid cohort). Erenumab, 70 mg, 140 mg, or placebo, once monthly for 24 weeks. The primary end point was MOH remission at month 6. Secondary end points included change from baseline in mean monthly acute headache medication days (AHMD) at month 6 and sustained MOH remission throughout the DBTP. Safety end points were adverse events and changes in vital signs. The primary analysis population included 584 participants in the nonopioid-treated cohort with a mean age of 44 years and 482 participants were female (82.5%). Baseline demographics and disease characteristics were balanced across groups. At month 6, 134 participants in the erenumab, 140 mg group (69.1%) (odds ratio [OR], 2.01; 95% CI, 1.33-3.05; P < .001 vs placebo) and 117 in the erenumab, 70 mg group (60.3%) (OR, 1.37; 95% CI, 0.92-2.05; P = .13 vs placebo) achieved MOH remission vs 102 participants in the placebo group (52.6%). AHMD use was also reduced in the erenumab groups vs placebo. Least squares mean (standard error) change from baseline in average monthly AHMD was -9.4 (0.4) days in the erenumab, 140 mg group (difference from placebo, -2.7; 95% CI, -3.9 to -1.6; P < .001) and -7.8 (0.4) days in the erenumab, 70 mg group (difference from placebo, -1.2; 95% CI, -2.4 to -0.1; P = .03), vs -6.6 (0.4) days in the placebo group. MOH remission throughout the DBTP was sustained in 119 participants (61.3%,) 96 participants (49.5%), and 73 participants (37.6%) in the erenumab, 140 mg, 70 mg, and placebo groups, respectively. Adverse events were consistent with the known safety profile of erenumab. Treatment-emergent adverse events incidence in the combined erenumab group was 66.8% (259 participants; constipation 15.2% (59 participants) and COVID-19 13.9% (54 participants) were most common. In this study, monthly, 140 mg, erenumab injections safely and effectively achieved MOH remission in patients with nonopioid CM-MOH within 6 months. ClinicalTrials.gov Identifier: NCT03971071.

Subarachnoid haemorrhage in the emergency department (SHED): a prospective, observational, multicentre cohort study

BackgroundPeople presenting to the ED with acute severe headache often undergo investigation to exclude subarachnoid haemorrhage (SAH). International guidelines propose that brain imaging within 6 hours of headache onset can...

Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial.

To describe exploratory endpoints from a previous phase 2b/3 placebo-controlled trial conducted in Japan and Korea, specifically investigating the effect of fremanezumab or placebo on migraine-associated symptoms and acute headache medication use in patients with episodic migraine (EM). EM is associated with non-head pain symptoms, including nausea, vomiting, photophobia, or phonophobia, which contribute substantially to the disease burden, healthcare resource utilization, and impaired quality of life. Current EM treatments include a mix of nonspecific/migraine-specific acute headache medications, but medication overuse can induce headaches and progression from EM to chronic migraine (CM). In multiple phase 2b/3 trials, the monoclonal antibody fremanezumab significantly reduced the average number of monthly migraine days experienced by patients with EM/CM compared with placebo. This was a prespecified analysis of exploratory endpoints in a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 trial conducted in Japanese and Korean patients with EM (NCT03303092). Patients were randomized to receive fremanezumab, either monthly or quarterly, or matching placebo, administered subcutaneously at 4-week/28-day ("monthly") intervals to maintain blinding. Exploratory endpoints reported here were the mean change from baseline in the number of days/month with (i) the use of any acute headache medication, (ii) the use of any migraine-specific acute headache medication, (iii) nausea or vomiting, and (iv) photophobia and phonophobia. Overall, 357 Japanese and Korean patients with EM received either monthly (n = 121) or quarterly (n = 119) fremanezumab or placebo (n = 117). Compared with placebo, fremanezumab administered monthly or quarterly was associated with a significant reduction from baseline in the average number of days/month with acute headache medication use over three months (difference vs. placebo -2.81 [95% confidence interval (CI) -3.52, -2.11]; p < 0.001 and -2.79 [95% CI -3.50, -2.08]; p < 0.001, respectively). Similar findings were observed in the monthly average number of days with migraine-specific acute headache medications (difference vs. placebo with monthly and quarterly fremanezumab, -2.63 [95% CI -3.31, -1.95] for both; p < 0.001), the average number of days/month with nausea or vomiting (difference vs. placebo -1.09 [95% CI -1.60, -0.58]; p < 0.001 for monthly fremanezumab and -1.37 [95% CI -1.88, -0.86]; p < 0.001 for quarterly fremanezumab), and the average number of days with photophobia and phonophobia (difference vs. placebo -1.22 [95% CI -1.80, -0.65]; p < 0.001 and -1.64 [95% CI -2.22, -1.06]; p < 0.001, respectively). Monthly and quarterly administered fremanezumab effectively prevented EM in Japanese and Korean patients. Fremanezumab also improved other disease aspects including the need for acute headache medications and the frequency of migraine-associated symptoms.

The impact of headache intensity on speech in participants with migraine and acute post-traumatic headache.

Slower speaking rates and higher pause rates are found in individuals with migraine or post-traumatic headache during headache compared to when headache-free. We aimed to determine whether headache intensity influences the speaking rate and pause rate of participants with migraine or acute post-traumatic headache (aPTH) following mild traumatic brain injury (mTBI). Using a speech elicitation tool, participants with migraine, aPTH, and healthy controls (HC) submitted speech samples over a period of 3 months. Speaking and pause rates were calculated when participants were headache-free and when they had mild or moderate headache. In this observational study, speaking and pause rates in participants with migraine and aPTH were compared to HC, controlling for age, sex, and days since mTBI (participants with aPTH only). A total of 2902 longitudinal speech samples from 13 individuals with migraine (mean age = 33.5, SD = 6.6; 12 females/1 male), 43 individuals with aPTH (mean age = 44.4, SD = 13.5; 28 females/15 males), and 56 HC (mean age = 40.8, SD = 13.0; 36 females/20 males) were collected. There was no difference in speaking rate between HC and the combined headache cohort of participants (migraine and aPTH) when they had headache freedom or a mild headache. When participants had moderate intensity headache, their speaking rate was significantly slower compared to that of HC and compared to their speaking rate during mild headache intensity or headache freedom. For the combined headache cohort of participants, pause rates were significantly higher when they had headache freedom or had a headache of mild or moderate intensity relative to HC. Compared to participants' pause rate during headache freedom, their pause rate was significantly higher during mild and moderate headache intensity. Participants with aPTH had significantly slower speaking rates compared to participants with migraine during headache freedom, mild headache intensity, and moderate headache intensity. Participants with aPTH had significantly higher pause rates compared to participants with migraine when experiencing moderate headache intensity. For both aPTH and migraine, more severe headache pain was associated with higher pause rates and slower speaking rates, suggesting that speaking rate and pause rate could serve as objective biomarkers for headache-related pain. Slower speaking rate in participants with aPTH could reflect additional consequences of TBI-related effects on motor control and speech production.

Aseptic meningitis with recurrent headache episodes, vomiting, and central fever as first manifestation of isolated neurosarcoidosis: a case report

BackgroundNeurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity.Case ReportA 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in β2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found.ConclusionsThis case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits.

Enhancing chronic migraine preventive therapy: low-level 810 nm laser acupuncture as an add-on treatment for patients with unsatisfactory pharmacological effect, a pilot single-blind randomized controlled trial

BackgroundLaser acupuncture is a proven non-invasive treatment with effects comparable to traditional acupuncture in different types of headaches, but there is still insufficient evidence for chronic migraine (CM) in adults. We aim to investigate the efficacy and safety of laser acupuncture (LA) as an add-on preventive therapy on CM.MethodsA single-blind randomized controlled trial was conducted from January 2022 to November 2023. CM patients with unsatisfactory pharmacological effects were randomly assigned in a 1:1 ratio to receive either LA or sham treatment over a course of 8 sessions spanning 4 weeks. The co-primary outcomes were changes in monthly migraine days (MMD) and acute headache medications usage days per month from baseline. Evaluations were taken at baseline (12 weeks before randomization), at 4th week (treatment completed), 8th week and 12th week from baseline.ResultsA total of 60 patients (30 in each group) were included in the intention-to-treat analyses. Baseline headache characteristics between trial groups were similar. Compared with the sham group, the LA group had a significant reduction in MMD (5.2 vs. 1.5 days at 8th week, p = 0.015; 7.3 vs. 1.8 days at 12th week, p = 0.001), and acute headache medications usage days per month (3.1 vs. 0.4 days at 4th week, p = 0.007; 3.2 vs. 0.0 days at 8th week, p = 0.005; 3.9 vs. 0.0 days at 12th week, p < 0.001). No serious adverse event was observed in both groups.ConclusionsLaser acupuncture was effective in reducing MMD and acute headache medications usage with promising safety. Specifically, the efficacy of LA exhibited a progressively more pronounced effect within the follow-up period. We suggested that LA is a promising add-on preventive therapy for CM, and trials focused on investigating the mechanism of LA’s effect and its long-term effects on CM prevention are justified.Trial registrationThe study was retrospectively registered at ISRCTN.org Identifier: ISRCTN11208146 (https://doi.org/10.1186/ISRCTN11208146). The registration date: 19, January, 2024.The date of first participant registration: 04, May, 2022.

Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design.

Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20mg of ropivacaine plus 4mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). The trial has a primary efficacy end point (oral morphine equivalent/day use within 24h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

International standard of Traditional Chinese Medicine Techniques: Traditional Chinese Medicine guidelines for acute primary headache (2022).

To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of acute primary headache and provide clinical practice guidance. The guidelines were developed in accordance with the World Health Organization guideline development manual. After the establishment of steering committee, panel and the registration and protocol formulation, the evidence on TCM for acute primary headache from published guidelines, clinical evidence, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation method was used to grade the evidence and make the recommendations. Based on the available evidence, the guidelines recommended three TCM herbal decoctions, six Chinese patent medicines, and two kinds of external application of Chinese herbal medicines. Diagnostic recommendations based on the expert experience and consensus were also included in the guidelines. TCM diagnosis and treatment of decoction, Chinese patent medicine and external application for treating acute primary headache were recommended. We hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.

Visual inspection versus spectrophotometry for xanthochromia detection in patients with sudden onset severe headache-A diagnostic accuracy study.

There is still disagreement about whether to routinely use spectrophotometry to detect xanthochromia in cerebrospinal fluid (CSF) or whether visual inspection is adequate. We aimed to evaluate the diagnostic accuracy of these methods in detecting an aneurysmal subarachnoid hemorrhage in patients with sudden onset severe headache. When a patient presents to the emergency department with a headache for which there is suspicion of a subarachnoid hemorrhage, the gold standard to rule this out is to perform a CSF analysis for xanthochromia with or without spectrophotometry if the cranial non-contrast computed tomography (CT) upon admission is negative. Having applied the gold standard, we retrospectively included patients with acute headache who underwent both CT scan and CSF spectrophotometry at our hospital in the period 2002-2020. Patients were excluded if the cranial CT was interpreted as positive, there was a bloody CSF, or if visual assessment data of the CSF was unavailable. We scrutinized the patients' medical records and evaluated the benefit of spectrophotometry compared to visual inspection. The net bilirubin absorbance cut-off for support of subarachnoid hemorrhage was set at >0.007 absorbance units. The spectrophotometry was also considered positive if the net bilirubin absorbance was ≤0.007 and net oxyhemoglobin absorbance was ≥0.1 absorbance units. We calculated and compared the sensitivity and specificity of CSF spectrophotometry and visual inspection of the CSF. In total, 769 patients, with a mean age of 42.3 ± (standard deviation [SD] = 17.3) years, were included. The headache onset was classified as a thunderclap headache in 41.5%, and 4.7% had a sudden loss of consciousness. Fifteen patients (2%) were finally diagnosed with a subarachnoid hemorrhage, six (0.8%) had an aneurysmal subarachnoid hemorrhage, seven (0.9%) had a perimesencephalic hemorrhage, one (0.1%) had a cortical cerebral sinus venous thrombosis, and one (0.1%) had a spinal epidural hematoma. Four patients (0.5%) had a subarachnoid hemorrhage that was not detected by visual inspection, and two were caused by an aneurysmal rupture. One of these two patients died just before intervention, and the other underwent coiling for an anterior communicating aneurysm. The number needed for lumbar puncture to detect a subarachnoid hemorrhage was 51, but 128 to detect an aneurysmal hemorrhage. The corresponding numbers needed for CSF spectrophotometric analysis were 192 and 385, respectively. Spectrophotometry was positive in 31 patients (4.0%), of whom 18 (2.3%) also had visually detected xanthochromia (11 true positive). The mean net bilirubin absorbance in the 13 samples with visually clear CSF was 0.0111 ± (SD = 0.0103) absorbance units, compared to 0.0017 ± (SD = 0.0013) in the CSF with negative spectrophotometry. The corresponding figures for net oxyhemoglobin absorbance were 0.0391 ± (SD = 0.0522) versus 0.0057 ± (SD = 0.0081). The sensitivity of spectrophotometric xanthochromia detection was 100% (95% confidence interval [CI], 78-100), compared to 73% (95% CI, 45-92) for visual xanthochromia detection. The specificity of spectrophotometric xanthochromia detection was 98% (95% CI, 97-99) compared to 99% (95% CI, 98-100) for visual xanthochromia detection. Both methods had high negative predictive values: 100% (95% CI, 99.5-100) versus 99.5% (95% CI, 98.6-99.9), respectively. Both visual inspection and spectrophotometry have high diagnostic accuracy for detecting CSF xanthochromia, but the lower sensitivity of visual assessment makes it unreliable, and we recommend the use of spectrophotometry in clinical practice.

Effectiveness and Safety of Pharmacopuncture on Inpatients with Tension Headache Caused by Traffic Accidents: A Pragmatic Randomized Controlled Trial.

Background: This study investigated the effectiveness and safety of pharmacopuncture for pain relief and functional improvement in patients with traffic accident (TA)-induced acute tension headaches. Methods: The study employed a parallel, single-centered, pragmatic, randomized controlled trial design. Eighty patients complaining of acute tension headaches were randomized into the integrative Korean medicine treatment (IKM treatment) group and the pharmacopuncture group on suboccipital muscles (suboccipital muscles pharmacopuncture + IKM treatment), with 40 participants assigned to each group. The patients in the pharmacopuncture group underwent pharmacopuncture as an add-on therapy, consisting of three sessions. Both groups were reassessed 2 months post-intervention. To assess the outcomes, the Numeric Rating Scale (NRS) for Headache, NRS for Neck Pain, Headache Disability Index, Headache Impact Test-6, EuroQol 5-Dimension, and Patient Global Impression of Change were used. Results: The improvement in the outcomes of the pharmacopuncture group was significantly greater than that of the comparison group on day 4 of hospitalization in terms of pain (difference in NRS of headache -2.59, 95% CI -3.06 to -2.12; NRS of Neck pain -1.05, 95% CI -1.50 to -0.59) and function (difference in HDI -24.78, 95% CI, -31.79 to -17.76; HIT-6 -6.13, 95% CI, -9.47 to -2.78). Additionally, in 2 months of follow-up, the recovery rate of headache was significantly higher in the pharmacopuncture group than in the comparison group. Conclusions: The pharmacopuncture group demonstrated superior outcomes in symptom improvement than the comparison group did, providing insights into novel and useful applications of pharmacopuncture in the clinical practice of Korean medicine.