The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines

The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (− 6.45 ± 0.82 mg/dl vs − 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (− 2.02 ± 0.30 ng/ml vs − 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.

Comparison of the efficacy of intranasal ketamine versus intravenous ketorolac on acute non-traumatic headaches: a randomized double-blind clinical trial

Introduction Non - traumatic headaches are one of the most common causes of referral to hospital emergency. This study aimed to compare the efficacy of intranasal ketamine and intravenous ketorolac on acute non-traumatic headaches. Methods This randomized and double-blind clinical trial was conducted in 2019. One hundred and forty samples were randomly divided into intranasal ketamine (A) and intravenous ketorolac (B). Group (A) received ketamine intranasal (0.75 mg/kg, max 75 mg), and group B received intravenous ketorolac (30 mg). Headache severity was measured on arrival, 30, 60, and 120 min after intervention with Visual Analogue Scale (VAS). The side effects were recorded an hour after the intervention. Result The mean difference of pain intensity 30, 60, and 120 min after the intervention between the two groups was statistically significant (p < 0.001). In the first 30 min, significant changes were observed in the VAS levels of the two groups. These changes were significantly greater in the intranasal ketamine group (p < 0.001). Side effects such as fatigue, dizziness, general discomfort, nausea, increased heart rate, and hypertension were significantly higher in the ketamine group (p < 0.05). Conclusion Intranasal ketamine and intravenous ketorolac both effectively reduced headaches. However, more analgesic effects of intranasal ketamine in a short time can be considered as a selective approach to reducing headaches. Trial registration IRCT20180108038276N3, Registered 29 September 2019. Ethics committee reference number IR.KUMS.REC.1398.068.

Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Treatment of Patients With Concussion

ObjectiveInvestigate the efficacy of 3 anti-Calcitonin Gene-Related Peptide monoclonal antibodies (anti-CGRP mAbs), fremanezumab, galcanezumab, and erenumab, in concussion patients with post-traumatic headache (PTH) with a migraine phenotype.BackgroundA study using monoclonal antibodies in mice with mild traumatic brain injury saw improvements in cutaneous allodynia.1 A study from Denmark using erenumab for PTH found patients had an 82% decrease in the number of headache days. This study also demonstrated that 44% of patients had a reduction in HIT-6 score = 5 after 9–12 weeks of treatment.2.Design/MethodsRetrospective chart review of patients diagnosed with PTH (n = 168) evaluated HIT-6, number of reported headache days, and the number of modifiable concussion variables (headache, dizziness, attention/concentration deficit, mood and sleep disturbance) prior to initiation of anti-CGRP mAbs and after at least 3 months of treatment were recorded.ResultsPatients saw a decrease in HIT-6 score (p < 0.0001), with a mean difference of −4.26 from pre-treatment to at least 3 months after treatment. When evaluating 5 concussion symptom categories, patients experienced x¯ = 2.35 symptoms prior to anti-CGRP mAbs treatment, and x¯ = 1.67 after at least 3 months of treatment. Patients also experienced a decrease in the number of headache days per month (<0.0001) with a mean difference of −7.25 (range 0–30) headache days per month. Seven patients experienced adverse effects (1 patient had 2 different adverse effects), including injection site rash, fatigue, constipation, and dizziness. Only one patient discontinued medication due to adverse event.ConclusionsAnti-CGRP mAbs used to treat PTH showed improved headache severity and frequency, as well as a decreased number of overall concussion symptoms. There was a subset of patients with a more robust response. Switching anti-CGRP mAbs was beneficial in some patients.

Outcomes of Surgical Treatment of Migraines: A Systematic Review & Meta-Analysis

Background: Migraine surgery at 1 of 6 identified “trigger sites” of a target cranial sensory nerve has rapidly grown in popularity since 2000. This study summarizes the effect of migraine surgery on headache severity, headache frequency, and the migraine headache index score which is derived by multiplying migraine severity, frequency, and duration. Materials and Methods: This is a PRISMA-compliant systematic review of 5 databases searched from inception through May 2020 and is registered under the PROSPERO ID: CRD42020197085. Clinical trials treating headaches with surgery were included. Risk of bias was assessed in randomized controlled trials. Meta-analyses were performed on outcomes using a random effects model to determine the pooled mean change from baseline and when possible, to compare treatment to control. Results: 18 studies met criteria including 6 randomized controlled trials, 1 controlled clinical trial, and 11 uncontrolled clinical trials treated 1143 patients with pathologies including migraine, occipital migraine, frontal migraine, occipital nerve triggered headache, frontal headache, occipital neuralgia, and cervicogenic headache. Migraine surgery reduced headache frequency at 1 year postoperative by 13.0 days per month as compared to baseline ( I2 = 0%), reduced headache severity at 8 weeks to 5 years postoperative by 4.16 points on a 0 to 10 scale as compared to baseline ( I2 = 53%), and reduced migraine headache index at 1 to 5 years postoperative by 83.1 points as compared to baseline ( I2 = 2%). These meta-analyses are limited by a small number of studies that could be analyzed, including studies with high risk of bias. Conclusion: Migraine surgery provided a clinically and statistically significant reduction in headache frequency, severity, and migraine headache index scores. Additional studies, including randomized controlled trials with low risk-of-bias should be performed to improve the precision of the outcome improvements.

Case Report on Cerebral Venous Sinus Thrombosis

Introduction: Cerebral venous sinus Thrombosis is the unusual cause of a stroke affecting both reproductively old and genetically or thrombotic risk factors (CVST). The superior sagittal sinus and the cross sinus are two most common places for thrombus formation. A 26-year-old Man was taken to the Acharya Vinoba Bhave Rural Hospital with a new-onset complex-partial convulsion with secondary generalization, headache, and emesis seven days before presentation. Later on he experienced headache which was acute in onset and continuous in nature which was associated with fever. Patient had 1 episode of seizers lasting for 3-4 mints. Which was associated with fall on ground. He complained about weakness in left upper limb. The patient was then transferred to our care institution for definitive management. On arrival, the patient’s neurological examination was done and he reported a severe headache. MRI imaging performed at our institution. The patient was followed clinically, and no posttreatment imaging studies were performed. Following a 3-day hospital stay, the patient reported a significant reduction in headache severity and was discharged home.

Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p &lt; 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p &lt; 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p &lt; 0.05). There was no significant efficacy difference between low (4–7 migraine days/month, n = 22) and high frequency (8–14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

Correlation between depression level and headache severity: A study among medical students during the COVID-19 pandemic

Headache is the most prevailing disorder and the third leading cause of disability worldwide. The prevalence of primary headaches has been reported to increase by 2-4 times in patients with psychiatric comorbidities, including depression. This study sought to assess the correlation between depression level and headache severity among medical students. To the best of our knowledge, this is the first study to evaluate the correlation between depression level and headache severity in Indonesia. A cross-sectional study was conducted among students of Airlangga University in 2021. To evaluate the level of depression and the severity of headache, Depression Anxiety Stress Scales (DASS-42) and Headache Impact Test 6 (HIT-6) were used, respectively. A set of validated questionnaires were used to assess students’ demographic characteristics. A total of 82 medical students were included in this study and most of them were female (86.6%). The third-semester students represented the highest proportion (45.2%) of subjects. The mean age and body mass index (BMI) were 19.88 ± 1.03 and 22.55±4.44, respectively. The average DASS-42 score was 10.98±11.47 which indicated a mild depression level. The average HIT-6 score was 45.74±6.130 which revealed a mild impact. The data of Spearman correlation suggested that headache severity was significantly correlated with depression level (r=0.396, p<0.001). This study provides insights on the importance of stress management and depression prevention to decrease the risk of headache, and vice versa.

Understanding the link between obesity and headache- with focus on migraine and idiopathic intracranial hypertension

Background Obesity confers adverse effects to every system in the body including the central nervous system. Obesity is associated with both migraine and idiopathic intracranial hypertension (IIH). The mechanisms underlying the association between obesity and these headache diseases remain unclear. Methods We conducted a narrative review of the evidence in both humans and rodents, for the putative mechanisms underlying the link between obesity, migraine and IIH. Results Truncal adiposity, a key feature of obesity, is associated with increased migraine morbidity and disability through increased headache severity, frequency and more severe cutaneous allodynia. Obesity may also increase intracranial pressure and could contribute to headache morbidity in migraine and be causative in IIH headache. Weight loss can improve both migraine and IIH headache. Preclinical research highlights that obesity increases the sensitivity of the trigeminovascular system to noxious stimuli including inflammatory stimuli, but the underlying molecular mechanisms remain unelucidated. Conclusions This review highlights that at the epidemiological and clinical level, obesity increases morbidity in migraine and IIH headache, where weight loss can improve headache morbidity. However, further research is required to understand the molecular underpinnings of obesity related headache in order to generate novel treatments.

Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension

Objective Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure. Methods IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed. Results Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36). Conclusions We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures. Trial registration This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486.

Headache in patients with systemic lupus erythematosus: characteristics, brain MRI patterns, and impact

Background The prevalence of primary headache in patients with systemic lupus erythematosus (SLE) varies widely and whether it should be attributed to neurological involvement is controversial. We aimed to investigate the prevalence and characteristics of headache in SLE patients, describe its association with disease-related variables and brain imaging, and explore its impact on life. Results The overall prevalence of headache was 54.4%, and migraine was the most common type among headache sufferers (48.4%). Headache severity (VAS) and impact (HIT-6) correlated with SLEDAI-2K (P = 0.019 and P < 0.001, respectively) as well as with each other (P = 0.006). Brain imaging abnormalities were found in 25.8%, with white-matter hyperintensities (WMH) being the most frequent pathology. Musculoskeletal manifestations, positive anti-phospholipid (aPL) antibodies, and SLEDAI score ≥ 13.5 were identified as predictors of headache. Conclusion Primary headache, especially migraine, is a common feature of patients with SLE, and its presence is associated with negative impact on quality of life. Musculoskeletal features, aPL positivity, and overall disease activity appear to predict primary headache in SLE.