Diagnostic Criteria For Acute Headache Attributed To Ischemic Stroke And For Sentinel Headache Before Ischemic Stroke.

Background: Defining the relationship between a headache and stroke is essential. The current diagnostic criteria of the ICHD-3 for acute headache attributed to ischemic stroke are based primarily on the opinion of experts rather than on published clinical evidence based on extensive case-control studies in patients with first-ever stroke. Diagnostic criteria for sentinel headache before ischemic stroke do not exist. The present study aimed to develop explicit diagnostic criteria for headache attributed to ischemic stroke and for sentinel headache.Methods: This prospective case-control study included 550 patients (mean age 63,1, 54% males) with first-ever ischemic stroke and 192 control patients (mean age 58.7, 36% males) admitted to the emergency room without any acute neurological deficits or severe disorders. Standardized semi-structured interview forms were used to evaluate past and present headaches during face-to-face interviews by a neurologist on admission to the emergency room in both groups of patients. All headaches were diagnosed according to the ICHD-3. We tabulated the onset of different headaches before a first-ever ischemic stroke and at the time of onset of stroke. We divided them into three groups: a new type of headache, the previous headache with altered characteristics and previous unaltered headaches. The same was done for headaches in control patients within one week before admission to the hospital and at the time of entry. These data were used to create and test diagnostic criteria for acute headache attributed to stroke and sentinel headache. Results: Our previous studies showed that headache at onset of ischemic stroke was present in 82 (14.9%) of 550 patients, and 81 (14.7%) patients had sentinel headache within the last week before a stroke. Only 60% of the headaches at stroke onset fulfilled the diagnostic criteria of ICHD-3. Therefore, we proposed alternative criteria with a sensitivity of 100% and specificity of 97%. Besides, we developed diagnostic criteria for sentinel headache for the first time with a specificity of 98% and a sensitivity of 100%. Conclusion: We suggest alternative criteria for acute headache attributed to ischemic stroke and new diagnostic criteria for sentinel headache with high sensitivity and specificity.

P.033 Eptinezumab reduced acute medication use in patients with chronic migraine and medication-overuse headache: subgroup analysis of Promise-2

Background: Eptinezumab is a preventive migraine treatment approved in the US. We evaluated the impact of eptinezumab on acute headache medication (AHM) use in patients diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) in PROMISE-2. Methods: PROMISE-2 randomized patients with CM to eptinezumab 100mg, 300mg, or placebo for 2 intravenous doses administered every 12 weeks. Trained investigators diagnosed MOH at screening using 3-month medication history and ICHD-3b criteria. Endpoints included days/month of any AHM use (days of ≥1 medication class), total AHM use (summed days for each medication class), and triptan use over Weeks 1-12 and 13-24. AHM classes included triptan, ergot, opioid, simple analgesic, and combination analgesic. Results: Of 1072 PROMISE-2 patients, 431 (40.2%) were diagnosed with MOH (100mg, n=139; 300mg, n=147; placebo, n=145). During the 28-day baseline period, mean days of any AHM was ~16.4, total AHM was ~20.4, and triptan was ~8.9 across treatment arms. Over Weeks 1-12, mean days/month of any AHM was 8.8 (100mg), 9.9 (300mg), and 11.8 (placebo); total AHM was 10.8, 12.2, and 14.8; triptan was 4.3, 4.4, and 6.4. Similar or lower rates were observed over Weeks 13-24. Conclusions: In patients diagnosed with both CM and MOH, eptinezumab treatment reduced AHM use.

Fovilles Syndrome a Case to Remember Case Report

The Foville’s Syndrome is a rare clinical feature of stroke or brain hemorrhage. This is very rare brain stem syndrome and only few cases have been reported worldwide. A case of Foville's syndrome secondary to infarction at the left paramedian pontine region, which was diagnosed and treated at Annapurna Neurological institute and allied Science, Kathmandu, Nepal. A 62 years old gentleman presented with acute headache with sudden onset of vertigo, tinnitus, slurred speech, difficulty while swallowing and numbness and hemiparesis on the right side of the body. The aim of this study was to report a rare case of Foville's syndrome with the infarction at the left paramedian pontine region. The clinical manifestations were well correlated with anatomical involvement. The CT-scan of head, Magnetic Resonance Imaging (MRI), MR-Angiogram (MRA) sequence of cerebral and carotid, etc. helped in the diagnosis of the case along with the other lab investigations.

Lack of knowledge on acute stroke in children, adolescents and adults from public schools

Introduction Stroke is an important cause of disability and death in adults worldwide. However, it is preventable in most cases. This community-based study investigated students' stroke knowledge, emergency medical services (EMS) activation, associated risk factors, warning signs and symptoms, and prior experience from different educational levels. Methods We conducted the survey with a structured questionnaire between March 2019 and December 2020. Results Students from the elementary school (n=1,187, ∼13 y.o., 14% with prior experience, 51% women), high school (n=806, ∼17 y.o., 13% with prior experience, 47% women) and University (n=1,961, ∼22 y.o., 9% with prior experience, 66% women) completed the survey. Among the students, the awareness of stroke general knowledge, associated risk factors, and warning signs and symptoms varied between 42–66%. When stimulated, less than 52% of the students associated stroke with hypercholesterolemia, smoking, diabetes, and hypertension. When stimulated, 62–65% of students recognised arm weakness, facial drooping, and speech difficulty; only fewer identified acute headache (43%). Interestingly, 67% knew the EMS phone number; 81% were willing to have stroke education included at school, and 75.2% found it essential and mandatory. Female, higher education and prior experience were associated with higher scores of stroke risk factors (OR: 1.28, 95% CI: 1.10–1.48; OR: 2.12, 95% CI:1.87–2.40; and OR: 1.46, 95% CI: 1.16–1.83; respectively), and signs and symptoms (OR: 2.22, 95% CI: 1.89–2.60; OR: 3.30, 95% CI: 2.81–3.87; and OR: 2.04, 95% CI: 1.58–2.63; respectively). Conclusion Being female, having prior experience, and a higher educational level increase the identification of associated risk factors and warning signs and symptoms. Stroke awareness should be emphasized among schoolchildren and adolescents. FUNDunding Acknowledgement Type of funding sources: None.

Adenovirus-Vectored COVID-19 Vaccine–Induced Immune Thrombosis of Carotid Artery: A Case Report

Objective:Venous thromboses and thrombocytopenia after vaccination with the adenovirus-vectored COVID-19 vaccine ChAdOx1 nCov-19 (AstraZeneca) have been linked to serum antibodies against platelet factor 4 (PF4)–polyanion complexes. We here report vaccine-induced isolated carotid arterial thrombosis.Methods:Imaging and laboratory findings, treatment decisions and outcome of this case are presented.Results:Eight days after having received the first dose of ChAdOx1 nCov-19 vaccine, a 31-year-old man was admitted to our stroke unit with acute headache, aphasia, and hemiparesis. D-dimers were slightly elevated, but platelet count and fibrinogen level were normal. MRI-confirmed mainstem occlusion of middle cerebral artery resolved within 1 hour after start of IV thrombolysis. A wall-adherent, non-occluding thrombus in the ipsilateral carotid bulb was identified as the source of embolism. Cardiac or paradoxical (venous) embolism was excluded. Screening for presence of heparin-induced thrombocytopenia-related antibodies was positive, and highly elevated serum IgG antibodies against PF4–polyanion complexes were subsequently proven. Treatment with aspirin and subcutaneous danaparoid, followed by phenprocoumon, led to thrombus shrinkage and dissolution within 19 days, and favorable clinical outcome.Discussion:Vaccine history is important in patients not only with venous but also with arterial thromboembolic events. Vaccine-induced immune thrombosis of brain-supplying arteries may well be handled.

Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials

Background In patients with migraine, overuse of acute medication, including migraine-specific medication (MSM) such as triptans and ergots, can lead to adverse health outcomes, including development of medication overuse headache. Here, we examined the effect of erenumab on reducing acute medication use, in particular MSM, in patients with episodic migraine (EM) and chronic migraine (CM). Methods The current post-hoc analyses were based on data from the double-blind treatment phase (DBTP) of two erenumab studies, a pivotal EM (N = 955) and a pivotal CM (N = 667) trial, and their respective extensions. Patients were administered subcutaneous placebo or erenumab (70 or 140 mg) once monthly. Daily acute headache medication use (including MSM and non-MSM) was recorded using an electronic diary during a 4-week pretreatment baseline period until the end of the treatment period. Outcome measures included change in monthly acute headache medication days (HMD) in acute headache medication users at baseline, and changes in monthly MSM days (MSMD) in MSM users at baseline and non-MSMD in non-MSM users at baseline. Results In total, 60 and 78 % of patients (all acute headache medication users) with EM and CM used MSM at baseline, respectively. For acute headache medication users, the change in mean monthly acute HMD over Months 4, 5 and 6 compared with the pre-DBTP was 1.5, 2.5, and 3.0 for placebo, erenumab 70 mg and 140 mg, respectively for the EM study. The respective change in monthly MSMD in MSM users was 0.5, 2.1 and 2.8, and in monthly non-MSMD in non-MSM users was 2.3, 2.6, and 2.7. In the acute headache medication users at baseline, the change in monthly acute HMD at Month 3 compared with pre-DBTP was 3.4, 5.5, and 6.5 for placebo, erenumab 70 mg and 140 mg, respectively for the CM study. The respective change in monthly MSMD in MSM users was 2.1, 4.5, and 5.4, and in monthly non-MSMD in non-MSM users was 5.9, 6.4, and 6.6. Reductions in MSMD versus placebo were sustained in the extension periods of both studies. Erenumab was also associated with a higher proportion of MSM users achieving ≥ 50 %, ≥ 75 and 100 % reduction from baseline in monthly MSMD versus placebo in both EM and CM. Conclusions In both EM and CM, treatment with erenumab is associated with a significant and sustained reduction in the use of acute headache medication, in particular MSM. Trial registrations NCT02456740; NCT02066415; NCT02174861.

Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study

Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab. Methods Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or ≥75% reduction in monthly migraine days were evaluated. Results Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%). Conclusion Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes. Trial registration ClinicalTrials.gov NCT03308968 (FOCUS).