Increased risk of functional neurological disorders following SARS-CoV-2 vaccination.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the possible correlation between SARS-CoV-2 vaccines and the onset of neurological syndromes. The aim was to challenge the association between SARS-CoV-2 vaccinations and the onset of acute functional neurological disorders (FNDs) compared to other neurological syndromes in hospitalized patients. METHODS: In this prospective cohort study, all adult inpatients consecutively admitted to a tertiary neurological centre were included. The prevalence and characteristics of neurological syndromes were compared between unvaccinated and vaccinated cases stratified according to the onset from vaccination. The study involved 843 subjects, namely 411 unvaccinated (UVC) and 432 vaccinated cases; these groups were comparable for demographics and clinical diagnosis distribution. RESULTS: Compared to UVC, subjects hospitalized within the first 30 days from vaccine exhibited higher prevalence of FNDs (12.3% vs. 3.6%; odds ratio 4.2, 95% confidence interval 1.6-11.1) and headache (10.8% vs. 5%; odds ratio 4.1, 95% confidence interval 1.9-8.8) but no other neurological syndromes. The FND cases following vaccinations showed similar premorbid conditions and severity but a higher percentage of sensory symptoms and pain compared to UVC FND cases. CONCLUSIONS: SARS-CoV-2 vaccination is associated with a significant short-term increased risk of FND and headache requiring hospitalization in an acute neurological setting.

Onabotulinumtoxin-A: Previous Prophylactic Treatment Might Improve Subsequent Anti-CGRP Monoclonal Antibodies Response in Patients with Chronic Migraine.

The aim of the present study was to evaluate whether previous preventive treatment with onabotulinumtoxin-A might influence subsequent clinical response following a switch to anti-CGRP monoclonal antibodies (mAbs). The present retrospective study was conducted at the Headache Centre-Neurology Clinic at the Spedali Civili Hospital of Brescia between November 2018 and May 2023. The primary objective was to assess clinical outcome (monthly headache days (MHDs), monthly migraine days (MMDs), mean analgesics consumption, and clinical disability according to Migraine Disability Assessment (MIDAS)) following three months (T3) of preventive treatment with anti-CGRP mAbs comparing patients who did and those who did not previously receive treatment with Onabotulinumtoxin-A. Moreover, we aimed to evaluate whether the clinical response to anti-CGRP mAbs was affected by the number of previous Onabotulinumtoxin-A administrations. At T3, compared to Onabotulinumtoxin-A naïve patients, patients who previously received Onabotulinumtoxin-A documented fewer MMDs (3.3 ± 3.7 versus 5.2 ± 5.0; p = 0.017) and a lower MIDAS score (23.2 ± 20.9 versus 37.4 ± 39.6; p = 0.013). Patients who received at least 3 onabotulinumtoxin-A administrations documented, at T3, lower MMDs compared to those who received fewer cycles (respectively, 2.1 ± 2.7 vs. 6.5 ± 4.4; p = 0.024). In conclusion, according to our data, previous treatment with onabotulinumtoxin-A might improve subsequent response to anti-CGRP mAbs preventive treatment.

An observational study on monoclonal antibodies against calcitonin-gene-related peptide and its receptor.

BACKGROUND AND PURPOSE: Based on their pharmacological target, two classes of calcitonin-gene-related peptide (CGRP) monoclonal antibodies (mAbs) have been identified: antibodies against the CGRP ligand-galcanezumab, fremanezumab, eptinezumab-and antibodies against the CGRP receptor (CGRP-R), erenumab. The aim of the present study was to compare anti-CGRP versus anti-CGRP-R mAbs in patients with high frequency episodic and chronic migraine. METHODS: All patients on monthly treatment with anti-CGRP mAbs with an available 6 months' follow-up at January 2022 were included. Data on efficacy outcome were collected following one (T1), three (T3) and six (T6) months of treatment, and included monthly headache/migraine days, the Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test 6 (HIT-6) scores, pain intensity, analgesics consumption and response rates (>50% headache days reduction compared to baseline). RESULTS: In all, 152 patients were enrolled, of whom 68 were in treatment with anti-CGRP mAbs (49 galcanezumab, 19 fremanezumab) and 84 with the anti-CGRP-R (erenumab). MIDAS scores were significantly lower in the anti-CGRP group at T1 and T3 (respectively p < 0.02 and p < 0.03) as well as the number of mean migraine days at T3 (p < 0.01). At T3 and T6 outcome measures were comparable, although a significantly higher percentage of super-responders was found in the anti-CGRP group (respectively p < 0.04 and p < 0.05), with a similar overall percentage of responders. CONCLUSIONS: The present study on a real-world sample confirms the beneficial effect of both anti-CGRP and anti-CGRP-R mAbs, with a more favorable outcome for anti-CGRP antibodies.

Migraine Disability Improvement during Treatment with Galcanezumab in Patients with Chronic and High Frequency Episodic Migraine.

BACKGROUND: The aim of the present study was to assess the migraine outcome, in particular migraine disability, in chronic (CM) and high frequency episodic migraine (HFEM) patients in treatment with galcanezumab. METHODS: The present study was conducted at the Headache Centre of Spedali Civili of Brescia. Patients were treated with galcanezumab 120 mg monthly. Clinical and demographical information were collected at the baseline (T0). Data about outcome, analgesics consumption and disability (MIDAS and HIT-6 scores) were collected quarterly. RESULTS: Fifty-four consecutive patients were enrolled. Thirty-seven patients had a diagnosis of CM, 17 of HFEM. During treatment, patients reported a significant reduction in terms of mean headache/migraine days (p < 0.001), the attacks' pain intensity (p = 0.001) and monthly consumed analgesics (p < 0.001). The MIDAS and HIT-6 scores also documented a significant improvement (p < 0.001). At the baseline, all patients documented a severe degree of disability (MIDAS score ≥ 21). Following six months of treatment, only 29.2% of patients still documented a MIDAS score ≥ 21, with one third of patients documenting little or no disability. A > 50% MIDAS reduction, compared to baseline, was observed in up to 94.6% of patients, following the first three months of treatment. A similar outcome was found for HIT-6 scores. A significant positive correlation was found between headache days and MIDAS at T3 and T6 (T6 > T3), but not baseline. DISCUSSION: Monthly prophylactic treatment with galcanezumab was found to be effective in both CM and HFEM, especially in reducing migraine burden and disability.

Migraine Disability and Severity Improvement during Long-Term Treatment with Erenumab.

The aim of the present study was to assess erenumab efficacy in migraine disability and intensity throughout the first treatment cycle, discontinuation, and the first 6 months of re-treatment in patients with high-frequency episodic migraine. The study design was retrospective and observational. Inclusion criteria were the following: diagnosis of high-frequency episodic migraine and ongoing treatment with erenumab 140 mg currently at their second treatment cycle. Data regarding migraine frequency, disability (MIDAS score), and severity of attacks (NRS score) were collected quarterly. Twenty-five patients were enrolled. At the end of the first treatment cycle, compared to baseline, a significant improvement of MIDAS scores was found (13.5 ± 11.1 vs. 72.5 ± 32.1; p = 0.005), with a subsequent worsening during treatment suspension (30.1 ± 26.9; p = 0.03). Pain intensity remained unmodified during the first treatment cycle (NRS score baseline: 7.6 ± 0.9 vs. 12 months: 7.5 ± 0.7; p = 0.13). During re-treatment, MIDAS scores documented a new significant improvement, reaching the same level at 6 months of re-treatment as at the end of the first cycle (30.1 ± 26.9 vs. 12.9 ± 5.4; p = 0.03). A significant improvement, compared to baseline, was observed for pain intensity during re-treatment (6.8 ± 2.2 vs. 5.6 ± 0.9 at RT3 vs. 5.2 ± 1.4 at RT6; p = 0.05). In conclusion, during re-treatment with erenumab 140 mg, migraine pain intensity and disability documented a significant and progressive improvement. Our data confirm the long-term efficacy, although in a very limited case series, of monoclonal antibodies targeting CGRP beyond headache frequency reduction.

Post COVID-19 vaccination headache: A clinical and epidemiological evaluation.

Introduction: This study aimed to assess the prevalence and clinical characteristics of headaches, in particular secondary headaches. Materials and Methods: This observational study was performed at the ASST Spedali Civili of Brescia, Italy. Visits to the Emergency Department (ED) and subsequent hospitalizations regarding a new or worsening headache in the 16 days following the administration of the COVID-19 vaccine between January 2021 and January 2022 were recorded and compared with those of January 2019-January 2020. Results: The ratio between ED admissions due to headaches and total ED admissions was significantly higher in 2021 compared with 2019 (4.84% vs. 4.27%; p < 0.0001). Two-hundred and eighty-nine ED headache admissions (10.8% of all ED headache admissions) were time-correlated to the COVID-19 vaccination, of which 40 were hospitalized in order to exclude a symptomatic etiology. At discharge, 32 patients had a diagnosis of benign headache not attributed to any cranial/extracranial disorder and eight patients of secondary headache, whose diagnoses were the following: Headache attributed to cranial and/or cervical vascular disorder (n = 4); headache attributed to nonvascular intracranial disorder (n = 2); headache or facial pain attributed to disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cervical structure (n = 1); and painful lesions of the cranial nerves (n = 1). The headache most frequently reported by patients had migraine-like characteristics: the localization was predominantly frontal or temporal, the pain was described as throbbing and severe in intensity and it was frequently accompanied by nausea/vomit, and photo-phonophobia. Over half-regardless of the final diagnosis-of hospitalized patients had a history of primary headaches. Conclusions: Following the spread of COVID-19 vaccination, the number of ED admissions due to headaches significantly increased. However, less than 14% of all the ED visits due to a headache time-correlated to the COVID-19 vaccination were actually hospitalized, with most patients documenting a benign headache, possibly related to the generic side effects of the vaccination. Only 8/40 hospitalized patients were diagnosed with a secondary headache. These benign headaches would actually fulfill diagnostic criteria for 8.1 Headaches attributed to the use of or exposure to a substance (ICHD-3), although, at the time being, it does not include vaccines as possible substances.The headache migraine-like characteristics' reported by most patients could suggest activation of the trigeminovascular pathway by all the cytokines and other pro-inflammatory molecules released following the vaccination.

Photophobia and migraine outcome during treatment with galcanezumab.

Background: Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in reducing ictal photophobia. Material and methods: This is a retrospective observational study, conducted at the Headache Center-ASST Spedali Civili Brescia. All patients in monthly treatment with galcanezumab with at least a 6-month follow-up in September 2022 with reported severe photophobia during migraine attacks were included. Data regarding headache frequency, analgesics consumption, and migraine disability were collected quarterly. Moreover, patients were asked the following information regarding photophobia: (1) whether they noticed an improvement in photophobia during migraine attacks since galcanezumab introduction; (2) the degree of photophobia improvement (low, moderate, and high); and (3) timing photophobia improvement. Results: Forty-seven patients were enrolled in the present study as they met the inclusion criteria. Seventeen patients had a diagnosis of high-frequency episodic migraine and 30 of chronic migraine. From baseline to T3 and T6, a significant improvement in terms of headache days (19.2 ± 7.6 vs. 8.6 ± 6.8 vs. 7.7 ± 5.7; p < 0.0001), migraine days (10.4 ± 6.7 vs. 2.9 ± 4.3 vs. 3.6 ± 2.8; p < 0.0001), analgesics consumption (25.1 ± 28.2 vs. 7.6 ± 7.5 vs. 7.6 ± 8.1; p < 0.0001), MIDAS score (82.1 ± 48.4 vs. 21.6 ± 17.6 vs. 18.1 ± 20.5; p < 0.0001), and HIT-6 score (66.2 ± 6.2 vs. 57.2 ± 8.6 vs. 56.6 ± 7.6; p < 0.0001) was found. Thirty-two patients (68.1%) reported a significant improvement in ictal photophobia, with over half of the patients reporting it within the first month of treatment. Photophobia improvement was more frequent in patients with episodic migraine (p = 0.02) and triptans responders (p = 0.03). Conclusions: The present study confirms previous reports regarding galcanezumab efficacy beyond migraine frequency. In particular, over 60% of patients, in our cohort, documented a significant improvement also in reducing ictal photophobia. This improvement was, in most patients, moderate to high, and within the first 6 months of treatment, regardless of the clinical response on migraine frequency.