RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.

Evaluation of the ICHD-3 diagnostic criteria for cardiac cephalalgia and new proposal.

BACKGROUND: The current International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria for cardiac cephalalgia were established according to previous case reports and the opinion of experts. We aimed to assess the ICHD-3 diagnostic criteria for cardiac cephalalgia. METHODS: We conducted a series of cases study and evaluated these criteria in 54 patients with cardiac cephalalgia. Next, we assessed whether the ICHD-3 diagnostic criteria B, C and D for migraine without aura were fulfilled by these patients. RESULTS: ICHD-3 criteria A, B, C1, C2 and D for cardiac cephalalgia were met by 100% of patients, whereas criterion C3 was fulfilled by 81.5%. The least frequently fulfilled sub-criterion was C3b (accompanied by nausea) (18.5%). Moreover, we found that ICHD-3 criteria B, C and D for migraine without aura were met by a low proportion of patients: 11.1%, 46.3% and 25.9%, respectively, and no patient fulfilled the three criteria simultaneously. CONCLUSION: Based on our results, we propose revised diagnostic criteria for cardiac cephalalgia. We suggest removing criterion C3 and C4. We also suggest removing the word "migraine-like" from its description.

Early Wearing-Off Effect of OnabotulinumtoxinA in Chronic Migraine: A Prospective Real-Life Study.

OBJECTIVE: Chronic migraine (CM) is a significant public health problem that affects 2.2% of the global population. Onabotulinumtoxin A (OnabotA) is a safe and effective prophylactic treatment for patients with CM. The standard injection interval for OnabotA is 12 weeks. Nevertheless, some patients experience a wearing-off effect (WOE) in the weeks preceding the next scheduled cycle. The objectives of this study are to determine the prevalence of early WOE, to analyze variables that could be clinical predictors and to specify which interval is the most appropriate to define the existence of this phenomenon. METHODS: This is a prospective single-center study of consecutive adult patients with CM who, after failing previous prophylactic therapies, started OnabotA treatment following the PREEMPT protocol between June and December of 2021. RESULTS: A total of 59 patients (93.2% female, age 44 ± 12 years) were included. A total of 37 patients (64.9%) fulfilled medication overuse criteria. Of the total patients, 40.6% reported WOE and this was more frequent after the first cycle (35.6%). Depression and anxiety disorder was a statistically significant clinical predictor of WOE (OR 3.4; CI 95% 1.22-10.84; p = 0.028). A better cut-off point to consider WOE seems to be at 10 weeks. CONCLUSIONS: Early WOE is common in patients on OnabotA treatment for CM. Individualizing the standard 12-week injection, using total doses of 195 U, and managing psychiatric comorbidities with pharmacological and non-pharmacological strategies may improve treatment outcomes and reduce OnabotA WOE.

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients.

BACKGROUND: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. METHODS: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. RESULTS: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). CONCLUSIONS: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.

Circadian rhythm of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy.

OBJECTIVE: To determine whether patients with drug-resistant mesial temporal lobe epilepsy present with an alteration in the autonomic circadian regulation of blood pressure. METHODS: A prospective case‒control study was designed, with a case group comprising patients with drug-resistant mesial temporal lobe epilepsy and a control group comprising healthy volunteers. Twenty-four-hour outpatient blood pressure monitoring was performed to assess the existence of a normal (dipping) or altered (non-dipping) circadian pattern. In addition, analytical and ultrasound parameters (carotid intima-media thickness) of vascular risk and sleep quality were evaluated. RESULTS: Twenty-four subjects were recruited in each study group, amongst whom no demographic differences or history of vascular risk were observed. A higher percentage of participants with a non-dipping pattern was observed in the group of patients with epilepsy (62.5% vs. 12.5, p = 0.001). In the case group, significant differences were also observed in carotid intima-media thickness, with a greater probability of presenting with pathological values (p = 0.022). CONCLUSION: The results suggest a disorder of the central autonomic control of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy, with a greater probability of developing an alteration of the circadian rhythm of blood pressure. This dysfunction may be a factor involved in the increased cardiovascular risk in this population.

Prevalence, clinical characteristics and associated factors of cardiac cephalalgia: A prospective study.

BACKGROUND: The prevalence of cardiac cephalalgia is unknown and there is limited information about its clinical features. We aimed to assess the prevalence of cardiac cephalalgia, its clinical characteristics and associated factors. METHODS: We conducted a prospective study of patients with suspected acute coronary syndrome admitted to the Cardiology Service at Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, over a one-year period. We interviewed patients within the first 24 hours of admission using a standardized case-report form to assess the presence of headache in relation to the acute coronary syndrome and its characteristics. RESULTS: We included 438 patients, 381 with confirmed myocardial ischemia. Prevalence of cardiac cephalalgia was 14.2% (n = 54). The most common features were frontal location, pressing quality and moderate intensity. Pain referred to the jaws (aOR 2.61; 95% CI 1.33-5.12; p = 0.005), palpitations (aOR 3.65; 95% CI 1.57-8.50; p = 0.003) and circumflex coronary artery as the culprit artery for the myocardial ischemia (aOR 3.8; 95% CI 1.07-13.74; p = 0.021) were related to cardiac whereas history of hypertension was inversely associated (aOR 0.37: 95% CI 0.18-0.74; p = 0.005). CONCLUSION: The prevalence of cardiac cephalalgia was 14.2%. Our study provides valuable information about cardiac cephalalgia characteristics that suggest revision of current diagnostic criteria.

Cardiac cephalalgia: a narrative review and ICHD-3 criteria evaluation.

BACKGROUND: Cardiac cephalalgia is an unusual condition that occurs during an episode of myocardial ischemia. Information about cardiac cephalalgia is scarce and its characteristics and physiopathology remain unclear. Our aim is to provide a narrative review of clinical characteristics and physiopathology of cardiac cephalalgia and to evaluate the current diagnostic criteria.  METHODS: A search through PubMed was undertaken for studies on cardiac cephalalgia published until 20th September 2022. We summarized the literature and provide a comprehensive review of the headache characteristics and possible mechanisms. We also evaluated current International Classification of Headache Disorders third edition diagnostic criteria based on prior reported cases.  RESULTS: In total, 88 cases were found. Headache characteristics were variable. Occipital location and throbbing pain were the most frequently reported. Headache was accompanied in most cases by cardiac symptoms. Criterion B was fulfilled by 98% of cases, criterion C1 by 72%, and criteria C2a and C2b by 37 and 93.2%, respectively. Regarding headache features described in diagnostic criterion C3, 'moderate to severe intensity', 'accompanied by nausea', 'not accompanied by photophobia or phonophobia' and 'aggravated by exertion', were reported in 75, 31, 55 and 55% of cases, respectively. CONCLUSION: Cardiac cephalalgia characteristics are variable and the headache features described in the diagnostic criterion C3 might not be adequate. Given that cardiac cephalalgia can be the manifestation of a life-threatening condition it is important to increase the knowledge about this entity.

Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke.

Background and Purpose: We aimed to determine the prevalence and predictors of delayed neurological improvement (DNI) after complete endovascular reperfusion in anterior circulation acute ischemic stroke (AIS). Methods: Retrospective analysis of an online multicenter prospective reperfusion registry of patients with consecutive anterior circulation AIS treated with endovascular thrombectomy (EVT) from January 2018 to June 2019 in tertiary stroke centers of the NORDICTUS (NORD-Spain Network for Research and Innovation in ICTUS) network. We included patients with AIS with a proximal occlusion in whom a modified Thrombolysis in Cerebral Infarction 3 reperfusion pattern was obtained. DNI was defined if, despite absence of early neurological improvement during the first 24 hours, patients achieved functional independence on day 90. Clinical and radiological variables obtained before EVT were analyzed as potential predictors of DNI. Results: Of 1565 patients with consecutive AIS treated with EVT, 1381 had proximal anterior circulation occlusions, 803 (58%) of whom achieved a modified Thrombolysis in Cerebral Infarction 3. Of these, 628 patients fulfilled all selection criteria and were included in the study. Mean age was 73.8 years, 323 (51.4%) were female, and median baseline National Institutes of Health Stroke Scale was 16. Absence of early neurological improvement was observed in 142 (22.6%) patients; 32 of these (22.5%) achieved good long-term outcome and constitute the DNI group. Predictors of DNI in multivariable-adjusted logistic regression were male sex (odds ratio, 6.4 [95% CI, 2.1­22.3] P=0.002), lower pre-EVT National Institutes of Health Stroke Scale score (odds ratio, 1.4 [95% CI, 1.2­1.5], P<0.001), and intravenous thrombolysis (odds ratio, 9.1 [95% CI, 2.7­30.90], P<0.001). Conclusions: One-quarter of patients with anterior circulation AIS who do not clinically improve within the first 24 hours after complete cerebral endovascular recanalization will achieve long-term functional independence, regardless of the poor early clinical course. Male sex, lower initial clinical severity, and use of intravenous thrombolysis before EVT predicted this clinical pattern.

Effects of the onabotulinumtoxinA follow-up delay in migraine course during the COVID-19 lockdown.

BACKGROUND: Face-to-face procedures have been postponed during COVID-19 pandemic. We aim to evaluate the impact of onabotulinumtoxinA follow-up delay in migraine during COVID-19 pandemic. METHODS: Subjective worsening, intensity of migraine attacks, and frequency of headache and migraine were retrospectively compared between patients with unmodified and interrupted onabotulinumtoxinA follow-up in Headache Units. RESULTS: We included 67 patients with chronic migraine or high-frequency episodic migraine under onabotulinumtoxinA treatment, 65 (97.0%) female, 44.5 ± 12.1 years old. Treatment administration was voluntarily delayed in 14 (20.9%) patients and nine (13.4%) were unable to continue follow-up. Patients with uninterrupted follow-up during lockdown presented 7.6 and 8.1 less monthly days with headache (adjusted p = 0.017) and migraine attacks (adjusted p = 0.009) compared to patients whose follow-up was interrupted, respectively. CONCLUSION: Involuntary delay of onabotulinumtoxinA follow-up in patients with migraine due to COVID-19 pandemic was associated with a higher frequency of headache and migraine attacks. Safe administration of onabotulinumtoxinA during lockdown should be promoted.

Acute migraine management in the emergency department: experience from a large Spanish tertiary hospital.

To assess the characteristics of the management of patients with migraine who present to the emergency department (ED) with a migraine attack. Retrospective, observational study analyzing demographic, clinical, diagnostic and therapeutic characteristics of patients with migraine diagnosis presenting to ED for a migraine attack between 2016 and 2019. We reviewed the clinical records of 847 cases. 82.2% were women with mean age of 34.9 years. 87.2% had episodic migraine and 12.2% chronic migraine. 62.3% (528/847) had taken analgesics before visiting the ED [non-steroidal-anti-inflammatory drugs (NSAIDs) (300/528; 56.9%) and triptans (261/528; 49.5%)]. 25.4% (215/847) received blood testing and 6.4% (55/847) received cranial CT. Medication was administered in 77.2% cases (654/847). The median time-to-treatment was 70 min (IQR 42-120). NSAIDs (81%, 530/654), antiemetics (43.1%, 282/654) and metamizole (39% 255/654) were the most used. Triptans were administered in 7 cases (1.1%) and opioids in 84 (12.8%). At discharge, preventive treatment was prescribed or modified in 8.2% of cases (69/839) and triptans were prescribed in 129 cases (15.3%). 70.5% (592/839) were instructed to follow-up with their primary care provider (PCP), 21.5% (181/839) with a general neurologist and 7.9% (66/839) with a headache specialist. The majority of migraine patients were not receiving the recommended acute migraine-specific medication, both in the outpatient and in the ED setting, being especially remarkable the rare use of triptans in the ED. Furthermore, we found an elevated use of urgent complementary tests, mainly blood tests.

Evaluation of the Impact of the COVID-19 Lockdown in the Clinical Course of Migraine.

OBJECTIVE: Previous studies have demonstrated that emotional stress, changes in lifestyle habits and infections can worsen the clinical course of migraine. We hypothesize that changes in habits and medical care during coronavirus disease 2019 (COVID-19) lockdown might have worsened the clinical course of migraine. DESIGN: Retrospective survey study collecting online responses from migraine patients followed-up by neurologists at three tertiary hospitals between June and July 2020. METHODS: We used a web-based survey that included demographic data, clinical variables related with any headache (frequency) and migraine (subjective worsening, frequency, and intensity), lockdown, and symptoms of post-traumatic stress. RESULTS: The response rate of the survey was 239/324 (73.8%). The final analysis included 222 subjects. Among them, 201/222 (90.5%) were women, aged 42.5 ± 12.0 (mean±SD). Subjective improvement of migraine during lockdown was reported in 31/222 participants (14.0%), while worsening in 105/222 (47.3%) and was associated with changes in migraine triggers such as stress related to going outdoors and intake of specific foods or drinks. Intensity of attacks increased in 67/222 patients (30.2%), and it was associated with the subjective worsening, female sex, recent insomnia, and use of acute medication during a headache. An increase in monthly days with any headache was observed in 105/222 patients (47.3%) and was related to symptoms of post-traumatic stress, older age and living with five or more people. CONCLUSIONS: Approximately half the migraine patients reported worsening of their usual pain during the lockdown. Worse clinical course in migraine patients was related to changes in triggers and the emotional impact of the lockdown.

Cognitive performance in patients with episodic cluster headache outside and inside the active cluster.

BACKGROUND: Previous studies have shown worse cognitive performance in cluster headache (CH) patients compared to healthy controls; however, little is known about cognitive performance in episodic CH (ECH) patients outside and inside the active cluster (AC). OBJECTIVE: Our aim is to compare cognitive function in ECH patients outside and inside the AC. METHODS: In this cross-sectional, observational study, four neuropsychological tests (Trail Making Test [TMT], Stroop Test [ST], verbal fluency [VF], and Symbol Digit Modalities Test [SDT]) were completed by 21 ECH patients at two different points in time: outside and inside the AC. We also assessed self-reported sleep quality and the presence of anxiety or depressive symptoms. Scores were compared. RESULTS: There was not any difference between the scores of the neuropsychological tests performed outside and inside the AC (TMT-A: 23 vs. 23.5; p = 0.984; TMT-B: 96.5 vs. 85.9; p = 0.104; ST word reading: 101.0 vs. 101.2; p = 0.938; ST color naming: 73.0 vs. 73.4; p = 0.858; ST color word: 44.0 vs. 46.0; p = 0.498; SDMT: 44.0 vs. 44.6; p = 0.961; VF phonemic: 29.5 vs. 30.2; p = 0.714; VF semantic: 20 vs. 21; p = 0.489). We found a worsening in the sleep quality component of the Pittsburgh Sleep Quality Index median scores in patients outside the AC (2 vs. 1; p = 0.046). CONCLUSIONS: Our findings suggest that patients with ECH have a similar cognitive performance outside and during the AC.

Análisis comparativo de la atención de pacientes con enfermedad neurológica en el servicio de urgencias hospitalario durante el periodo de confinamiento por COVID-19 / Care of neurology patients in a hospital emergency department during the lockdown period for COVID-19: a comparative analysis

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Impact of 24-Hour On-Call Shifts on Headache in Medical Residents: A Cohort Study.

BACKGROUND: During 24-hour on-call shifts medical residents are exposed to diverse circumstances such as sleep deprivation and stress. OBJECTIVE: Our aim is to assess the effect of 24-hour on-call shifts on medical residents' headache-related disability. METHODS: The Migraine Disability Assessment Scale (MIDAS), the Headache Impact Test (HIT-6), the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS) questionnaires were administered to medical residents who had never performed on-call shifts at baseline and 6 months after beginning 24-hour on-call shifts. Scores were compared. RESULTS: About 66 medical residents completed this study. About 21.2% (n = 14) had history of migraine, 42.4% (n = 28) had a history of tension-type headache (TTH) and 12.1% (n = 8) had a history of both migraine and TTH. Among medical residents with migraine, the median MIDAS score was significantly higher after starting 24-hour on-call shifts than at a baseline (4.0 vs 8.0; Wilcoxon, P = .001), meaning that, on average, disability increased from little or no disability, to moderate disability. No difference in HIT-6 scores was found. The median score of PSQI and HADS was higher at 6 months (PSQI: 7.0 vs 8.0; P = .003), (HADS: 5.0 vs 8.0; P < .001) for the general group. CONCLUSIONS: In medical residents with migraine, migraine-related disability increased after starting 24-hour on-call shifts. We also found a worsening in depression and anxiety symptoms and self-reported sleep quality in medical residents with and without headache history.

Encefalitis Límbica Autoinmune Asociada A Anticuerpos LGI1: Presentación De Un Caso Y Revisión De La Bibliografía / Autoimmune Limbic Encephalitis Associated With LGI1 Antibodies: Case Report And Review Of The Literature

RESUMEN Introducción: La encefalitis asociada a anticuerpos dirigidos contra la proteína 1 inactivada del glioma rica en leucina (LGI1) es una entidad poco frecuente de inicio subagudo que se caracteriza clínicamente por la presencia de alteraciones cognitivas, alteraciones conductuales y crisis epilépticas. El pronóstico en la mayoría de los casos es favorable, aunque son frecuentes los déficits amnésicos residuales. Caso clínico: Mujer de 76 años que comenzó de manera súbita con una serie de crisis tónico - clónicas generalizadas y posterior alteración del nivel de consciencia. Se inició tratamiento anticonvulsivante con discreta mejoría clínica. En la resonancia magnética realizada durante el ingreso se observó hiperintensidad en hipocampo izquierdo en secuencias T2 y T2-FLAIR. Ante la sospecha de encefalitis límbica autoinmune se inició tratamiento inmunomodulador con corticoesteriodes e inmunoglobulinas con mejoría clínica. Posteriormente se detectaron anticuerpos anti - LGI1 en líquido cefalorraquídeo. Conclusiones: La encefalitis autoinmune asociada a anticuerpos anti-LGI1 puede producir clínica neurológica variada y orden de instauración variable, incluso en ocasiones agudo. El tratamiento con inmunoterapia precoz es importante tanto para la mejoría clínica en la fase aguda como para el pronóstico a largo plazo.

Abstract Introduction: Leucine rich glioma inactivated protein 1 (LGI1) antibody encephalitis is a rare disease characterized by subacute memory impairment, behavioral disorders and epileptic seizures. Even most cases have a good outcome, residual cognitive deficits are common. Case report: 76-year-old woman who started with acute onset generalized tonic - clonic seizures and subsequent impaired level of consciousness. Antiepileptic treatment was started with slight clinical improvement. In magnetic resonance imaging performed during admission left hippocampal hyperintensity was seen in T2 and T2-FLAIR sequences. As autoimmune limbic encephalitis was suspected, immunomodulatory treatment with intravenous corticosteroids and immunoglobulins was started with clinical improvement. Afterwards, anti -LGI1 antibodies were positive in cerebrospinal fluid testing. Conclusions: anti - LGI1 antibody related encephalitis can produce different neurological manifestations and diverse onset, even acute. Early immunomodulatory treatment is important to improve both clinical manifestations and long - term outcome.