Clinical predictors of therapeutic failure of occipital nerve stimulation in refractory chronic cluster headache.

BACKGROUND: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. METHODS: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. RESULTS: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. CONCLUSIONS: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.

CandeSpartan Study: Candesartan Spanish Response-prediction and Tolerability study in migraine.

INTRODUCTION: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine. METHODS: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8-12 and 20-24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models. RESULTS: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3-50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75-3) prior preventive treatments. At baseline patients had 14 (10-24) headache and 8 (5-11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8-12, and 48.8%, 36%, and 18.6% between weeks 20-24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0-12 and 12-24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20-24. CONCLUSION: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials' efficacy.Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316).

Evaluation of the concomitant use of prophylactic treatments in patients with migraine under anti-calcitonin gene-related peptide therapies: The PREVENAC study.

BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine. METHODS: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. RESULTS: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). CONCLUSIONS: Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions.

Effectiveness, tolerability, and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: a multicenter real-world case-control study.

OBJECTIVE: To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. DESIGN: We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. METHODS: We included the demographic characteristics, effectiveness-reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates-and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20-24; exploratory 50% response predictors in the elderly were evaluated. RESULTS: In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66-86); mean age of controls was 42.9 years old(range: 38-49). Cases had a higher percentage of vascular risk factors (P < .05),older age of onset (P < .001) and more reported prior preventive treatments (P < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20-24 weeks, with lower reduction in the MHD at 8-12 weeks (5 [7.2], 8 [9.1]; P = .001) and a higher reduction in MMD at 20-24 weeks (10.7 [9.1], 9.2 [7.7]; P = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P = .03) and lower number of MHD at baseline (P = .001) were associated with a 50% response in the elderly in univariate analysis. CONCLUSIONS: Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly.

The profile of refractory chronic cluster headache.

INTRODUCTION: Chronic cluster headache (CCH) is a relatively rare primary headache disorder whose management is often challenging. The prevalence of refractory CCH (rCCH) is unknown. Our aim is to describe the frequency of rCCH within a population of CCH, define the clinical profile of the refractory patients and the treatments they underwent. METHODS: We conducted a cross-sectional study through a review of the medical records of CCH patients in six hospitals in Madrid, Spain. Data on epidemiological, clinical presentation, treatment and disease activity at the moment were collected. The European Headache Federation diagnostic criteria were used for rCCH definition. High disease activity was defined as having at least 3 severe attacks per week that impact quality of life despite treatment. Non-rCCH and rCCH groups were compared. RESULTS: 88 CCH patients were analyzed, 68.2% (60/88) met rCCH criteria at some point in their evolution. A longer diagnostic delay (4.6 ± 7.1 vs. 3.2 ± 3.7 years, p = 0.017) was observed in rCCH. All rCCH patients tried therapies without established evidence from randomized clinical trials. OnabotulinumtoxinA and galcanezumab were initiated in 77.3% (68/88) and 5.7% (5/88), but discontinued in 52.9% (36/68) and 60.0% (3/5), respectively. Occipital nerve stimulation (ONS) was implanted in 29.6% (26/88), with 50.0% (13/26) still active. Other treatment options are described and discussed. Despite treatment, 60.2% (53/88) still have high disease activity. CONCLUSION: CCH is a disorder with poor prognosis, meeting refractoriness criteria in more than half. OnabotulinumtoxinA and ONS could be the effective in refractory patients.

Neurotological emergencies: a narrative review.

INTRODUCTION: Vestibular symptoms, including vertigo, dizziness, and gait unsteadiness, are a frequent reason of urgent medical assistance. Their causes are numerous and diverse, including neurological, otorhinolaryngological, and systemic diseases. Therefore, following a systematic approach is essential to differentiate striking but benign conditions from others that can compromise the patient's life. This study is intended to review vestibular disorders from a practical perspective and provide guidance to physicians involved in the emergency care of patients with vestibular symptoms. MATERIALS AND METHODS: A narrative review was performed, revisiting the main causes of vestibular disorders. RESULTS: Based on the speed of onset, duration, and history of similar episodes in the past, vestibular disorders can be categorized into three syndromic entities (acute, recurrent, and chronic vestibular syndromes). The most representative conditions pertaining to each group were reviewed (including their diagnosis and treatment) and a practical algorithm was proposed for their correct management in the acute care setting. CONCLUSIONS: Carrying out a correct categorization of the vestibular disorders is essential to avoid diagnostic pitfalls. This review provides useful tools for clinicians to approach their patients with vestibular symptoms at the emergency room.

Incidence, clinical, risk factors and outcomes of Guillain-Barré in Covid-19.

We diagnosed 11 Guillain-Barré syndrome (GBS) cases among 71,904 COVID patients attended at 61 Spanish emergency departments (EDs) during the 2-month pandemic peak. The relative frequency of GBS among ED patients was higher in COVID (0.15‰) than non-COVID (0.02‰) patients (odds ratio [OR] = 6.30, 95% confidence interval [CI] = 3.18-12.5), as was the standardized incidence (9.44 and 0.69 cases/100,000 inhabitant-years, respectively, OR = 13.5, 95% CI = 9.87-18.4). Regarding clinical characteristics, olfactory-gustatory disorders were more frequent in COVID-GBS than non-COVID-GBS (OR = 27.59, 95% CI = 1.296-587) and COVID-non-GBS (OR = 7.875, 95% CI = 1.587-39.09) patients. Although COVID-GBS patients were more frequently admitted to intensive care, mortality was not increased versus control groups. Our results suggest SARS-CoV-2 could be another viral infection causing GBS. ANN NEUROL 2021;89:598-603.

Sensitivity of the SNNOOP10 list in the high-risk secondary headache detection.

AIM: To evaluate the diagnostic accuracy of the SNNOOP10 list in the detection of high-risk headaches. METHODS: Patients that visited the Hospital Clínico San Carlos (Madrid) emergency department due to headache that were allocated to a Manchester Triage System level between critical and urgent were prospectively included but retrospectively analysed. A researcher blind to the patients' diagnosis administered a standardised questionnaire and afterwards a neurologist blind to the questionnaire results diagnosed the patient according to the International Classification of Headache Disorders. The primary endpoint was to assess the sensitivity of the SNNOOP10 list in the detection of high-risk headaches. Secondary endpoints included the evaluation of the sensitivity, specificity, positive predictive value, negative predictive value and area under the curve of each SNNOOP10 item. RESULTS: Between April 2015 and October 2021, 100 patients were included. Patients were 44 years old (inter-quartile range: 33.6-64.7) and 57% were female. We identified 37 different diagnoses. Final diagnosis was a primary headache in 33%, secondary headache in 65% and cranial neuralgia in 2%. There were 46 patients that were considered as having high-risk headache. Patients from the primary headache group were younger and more frequently female. Sensitivity of SNNOOP10 list was 100% (95% confidence interval: 90.2%-100%). The items with higher sensitivity were neurologic deficit or disfunction (75.5%), pattern change or recent onset of the headache (64.4%), onset after 50 years (64.4%). The most specific items were posttraumatic onset of headache (94.5%), neoplasm in history (89.1%) and systemic symptoms (89%). The area under the curve of the SNNOOP10 list was 0.66 (95% CI: 0.55-0.76). CONCLUSION: The red flags from the SNNOOP10 list showed a 100% sensitivity in the detection of high-risk headache disorders.

Post-COVID-19 persistent headache: A multicentric 9-months follow-up study of 905 patients.

BACKGROUND: Headache is a frequent symptoms of coronavirus disease 2019 (COVID-19). Its long-term evolution remains unknown. We aim to evaluate the long-term duration of headache in patients that presented headache during the acute phase of COVID-19. METHODS: This is a post-hoc multicenter ambisective study including patients from six different third-level hospitals between 1 March and 27 April 2020. Patients completed 9 months of neurological follow-up. RESULTS: We included 905 patients. Their median age was 51 (IQR 45-65), 66.5% were female, and 52.7% had a prior history of primary headache. The median duration of headache was 14 (6-39) days; however, the headache persisted after 3 months in 19.0% (95% CI: 16.5-21.8%) and after 9 months in 16.0% (95% confidence interval: 13.7-18.7%). Headache intensity during the acute phase was associated with a more prolonged duration of headache (Hazard ratio 0.655; 95% confidence interval: 0.582-0.737). CONCLUSION: The median duration of headache was 2 weeks, but in approximately a fifth of patients it became persistent and followed a chronic daily pattern.

Clinical exacerbation of SARS-CoV2 infection after fingolimod withdrawal.

The role of disease-modifying therapies in patients with autoimmune disorders during severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is controversial. Immunocompromised patients could have a more severe coronavirus disease-2019 (COVID-19) due to the absence of an adequate immune response against the SARS-CoV-2. However, therapies that act on immune response could play a protective role by dampening the cytokine-release syndrome. Fingolimod is a drug used for immune therapy in patients with multiple sclerosis (MS) through the sequestration of activated lymphocytes in the lymph nodes. We report the case of a 57-year-old man with relapsing-remitting MS treated with fingolimod that showed a reactivation of COVID-19 with signs of hyperinflammation syndrome after fingolimod withdrawal. Our case suggests that discontinuation of fingolimod during COVID-19 could imply a worsening of SARS-CoV2 infection.