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Background This meta-analysis evaluated the real-world effectiveness of onabotulinumtoxinA (BOTOX®), the first preventive treatment FDA-approved specifically for chronic migraine in 2010. Methods We systematically reviewed onabotulinumtoxinA observational data in chronic migraine published between 1 January 2010 and 31 March 2021. Random-effects models evaluated available data for primary and secondary endpoints defined in onabotulinumtoxinA pivotal trials at approximately 24 weeks and 52 weeks. Results Of the 44 full-text eligible studies (29 prospective; 13 retrospective; 2 other), seven evaluated change from baseline (mean[confidence interval]) at ∼24 weeks and ∼52 weeks, respectively, for onabotulinumtoxinA in: number of headache days/month: (–10.64 [–12.31, –8.97]; –10.32 [−14.92, –5.73]); number of days of acute headache pain medication intake per month (–7.40 [–13.04, –1.77]; overlapping CIs at 52 weeks); total Headache Impact Test-6 score (–11.70 [–13.86, –9.54]); –11.80 [14.70, –8.90]); and Migraine-Specific Quality-of-Life v2.1 score (MSQ; 23.60 [CI: 21.56, 25.64]; 30.90 [CI: 28.29, 33.51]). At ∼24 weeks onabotulinumtoxinA showed total Migraine Disability Assessment score of 44.74 [28.50, 60.99] and ≥50% reduction in migraine days response rate of 46.57% [29.50%, 63.65%]. A sensitivity analysis at study-end suggested durability of onabotulinumtoxinA effectiveness on MSQ. Conclusion The meta-analysis reflecting real-world practice broadly corroborated with evidence from pivotal and long-term open-label studies of onabotulinumtoxinA in chronic migraine preventive treatment.

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) has a heterogenous clinical and radiological presentation. We investigated whether RCVS complications vary according to age. Patients and methods In a pooled French cohort of 345 patients with RCVS, we assessed (1) rates of clinical and radiological complications, and (2) the functional outcome at 3 months according to age as a continuous variable, and in young patients aged ≤ 49 years versus those aged ≥ 50 years. The Commission Nationale Informatique et Liberté and the local ethics committee approved this study (registration number: 202100733). Results The risk for any focal deficit and for any brain lesion were independently associated with increasing age (OR 1.4, 95% CI 1.1–1.8; p = 0.014, and OR 1.6, 95% CI 1.2–2.1; p p p = 0.023). Frequency of cervical artery dissections peaked at age 30–39, and young age was independently associated with cervical artery dissections (OR 13.6, 95% CI 2.4–76.6; p = 0.003). Age had no impact on the functional outcome, with a modified Rankin scale score of 0–1 in > 96% of patients. Conclusion Age seems to influence rates and types of complications of RCVS, with young age being associated with cervical artery dissections, and increasing age with haemorrhagic complications. If confirmed in larger prospective studies, recognition of age-specific patterns might help to guide clinical management and to identify complications in cases of RCVS and vice versa.

Background and Purpose: Reversible cerebral vasoconstriction syndrome (RCVS) is a well-established cause of stroke, but its demographics and outcomes have not been well delineated. Methods: Analysis of the United States Nationwide Inpatient Sample database (2016–2017) to characterize the frequency of hospitalizations for RCVS, demographic features, inpatient mortality, and discharge outcomes. Results: During the 2-year study period, 2020 patients with RCVS were admitted to Nationwide Inpatient Sample hospitals, representing 0.02 cases per 100 000 national hospitalizations. The mean age at admission was 47.6 years, with 85% under 65 years of age, and 75.5% women. Concomitant neurological diagnoses during hospitalization included ischemic stroke (17.1%), intracerebral hemorrhage (11.0%), subarachnoid hemorrhage (32.7%), seizure disorders (6.7%), and reversible brain edema (13.6%). Overall, 70% of patients were discharged home, 29.7% discharged to a rehabilitation facility or nursing home and 0.3% died before discharge. Patient features independently associated with the poor outcome of discharge to another facility or death were advanced age (odds ratio [OR], 1.04 [95% CI, 1.03–1.04]), being a woman (OR, 2.45 [1.82–3.34]), intracerebral hemorrhage (OR, 2.91 [1.96–4.31]), ischemic stroke (OR, 5.72 [4.32–7.58]), seizure disorders (OR, 2.61 [1.70–4.00]), reversible brain edema (OR, 6.26 [4.41–8.89]), atrial fibrillation (OR, 2.97 [1.83–4.81]), and chronic kidney disease (OR, 3.43 [2.19–5.36]). Conclusions: Projected to the entire US population, >1000 patients with RCVS are hospitalized each year, with the majority being middle-aged women, and about 300 required at least some rehabilitation or nursing home care after discharge. RCVS-related inpatient mortality is rare.

Background and ObjectivePRRT2 variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of PRRT2 in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands.MethodsPRRT2 was analyzed in 860 probands with hemiplegic migraine, and PRRT2 variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed.ResultsPRRT2 variations were found in 12 of 163 probands who previously tested negative for CACNA1A, ATP1A2, and SCN1A variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in ATP1A2 (42%), followed by CACNA1A (26%), PRRT2 (17%), and SCN1A (15%). The PRRT2 variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole PRRT2 gene. Among the 49 patients with variations in PRRT2, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic.DiscussionPRRT2 should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function PRRT2 variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.

The French Headache Society proposes updated French guidelines for the management of migraine. The first part of these recommendations is focused on the diagnosis and assessment of migraine. First, migraine needs to be precisely diagnosed according to the currently validated criteria of the International Classification of Headache Disorders , 3d version (ICHD-3). Migraine-related disability has to be assessed and we suggest to use the 6 questions of the headache impact test (HIT-6). Then, it is important to check for risk factors and comorbidities increasing the risk to develop chronic migraine , especially frequency of headaches, acute medication overuse and presence of depression. We suggest to use a migraine calendar and the Hospital Anxiety and Depression scale (HAD). It is also necessary to evaluate the efficacy and tolerability of current migraine treatments and we suggest to systematically use the self-administered Migraine Treatment Optimization Questionnaire (M-TOQ) for acute migraine treatment. Finally, a treatment strategy and a follow-up plan have to be proposed. Guidelines for pharmacological and non-pharmacological treatments are presented in the second and third part of the recommendations.

Background: In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without thunderclap headache (TCH), and tended to present more severe forms of RCVS than patients with TCH. We aimed to analyze the risk for complications of RCVS in patients with and without TCH at onset. Methods: In a pooled cohort of 345 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of neurological complications, and the functional outcome at 3 months. Results: As compared to the 281 patients with TCH at onset, the 64 patients without TCH had a higher risk for any neurological complication (61% vs. 24%, OR 4.9, 95% CI 2.8-8.7, p < 0.001). The association was strongest for cervical artery dissections (28% vs. 5%, OR 8.1, 95% CI 3.7-17.6, p < 0.001), followed by posterior reversible encephalopathy syndrome (17% vs. 3%, OR 7.1, 95% CI 2.7-18.4, p < 0.001), seizures (9% vs. 2.5%, OR 4.1, 95% CI 1.3-12.5, p = 0.019), and subarachnoid hemorrhage (41% vs. 16%, OR 3.5, 95% CI 1.9-6.3, p < 0.001). In multivariable analysis, the risk for any neurological complication remained significantly elevated in the absence of TCH (OR 3.5, 95% CI 1.8-6.8, p < 0.001). The functional outcome was equal in both groups, with a modified Rankin scale score of 0-1 in ≥90% of patients. Conclusions: Absence of TCH at onset might predict a higher risk of complications in RCVS. Our results warrant further multicentric studies to prove this finding.

The treatment of patients with headache represents an important part of a neurologist's activity. It requires sufficient training for neurology residents. In France, residents in neurology can complete this training by attending specialized consultations or by participating in a postgraduate training program called "Diplôme Inter-Universitaire Migraine et Céphalées" (DIUMC).The objective of this cross-sectional study was to investigate the French residents' knowledge in headache medicine and the impact of different types of training in headache medicine that are available in France.An anonymous survey was carried out among 548 French residents in neurology.The questionnaires of 121 residents (22.1%) were analyzed. Among them, 54.5% (66/121) had no complementary training apart from the internship (Group 1), 21.5% (26/121) had attended only specialized consultations (Group 2), and 24% (29/121) had participated in the DIUMC (Group 3). There was no difference between all groups regarding the knowledge of the prevalence of primary or chronic headaches. There was almost no difference between the groups in the management of episodic migraine. In contrast, the management of tension-type headache and chronic headache was better known by residents of Group 3 than residents of Group 1. In these two diseases, residents of Group 3 offered prophylactic treatment more often. Almost 29% of the residents (35/121) had read the French guidelines for the diagnosis and management of migraine. In Group 3, residents had read them significantly more often (1.6% in Group 1, 38.5% in Group 2 and 62.1% in Group 3, p 0.001).This study shows the lack of knowledge among French neurology residents regarding headache medicine. It highlights the interest of specific training programs that could improve the practical and theoretical knowledge of future neurologists.

Primary angiitis of the central nervous system (PACNS) is a relapsing-remitting disease with a heterogeneous course. Case series have delineated the long-term disease course but not acute outcomes or their determinants. The national United States hospital burden of PACNS has not been quantified.Analysis of the United States Nationwide Readmissions Database (2016-2018) to characterize the frequency of PACNS hospitalizations, demographic features, inpatient mortality, and discharge outcomes.During the 3-year study period, unweighted 1843 (weighted 3409) patients with PACNS were admitted to the 1078 Healthcare Cost and Utilization Project HCUP participating hospitals; with weighting, this value indicates that 1136 patients were admitted each year to US hospitals, representing yearly 0.01 cases per 100 000 national hospitalizations. The majority of patients were hospitalized in metropolitan teaching hospitals (81.6%). The median age at admission was 54.9 (IQR: 44.0-66.5) years and 59.4% were women. Neurologic manifestations included ischemic stroke in 38.2%, transient ischemic attack in 20.2%, seizure disorder in 22.8%, and intracranial hemorrhage in 13.0%. Overall, 60.0% of patients were discharged home, 35.0% discharged to a rehabilitation facility or nursing home and 5.0% died before discharge. Patient features independently associated with the discharge to another facility or death included older age (odds ratio [OR], 1.03 [95% CI, [1.03-1.04]]), male sex (OR, 1.22 [1.04-1.43]), intraparenchymal hemorrhage (OR, 1.41 [1.08-1.84]), ischemic stroke (OR, 2.79 [2.38-3.28]), and seizure disorder (OR, 1.57 [1.31-1.89]).Our study showed PACNS is still a rare inflammatory disorder of the blood vessels of the central nervous system suggesting an annual hospitalization of 5.1 cases per 1,000,000 person-years in the more diverse and contemporary US population. Overall, 4 in 10 had unfavorable discharge outcome, being unable to be discharged home, and 1 in 20 died before discharge.

Objective To evaluate the frequency, distribution, and clinical associations of the dilated appearance of cerebral cortical veins, termed cortical veins sign on T2*-weighted gradient recalled-echo (T2*-GRE) in the acute setting of migraine with aura attack in adult patients. Methods We conducted a retrospective analysis of 60 consecutive patients admitted for acute neurological symptoms with a final diagnosis of migraine with aura (42%) or probable migraine with aura (58%) who underwent emergency brain magnetic resonance imaging and 60 non-migrainous control adults. The cortical veins sign was defined as a marked hypo-intensity and/or an apparent increased diameter of at least one cortical vein. We examined the prevalence, the spatial distribution, and the associations of cortical veins sign with clinical characteristics of migraine with aura. Results We detected the cortical veins sign in 25 patients (42%) with migraine with aura, compared to none in the control group ( p Conclusion In the setting of acute neurological symptoms, the presence of cortical veins sign is frequent in patients with migraine with aura and can be detected with good reliability. This imaging marker may help clinicians identify underlying migraine with aura.

International audience; The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the second part of the guidelines, which is focused on the pharmacological treatment of migraine, including both the acute treatment of attacks and the prophylaxis of episodic migraine as well as chronic migraine with and without medication overuse. The specific situations that can be encountered in women with migraine are also discussed, including pregnancy, menstrual migraine, contraception and hormonal replacement therapy.

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up. In this Consensus Statement, which is endorsed by the European Headache Federation and the European Academy of Neurology, an expert panel provides recommendations for the diagnosis and management of migraine to support clinical decision-making by general practitioners, neurologists and headache specialists.

International audience; Reversible cerebral vasoconstriction syndrome (RCVS) is a common cause of thunderclap headache (TCH), mainly recurrent, sometimes associated with seizures and/or neurological deficit. Association with amnesia is exceptional. We report a case series of RCVS concomitant with transient global amnesia (TGA) and propose pathophysiologic hypotheses. Methods: We retrospectively reviewed clinical and radiological features of patients diagnosed with confirmed concomitant RCVS and TGA between 2012 and 2018 in two specialized institutions.Results: Two women aged 67 and 53, and a 64-year-old man had a first thunderclap headache triggered by an acute emotional stress, rapidly followed by TGA. Amnesia resolved within a few hours and RCVS was proven for all, with complete resolution of vasospasms within 3 months. All three patients had excellent outcome.Conclusions: RCVS and TGA can occur simultaneously, which suggests common mechanisms such as aberrant responses to physical or emotional stress and cerebral vasoconstriction.

The aim of genetic studies in migraine is to identify key proteins in order to better understand the molecular mechanisms of this frequent but still incompletely understood condition. This review describes the current knowledge in the field of migraine genetics. Migraine genes have been, and still are, difficult to identify. The more common varieties of migraine are characterized by a high prevalence in the general population, and a high phenotypic variability. In the absence of any objective diagnosis marker, the status for genetic studies is established only clinically. The first breakthrough was permitted by the study of familial hemiplegic migraine, a variety of migraine with motor aura. This rare condition has a monogenic, autosomal dominant mode of inheritance, thus enabling genetic studies. The three first genes, identified from 1996 to 2005, all encode ion-channel transporters: a neuronal calcium channel (CACNA1A, FHM1), a glial sodium/potassium pump (ATP1A2, FHM2) and a neuronal sodium channel (SCN1A, FHM3). Study of cellular and animal models have shown that mutations in CACNA1A and ATP1A2 facilitated the initiation of cortical spreading depression waves, the mechanism underlying the migraine aura, and most likely increased neuronal excitability with an excess of glutamatergic neurotransmission. In 2012, PRRT2 has been identified as the fourth FHM gene, and encodes an axonal protein associated to the exocytosis complex. In the 1990s, family and twin studies showed that the more common varieties of migraine (migraine without aura and migraine with typical aura) were polygenic, with an overall heritability nearing 50 %. These genetic factors interact with environmental factors. The initial attempts to identify migraine genes by candidate gene approaches or by linkage studies were deceiving. Since 2010, three large genome-wide association studies (GWAS) have identified six genetic variants associated with migraine. Each variant has only a modest contribution to the overall genetic risk of migraine, suggesting a marked genetic heterogeneity. Three of the migraine-associated variants affect genes involved in glutamate homeostasis. Another variant concerns a gene encoding a protein implicated in nociception. Three of the four polymorphisms are associated both with migraine without aura and migraine with aura, supporting the existence of molecular mechanisms shared by all varieties of migraine. The vast majority of the migraine genes are still to be identified. Future researches will rely on new GWAS on larger cohorts of patients and controls, with a better phenotypic assessment, and on extensive sequencing.

OBJECTIVE The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS). METHODS We prospectively recruited 3 independent cohorts of patients with RCVS and age-matched and sex-matched controls in a single medical center. Next-generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross-validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis. RESULTS We identified a panel of miRNAs including miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, and let-7f-5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let-7a-5p, let-7b-5p, and let-7f-5p, but not miR-130a-3p nor miR-130b-3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor-β signaling pathway and endothelin-1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients' cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR-130a-3p was associated with imaging-proven disruption of the blood-brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model. INTERPRETATION We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459-473.

International audience; Currently many patients with severe migraine do not receive appropriate treatment and are never referred to specialist headache centres. On the other hand, specialist headache centres are frequently attended by patients whose migraines could be managed adequately in the community. One reason for this may be the absence of standardised definitions of migraine severity and control and of a treatment algorithm for orientating difficult-to-treat patients to specialist headache centres. Based on a review of the relevant literature and consensus meetings, proposals have been made for these items. We propose that migraine should be considered severe if headache frequency is at least eight migraine days per month or, if headaches are less frequent, the HIT-6 score is ≥60 or ≥50% of headaches require complete interruption of activity. The proposed definition of migraine control is defined on the basis of appropriate response to acute headache therapy and to preventative therapy. A treatment algorithm is proposed to assess migraine control regularly and to adapt therapy accordingly. These proposals may contribute to developing and testing strategies for management of severe disease with appropriate and effective preventive treatment strategies. With the anticipated introduction of new possibilities for migraine prevention in the near future, the time is ripe for a holistic approach to migraine management.

International audience; Background and purpose: The purpose was to evaluate, in a consecutive series of patients with isolated acute retinal ischaemia, the proportion of patients with acute silent brain infarcts (SBIs) on diffusion-weighted imaging (DWI) and to assess risk of recurrence within 3 months.Methods: In all, 103 consecutive patients with isolated acute retinal ischaemia (central retinal artery occlusion, branch retinal artery occlusion or transient monocular vision loss) were included between January 2015 and December 2016. They all had cerebral magnetic resonance imaging including DWI as well as a standardized aetiological workup and 3 months of follow-up. The presence of DWI-positive cerebral lesions was recorded. Main clinical and radiological characteristics between DWI-positive and DWI-negative patients were compared.Results: Of the 103 patients (including 42 transient monocular vision loss), 20 (19.5%) had SBIs on DWI, which were ipsilateral to the acute retinal ischaemia in 30% and involved different and/or multiple vascular territories in 70% of cases. Ipsilateral carotid stenosis and occlusion were respectively identified in 17 and eight patients whereas cardioaortic embolism was found in 19 patients. Overall, patients with and without acute SBIs were comparable. The topography of SBIs was related to the aetiology of the acute retinal ischaemia. At 3 months of follow-up, one patient suffered from ischaemic stroke and five had recurrent retinal ischaemia.Conclusions: Irrespective of the baseline characteristics of the patients, SBIs are present in about 20% of patients with isolated acute retinal ischaemia and may be of interest in the aetiological workup. Overall risk of recurrence is low, favoured by rapid aetiological workup and appropriate treatment.

BACKGROUND AND PURPOSE: Few data are available regarding the influence of the timing of ischemic stroke management, such as daytime and nighttime hours, on the delay of mechanical thrombectomy, the effectiveness of revascularization, and clinical outcomes. We aimed to investigate whether admission during nighttime hours could impact the clinical outcome (mRS at 90 days) of patients with acute ischemic stroke treated by mechanical thrombectomy. MATERIALS AND METHODS: We retrospectively analyzed 169 patients (112 treated during daytime hours and 57 treated during nighttime hours) with acute ischemic stroke in the anterior cerebral circulation. The main outcome was the rate of patients achieving functional independence at 90 days (mRS ≤2), depending on admission time. RESULTS: In patients admitted during nighttime hours, the rate of mRS ≤ 2 at 90 days was significantly higher (51% versus 35%, P = .05) compared with those admitted in daytime hours. Patients in daytime and nighttime hours were comparable regarding admission and treatment characteristics. However, patients in nighttime hours tended to have a higher median NIHSS score at admission (P = .08) and to be younger (P = .08), especially among the mothership group (P = .09). The multivariate logistic regression analysis confirmed that patients in nighttime hours had better functional outcomes at 90 days than those in daytime hours (P = .018; 95% CI, 0.064–0.770; OR = 0.221). CONCLUSIONS: In a highly organized stroke care network, mechanical thrombectomy is quite effective in the nighttime hours among acute ischemic stroke presentations. Unexpectedly, we found that those patients achieved favorable clinical outcomes more frequently than those treated during daytime hours. Larger series are needed to confirm these results.

Background and Purpose— We aimed to further investigate the long-term outcomes after reversible cerebral vasoconstriction syndrome (RCVS). Methods— A longitudinal follow-up study was conducted in 173 RCVS patients. Results— Of the 172 patients who completed a mean follow-up of 9.2±3.3 years, 10 had a recurrent RCVS that was benign in all. Independent predictors of relapse were having a history of migraine and having exercise as a trigger for thunderclap headache during initial RCVS. After new delivery, the rate of postpartum RCVS was 9%. Conclusions— Overall, long-term outcome after RCVS is excellent.

Introduction Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances. Main body Definitions were established with a consensus process using the Delphi method. Patients with migraine with or without aura or with chronic migraine can be defined as having resistant migraine and refractory migraine according to previous preventative failures. Resistant migraine is defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts. Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 consecutive months. Drug failure may include lack of efficacy or lack of tolerability. Debilitating headache is defined as headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required. Conclusions We hope, that the updated EHF definition will be able to solve the conflicts that have limited the use of definitions which have been put forward in the past. Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved. This new definition has also the aim to increase the understanding of the impact of the migraine as a disease with all of its social, legal and healthcare implications. It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

ObjectivesTo further improve the distinction between primary angiitis of the CNS (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS).MethodsWe compared 2 large French cohorts of patients with PACNS (n = 110, retrospectively and prospectively enrolled) and RCVS (n = 173, prospectively enrolled).ResultsPatients with RCVS were predominantly female (p < 0.0001), with migraines (p < 0.0001), and were more often exposed to vasoactive substances (p < 0.0001) or postpartum (p = 0.002) than patients with PACNS. Headache, especially thunderclap headache, was more frequent in RCVS (both p < 0.0001). Thunderclap headache was absent in only 6% of patients with RCVS and was mainly recurrent (87%) and provoked (77%) mostly by sexual intercourse, exertion, or emotion. All other neurologic symptoms (motor deficit, seizure, cognitive disorder, or vigilance impairment, all p < 0.0001) were more frequent in PACNS. At admission, brain CT or MRI was abnormal in all patients with PACNS and in 31% of patients with RCVS (p < 0.0001). Acute ischemic stroke was more frequent in PACNS than in RCVS (p < 0.0001). Although intracerebral hemorrhage was more frequent in PACNS (p = 0.006), subarachnoid hemorrhage and vasogenic edema predominated in RCVS (p = 0.04 and p = 0.01, respectively). Multiple small deep infarcts, extensive deep white matter lesions, tumor-like lesions, or multiple gadolinium-enhanced lesions were observed only in PACNS, whereas cervical artery dissection was found only in RCVS.ConclusionsOur study confirms that careful analysis of clinical context, headache features, and patterns of brain lesions can distinguish PACNS and RCVS within the first few days of admission in most cases. However, diagnosis remains challenging in a few cases.

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Background Migraine with brainstem aura is defined as a migraine with aura including at least two of the following symptoms: dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia and/or decreased level of consciousness. Aim The aim of this study is to review data coming from clinical observations and functional mapping that support the role of the cerebral cortex in the initiation of brainstem aura symptoms. Results Vertigo can result from a vestibular cortex dysfunction, while tinnitus and hypacusis can originate within the auditory cortex. Diplopia can reflect a parieto-occipital involvement. Dysarthria can be caused by dysfunctions located in precentral gyri. Ataxia can reflect abnormal processing of vestibular, sensory, or visual inputs by the parietal lobe. Alteration of consciousness can be caused by abnormal neural activation within specific consciousness networks that include prefrontal and posterior parietal cortices. Conclusion Any symptom of so-called brainstem aura can originate within the cortex. Based on these data, we suggest that brainstem aura could have a cortical origin. This hypothesis would explain the co-occurrence of typical and brainstem aura during attacks and would fit with the theory of cortical spreading depression. We propose that migraine with brainstem aura should be classified as a typical migraine aura.

The French guidelines for the treatment of trigeminal neuralgia have been recently published. The first-line medical treatment is carbamazepine 400–1 600 mg per day according to the patient’s response. The daily dosage should be increased gradually, with 2 or 3 doses per day. Side effects, common in the elderly (drowsiness, dizziness with vestibulo-cerebellar syndrome), should be monitored. Oxcarbazepine may be used in case of intolerance to carbamazepine. In the event of intolerance or failure of both previous treatments, lamotrigine may be used. Baclofen may be used alone or in combination with carbamazepine or oxcarbazepine. Other antiepileptics are not recommended as firstline drugs, but are used in practice in the event of failure or intolerance to carbamazepine, oxcarbazepine or lamotrigine. These are gabapentin, pregabalin, topiramate and levetiracetam.

Resume Le syndrome de vasoconstriction cerebrale reversible associe des cephalees severes, typiquement en coup de tonnerre et multiples, et une vasoconstriction segmentaire diffuse des arteres cerebrales, regressive en 3 mois. Il est attribue a un dysfonctionnement transitoire de la regulation du tonus vasculaire cerebral, d’evolution le plus souvent favorable. Cependant, un œdeme cerebral, des hemorragies intracrâniennes ou des infarctus cerebraux peuvent survenir d’emblee ou apres une phase de cephalees isolees. Ces complications peuvent probablement etre evitees par une prise en charge precoce des les premieres cephalees. Le diagnostic est difficile lorsque l’angiographie initiale est normale, comme dans 20 % des cas, car la vasoconstriction culmine 2 a 3 semaines apres le debut. Plus de la moitie des cas surviennent apres consommation de substances vasoactives ou lors du post-partum. Le traitement consiste en l’eviction des substances vasoactives, le repos et le controle de la pression arterielle. La nimodipine semble reduire les cephalees, mais ne previent pas completement les AVC.

Cluster headache and other trigeminal autonomic cephalalgias (TACs) are rare and often severe primary headache disorders. Family and twin studies in cluster headache have demonstrated a clear genetic component, but the mode of transmission and the amount of heritability remain to be determined. A few familial cases of other TACs have been reported, but it is at present unknown to what extent these disorders are genetic. As a consequence, all genetic studies to date have focussed on the identification of genetic factors in cluster headache, foremost the testing of single nucleotide polymorphisms (SNPs) in candidate genes that were selected on presumed knowledge of the pathophysiology, but this did not result in any robust associations. More recently, the first genome-wide association study (GWAS) was conducted, albeit with limited success. Here we will (1) present current knowledge of the genetics of cluster headache and other TACs and (2) discuss factors potentially explaining why genetic studies were less successful in TACs than in migraine. Learning from the past, genetic studies in cluster headache and other TACs may hopefully be more fruitful in the future.

Objective: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). Methods: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. Results: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. Conclusion: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.

A 16-year-old boy with recurrent transient visual loss had bilateral papilledema. MRI revealed giant arachnoid granulations (GAG) in both transverse sinuses and signs of intracranial hypertension (figure). CSF opening pressure was 420 mm H2O. After depletive lumbar puncture, the size of GAG decreased and sinus lumen stenosis resolved (figure). Arachnoid granulations (AG) are CSF herniations through dural defects into sinuses.1 Since CSF removal led to their regression, GAG might be a consequence of intracranial hypertension. Our case supports the Krisch theory, which considers AG as a buffer of CSF compartment rather than a site of CSF absorption.2

Neurochirurgie - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le lundi 18 juin 2018

La sindrome di vasocostrizione cerebrale reversibile associa delle cefalee improvvise inusuali, in genere a colpo di tuono, e una vasocostrizione segmentaria diffusa delle arterie intracraniche, che regredisce in tre mesi. Essa e attribuita a un malfunzionamento acuto e transitorio della regolazione del tono vascolare intracranico, di evoluzione, il piu delle volte, favorevole. Tuttavia, possono presentarsi delle complicanze, come degli infarti cerebrali, delle emorragie intracraniche o un edema cerebrale, o immediatamente o dopo una fase di cefalee isolate, rendendo necessarie una diagnosi e una gestione precoci. La sindrome di vasocostrizione cerebrale reversibile puo essere idiopatica o secondaria, il piu delle volte in un contesto di post-partum o di consumo di agenti tossici o di farmaci vasoattivi. Il suo trattamento consiste nell’eliminazione di un eventuale fattore scatenante, associata a misure sintomatiche ed empiricamente a un trattamento con calcioantagonista vasodilatatore.

Post-lumbar puncture headache (PLPH) is a well-known syndrome resulting from spinal fluid leakage and delayed closure of a dural defect. The main symptom of PLPH is headache in upright posture relieved by lying down. Outcome is usually benign and complications are uncommon. The functional impact can however be important, leading to delayed discharge, sick leave and, if information delivery is ineffective, iterative consultations. Preventive measures have been published, but the prevalence of PLPH remains high (15 to 40% after diagnostic lumbar puncture). Needle size and type are probably the most important factors for reducing the risk of PLPH. Recovery can be rapid, within a few days. If PLPH persists after four days, an epidural blood patch should be discussed. The objective of this review is to summarize the literature on PLPH, and share the experience of our emergency headache center with an atraumatic 25-gauge needle (pencan, 0.5×90mm or 0.5×103mm, Braun, Germany).

Introduction Le diagnostic de la severite de l’infarctus cerebral est fortement base sur l’imagerie cerebrale realisee a la phase aigue. Le volume de la necrose ischemique peut etre evalue par imagerie de diffusion. L’objectif de cette etude est d’evaluer la mesure du volume ischemique chez des patients victimes d’un infarctus cerebral pour deux sequences d’imagerie de diffusion : la sequence Spin Echo-EPI (Echo Planar Imaging) et la sequence RESOLVE (REadout Segmentation Of Variable Echo trains). Patients et methodes 56 patients victimes d’un infarctus cerebral ischemique [31 femmes (âge median = 73,1 ± 14)], presentant une occlusion de la circulation anterieure ont ete explore a la phase aigue par imagerie de diffusion Spin-Echo-EPI et RESOLVE. Les deux sequences de diffusion avaient la meme resolution spatiale, un temps de repetition et temps d’echo semblable. Une analyse volumique pour ces deux sequences a ete realisee a l’aide du logiciel RAPID (seuil du Coefficient de Diffusion Apparent (CDA) Une analyse de concordance Bland–Altman Plot a ete effectuee. Resultats L’analyse Bland–Altmann montre une moyenne des differences de 12,6 ml. Lorsque le volume ischemique augmente la difference volumique augmente. Une mauvaise concordance est observee entre ces deux sequences Concordance correlation coefficient ρc = 0,8151 et un intervalle de confiance a 95 % = [0,7458 – 0,8670]. Pour ces deux sequences, le volume lesionnel reste significativement associe a la recuperation fonctionnelle (mRs) a 3 mois. L’analyse du CDA dans le parenchyme sain ne montre pas de difference significative entre ces deux sequences. Conclusion Sur la base de l’algorithme RAPID, le volume lesionnel en RESOLVE est superieur a celui obtenu par SE-EPI. Il semble donc que les valeurs de CDA obtenues a partir de la sequence RESOLVE soient plus faibles au sein de la lesion ischemique.

Introduction Peu de donnees ont ete rapportees concernant l’influence du moment de la prise en charge (Jour/Nuit) sur les delais de la procedure endovasculaire, l’efficacite de la revascularisation, et la recuperation fonctionnelle a 3 mois. Nous cherchons a determiner si la prise en charge de nuit a un impact sur la recuperation fonctionnelle a 3 mois. Patients et methodes Au total, 169 patients victimes d’un infarctus cerebral (occlusion circulation anterieure) ont ete inclus dans l’etude, 112 [âge = 77(25–98), 55 hommes] traites le jour [08 h–20 h] et 57 [âge = 74(20–89), 30 hommes] traites la nuit [20 h–08 h]. Les variables categorielles ont ete analysees a l’aide d’un test de Fisher et les variables continues a l’aide d’un test de Mann–Whitney (seuil de significativite p = 0,05, analyse univariee). Resultats Aucune difference significative n’a ete trouvee entre l’activite de nuit versus celle de jour pour l’heure d’apparition des symptomes, le NIHSS a l’admission, le volume ischemique, le taux de thrombolyse IV, la duree entre l’admission et la reperfusion et la duree entre le point de ponction et la reperfusion (TICI = 3). Une difference significative est observee pour la duree entre l’admission et le point de ponction. Elle est plus importante chez les patients traites de nuit (94 vs 82 min, p = 0,009). La comparaison nuit/jour montre une difference significative pour le mRs a 3 mois. Le groupe traite de nuit presente un mRs plus faible (mRs ≤ 2, p = 0,05). Cette difference est d’autant plus marquee lorsque l’on compare des sujets pour lesquels l’heure de debut des symptomes est connue (p = 0,02). Conclusion Une analyse multivariee devrait permettre de confirmer ces premiers resultats qui tendent a montrer une meilleure recuperation chez les patients traites de nuit.