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Rory C Monahan,1 Hannelore JL Beaart,1 Rolf Fronczek,2,3 Gisela M Terwindt,2 Liesbeth JJ Beaart-van de Voorde,1 Jeroen de Bresser,4 Margreet Kloppenburg,1,5 Nic JA van der Wee,6 Tom WJ Huizinga,1 Gerda M Steup-Beekman1,7 1Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, the Netherlands; 2Department of Neurology, LUMC, Leiden, the Netherlands; 3Sleep-Wake Center SEIN, Heemstede, the Netherlands; 4Department of Radiology, LUMC, Leiden, the Netherlands; 5Department of Clinical Epidemiology, LUMC, Leiden, the Netherlands; 6Department of Psychiatry, LUMC, Leiden, the Netherlands; 7Department of Rheumatology, Haaglanden Medical Center, The Hague, the NetherlandsCorrespondence: Rory C MonahanDepartment of Rheumatology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the NetherlandsTel +3171-5265762Fax +3171-5266752Email r.c.monahan@lumc.nlPurpose: To evaluate the use of immunosuppressive treatment, clinical outcome and diagnostic strategy in patients with systemic lupus erythematosus (SLE) presenting with clinical features of transverse myelitis (TM), but normal MRI of the spinal cord (sMRI) and normal cerebrospinal fluid (CSF) assessment, and to suggest a clinical guideline.Patients and Methods: All patients with SLE and clinical features compatible with (sub)acute TM visiting the NPSLE clinic of the LUMC between 2007 and 2020 were included. Information on baseline characteristics, investigations, treatment and outcomes was collected from electronic medical records. In addition, a systematic review of individual participant data was performed up to April 2020 in PubMed, Embase and Web of Science, identifying all patients with TM, SLE and sMRI assessment. Data regarding sMRI, CSF analysis, treatment and outcome were extracted, and outcome was compared between patients with normal sMRI and CSF (sMRI-/CSF-) and patients with abnormalities.Results: Twelve SLE patients with a clinical diagnosis of TM were identified: four sMRI-/CSF- and one sMRI- with CSF not available. All patients received immunosuppressive treatment, but outcome in sMRI-/CSF- patients was worse: no recovery (n=1) or partial recovery (n=3) compared to partial recovery (n=4) and (nearly) complete recovery (n=3) in MRI+ patients. The systematic literature review yielded 146 articles eligible for inclusion, 90% case reports. A total of 427 SLE patients with TM were identified, of which only four cases were sMRI-/CSF- (1%), showing no improvement (n=1), partial improvement (n=2) and complete recovery (n=1) after immunosuppressive treatment.Conclusion: Outcome in SLE patients presenting with clinically suspected TM with normal sMRI and CSF is less favorable, despite treatment with immunosuppressive therapy. Taking a functional neurological disorder into consideration may be helpful in order to start other therapeutic strategies. We suggest prescribing immunosuppressive treatment for a restricted period of time to evaluate its effect in cases where a functional disorder initially is considered unlikely.Keywords: lupus, neuropsychiatric, transverse myelitis, MRI, CSF

Background and aim: The revised Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) add two radiological markers to the existing criteria: severe visible perivascular spaces in the centrum semiovale and white matter hyperintensities (WMHs) in a multispot pattern. This study aims to determine the sensitivity of the updated criteria in mutation carriers with Dutch-type hereditary CAA (D-CAA) in an early and later disease stage. Methods: In this cross-sectional study, we included presymptomatic and symptomatic D-CAA mutation carriers from our prospective natural history study (AURORA) at the Leiden University Medical Center between 2018 and 2021. 3-Tesla scans were assessed for CAA-related magnetic resonance imaging (MRI) markers. We compared the sensitivity of the Boston criteria v2.0 to the previously used modified Boston criteria v1.5. Results: We included 64 D-CAA mutation carriers (mean age 49 years, 55% women, 55% presymptomatic). At least one white matter (WM) feature was seen in 55/64 mutation carriers (86%: 74% presymptomatic, 100% symptomatic). Fifteen (23%) mutation carriers, all presymptomatic, showed only WM features and no hemorrhagic markers. The sensitivity for probable CAA was similar between the new and the previous criteria: 11/35 (31%) in presymptomatic mutation carriers and 29/29 (100%) in symptomatic mutation carriers. The sensitivity for possible CAA in presymptomatic mutation carriers increased from 0/35 (0%) to 15/35 (43%) with the new criteria. Conclusion: The Boston criteria v2.0 increase the sensitivity for detecting possible CAA in presymptomatic D-CAA mutation carriers and, therefore, improve the detection of the early phase of CAA. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA). Aims: We investigated the proportion of cerebellar ICH and asymptomatic macro- and microbleeds in Dutch-type hereditary CAA (D-CAA), a severe and essentially pure form of CAA. Methods: Symptomatic patients with D-CAA (defined as ≥1 symptomatic ICH) and presymptomatic D-CAA mutation-carriers were included. We assessed magnetic resonance imaging scans for symptomatic (cerebellar) ICH and asymptomatic cerebellar macro- and microbleeds according to the STRIVE-criteria. Location was assessed as superficial-cerebellar (cortex, vermis or juxta-cortical) or deep-cerebellar (white matter, pedunculi cerebelli and gray nuclei). Results: We included 63 participants (mean age 58 years, 60% women, 42 symptomatic). In total, the 42 symptomatic patients with D-CAA had 107 symptomatic ICH (range 1–7). None of these ICH were located in the cerebellum. Six of 42 (14%, 95%CI 4–25%) symptomatic patients and none of the 21 (0%, 95%CI 0–0%) presymptomatic carriers had ≥ 1 asymptomatic cerebellar macrobleed(s). All macrobleeds were superficially located. Cerebellar microbleeds were found in 40 of 63 (64%, 95%CI 52–76) participants (median 1.0, range 0–159), 81% in symptomatic patients and 29% in presymptomatic carriers. All microbleeds were strictly or predominantly superficially (ratio superficial versus deep 15:1) located. Conclusions: Superficially located asymptomatic cerebellar macrobleeds and microbleeds are common in D-CAA. Cerebellar microbleeds are already present in the presymptomatic stage. Despite the high frequency of cerebellar micro and macrobleeds, CAA pathology did not result in symptomatic cerebellar ICH in patients with D-CAA. [ABSTRACT FROM AUTHOR]

Background and aim: To investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH). Methods: We performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. Results: We included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging. Conclusion: Whereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA. [ABSTRACT FROM AUTHOR]

Abstract Background: Headache is a common symptom during space travel, both isolated and as part of space motion syndrome. Head-down-tilted bed rest (HDTBR) studies are used to simulate outer space microgravity on Earth, and allow countermeasure interventions such as artificial gravity and training protocols, aimed at restoring microgravity-induced physiological changes. Objectives: The objectives of this article are to assess headache incidence and characteristics during HDTBR, and to evaluate the effects of countermeasures. Methods: In a randomized cross-over design by the European Space Agency (ESA), 22 healthy male subjects, without primary headache history, underwent three periods of -6-degree HDTBR. In two of these episodes countermeasure protocols were added, with either centrifugation or aerobic exercise training protocols. Headache occurrence and characteristics were daily assessed using a specially designed questionnaire. Results: In total 14/22 (63.6%) subjects reported a headache during ≥1 of the three HDTBR periods, in 12/14 (85.7%) non-specific, and two of 14 (14.4%) migraine. The occurrence of headache did not differ between HDTBR with and without countermeasures: 12/22 (54.5%) subjects vs. eight of 22 (36.4%) subjects; p=0.20; 13/109 (11.9%) headache days vs. 36/213 (16.9%) headache days; p=0.24). During countermeasures headaches were, however, more often mild (p=0.03) and had fewer associated symptoms (p=0.008). Conclusions: Simulated microgravity during HDTBR induces headache episodes, mostly on the first day. Countermeasures are useful in reducing headache severity and associated symptoms. Reversible, microgravity-induced cephalic fluid shift may cause headache, also on Earth. HDTBR can be used to study space headache on Earth. [ABSTRACT FROM AUTHOR]

It has been suggested that mitochondrial mutations cause migraine(-like) symptoms. The presence of mtDNA mutations (3243, 3271, 11084, and deletions) was investigated in three migraine subgroups (maternally transmitted migraine with and without aura, migrainous infarction, and nonfamilial hemiplegic migraine). No mutations were found. These mutations and deletions probably are not involved in the migraine subgroups studied, although an investigation of other material (e.g., muscle tissue) would have shown this with more certainty. [ABSTRACT FROM AUTHOR]

We compared the clinical characteristics of 46 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39% vs 15%; p < 0.05) and provocation of attacks by mild head trauma (70% vs 40%; p < 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features. [ABSTRACT FROM AUTHOR]

Background: The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive symptoms (mood changes) and the various phases of the migraine attack has not yet been examined.Methods: We performed a prospective diary study in n = 487 participants with migraine. Participants filled out a daily diary on migraine and acute depressive symptoms during a 1-month period. We randomly selected one migraine attack per participant, consisting of six days around an attack, including the interictal, premonitory, ictal, and postdromal phases. Acute depressive symptoms covered five major items from the DSM-5 classification. Primary analysis was performed using a mixed model with post-hoc testing. We also tested whether lifetime depression influenced the presence of acute depressive symptoms.Results: During a migraine headache day, patients scored higher on acute depressive symptoms than on all other days of the migraine attack (p < 0.001). There were no early warning signs for an upcoming headache attack through acute depressive symptomatology. Migraine patients with lifetime depression scored overall higher during the migraine attack than those without lifetime depression (p < 0.001).Limitations: Migraine attacks were based on self-reported migraine and one migraine attack per patient was randomly selected.Conclusion: We now clearly demonstrate that during the migraine headache phase, but not in the prodromal phase, patients report increased depressive symptomatology. No evidence was found for mood changes as an early warning sign for an upcoming migraine attack. [ABSTRACT FROM AUTHOR]

Introduction Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterized by attacks of hemiplegia and mental retardation. It has been often associated with migraine. The CACNA1A gene on chromosome 19 is involved in familial hemiplegic migraine and other episodic cerebral disorders, but also with progressive neuronal damage. Methods We performed mutation analysis in this gene in four AHC patients, using single strand conformation polymorphism analysis. Results We found nine polymorphisms, but no mutations in any of the 47 exons. Conclusions Other cerebral ion channel genes remain candidate genes for AHC. [ABSTRACT FROM AUTHOR]

Background: Capsaicin induces the release of calcitonin gene-related peptide (CGRP) via the transient receptor potential channel V1 (TRPV1). The CGRP response after capsaicin application on the tongue might reflect the "activation state" of the trigeminal nerve, since trigeminal CGRP-containing vesicles are depleted on capsaicin application. We tested (i) the quantitative CGRP response after oral capsaicin application; (ii) the optimal concentration of red chili homogenate; and (iii) the day-to-day variability in this response. Methods: Saliva was collected for two consecutive days after oral application of eight capsaicin dilutions (red chili homogenates) of increasing concentrations in 13 healthy individuals. Effects of homogenate concentration were assessed. Consecutively, saliva was sampled after application of vehicle and undiluted homogenates. Results: CGRP secretion (pg/ml) increased dose-dependently with homogenate concentration (p<0.001). CGRP levels were highest after application of nondiluted homogenate (vs. baseline: 13.3 (5.0) vs. 9.7 (2.9); p=0.003, as was total CGRP secretion in five minutes (pg) with undiluted (vs. baseline): 89.2 (44.1) vs. 14.1 (2.8); p<0.001. The dosedependent response in CGRP was not affected by day (p=0.14) or day*concentration (p=0.60). Increase in CGRP (undiluted - baseline; pg/ml) did not differ between measurements on dose-finding (p=0.67) and follow-up days (p=0.46). Conclusion: Oral application of red chili homogenate is well tolerated and causes a dose-dependent CGRP release in saliva, without day-to-day effects in this response. This model could be used to noninvasively study the activation state of the trigeminal nerve innervating salivary glands. [ABSTRACT FROM AUTHOR]

Introduction: Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process. Methods:We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with highfrequency migraine (HFM). Subsequently, SNPs with p values<0.05 were forwarded to the replication stage containing 531 patients with CM or HFM. Results: Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage. Discussion: We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification. [ABSTRACT FROM AUTHOR]

Introduction: There is a strong association between migraine and depression. The aim of this study is to identify migrainespecific factors involved in this association. Methods: We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted. Results: Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption. Conclusion: This study identified allodynia, in addition to high migraine attack frequency, as a new migraine-specific factor associated with depression [ABSTRACT FROM AUTHOR]

The article presents a study that assesses biochemical changes in the brain of patients with hemiplegic migraine in between attacks. The study included eighteen patients with hemiplegic migraine of whom eight had a known familial hemiplegic migraine (FHM) mutation. It reveals a decreased cerebellar tNAA/tCre ratio that might serve as an early biomarker for neuronal dysfunction and/or loss.

Objective: To assess validity of a self-administered web-based migraine-questionnaire in diagnosing migraine aura for the use of epidemiological and genetic studies. Methods: Self-reported migraineurs enrolled via the LUMINA website and completed a web-based questionnaire on headache and aura symptoms, after fulfilling screening criteria. Diagnoses were calculated using an algorithm based on the International Classification of Headache Disorders (ICHD-2), and semi-structured telephone-interviews were performed for final diagnoses. Logistic regression generated a prediction rule for aura. Algorithm-based diagnoses and predicted diagnoses were subsequently compared to the interview-derived diagnoses. Results: In 1 year, we recruited 2397 migraineurs, of which 1067 were included in the validation. A seven-question subset provided higher sensitivity (86% vs. 45%), slightly lower specificity (75% vs. 95%), and similar positive predictive value (86% vs. 88%) in assessing aura when comparing with the ICHD-2-based algorithm. Conclusions: This questionnaire is accurate and reliable in diagnosing migraine aura among self-reported migraineurs and enables detection of more aura cases with low false-positive rate. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that migraine is a risk factor for brain lesions, but methodological issues hampered drawing definite conclusions. Therefore, we initiated the magnetic resonance imaging (MRI) 'CAMERA' (Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis) study. We summarize our previously published results. A total of 295 migraineurs and 140 controls were randomly selected from a previously diagnosed population-based sample (n = 6039), who underwent an interview, physical examination and a brain MRI scan. Migraineurs, notably those with aura, had higher prevalence of subclinical infarcts in the posterior circulation [odds ratio (OR) 13.7; 95% confidence interval (CI) 1.7, 112]. Female migraineurs were at independent increased risk of white matter lesions (WMLs; OR 2.1; 95% CI 1.0, 4.1), and migraineurs had a higher prevalence of brainstem hyperintense lesions (4.4% vs. 0.7%, P = 0.04). We observed a higher lifetime prevalence of (frequent) syncope and orthostatic insufficiency in migraineurs; future research needs to clarify whether autonomic nervous system dysfunction could explain (part of) the increased risk of WMLs in female migraineurs. Finally, in migraineurs aged < 50 years, compared with controls, we found evidence of increased iron concentrations in putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Higher risks in those with higher attack frequency or longer disease duration were found consistent with a causal relationship between migraine and lesions. This summary of our population-based data illustrates that migraine is associated with a significantly increased risk of brain lesions. Longitudinal studies are needed to assess whether these lesions are progressive and have relevant (long-term) functional correlates. [ABSTRACT FROM AUTHOR]

Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm 2 /s × 10 -4 ) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm 2 /s × 10 -4 ) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N. Vlegels reports support by the Netherlands CardioVascular Research Initiative–the Dutch Heart Foundation (CVON 2018–28 & 2012–06). M.R. Schipper reports independent support from the TRACK D-CAA consortium, consisting of Alnylam, Biogen, the Dutch CAA foundation, Vereniging HCHWA-D, and researchers from Leiden, Boston, and Perth. A. De Luca reports independent support from Alzheimer Nederland (WE-03-2022-11) as well as from ZonMW. R. van Dort is funded by the TRACK D-CAA consortium, consisting of Biogen, Alnylam, the Dutch CAA foundation, Vereniging HCHWA-D, and researchers from Leiden, Boston, and Perth. G.M. Terwindt reports independent support from the Dutch Research Council (NWO), European Community, the Dutch Heart Foundation, the Dutch Brain Foundation, and the Dutch CAA foundation.M.J.P. van Osch reports support by a NWO-VICI grant (016.160.351) and a NWO-Human Measurement Models 2.0 grant (18969) as well as support from the Dutch Research Council (NWO), European Community, the Dutch Heart Foundation, and the Dutch Brain Foundation.M.J.H. Wermer reports independent support from de Nederlandse Organisatie voor Wetenschappelijk Onderzoek ZonMw (VIDI grant 91717337), the Netherlands Heart Foundation, and the Dutch CAA foundation. The others report no conflicts.

Introduction: Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited., Methods: We included Dutch-type hereditary CAA (D-CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age-matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI-cSVD burden and cognition., Results: D-CAA ICH- mutation carriers exhibited poorer global cognition and executive function compared to age-matched controls. Patients with sCAA performed worse across all cognitive domains compared to D-CAA ICH+ mutation carriers and age-matched controls. MRI-cSVD burden is associated with decreased processing speed., Discussion: CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI-cSVD burden being associated with slower processing speed., Highlights: Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH). Presymptomatic Dutch-type CAA (D-CAA) mutation carriers show worse cognition than age-matched controls. More early awareness of cognitive dysfunction in CAA before first sICH is needed. Increased cerebral small vessel disease CAA-burden on magnetic resonance imaging is linked to a decrease in processing speed., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Purpose: Data on health-related quality of life (HRQoL) and mood in cerebral amyloid angiopathy (CAA), a disease characterized by stroke and cognitive decline, are limited. We aimed to investigate the impacted domains of life, value-based HRQoL and the prevalence of depression and anxiety in patients with CAA., Methods: We conducted a cross-sectional study of patients with sporadic (s)CAA, lobar dominant mixed CAA and hypertensive arteriopathy (mixed CAA-HTA), or Dutch-type hereditary (D-)CAA, from prospective outpatient clinic cohorts. Participants completed four questionnaires: the EuroQoL 5 dimensions 5-level questionnaire (EQ-5D-5L; EQ-VAS for visual analogue scale; EQ-Index for index rating), the Short-Form 36 questionnaire (SF-36), the Center for Epidemiologic Studies-Depression scale (CES-D), and the Hospital Anxiety and Depression Scale (HADS; -D for depression and -A for anxiety subscales). The EQ-5D-5L assesses the domains mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The SF-36 domains are physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, vitality, bodily pain, and general health perceptions. We compared age- and sex- adjusted HRQoL (SF-36 domain scores; EQ-VAS; EQ-Index) to the Dutch normative population, and estimated the prevalences of current depression (either: history of depression or current use of antidepressants, with high score on CES-D [≥16] and/or HADS-D [≥8]; or high score on both depression questionnaires) and anxiety (HADS-A ≥ 8)., Results: We included 179 patients: 77 with sCAA (mean age: 72 years, women: 36%), 31 with mixed CAA-HTA (68 years, women: 29%), and 71 with D-CAA (56 years, women: 52%, symptomatic: 35 [49%]). The SF-36 profiles of all patient groups were similar, negatively differing from the norm in emotional role functioning, social functioning and vitality. The EQ-VAS score of patients (mean [SD] sCAA: 76 [16], D-CAA: 77 [15]) was similar to the norm, as was the EQ-Index score. Fifteen patients with sCAA (23%; 95% confidence interval [CI] 13%-33%), seven with mixed CAA-HTA (27%; 95% CI 10%-44%) and eight with D-CAA (14%; 95% CI 5%-22%) were noted as having depression. The prevalences of anxiety and depression were equivalent., Conclusions: We found that CAA influenced emotional role functioning and aspects linked to social engagement consistently across its subtypes. One quarter of patients exhibited depressive or anxiety symptoms. Recognizing these impacted domains could enhance overall well-being., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from Abbvie and Teva. Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer. Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs. Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of Journal of Headache Pain, and associate editor of Brain. Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an associate editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the editorial board for Journal of Headache Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society. Eric Liebler declares consulting fees from ElecroCore, Inc. Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health. Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant. Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler. Esme Ekizoğlu declares honoraria from Allergan-AbbVie. David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer. Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain. Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva. Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita Pharm. Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma. Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, International Headache Society (IHS), National Institute for Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB. Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris. Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis. Mi Ji Lee declares consulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu. Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan. Daniele Martinelli declares honoraria from AbbVie and Lundbeck. Teshamae S. Monteith has the following disclosures over the past three years: clinical trial site principal investigator for studies sponsored by Abbvie, Eli Lilly, Ipsen and Rehaler, participation in advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. Dr Monteith has provided unpaid service on the board of directors for the International Headache Society (2021-2023) and currently on the executive board for the Florida Society of Neurology. Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva. Aynur Özge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan. Mario Peres accepted honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. MP is president of ABRACES. Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva. Todd J. Schwedt declares grants/contracts with American Heart Association, Amgen, Henry Jackson Foundation, National Headache Foundation, National Institutes of Health, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, United States Department f Defense, American Migraine Foundation and Mayo Clinic. Consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix. He declares royalties from UpToDate and stock options from Aural. Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly. Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma. Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea. Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent. Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen. Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from AbbVie, Eli Lilly, Dompé, Ipsen, Lundbeck, Pfizer, Medscape, Teva. All remaining authors report no disclosures or conflicts of interest

Introduction: MRI rating criteria for small vessel disease markers include definitions for microbleeds and macrobleeds but do not account for small (&lt;10 mm) hemorrhages with a cystic cavity and/or irregular shape. Such hemorrhages, however, are often present in patients with cerebral amyloid angiopathy (CAA). In this study, we aimed to investigate the frequency, diameter, and volume distribution of these hemorrhages (which we called mesobleeds) in patients with CAA., Methods: We selected participants with Dutch-type hereditary CAA (D-CAA) and sporadic CAA (sCAA) and scored microbleeds, mesobleeds, and macrobleeds on 3T susceptibility-weighted images MRI. Hemorrhage diameter and volume were calculated in a subset of participants using a semi-automatic tool; their distribution was evaluated on a logarithmic scale., Results: We included 25 participants with D-CAA (mean age 56 years) and 25 with sCAA (mean age 73 years). In total, 11,007 microbleeds, 602 mesobleeds, and 195 macrobleeds were observed. Eighty-two percent of participants had ≥1 mesobleed. Hemorrhage diameter and volume were calculated in four participants with 272 microbleeds (median diameter 1.52 mm, volume 0.004 mL), 84 mesobleeds (median diameter 5.61 mm, volume 0.06 mL), and 37 macrobleeds (median diameter 19.58 mm, volume 1.33 mL). Mesobleed diameter and volume were larger than microbleeds (optimal cut-off 0.02 mL) but showed overlap with macrobleeds., Conclusion: Hemorrhages &lt;10 mm with an irregular shape and/or cystic cavity are frequently found in participants with CAA and have a distinct diameter and volume distribution. We propose to name these hemorrhage mesobleeds and to rate them separately from micro- and macrobleeds. Future research is necessary to investigate their pathophysiology and prognostic value., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: We investigated whether quantitative electroencephalography (qEEG) correlates with cognition and cortical superficial siderosis (cSS) in cerebral amyloid angiopathy., Methods: We included patients with sporadic (sCAA) and hereditary Dutch-type CAA (D-CAA). Spectral measures and the phase lag index (PLI) were analyzed on qEEG. Cognition was assessed with the MoCA and cSS presence was scored on 3T-MRI. Linear regression analyses were performed to investigate these qEEG measures and cognition. Independent samples T-tests were used to analyze the qEEG measure differences between participants with and without cSS., Results: We included 92 participants (44 D-CAA; 48 sCAA). A lower average peak frequency (β[95 %CI] = 0.986[0.252-1.721]; P = 0.009) and a higher spectral ratio (β[95 %CI] = -0.918[-1.761--0.075]; P = 0.033) on qEEG correlated with a lower MoCA score, irrespective of a history of symptomatic intracerebral hemorrhage (sICH). The PLI showed no correlation to the MoCA. qEEG slowing was not different in those with or without cSS., Conclusions: Spectral qEEG (but not PLI) reflects cognitive performance in patients with CAA with and without a history of sICH. We found no association between qEEG slowing and cSS., Significance: qEEG could be a valuable biomarker, especially in challenging cognitive testing situations in CAA, and a potential predictive tool in future studies., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications., Methods: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group., Results: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained., Conclusion: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from TEVA.Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer.Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs.Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of the Journal of Headache and Pain, and associate editor of Brain.Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an Associate Editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the Editorial Board for the Journal of Headache and Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society.Eric Liebler declares consulting fees from ElecroCore, Inc.Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant.Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler.Esme Ekizoğlu declares honoraria from Allergan‐AbbVie.David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer.Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain.Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva.Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita pharm.Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma.Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, IHS, National Institute of Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB.Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris.Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis.Mi Ji Lee declares onsulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu.Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan.Daniele Martinelli declares honoraria from AbbVie and Lundbeck.Teshamae S. Monteith has the following disclosures over the past 3 years: clinical trial site principal investigator for studies sponsored by Eli Lilly and AbbVie (all paid to the institution), participation in an advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. TSM has provided unpaid service on the board of directors for the International Headache Society (2021–2023) and currently on the executive board for the Florida Society of Neurology.Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva.Aynur Ozge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan.Mario Peres accepted honoraria for lectures, presentations, speakers bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. Mario Peres is president of ABRACES.Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva.Todd J. Schwedt declares grants/contracts with AHA, Amgen, Henry Jackson Foundation, NIH, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, US Dept. of Defense, AMF, NHF and Mayo Clinic with consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix.Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly.Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma.Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea.Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent.Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen.Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from Eli Lilly, Dompé, Teva, Lundbeck, Pfizer, Medscape.All remaining authors report no disclosures or conflicts of interest.

Introduction: Dutch-type cerebral amyloid angiopathy (D-CAA) is an autosomal dominant hereditary form of CAA causing intracerebral hemorrhage (ICH) and cognitive decline. The age of onset of ICH in D-CAA mutation carriers is strikingly variable and ranges from late thirties up to 70 years. We investigated the presence of genetic anticipation and assessed the influence of parental age at onset and sex on age of ICH onset in offspring., Methods: We included (potential) D-CAA mutation carriers from our prospective D-CAA family database. Participants were sent a questionnaire by mail and asked for the onset age of symptomatic ICH and the onset age of symptomatic ICH of their affected first-degree relative(s), their siblings and affected parent. We used a Cox regression model with the age of onset of the parent as the covariate and the sex of the offspring as the factor. Next, we replaced the sex of the offspring with a factor with four levels: mother/daughter, mother/son, father/daughter, and father/son. We used a random effect per household., Results: A total of 66 respondents completed the questionnaire. Reported mean age of first symptomatic ICH was similar (both 52 years, p = 0.87) for D-CAA parents (n = 60) and their offspring (n = 100). Offspring with a mother with D-CAA seemed to have an earlier ICH onset (50 years, standard deviation [SD] ± 7) than offspring with a paternal inheritance (54 years, SD ± 6, p = 0.03). There was no association between onset of first ICH of the parent and offspring after adding sex of the offspring to the Cox regression model: hazard ratio 0.99, 95% CI: 0.94-1.03, p = 0.51. The interaction between parent's sex and child's sex was not significant (p = 0.70). The results with and without random effect were essentially identical., Conclusion: We found no indication for genetic anticipation in D-CAA in general, although maternal inheritance seemed to be associated with an earlier ICH onset., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Telemedicine offers a promising solution to enhance the delivery and personalization of headache care. Integrating electronic (e-)tools enables the objective monitoring of migraine. Objectives: This study aims to demonstrate the relevance of e-tools for personalized headache care, assess patient and caregiver compliance and satisfaction, and present their use in enhancing care. Methods: Firstly, a systematic review was performed to validate the diagnostic accuracy of e-diaries for diagnosing migraine. Secondly, we collected e-diary data prospectively from diagnosed adult migraine patients at the Leiden Headache Center. Finally, questionnaires were sent to evaluate satisfaction of patients and health care providers with the Leiden e-headache diary and video consultations. Results: In the systematic review, the Leiden Headache Center's e-diary was the only validated tool. Patients ( n = 1,009) were followed for a median of 181 days (interquartile range [IQR] 84-240). Compliance was 96.4% (IQR 85.2 - 99.1%), with 10.8% of days missing. Factors positively associated with compliance were older age ( p < 0.001), female sex ( p < 0.001), higher e-diary grade ( p < 0.001), and clinical use ( p = 0.04). The e-diary received a median score of 8/10 and was well-liked by patients ( n = 535) and providers ( n = 23). Video consultations were a good alternative for physical visits according to 76.9% of patients and 84.6% of providers. Conclusion: Validated e-headache diaries and video consultations in telemedicine enhance headache care accessibility, providing convenient care at preferred times and locations.

Background: Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)., Methods: NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning., Results: Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*10 2  pg/mL vs. 3.9*10 2  pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*10 2  pg/mL vs. 1.9*10 2  pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (β[95%CI] = - 2.86 [- 5.58 to - 0.13], p = 0.04 and β[95%CI] =  - 6.85 [- 11.54 to - 2.15], p = 0.01, respectively) and prolonged psychomotor test times (β[95%CI] = 6.71 [0.78-12.65], p = 0.03 and β[95%CI] = 13.84 [3.09-24.60], p = 0.01)., Discussion: Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls., (© 2024. The Author(s).)

Migraine is a highly prevalent brain condition with paroxysmal changes in brain excitability believed to contribute to the initiation of an attack. The attacks and their unpredictability have a major impact on the lives of patients. Clinical management is hampered by a lack of reliable predictors for upcoming attacks, which may help in understanding pathophysiological mechanisms to identify new treatment targets that may be positioned between the acute and preventive possibilities that are currently available. So far, a large range of studies using conventional hospital-based EEG recordings have provided contradictory results, with indications of both cortical hyper- as well as hypo-excitability. These heterogeneous findings may largely be because most studies were cross-sectional in design, providing only a snapshot in time of a patient's brain state without capturing day-to-day fluctuations. The scope of this narrative review is to (i) reflect on current knowledge on EEG changes in the context of migraine, the attack cycle, and underlying pathophysiology; (ii) consider the effects of migraine treatment on EEG features; (iii) outline challenges and opportunities in using EEG for monitoring attack susceptibility; and (iv) discuss future applications of EEG in home-based settings.

Background: Patients with sporadic cerebral amyloid angiopathy (sCAA) frequently report cognitive or neuropsychiatric symptoms. The aim of this study is to investigate whether in patients with sCAA, cognitive impairment and neuropsychiatric symptoms are associated with a cerebrospinal fluid (CSF) biomarker profile associated with Alzheimer's disease (AD)., Methods: In this cross-sectional study, we included participants with sCAA and dementia- and stroke-free, age- and sex-matched controls, who underwent a lumbar puncture, brain MRI, cognitive assessments, and self-administered and informant-based-questionnaires on neuropsychiatric symptoms. CSF phosphorylated tau, total tau and Aβ42 levels were used to divide sCAA patients in two groups: CAA with (CAA-AD+) or without a CSF biomarker profile associated with AD (CAA-AD-). Performance on global cognition, specific cognitive domains (episodic memory, working memory, processing speed, verbal fluency, visuoconstruction, and executive functioning), presence and severity of neuropsychiatric symptoms, were compared between groups., Results: sCAA-AD+ (n=31; mean age: 72 ± 6; 42%, 61% female) and sCAA-AD- (n=23; 70 ± 5; 42% female) participants did not differ with respect to global cognition or type of affected cognitive domain(s). The number or severity of neuropsychiatric symptoms also did not differ between sCAA-AD+ and sCAA-AD- participants. These results did not change after exclusion of patients without prior ICH., Conclusions: In participants with sCAA, a CSF biomarker profile associated with AD does not impact global cognition or specific cognitive domains, or the presence of neuropsychiatric symptoms., (© 2024. The Author(s).)

Background: Anti-CGRP-(receptor-)monoclonal antibodies (anti-CGRP(R)-mAbs) represent a novel class of drugs for migraine treatment, but their long-term cerebrovascular and cardiovascular (CV) safety warrants further examination., Methods: In this observational cohort study we assessed the CV safety for erenumab and fremanezumab in a real-world setting during a follow-up period of at least 1 year. Patients with hypertension or CV history were excluded. We conducted ECGs and collected clinical data at treatment initiation and thereafter every 3 months, including liver and kidney function, lipid-, electrolyte-and glucose levels., Results: Among patients receiving erenumab ( n = 101) or fremanezumab ( n = 92), 3.1% (6/193) developed abnormal ECGs or CV adverse events. Of these, three (1.6%) experienced moderate to severe CV adverse events (cerebellar stroke, spontaneous coronary artery dissection, and pericarditis) and discontinued treatment. The remaining three (1.6%) developed non-threatening ECG abnormalities without physical complaints. No significant changes were observed in liver and kidney function, lipid-, electrolyte-, or glucose levels., Discussion: We observed CV events in 1.6% of patients with 1.5-year follow-up of anti-CGRP(R)-mAbs treatment. We advise awareness regarding CV events in patients with migraine undergoing CGRP-targeted treatment, not as a confirmation of increased risk but as a proactive measure to address potential multifactorial influences., Competing Interests: BA and GT report independent support from the Dutch Research Council (849200007) and the Dutch Brain Foundation (HA2017.01.05). GT reports consultancy or industry support from Abbvie/Allergan, Lilly, Lundbeck, Novartis, Pfizer, Teva, and Interactive Studios BV, and independent support from the European Community, Dutch Heart and Brain Foundations, Dutch Research Council, and Dioraphte. MO received payment for lectures from TEVA, Novo Nordic, Boehringer & Ingelheim and AstraZeneca. AM reports consultancy or industry support from Lilly, Novartis, Teva, and independent support from the Dutch Brain Foundation (HA2017.01.05) and the Dutch Research Council (849200007). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Van Der Arend, Van Veelen, De Ruijter, Olsen, MaassenVanDenBrink and Terwindt.)

Background: Neurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in cerebral amyloid angiopathy (CAA), but studies investigating the potential of NFL and GFAP as markers for CAA are lacking. We aimed to investigate NFL and GFAP as biomarkers for neuroaxonal damage and astrocytosis in CAA., Methods: For this cross-sectional study serum and cerebrospinal fluid (CSF) samples were collected between 2010 and 2020 from controls, (pre)symptomatic Dutch-type hereditary (D-CAA) mutation-carriers and participants with sporadic CAA (sCAA) from two prospective CAA studies at two University hospitals in the Netherlands. NFL and GFAP levels were measured with Simoa-assays. The association between NFL and GFAP levels and age, cognitive performance (MoCA), CAA-related MRI markers (CAA-CSVD-burden) and Aβ40 and Aβ42 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and ≥55 years to match the specific groups., Results: We included 187 participants: 28 presymptomatic D-CAA mutation-carriers (mean age 40 years), 29 symptomatic D-CAA participants (mean age 58 years), 59 sCAA participants (mean age 72 years), 33 controls < 55 years (mean age 42 years) and 38 controls ≥ 55 years (mean age 65 years). In presymptomatic D-CAA, only GFAP in CSF (7.7*10 3 pg/mL vs. 4.4*10 3 pg/mL in controls; P<.001) was increased compared to controls. In symptomatic D-CAA, both serum (NFL:26.2pg/mL vs. 12.5pg/mL; P=0.008, GFAP:130.8pg/mL vs. 123.4pg/mL; P=0.027) and CSF (NFL:16.8*10 2 pg/mL vs. 7.8*10 2 pg/mL; P=0.01 and GFAP:11.4*10 3 pg/mL vs. 7.5*10 3 pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only NFL levels were increased compared to controls in both serum (25.6pg/mL vs. 12.5pg/mL; P=0.005) and CSF (20.0*10 2 pg/mL vs 7.8*10 2 pg/mL; P=0.008). All levels correlated with age. Serum NFL correlated with MoCA (P=0.008) and CAA-CSVD score (P<.001). NFL and GFAP in CSF correlated with Aβ42 levels (P=0.01/0.02)., Conclusions: GFAP level in CSF is an early biomarker for CAA and is increased years before symptom onset. NFL and GFAP levels in serum and CSF are biomarkers for advanced CAA., (© 2024. The Author(s).)