Background and purposeThe aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to... Show moreBackground and purposeThe aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response.MethodsPatients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E-headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS-D and CES-D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti-CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables.ResultsIn total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti-CGRP medication was positively associated with a reduction in the HADS-D (β = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES-D (β = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09).ConclusionAnti-CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab. Show less
Background and purposePatients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic... Show moreBackground and purposePatients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported.MethodsIn this cohort study, patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands were included. The frequency and recurrence rates of neurological manifestations before and after initiation of tumor necrosis factor α (TNF-α) inhibiting therapy were analyzed.ResultsTwenty-nine patients were included with a median age at presentation of 5 years (interquartile range 1–17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. Transient ischaemic attack (TIA)/ischaemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischaemic strokes occurred in 12 patients, one after initiation of TNF-α inhibiting therapy and one whilst switching between TNF-α inhibitors. None was large-vessel occlusion stroke. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischaemic strokes and seldom recurred after initiation of TNF-α inhibiting therapy.ConclusionsNeurological manifestations, especially TIA/ischaemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness amongst neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischaemic stroke without an identified cause should be considered. Show less
Tjerkstra, M.A.; Mueller, M.C.A.; Coert, B.A.; Hoefnagels, F.W.A.; Vergouwen, M.D.I.; Vliet, P. van; ... ; Verbaan, D. 2023
Background: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its... Show moreBackground: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI.Methods: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4-6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses.Results: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17-2.27) and at day 5 after DCI 1.04 (95% CI 0.84-1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results.Conclusions: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3-/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI. Show less
Verhagen, I.E.; Lentsch, S.D.; Arend, B.W.H. van der; Cessie, S. le; MaassenVanDenBrink, A.; Terwindt, G.M. 2023
Background and purpose Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies effectively reduce overall migraine attack frequency, but whether there are differences in effect between... Show moreBackground and purpose Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies effectively reduce overall migraine attack frequency, but whether there are differences in effect between perimenstrual and nonperimenstrual migraine days has not been investigated.Methods We performed a single-arm study among women with migraine. Participants were followed with electronic E-diaries during one (pretreatment) baseline month and 6 months of treatment with either erenumab or fremanezumab. Differences in treatment effect on perimenstrual and nonperimenstrual migraine days were assessed using a mixed effects logistic regression model, with migraine day as dependent variable; treatment, menstrual window, and an interaction term (treatment x menstrual window) as fixed effects; and patient as a random effect.Results There was no interaction between the menstrual window and treatment effect, indicating that the reduction in migraine days under treatment was similar during the menstrual window and the remainder of the menstrual cycle (odds ratio for treatment = 0.44, 95% confidence interval = 0.38-0.51).Conclusions Our findings support prophylactic use of anti-CGRP (receptor) antibodies for women with menstrual migraine, as this leads to consistent reductions in number of migraine days during the entire menstrual cycle. Show less
Fanciulli, A.; Leys, F.; Skoric, M.K.; Carneiro, D.R.; Calandra-Buonaura, G.; Camaradou, J.; ... ; Collaborators European Network Neu 2023
Background and purposeThe objective was to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on European clinical autonomic practice.MethodsEighty-four neurology-driven or... Show moreBackground and purposeThe objective was to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on European clinical autonomic practice.MethodsEighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021.ResultsForty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every third center reported major adverse events due to postponed examinations or visits. The most frequent newly diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome, orthostatic hypotension and recurrent vasovagal syncope, deemed to be likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new onset of orthostatic intolerance but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently postural orthostatic tachycardia syndrome and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50%–100% recovery rates at follow-up.ConclusionsCardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, whilst the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints. Show less
Background and purpose Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in MG is... Show moreBackground and purpose Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in MG is unclear. We sought to evaluate this landscape through systematically assessing the evidence, testing the impact of predefined variables on any relationship, and augmenting with expert opinion. Methods In October 2020, a forum of leading clinicians and researchers in neurology from across Europe (Expert Forum for Rare Autoantibodies in Neurology in Myasthenia Gravis) participated in a series of virtual meetings that took place alongside the conduct of a systematic literature review (SLR). Results Forty-two studies were identified meeting inclusion criteria. Of these, 10 reported some correlation between a patient's autoantibody level and disease severity. Generally, decreased autoantibody levels (acetylcholine receptor, muscle-specific kinase, and titin) were positively and significantly correlated with improvements in disease severity (Quantitative Myasthenia Gravis score, Myasthenia Gravis Composite score, Myasthenia Gravis Activities of Daily Living score, Myasthenia Gravis Foundation of America classification). Given the limited evidence, testing the impact of predefined variables was not feasible. Conclusions This first SLR to assess whether a correlation exists between autoantibody levels and disease activity in patients with MG has indicated a potential positive correlation, which could have clinical implications in guiding treatment decisions. However, in light of the limited and variable evidence, we cannot currently recommend routine clinical use of autoantibody level testing in this context. For now, patient's characteristics, clinical disease course, and laboratory data (e.g., autoantibody status, thymus histology) should inform management, alongside patient-reported outcomes. We highlight the need for future studies to reach more definitive conclusions on this relationship. Show less
Habek, M.; Leys, F.; Skoric, M.K.; Carneiro, D.R.; Calandra-Buonaura, G.; Camaradou, J.; ... ; European Network Clinical ANS Labs 2022
Background and purpose: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries.... Show moreBackground and purpose: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. Methods: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. Results: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). Conclusions: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe. Show less
Background and purpose Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused... Show moreBackground and purpose Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused medication. We assessed in a double-blind manner the efficacy of a behavioural intervention during medication withdrawal therapy. Methods In this concealed, double-blind, randomized controlled trial in medication overuse headache, conducted at the Leiden University Medical Centre, we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy. Maximal intervention consisted of an intensive contact schedule, comprising education, motivational interviewing, and value-based activity planning during 12 weeks of withdrawal therapy. Minimal intervention consisted of a short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating botulinum toxin A. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period. Results We enrolled 179 patients (90 maximal, 89 minimal intervention). At Week 12, most patients achieved withdrawal in both groups (82/90 [93%] maximal intervention vs. 75/89 [86%] minimal intervention, odds ratio = 2.44, 95% confidence interval [CI] = 0.83-7.23, p = 0.107). At Week 24, patients in the maximal intervention group had fewer medication days (mean difference = -2.23, 95% CI = -3.76 to -0.70, p = 0.005). This difference receded over time. Change in monthly migraine days did not differ between groups (-6.75 vs. -6.22). Conclusions This trial suggests modest benefit of behavioural intervention by a headache nurse during withdrawal therapy for medication overuse headache, to reduce acute medication use during and shortly after intervention, but extension seems warranted for a prolonged effect Show less
Background and purpose Differentiation between acute flaccid myelitis (AFM) and Guillain-Barre syndrome (GBS) can be difficult, particularly in children. Our objective was to improve the diagnostic... Show moreBackground and purpose Differentiation between acute flaccid myelitis (AFM) and Guillain-Barre syndrome (GBS) can be difficult, particularly in children. Our objective was to improve the diagnostic accuracy by giving recommendations based on a comparison of clinical features and diagnostic criteria in children with AFM or GBS. Methods A cohort of 26 children with AFM associated with enterovirus D68 was compared to a cohort of 156 children with GBS. The specificity of the Brighton criteria, used for GBS diagnosis, was evaluated in the AFM cohort and the specificity of the Centers for Disease Control and Prevention (CDC) AFM diagnostic criteria in the GBS cohort. Results Children with AFM compared to those with GBS had a shorter interval between onset of weakness and nadir (3 vs. 8 days, p < 0.001), more often had asymmetric limb weakness (58% vs. 0%, p < 0.001), and less frequently had sensory deficits (0% vs. 40%, p < 0.001). In AFM, cerebrospinal fluid leukocyte counts were higher, whereas protein concentrations were lower. Spinal cord lesions on magnetic resonance imaging were only found in AFM patients. No GBS case fulfilled CDC criteria for definite AFM. Of the AFM cases, 8% fulfilled the Brighton criteria for GBS, when omitting the criterion of excluding an alternate diagnosis. Conclusions Despite the overlap in clinical presentation, we found distinctive early clinical and diagnostic characteristics for differentiating AFM from GBS in children. Diagnostic criteria for AFM and GBS usually perform well, but some AFM cases may fulfill clinical diagnostic criteria for GBS. This underlines the need to perform diagnostic tests early to exclude AFM in children suspected of atypical GBS. Show less
Background and purpose We investigated whether the annual volume of patients with acute ischemic stroke referred from a primary stroke center (PSC) for endovascular treatment (EVT) is associated... Show moreBackground and purpose We investigated whether the annual volume of patients with acute ischemic stroke referred from a primary stroke center (PSC) for endovascular treatment (EVT) is associated with treatment times and functional outcome. Methods We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) registry (2014-2017). We included patients with acute ischemic stroke of the anterior circulation who were transferred from a PSC to a comprehensive stroke center (CSC) for EVT. We examined the association between EVT referral volume of PSCs and treatment times and functional outcome using multivariable regression modeling. The main outcomes were time from arrival at the PSC to groin puncture (PSC-door-to-groin time), adjusted for estimated ambulance travel times, time from arrival at the CSC to groin puncture (CSC-door-to-groin time), and modified Rankin Scale (mRS) score at 90 days after stroke. Results Of the 3637 patients in the registry, 1541 patients (42%) from 65 PSCs were included. Mean age was 71 years (SD +/- 13.3), median National Institutes of Health Stroke Scale score was 16 (interquartile range [IQR]: 12-19), and median time from stroke onset to arrival at the PSC was 53 min (IQR: 38-90). Eighty-three percent had received intravenous thrombolysis. EVT referral volume was not associated with PSC-door-to-groin time (adjusted coefficient: -0.49 min/annual referral, 95% confidence interval [CI]: -1.27 to 0.29), CSC-door-to-groin time (adjusted coefficient: -0.34 min/annual referral, 95% CI: -0.69 to 0.01) or 90-day mRS score (adjusted common odds ratio: 0.99, 95% CI: 0.96-1.01). Conclusions In patients transferred from a PSC for EVT, higher PSC volumes do not seem to translate into better workflow metrics or patient outcome. Show less
Background and purpose New prophylactics for migraine, targeting calcitonin gene-related peptide (CGRP), have recently emerged. Real-world data are important for a comprehensive understanding of... Show moreBackground and purpose New prophylactics for migraine, targeting calcitonin gene-related peptide (CGRP), have recently emerged. Real-world data are important for a comprehensive understanding of treatment response. We assessed the consistency of response to erenumab, a monoclonal CGRP receptor antibody, in a real-world setting, in order to determine which patients may be considered responders in clinical practice. Methods All erenumab-treated patients (n = 100) completed a time-locked daily electronic diary, and an automated algorithm was used to monitor treatment response. Monthly migraine days (MMD), non-migrainous headache days, days of acute medication use (MAMD), well-being and coping with pain were assessed for a 6-month period. The primary outcome was reduction in MMD compared to baseline. Results The numbers of MMD and MAMD decreased in all months, in both episodic and chronic migraine patients, compared to baseline (p < 0.001), while general well-being (p < 0.001) and coping with pain (p < 0.001) also improved. Of all patients, 36% had an MMD reduction of >= 50% in >= 3/6 months, and 6% had such a reduction in all 6 months. For a >= 30% MMD reduction, the figures were 60% and 24%, respectively. Almost 90% of patients with an average MMD reduction of >= 30% over the first 3 months had a sustained response in the last 3 months. In addition, 20% of patients without an initial response (average <30%), had a delayed response (average >= 30%) in the last 3 months. Conclusion Erenumab was effective in migraine patients who were highly refractory to previous prophylactics. As a practical guideline, we propose that treatment be continued for at least 6 months and that patients with a >= 30% MMD reduction in at least half of the treatment period should be considered to be responders. Show less
Rakusa, M.; Sieminski, M.; Rakusa, S.; Falup-Pecurariu, C.; Fronczek, R.; Hidalgo, H.; ... ; Kallweit, U. 2021
Objectives Sleep-wake disorders are common in the general population and in most neurological disorders but are often poorly recognized. With the hypothesis that neurologists do not get sufficient... Show moreObjectives Sleep-wake disorders are common in the general population and in most neurological disorders but are often poorly recognized. With the hypothesis that neurologists do not get sufficient training during their residency, the Young European Sleep Neurologist Association (YESNA) of the European Academy of Neurology (EAN) performed a survey on postgraduate sleep education. Methods A 16-item questionnaire was developed and distributed among neurologists and residents across European countries. Questions assessed demographic, training and learning preferences in sleep disorders, as well as a self-evaluation of knowledge based on five basic multiple-choice questions (MCQs) on sleep-wake disorders. Results The questionnaire was completed by 568 participants from 20 European countries. The mean age of participants was 31.9 years (SD 7.4 years) and was composed mostly of residents (73%). Three-quarters of the participants reported undergraduate training in sleep medicine, while fewer than 60% did not receive any training on sleep disorders during their residencies. Almost half of the participants (45%) did not feel prepared to treat neurological patients with sleep problems. Only one-third of the participants correctly answered at least three MCQs. Notably, 80% of participants favoured more education on sleep-wake disorders during the neurology residency. Conclusions Education and knowledge on disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. The results of our study may be useful for improving the European neurology curriculum and other postgraduate educational programmes. Show less
Background and purpose Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines... Show moreBackground and purpose Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. Methods The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. Results A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. Conclusion The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail. Show less
Background and purpose This study was undertaken to investigate migraine prevalence in persons with hallucinogen persisting perception disorder (HPPD) presenting as visual snow syndrome (VSS)... Show moreBackground and purpose This study was undertaken to investigate migraine prevalence in persons with hallucinogen persisting perception disorder (HPPD) presenting as visual snow syndrome (VSS).Methods Persons with visual snow as a persisting symptom after illicit drug use (HPPD) were recruited via a Dutch consulting clinic for recreational drug use. A structured interview on (visual) perceptual symptomatology, details of drugs use, and medical and headache history was taken. As a control group, persons with visual snow who had never used illicit drugs prior to onset were included. The primary outcome was lifetime prevalence of migraine. Symptom severity was evaluated by the Visual Snow Handicap Inventory (VHI), a 25-item questionnaire.Results None of the 24 HPPD participants had migraine, whereas 20 of 37 (54.1%) controls had migraine (p < 0.001). VHI scores did not differ significantly between the two groups; in both groups, the median score was 38 of 100. In most HPPD cases (17/24, 70.9%), visual snow had started after intake of ecstasy; other psychedelic drugs reported included cannabis, psilocybin mushrooms, amphetamine, 4-fluoroamphetamine, 3-methylmethcathinone, 4-Bromo-2,5-dimethoxypenethylamine, and nitrous oxide.Conclusions Whereas none of the HPPD participants had migraine, more than half of the visual snow controls without prior use of illicit drugs had migraine. This suggests that at least partly different pathophysiological factors play a role in these disorders. Users of ecstasy and other hallucinogens should be warned of the risk of visual snow. Further studies are needed to enhance understanding of the underlying neurobiology of HPPD and VSS to enable better management of these conditions. Show less
Kuitwaard, K.; Doorn, P.A. van; Bengrine, T.; Rijs, W. van; Baas, F.; Nagelkerke, S.Q.; ... ; Huizinga, R. 2021
Background and purpose Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous... Show moreBackground and purpose Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange are proven effective treatments for CIDP. The clinical response to IVIg is variable between patients and currently unexplained. Finding biomarkers related to treatment response can help to understand the diversity of CIDP and personalise treatment choice.Methods We investigated whether genetic variation between patients may explain some of these differences in treatment response. Based on previous publications, we selected six candidate genes that might affect immune and axonal functions, IVIg metabolism, and treatment response in CIDP. Genetic variants were assessed in 172 CIDP patients treated with at least one course of IVIg (2 g/kg). A response to IVIg was defined by >= 1 grade improvement on the modified Rankin Scale. Blood samples were tested for variations in CNTN2, PRF1, FCGRT, FCGR2B, GJB1, and SH2D2A genes.Results In univariate analysis, patients with the FCGR2B promoter variant 2B.4/2B.1 responded more often to IVIg than patients with the 2B.1/2B.1 variant (odds ratio [OR] = 6.9, 95% confidence interval [CI] = 1.6-30; p = 0.003). Patients with the p.(Ala91Val) variant of PRF1 were less often IVIg responsive (OR = 0.34, 95% CI = 0.13-0.91; p = 0.038). In multivariate analysis, both PRF1 and FCGR2B showed discriminative ability to predict the chance of IVIg response (area under the curve = 0.67).Conclusions Variations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP. Show less
Etten, E.S. van; Boer, I. de; Steenmeijer, S.R.; Al-Nofal, M.; Wermer, M.J.H.; Notting, I.C.; Terwindt, G.M. 2020
Background and purpose Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages... Show moreBackground and purpose Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers. Methods Twenty-one D-CAA mutation carriers (n = 8 presymptomatic,n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of >= 1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age. Results The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) mu m vs. 99 (87-108) mu m;P = 0.006]. Both presymptomatic [111 (93-122) mu m vs. 131 (123-143) mu m;P < 0.001] and symptomatic carriers [119 (95-128) mu m vs. 131 (123-143) mu m;P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls. Conclusions Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression. Show less
Background and purpose Migraine is recognized as a vascular risk factor, especially in women. Presumably, migraine, stroke and cardiovascular events share pathophysiological mechanisms. Self... Show moreBackground and purpose Migraine is recognized as a vascular risk factor, especially in women. Presumably, migraine, stroke and cardiovascular events share pathophysiological mechanisms. Self-reported cold extremities were investigated as a marker for vascular dysfunction in migraine. Secondly, it was hypothesized that suffering from cold extremities affects sleep quality, possibly exacerbating migraine attack frequency.Methods In this case-control study, a random sample of 1084 migraine patients and 348 controls (aged 22-65 years) from the LUMINA migraine cohort were asked to complete questionnaires concerning cold extremities, sleep quality and migraine.Results A total of 594 migraine patients and 199 controls completed the questionnaires. In women, thermal discomfort and cold extremities (TDCE) were more often reported by migraineurs versus controls (odds ratio 2.3, 95% confidence interval 1.4-3.7; P < 0.001), but not significantly so in men (odds ratio 2.5, 95% confidence interval 0.9-6.9; P = 0.09). There was no difference in TDCE comparing migraine with or without aura. Female migraineurs who reported TDCE had higher attack frequencies compared to female migraineurs without TDCE (4 vs. 3 attacks per month; P = 0.003). The association between TDCE and attack frequency was mediated by the presence of difficulty initiating sleep (P = 0.02).Conclusion Women with migraine more often reported cold extremities compared with controls, possibly indicating a sex-specific vascular vulnerability. Female migraineurs with cold extremities had higher attack frequencies, partly resulting from sleep disturbances. Future studies need to demonstrate whether cold extremities in female migraineurs are a predictor for cardiovascular and cerebrovascular events. Show less
Mancuso, M.; Arnold, M.; Bersano, A.; Burlina, A.; Chabriat, H.; Debette, S.; ... ; Markus, H.S. 2020
Background and purpose Guidelines on monogenic cerebral small-vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of... Show moreBackground and purpose Guidelines on monogenic cerebral small-vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of Neurology, a group of experts has provided recommendations on selected monogenic cSVDs, i.e. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant High Temperature Requirement A Serine Peptidase 1 (HTRA1), cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), Fabry disease, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and type IV collagen (COL4)A1/2.Methods We followed the Delphi methodology to provide recommendations on several unanswered questions related to monogenic cSVD, including genetic testing, clinical and neuroradiological diagnosis, and management.Results We have proposed 'red-flag' features suggestive of a monogenic disease. General principles applying to the management of all cSVDs and specific recommendations for the individual forms of monogenic cSVD were agreed by consensus.Conclusions The results provide a framework for clinicians involved in the diagnosis and management of monogenic cSVD. Further multicentre observational and treatment studies are still needed to increase the level of evidence supporting our recommendations. Show less
Background and purpose Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication-refractory motor complications in patients with Parkinson's disease. However, it... Show moreBackground and purpose Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication-refractory motor complications in patients with Parkinson's disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality. Methods Main databases were systematically searched up to March 2019 to identify studies that investigated factors associated with QoL after STN DBS in patients with idiopathic Parkinson's disease. Results In all, 869 studies were identified, of which 18 fulfilled the inclusion criteria. Higher QoL after DBS appears to be associated with a large preoperative difference between ON and OFF motor function in some studies, although there was no clear association of severity of motor function or motor complications with postoperative QoL. Lower severity of dyskinesias was associated with greater postoperative QoL improvement but has been insufficiently studied. Higher baseline QoL was suggestive of higher postoperative QoL. Four studies suggested that older age at surgery is associated with a lower improvement, although six other studies reported no association. No or limited evidence was found for cognitive impairment or psychiatric dysfunction. Conclusion Various relative contraindications for STN DBS such as cognitive impairment and psychiatric dysfunction appear to be unrelated to postoperative QoL. However, the lack of clear correlations with disease-related variables suggests that QoL may be individually influenced by other factors, indicating that an ideal preoperative patient profile with regard to QoL improvement cannot be readily provided. Show less
