cover image European Journal of Neurology

European Journal of Neurology

2024 - Volume 31
Issue 7 | July 2024
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ISSUE INFORMATION

Issue Information

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Article first published online:
07 Jun 2024 | DOI: 10.1111/ene.15883

LETTER TO THE EDITOR

Type 2 diabetes mellitus duration and subsequent risk of Alzheimer disease

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Authors:
Tomoyuki Kawada
Article first published online:
07 Mar 2024 | DOI: 10.1111/ene.16274

CONSENSUS STATEMENT

Background and purpose

Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy.

Methods

A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement.

Results

A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in disease, vigabatrin in patients with γ‐aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted.

Conclusions

These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug‐related adverse events in individuals living with PMD‐related epilepsy.

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Authors:
Michelangelo Mancuso, Maria T. Papadopoulou, Yi Shiau Ng, Anna Ardissone, Marcello Bellusci, Enrico Bertini, Lidia Di Vito, Teresinha Evangelista, Carmen Fons, Omar Hikmat, Rita Horvath, Thomas Klopstock, Cornelia Kornblum, Costanza Lamperti, Laura Licchetta, Maria Judit Molnar, Kristin N. Varhaug, Mar O'Callaghan, Ronit M. Pressler, Manuel Schiff, Serenella Servidei, Nora Szabo, Gráinne S. Gorman, J Helen Cross and Shamima Rahman
Article first published online:
04 Apr 2024 | DOI: 10.1111/ene.16275

CASE REPORT

Background and purpose

This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)‐associated neurological immune‐related adverse events (nirAE).

Methods

A systematic literature review was made, with case observations of a melanoma and a non‐small cell lung cancer (NSCLC) patient who developed ICI‐associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.

Results

Two patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c‐LETM), respectively. Intrathecal inflammation with chemokine C‐X‐C motif ligand (CXCL13) elevation was present in both patients; the triple M case had acetylcholine receptor antibodies, antititin reactivity, altered CD4/CD8 T cell ratio in blood, and depressed programmed death‐1 (PD‐1) expression on CSF T cells; the c‐LETM case showed intrathecal antibody production and plasma cells. Both patients insufficiently responded to first‐line treatment. The NSCLC case improved upon administration of B cell‐depleting therapy with rituximab, whereas the melanoma patient died before escalation therapy was initiated. Literature research revealed one additional ICI‐associated LETM case with intrathecal CXCL13 elevation, three cases with ICI‐associated aquaporin‐4 antibody neuromyelitis spectrum disorder, and evidence of B cell‐mediated toxicity based on antibody‐mediated immune pathologies in ICI‐associated immune‐related adverse events.

Conclusions

The case observations highlight the plethora of uncertainties in diagnosis and treatment of ICI‐associated nirAE, exemplify the heterogeneity of immune mechanisms involved, and suggest a role of B cells, which may be underdiagnosed. Intrathecal CXCL13 may serve as a biomarker of B cell involvement in nirAE, supported by intrathecal immunoglobulin synthesis, presence of plasma cells, and/or recruitment of cognate immune cells.

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Authors:
Ferdinand Otto, Michael Seiberl, Lara Bieler, Tobias Moser, Waltraud Kleindienst, Walter Wallner‐Essl, Peter Koelblinger, Peter Wipfler and Andrea Harrer
Article first published online:
31 Mar 2024 | DOI: 10.1111/ene.16279

POSITION PAPER

Background

Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert‐derived consensus recommendations for good practice.

Methods

A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub‐committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence‐based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1–10.

Results

Eighteen expert‐ and evidence‐based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG‐ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State [PASS]) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG‐ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds.

Conclusions

This process provided evidence‐ and expert consensus‐based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients.

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Authors:
Andreas Meisel, Francesco Saccà, Jennifer Spillane and John Vissing
Article first published online:
24 Mar 2024 | DOI: 10.1111/ene.16280

ORIGINAL ARTICLE

Background and purpose

Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non‐invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta‐analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS.

Methods

A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls.

Results

In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1–7 ms) exhibited the highest standardized mean difference with moderate heterogeneity (−0.994, 95% confidence interval −1.12 to −0.873,  < 0.001;  = 38.61,  < 0.05;  = 40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences.

Conclusion

This large meta‐analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta‐analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.

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Authors:
Mana Higashihara, Nathan Pavey, Parvathi Menon, Mehdi van den Bos, Kazumoto Shibuya, Satoshi Kuwabara, Matthew C. Kiernan, Masayoshi Koinuma and Steve Vucic
Article first published online:
20 Mar 2024 | DOI: 10.1111/ene.16281

ORIGINAL ARTICLE

Background and purpose

Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials.

Methods

Muscle magnetic resonance imaging, patient‐reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed‐function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow‐up.

Results

Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32‐item Motor Function Measurement (MFM‐32) scale (−1.3%,  = 0.017), North Star Ambulatory Assessment (−1.3 points,  = 0.010) and patient‐reported activity limitations scale (−0.3 logits,  = 0.018) deteriorated significantly after 9 months. The 6‐min walk distance (−28.7 m,  = 0.042), 10‐m walking test (−0.1 m/s,  = 0.032), time to climb four stairs test (−0.03 m/s,  = 0.028) and Biodex peak torque measurements of quadriceps (−4.6 N m,  = 0.014) and hamstrings (−5.0 N m,  = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM‐32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15).

Discussion

It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow‐up. Finally, significant changes are reported in a wide range of clinical and patient‐reported outcome measures, of which the MFM‐32 appeared to be the most sensitive to change in adults with BMD.

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Authors:
Bram De Wel, Louise Iterbeke, Lotte Huysmans, Ronald Peeters, Veerle Goosens, Nicolas Dubuisson, Peter van den Bergh, Vinciane Van Parijs, Gauthier Remiche, Liesbeth De Waele, Frederik Maes, Patrick Dupont and Kristl G. Claeys
Article first published online:
20 Mar 2024 | DOI: 10.1111/ene.16282

ORIGINAL ARTICLE

Background and purpose

Pyruvate dehydrogenase complex deficiency is in up to 90% caused by pathogenic variants in the X‐linked gene. We aimed to investigate female relatives of index patients with ‐related disease to (i) describe the prevalence of female carriers, (ii) determine whether they had symptoms and signs, and (iii) delineate the associated phenotype.

Methods

In a national population‐based study, we identified 37 patients with pathogenic variants in . Sanger sequencing for the presence of the pathogenic variant was performed in their mothers and female relatives. The identified female carriers were clinically assessed, and their medical records were reviewed.

Results

The proportion carrying a de novo variant was 86%. We identified seven female carriers from five families. Five of them exhibited clinical features of the disease and were previously undiagnosed; all had signs of peripheral axonal neuropathy, four presented with strokelike episodes including two with Leigh‐like lesions, and three had facial stigmata.

Conclusions

‐related disease is underrecognized in heterozygous female carriers. Peripheral axonal neuropathy, strokelike and Leigh‐like changes, and facial dysmorphism should raise suspicion of the disorder. Genetic analysis and clinical examination of potential female carriers are important for genetic counseling and have implications for treatment.

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Authors:
Antri Savvidou, Kalliopi Sofou, Erik A. Eklund, Johan Aronsson and Niklas Darin
Article first published online:
18 Mar 2024 | DOI: 10.1111/ene.16283

REVIEW ARTICLE

Objective

This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP‐A), a rare but severe neuroinflammatory disorder, to facilitate early diagnosis and appropriate treatment.

Methods

A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analysis)‐conforming systematic review and meta‐analysis was performed on all available data from January 2016 to June 2023. Clinical and neuroimaging phenotypes were extracted for both adult and paediatric forms.

Results

A total of 93 studies with 681 cases (55% males; median age = 46, range = 1–103 years) were included. Of these, 13 studies with a total of 535 cases were eligible for the meta‐analysis. Clinically, GFAP‐A was often preceded by a viral prodromal state (45% of cases) and manifested as meningitis, encephalitis, and/or myelitis. The most common symptoms were headache, fever, and movement disturbances. Coexisting autoantibodies (45%) and neoplasms (18%) were relatively frequent. Corticosteroid treatment resulted in partial/complete remission in a majority of cases (83%). Neuroimaging often revealed T2/fluid‐attenuated inversion recovery (FLAIR) hyperintensities (74%) as well as perivascular (45%) and/or leptomeningeal (30%) enhancement. Spinal cord abnormalities were also frequent (49%), most commonly manifesting as longitudinally extensive myelitis. There were 88 paediatric cases; they had less prominent neuroimaging findings with lower frequencies of both T2/FLAIR hyperintensities (38%) and contrast enhancement (19%).

Conclusions

This systematic review and meta‐analysis provide high‐level evidence for clinical and imaging phenotypes of GFAP‐A, which will benefit the identification and clinical workup of suspected cases. Differential diagnostic cues to distinguish GFAP‐A from common clinical and imaging mimics are provided as well as suitable magnetic resonance imaging protocol recommendations.

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Authors:
Caroline Hagbohm, Russell Ouellette, Eoin P. Flanagan, Dagur I. Jonsson, Fredrik Piehl, Brenda Banwell, Ronny Wickström, Ellen Iacobaeus, Tobias Granberg and Benjamin V. Ineichen
Article first published online:
20 Mar 2024 | DOI: 10.1111/ene.16284

ORIGINAL ARTICLE

Background and purpose

Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV‐induced neuropathy (BV‐CN) is a mild distal sensory axonal polyneuropathy. Severe BV‐induced inflammatory neuropathies (BV‐IN) have been described. BV‐IN contribute to lymphoma‐associated morbidity but might be immunotherapy‐responsive. Our primary objective was to evaluate the rate of BV‐IN. Our secondary objectives were to determine risk factors and warning signs.

Methods

We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV‐induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV‐IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV‐CN.

Results

Among 83 patients, 41 (49%) developed neuropathy: 35 BV‐CN and 6 BV‐IN. Thus, the rate of BV‐IN was 7.2%. Compared to patients with BV‐CN, no predisposing factor was identified. However, patients with BV‐IN more frequently presented muscle weakness (67% vs. 5.7%,  < 0.05), gait disorders (83% vs. 20%,  < 0.05), or acute or subacute onset (67% vs. 14%,  < 0.05). BV‐IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%,  < 0.05). Four patients were treated with immunotherapy.

Conclusions

Brentuximab vedotin‐induced neuropathy is an overlooked complication. Based on four easily identifiable “red flags”, we provide an algorithm to help non‐neurologist physicians that care for BV‐treated patients to detect BV‐IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.

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Authors:
Arthur Matthys, Benjamin Bardel, Fabien Le Bras, Alain Créange, Tarik Nordine, Romain Gounot, Saskia Ingen‐Housz‐Oro, Muriel Carvalho, Jean‐Pascal Lefaucheur, Corinne Haioun, Violaine Planté‐Bordeneuve and Thierry Gendre
Article first published online:
21 Mar 2024 | DOI: 10.1111/ene.16285

ORIGINAL ARTICLE

Introduction

People with Parkinson's disease (PD) often present with disabling neuropsychiatric symptoms. Compassionate mind training (CMT) is a psychological approach effective in reducing stress and promoting psychological well‐being. Heart rate variability (HRV), a measure reflecting sympathovagal balance, has been associated with psychological well‐being and a compassionate attitude.

Aim

To assess the feasibility and effectiveness of CMT in enhancing the quality of life and psychological well‐being in PD patients. Additionally, we evaluated HRV as a physiomarker for assessing the CMT outcomes.

Methods

Twenty‐four PD patients participated in the study. A 6‐week online CMT intervention was delivered on a weekly basis. At baseline and post‐intervention patients completed questionnaires assessing depression, anxiety and quality of life. In a subsample of 11 patients, HRV was measured at baseline and post‐intervention in three conditions: at rest, during stress and after 3 min of deep breathing.

Results

The attendance rate was 94.3%. Quality of life and perceived stigma improved post‐intervention as compared with baseline ( = 0.02 and  = 0.03 for PD Questionnaire‐39 total score and Stigma subscore, respectively). After CMT, patients presented better physiological regulation to stress, as measured by higher HRV as compared with baseline ( = 0.005). Notably, patients who were more resilient to stress at baseline (less decrease in HRV during stress) experienced a more substantial reduction in anxiety and depression following CMT.

Conclusions

CMT is feasible and can improve quality of life and stigma in PD patients. HRV emerges as a promising physiomarker for predicting and measuring the outcomes of psychological interventions in PD.

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Authors:
Silvia Della Morte, Elena Berti, Carolina Lalli, Nicola Modugno, Francesca Morgante, Anette Schrag, Elena Makovac and Lucia Ricciardi
Article first published online:
23 Mar 2024 | DOI: 10.1111/ene.16286

ORIGINAL ARTICLE

Background and purpose

Women with acute ischemic stroke (AIS) are older and have greater preexisting handicap than men. Given that these factors do not fully explain their poorer long‐term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients.

Methods

We analyzed all patients from ASTRAL (Acute Stroke Registry and Analysis of Lausanne) from March 2003 to December 2019. Multivariable analyses were performed on acute time metrics, revascularization therapies, ancillary examinations for stroke workup, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care), and length of hospital stay.

Results

Of the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset‐to‐door (adjusted hazard ratio [aHR] = 1.09, 95% confidence interval [CI] = 1.04–1.14) and door‐to‐endovascular‐puncture intervals (aHR = 1.15, 95% CI = 1.05–1.25). Women underwent numerically fewer diagnostic examinations (adjusted odds ratio [aOR] = 0.94, 95% CI = 0.85–1.04) and fewer subacute carotid revascularizations (aOR = 0.69, 95% CI = 0.33–1.18), and had longer hospital stays (aHR = 1.03, 95% CI = 0.99–1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments.

Conclusions

This retrospective analysis of a large, consecutive AIS cohort suggests that female sex is associated with unfavorable pre‐ and in‐hospital time metrics, such as a longer onset‐to‐door and door‐to‐endovascular‐puncture intervals. Such indicators of less effective stroke care delivery may contribute to the poorer long‐term functional outcomes in female patients and require further attention.

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Authors:
Friedrich Medlin, Davide Strambo, Dimitris Lambrou, Valeria Caso and Patrik Michel
Article first published online:
30 Mar 2024 | DOI: 10.1111/ene.16287

ORIGINAL ARTICLE

Background and purpose

The eye is a well‐established model of brain structure and function, yet region‐specific structural correlations between the retina and the brain remain underexplored. Therefore, we aim to explore and describe the relationships between the retinal layer thicknesses and brain magnetic resonance image (MRI)‐derived phenotypes in UK Biobank.

Methods

Participants with both quality‐controlled optical coherence tomography (OCT) and brain MRI were included in this study. Retinal sublayer thicknesses and total macular thickness were derived from OCT scans. Brain image‐derived phenotypes (IDPs) of 153 cortical and subcortical regions were processed from MRI scans. We utilized multivariable linear regression models to examine the association between retinal thickness and brain regional volumes. All analyses were corrected for multiple testing and adjusted for confounders.

Results

Data from 6446 participants were included in this study. We identified significant associations between volumetric brain MRI measures of subregions in the occipital lobe (intracalcarine cortex), parietal lobe (postcentral gyrus), cerebellum (lobules VI, VIIb, VIIIa, VIIIb, and IX), and deep brain structures (thalamus, hippocampus, caudate, putamen, pallidum, and accumbens) and the thickness of the innermost retinal sublayers and total macular thickness (all  < 3.3 × 10). We did not observe statistically significant associations between brain IDPs and the thickness of the outer retinal sublayers.

Conclusions

Thinner inner and total retinal thicknesses are associated with smaller volumes of specific brain regions. Notably, these relationships extend beyond anatomically established retina–brain connections.

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Authors:
Zihan Sun, Bing Zhang, Stephen Smith, Denize Atan, Anthony P. Khawaja, Kelsey V. Stuart, Robert N. Luben, Mahantesh I. Biradar, Thomas McGillivray, Praveen J. Patel, Peng T. Khaw, Axel Petzold and Paul J. Foster
Article first published online:
08 May 2024 | DOI: 10.1111/ene.16288

ORIGINAL ARTICLE

Background and purpose

Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real‐world rates of persistence on disease‐modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation.

Methods

Treatment data on 4366 consecutive people with relapse‐onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan–Meier survival analyses were used to express DMT persistence.

Results

In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1–4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate.

Conclusions

Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

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Authors:
Emma C. Tallantyre, Ruth Dobson, Joseph L. J. Froud, Frederika A. St John, Valerie M. Anderson, Tarunya Arun, Lauren Buckley, Nikos Evangelou, Helen L. Ford, Ian Galea, Sumi George, Orla M. Gray, Aimee M. Hibbert, Mo Hu, Stella E. Hughes, Gillian Ingram, Seema Kalra, Chia‐Hui E. Lim, Joela T. M. Mathews, Gavin V. McDonnell, Naomi Mescall, Sam Norris, Stephen J. Ramsay, Claire M. Rice, Melanie J. Russell, Marianne J. Shawe‐Taylor, Thomas E. Williams, Katharine E. Harding and Neil P. Robertson
Article first published online:
03 Apr 2024 | DOI: 10.1111/ene.16289

ORIGINAL ARTICLE

Background and purpose

Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller–Fisher syndrome (MFS) and Guillain–Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross‐responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant.

Methods

In this 10‐year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti‐Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross‐responsiveness.

Results

Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross‐responsiveness was observed in 39.6% of all positive serum AGA.

Conclusions

Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross‐responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.

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Authors:
Niklas Giesche, Samuel Tobias Böhm‐Gonzalez, Benedict Kleiser, Markus C. Kowarik, Evelyn Dubois, Elke Stransky, Marcel Armbruster, Alexander Grimm and Justus Marquetand
Article first published online:
31 Mar 2024 | DOI: 10.1111/ene.16290

SHORT COMMUNICATION

Background

The factors underlying the topography of nitrous oxide (NO)‐induced neurological complications are unknown.

Methods

We included all consecutive patients admitted to the university hospital of Marseille for NO‐induced neurological complications in a prospective observational study. Patients underwent neurological examination, spinal cord magnetic resonance imaging, and nerve conduction studies within the first 4 weeks after admission.

Results

In total, 61 patients were included: 45% with myeloneuropathy, 34% with isolated myelopathy, and 21% with isolated neuropathy. On multivariable analysis, the odds of myelopathy were associated with the amount of weekly NO consumption (~600 g cylinder per week, odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.001–1.24). The extent of the myelopathy (number of vertebral segments) was correlated with the number of ~600‐g cylinders consumed weekly (ρ = 0.40,  < 0.005). The odds of neuropathy were associated with the duration of consumption (per month; OR = 1.29, 95% CI = 1.05–1.58). Mean lower‐limb motor nerve amplitude was correlated with the duration of consumption (in months; ρ = −0.34,  < 0.05).

Conclusions

The odds of myelopathy increased with the amount of NO consumption, and the odds of neuropathy increased with the duration of NO exposure, which suggests distinct pathophysiological mechanisms underlying these two neurological complications.

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Authors:
Eva Sole Cruz, Etienne Fortanier, Frederic Hilezian, Adil Maarouf, Clémence Boutière, Sarah Demortière, Audrey Rico, Emilien Delmont, Jean Pelletier, Shahram Attarian and Bertrand Audoin
Article first published online:
26 Mar 2024 | DOI: 10.1111/ene.16291

ORIGINAL ARTICLE

Introduction

Late‐onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α‐glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long‐term treatment results vary. Avalglucosidase alfa demonstrated non‐inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.

Methods

Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow‐up. Respiratory (forced vital capacity [FVC]) and motor functions (Six‐Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.

Results

Twenty‐nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.

Discussion

At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.

Conclusion

Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.

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Authors:
Céline Tard, Françoise Bouhour, Maud Michaud, Stephane Beltran, Maxime Fournier, Florence Demurger, Emmeline Lagrange, Sylvain Nollet, Sabrina Sacconi, Jean‐Baptiste Noury, Armelle Magot, Pascal Cintas, Dimitri Renard, Joëlle Deibener‐Kaminsky, Claire Lefeuvre, Jean‐Baptiste Davion, Emmanuelle Salort‐Campana, Azzeddine Arrassi, Nadjib Taouagh, Marco Spinazzi, D Orlikowski, M Masingue, T Stojkovic, A Béhin, PY Garcia, F Lallement, G Bassez, D Germain, L Kouton, A Verschueren, A Furby, AL Kaminsky, A Lacour, J Praline, G Sole, F Duval, F Bouibede, F Chapon, MC Minot, J Hubert, Y Pereon, B Acket, A Nadaj‐Pakleza, RJ Morales, F Esselin, P Petiot, R Jaussaud, S Mohamed, YA Echaniz‐Laguna, L Magy, E Krim, F Taithe, AL Bedat‐Millet, S Toquet, E Diab, M Maillet‐Vioud, Shahram Attarian and Pascal Laforêt
Article first published online:
08 Apr 2024 | DOI: 10.1111/ene.16292

ORIGINAL ARTICLE

Background and purpose

Residual symptoms after treatment of Lyme disease, sometimes called post‐treatment Lyme disease symptoms (PTLDs), are a matter of ongoing controversy. To guide treatment recommendations, a systematic review was performed of the available literature on specific treatment for PTLDs.

Methods

A systematic literature search of MEDLINE and CENTRAL was performed. No restrictions on case definitions, study types or specific interventions were applied to enable a comprehensive overview of the available literature. Risk of bias was assessed using the Cochrane risk of bias tools for randomized controlled trials. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Outcomes of interest were quality of life, fatigue, depression and cognition as well as adverse events.

Results

After screening 1274 records, eight eligible randomized controlled trials were included. Heterogeneity was observed regarding inclusion criteria, intervention, length of treatment and outcome measures. For efficacy outcomes, results are presented narratively due to heterogeneity. Eligible studies show no statistically significant difference between antibiotics and placebo regarding quality of life, cognition and depression. Results for fatigue were inconsistent whilst studies with low risk of bias showed no statistically significant difference between antibiotics and placebo. Meta‐analysis of safety outcomes showed statistically significantly more adverse events for antibiotics compared to placebo.

Conclusions

Available literature on treatment of PTLDs is heterogeneous, but overall shows evidence of no effect of antibiotics regarding quality of life, depression, cognition and fatigue whilst showing more adverse events. Patients with suspected PTLDs should not be treated with antibiotics.

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Authors:
Rick Dersch, Gabriel Torbahn and Sebastian Rauer
Article first published online:
12 Apr 2024 | DOI: 10.1111/ene.16293

ORIGINAL ARTICLE

Background and purpose

The prevalence of dementia is rapidly increasing. Attempts to further understand modifiable risk factors such as diabetes mellitus (DM) are urgently needed to inform public health policies for prevention. Thus, the objective of the current study was to assess the relationship between DM and risk of dementia and non‐dementia mortality amongst women in the California Teachers Study prospective cohort.

Methods

Women ( = 124,509) aged 22–104 years at baseline were included. DM was ascertained from self‐reported questionnaires and hospital‐linked records. Dementia‐related deaths were ascertained from state and national records. Competing risk regression models were used to estimate cause‐specific hazard ratios and 95% confidence intervals for the association of DM with dementia‐ and non‐dementia‐related mortality.

Results

There were 10,511 total DM cases and 3625 deaths due to dementia over a mean of 21.3 years of follow‐up. Fully adjusted cause‐specific hazard ratios of the association with DM were 2.26 (2.01, 2.55) for dementia‐related and 1.97 (1.89, 2.05) for the competing risk of non‐dementia‐related mortality. This association was strongest amongst participants with incident DM, younger age at baseline and higher alcohol consumption or who were overweight.

Conclusions

In the California Teachers Study, women with DM had increased risk of mortality due to both dementia and non‐dementia causes; however, the risk of mortality due to dementia was elevated compared to non‐dementia causes only amongst participants with incident DM.

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Authors:
Cathleen Morgan, Bradon Annegers, Matthew K. Taylor, Sara Shuger Fox and Tyler J. Titcomb
Article first published online:
02 Apr 2024 | DOI: 10.1111/ene.16294

ORIGINAL ARTICLE

Background and purpose

The ratio of serum uric acid (SUA) to serum creatinine (SCr), representing normalized SUA for renal function, is associated with functional outcome in acute ischaemic stroke (AIS) patients. However, its effect on AIS patients undergoing mechanical thrombectomy (MT) remains unknown. This study aimed to investigate the influence of the SUA/SCr ratio on clinical outcome in MT‐treated AIS patients.

Methods

Acute ischaemic stroke patients who underwent MT were continuously enrolled from January 2018 to June 2023. Upon admission, SUA and SCr levels were recorded within the initial 24 h. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. Clinical outcome included poor functional outcome (modified Rankin Scale score >2) at 90 days, symptomatic intracranial haemorrhage and death.

Results

Amongst 734 patients, 432 (58.8%) exhibited poor functional outcome at 90 days. The SUA/SCr ratio exhibited a negative correlation with NIHSS score ( = −0.095,  = 0.010). Univariate analysis revealed a significant association between SUA/SCr ratio and poor functional outcome. After adjusting for confounders, the SUA/SCr ratio remained an independent predictor of functional outcome (adjusted odds ratio 0.348, 95% confidence interval 0.282–0.428,  < 0.001). Receiver operating characteristic curve analysis highlighted the ability of the SUA/SCr ratio to predict functional outcome, with a cutoff value of 3.62 and an area under the curve of 0.757 (95% confidence interval 0.724–0.788,  < 0.001).

Conclusion

The SUA/SCr ratio is correlated with stroke severity and may serve as a predictor of 90‐day functional outcome in AIS patients undergoing MT.

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Authors:
Jinghan Xu, Xin Jiang, Qian Liu, Jiaxin Liu, Jinghuan Fang and Li He
Article first published online:
08 Apr 2024 | DOI: 10.1111/ene.16296

ORIGINAL ARTICLE

Background and purpose

Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study.

Methods

We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM‐BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty‐eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada.

Results

Remote atrophy was observed in the cervical cord ( = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter ( = 0.014), thalamus ( = 0.001), corpus callosum ( = 0.0001), and cranial corticospinal tract ( = 0.03). R2* was increased in the primary somatosensory cortices ( = 0.008). Sensory impairments were associated with increased iron‐sensitive R2* in the thalamus and periaqueductal grey matter in DCM.

Conclusions

Simultaneous assessment of the spinal cord and brain revealed DCM‐induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level.

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Authors:
Patrick Freund, Viveka Boller, Tim M. Emmenegger, Muhammad Akbar, Markus Hupp, Nikolai Pfender, Claudia Angela Michela Gandini Wheeler‐Kingshott, Julien Cohen‐Adad, Michael G. Fehlings, Armin Curt and Maryam Seif
Article first published online:
07 May 2024 | DOI: 10.1111/ene.16297

ORIGINAL ARTICLE

Background and purpose

Coronavirus disease 2019 (COVID‐19) vaccination has been associated with a dampened humoral and/or cellular immune response in patients with multiple sclerosis (MS) who were concurrently on disease‐modifying treatment (DMT) with B‐cell depleting agents or sphingosine‐1‐phosphate receptor modulators (S1PRMs). Our main goal was to investigate the impact of these DMT classes on the clinical effectiveness of COVID‐19 vaccination.

Methods

Since March 2020, demographics and clinical data of patients with MS who developed COVID‐19 have been collected at the Belgian National MS Centre in Melsbroek. Patients were considered to be ‘protected by vaccination’ if they were (i) fully vaccinated and (ii) tested positive for COVID‐19 in the period ranging from 14 days to 6 months after the last administered vaccine.

Results

On 19 December 2022, 418 COVID‐19 cases were retrospectively identified in 389 individual patients. Hospitalization and mortality rates resulting from the infection were 10.8% and 2.4%, respectively. Being ‘unprotected by vaccination’ was significantly associated with a worse COVID‐19 outcome (i.e., hospitalization and/or death) in the total cohort ( = 418, odds ratio [OR] 3.96), in patients on ongoing DMT other than anti‐CD20 agents or S1PRMs ( = 123, OR 31.75) and in patients without DMT ( = 182, OR 5.60), but not in those receiving anti‐CD20 agents ( = 91, OR 0.39); the S1PRMs subgroup was considered too small (22 infections) for any meaningful analysis.

Conclusions

Coronavirus disease 2019 vaccination protects against severe infection in patients with MS but it was not possible to confirm this effect in those on DMT with B‐cell depleting agents.

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Authors:
Marijke De Troyer, Ann Van Remoortel, Jeroen Van Schependom, Laetitia Della Faille, Marie B. D'hooghe, Gertjan Peeters, Guy Nagels and Miguel D'haeseleer
Article first published online:
19 Apr 2024 | DOI: 10.1111/ene.16300

SHORT COMMUNICATION

Background and purpose

Cryopyrin‐associated periodic syndrome is a rare autoinflammatory disease caused by gain‐of‐function mutations or variants in the gene. Clinically, patients suffer from a broad spectrum of both systemic and neurological symptoms. The aim of this study was to determine whether systemic inflammation demonstrated by serum amyloid A (SAA) elevation is associated with neuroinflammation assessed by optical coherence tomography (OCT).

Methods

Thirty eyes of 15 patients with NLRP3 low penetrance mutations (PwNLRP3) and 20 eyes of 10 age‐ and sex‐matched healthy controls were examined by spectral‐domain OCT as part of routine clinical care. All retinal layers and clinical features were evaluated.

Results

At baseline no significant retinal neuroaxonal inflammation or degeneration was observed in all measured retinal layers amongst PwNLRP3 compared with healthy controls. In a pooled analysis of all individual OCT time points a significant difference regarding the macular retinal nerve fibre layer was detected. Increased levels of SAA showed a positive association with averaged combined outer plexiform layer and outer nuclear layer volumes ( < 0.0001,  = 0.35).

Conclusion

In cryopyrin‐associated periodic syndrome increased combined outer plexiform layer and outer nuclear layer volumes are mirrored by SAA increase, an acute phase reactant indicating systemic inflammation. Our findings identify OCT as a candidate biomarker to monitor subclinical neuroinflammation and to assess disease activity in PwNLRP3.

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Authors:
E. Mulazzani, L. Böhm, T. Christmann, M. Krumbholz, T. Kümpfel and J. Havla
Article first published online:
16 Apr 2024 | DOI: 10.1111/ene.16301

ORIGINAL ARTICLE

Background and purpose

Swallowing is a complex task, moderated by a sophisticated bilateral network including multiple supratentorial regions, the brainstem and the cerebellum. To date, conflicting data exist about whether focal lesions to the cerebellum are associated with dysphagia. Therefore, the aim of the study was to evaluate dysphagia prevalence, recovery and dysphagia pattern in patients with ischaemic cerebellar stroke.

Methods

A retrospective analysis of patients consecutively admitted to an academic stroke centre with ischaemic stroke found only in the cerebellum was performed. The presence of dysphagia was the primary end‐point and was assessed by a speech‐language pathologist, according to defined criteria. Dysphagia pattern was evaluated by analysing the videos of the flexible endoscopic evaluation of swallowing. Brain imaging was used to identify lesion size and location associated with dysphagia.

Results

Between January 2016 and December 2021, 102 patients (35.3% female) with a mean age of 52.8 ± 17.3 years were included. Thirteen (12.7%) patients presented with dysphagia. The most frequently observed flexible endoscopic evaluation of swallowing phenotype was premature spillage ( = 7; 58.3%), whilst significant residues or aspiration did not occur. One patient died (7.7%); the other patients showed improvement of dysphagia and one patient (7.7%) was discharged with dietary restrictions.

Conclusions

Although the involvement of the cerebellum in deglutition has become increasingly evident, isolated lesions to the cerebellum are less likely to cause clinically relevant and persisting dysphagia compared to other brain regions. The observed dysphagia pattern shows a lack of coordination and control, resulting in premature spillage or fragmented bolus transfer in some patients.

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Authors:
Jan Hendrik Schaefer, Felix Luft, Alexander Seiler, Elena Harborth, Sara Kaffenberger, Christoph Polkowski, Christian Foerch and Sriramya Lapa
Article first published online:
17 Apr 2024 | DOI: 10.1111/ene.16303

ORIGINAL ARTICLE

Background and purpose

Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD‐associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom‐based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum.

Methods

An international lvPPA caregiver cohort was surveyed on symptom development under an ‘exploratory’ survey (34 UK caregivers). Feedback from this survey informed the development of a ‘consolidation’ survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed‐methods approach.

Results

Six clinical stages were endorsed. Early symptoms included word‐finding difficulty, with loss of message comprehension and speech intelligibility signalling later‐stage progression. Additionally, problems with hearing in noise, memory and route‐finding were prominent early non‐verbal symptoms. ‘Milestone’ symptoms were identified that anticipate daily‐life functional transitions and care needs.

Conclusions

This work introduces a new symptom‐based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum.

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Authors:
Chris J. D. Hardy, Cathleen Taylor‐Rubin, Beatrice Taylor, Emma Harding, Aida Suarez Gonzalez, Jessica Jiang, Laura Thompson, Rachel Kingma, Anthipa Chokesuwattanaskul, Ffion Walker, Suzie Barker, Emilie Brotherhood, Claire Waddington, Olivia Wood, Nikki Zimmermann, Nuriye Kupeli, Keir X. X. Yong, Paul M. Camic, Joshua Stott, Charles R. Marshall, Neil P. Oxtoby, Jonathan D. Rohrer, Frankie O'Shea, Anna Volkmer, Sebastian J. Crutch and Jason D. Warren
Article first published online:
26 Apr 2024 | DOI: 10.1111/ene.16304

ORIGINAL ARTICLE

Background

To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3–37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow‐up.

Results

At follow‐up, the Z‐score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment‐free period of 0.3 years (0.2–0.4), there was no progression of axonal loss ( = 0.2), whereas a trend toward further axonal loss by 1.3 Z‐scores (0.9–17.0,  = 0.06) was observed in five patients with a treatment‐free period of 4.0 years (0.9–9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay ( = 0.02). Also, there was an association between treatment delay and ongoing axonal loss ( = 0.004). The electrophysiological findings at follow‐up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss.

Conclusion

Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.

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Authors:
Ali Al‐Zuhairy, Johannes Jakobsen and Christian Krarup
Article first published online:
23 Apr 2024 | DOI: 10.1111/ene.16305

SHORT COMMUNICATION

Background and purpose

This study was undertaken to highlight neonatal Fc receptor inhibition (efgartigimod) as a valuable therapeutic option for patients with refractory seronegative myasthenia gravis (MG) and to emphasize the concept that seronegative MG is greatly constrained by the limitations of currently available diagnostic methods and therapeutic measures.

Methods

We describe the first refractory, generalized MG (gMG) patient successfully treated with efgartigimod after testing negative on standard autoantibody detection tests.

Results

Our patient presented with severe fluctuating bulbar and generalized weakness, resulting in multiple myasthenic crises requiring intubation. After a 28‐year medical history of multiple failed lines of treatment, our patient was started on efgartigimod. Over five treatment cycles, a definite improvement in her clinical condition was observed (Myasthenia Gravis Foundation of America class: IIIb to IIb; MG‐Activities of Daily Living score: 11 to 0; MG‐Quality of Life 15 score: 30 to 0; Quantitative MG score: 28 to 6). Standard autoantibody detection tests failed to detect known pathogenic autoantibodies, but cell‐based assay (CBA) identified autoantibodies against clustered adult acetylcholine receptor (AChR).

Conclusions

In light of recent approvals of efgartigimod by the European Medicines Agency and US Food and Drug Administration exclusively for AChR‐positive gMG forms, our case highlights evidence suggesting that such an approach might be shortsighted and could limit therapeutic options for patients with refractory seronegative gMG. Additionally, introducing more sensitive analytical techniques, exemplified by CBA, may help bridge the gap between seronegative and seropositive patients. This represents an urgent unmet need for gMG patients, as the antibody profile dramatically influences the therapeutic approach.

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Authors:
Benedetta Sorrenti, Christian Laurini, Luca Bosco, Camilla Mirella Maria Strano, Marina Scarlato, Matteo Gastaldi, Massimo Filippi, Stefano Carlo Previtali and Yuri Matteo Falzone
Article first published online:
08 May 2024 | DOI: 10.1111/ene.16306

LETTER TO THE EDITOR

Headaches during/after SARS‐CoV‐2 infection/vaccination can be primary and secondary as well as acute and chronic

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Authors:
Josef Finsterer and Sounira Mehri
Article first published online:
15 Apr 2024 | DOI: 10.1111/ene.16307

LETTER TO THE EDITOR

Reply to the letter: Headaches during/after SARS‐CoV‐2 infection/vaccination can be primary and secondary as well as acute and chronic, by Finsterer J and Mehri S

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Authors:
Dimos‐Dimtirios D. Mitsikostas, Edoardo Caronna, Marina De Tommaso, Christina I. Deligianni, Esme Ekizoglu, Hayrunnisa Bolay, Carl H. Göbel, Espen Saxhaug Kristoffersen, Christian Lampl, Elena Moro, Patricia Pozo‐Rosich, Johann Sellner, Gisela Terwindt and Pablo Irimia‐Sieira
Article first published online:
16 Apr 2024 | DOI: 10.1111/ene.16308