cover image European Journal of Neurology

European Journal of Neurology

2022 - Volume 29
Issue 1 | January 2022
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Article first published online:
08 Dec 2021 | DOI: 10.1111/ene.14921

ORIGINAL ARTICLE

Background and purpose

Many countries worldwide, including Germany, reported that the first wave of the coronavirus disease 2019 (COVID‐19) pandemic in early 2020 influenced the care of acute ischemic stroke (AIS) patients, but data are lacking for further pandemic wave periods.

Methods

We conducted a nationwide, retrospective, cross‐sectional study of all hospitalized patients with the main diagnosis of AIS in 2019 and 2020. Primary outcomes were the number of hospitalizations for AIS, the application of stroke unit care, intravenous thrombolysis (IVT), and mechanical thrombectomy (MT), as well as the in‐hospital mortality during the different pandemic periods in 2020 compared to the corresponding periods in 2019. Secondarily, we analyzed differences in outcomes between patients with and without concurrent COVID‐19.

Results

We included 429,841 cases with AIS, of which 1268 had concurrent COVID‐19. Hospitalizations for AIS declined during both pandemic wave periods in 2020 (first wave: −10.9%, second wave: −4.6%). MT rates were consistently higher throughout 2020 compared to 2019, whereas the IVT rate dropped during the second wave period (16.0% vs. 17.0%,  < 0.001). AIS patients with concurrent COVID‐19 frequently received recanalization treatments, with an overall MT rate of 8.4% and IVT rate of 15.9%. The in‐hospital mortality was high (22.8% vs. 7.5% in noninfected AIS patients,  < 0.001).

Conclusions

These findings demonstrate a smaller decline in hospitalizations for AIS in the more severe second wave of the COVID‐19 pandemic. AIS patients with and without concurrent COVID‐19 who did seek acute care continued to receive recanalization treatments in Germany.

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Authors:
Daniel Richter, Jens Eyding, Ralph Weber, Dirk Bartig, Armin Grau, Werner Hacke and Christos Krogias
Article first published online:
22 Aug 2021 | DOI: 10.1111/ene.15057

ORIGINAL ARTICLE

Background and purpose

Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD.

Methods

CSF and serum NfL, as well as conventional CSF Alzheimer's disease (AD) biomarkers (Aβ42, t‐Tau, p‐Tau181), were determined in 63 FTD patients (30 sporadic‐FTD, 20 with progranulin () mutations [FTD‐GRN], 13 with chromosome 9 open reading frame 72 [] expansions [C9orf72‐FTD]), 37 AD patients, and 31 neurologic controls. Serum NfL was also quantified in 37 healthy individuals. Correlations between baseline CSF and serum NfL levels, standardized neuropsychological tests, and the rate of cognitive decline in FTD patients were assessed.

Results

CSF and serum NfL presented with significantly higher levels in FTD than in AD patients and both control groups. Within FTD subtypes, genetic cases, and particularly FTD‐GRN, had higher CSF and serum NfL levels. Significant correlations between NfL levels and overall cognitive function, abstract reasoning (CSF and serum), executive functions, memory, and language (serum) were found. A relationship between increased baseline CSF and serum NfL and a decay in cognitive performance over time was also observed.

Conclusions

Our findings highlight the potential of serum NfL as a useful surrogate end point of disease severity in upcoming targeted treatments.

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Authors:
Anuschka Silva‐Spínola, Marisa Lima, Maria João Leitão, João Durães, Miguel Tábuas‐Pereira, Maria Rosário Almeida, Isabel Santana and Inês Baldeiras
Article first published online:
03 Sep 2021 | DOI: 10.1111/ene.15058

ORIGINAL ARTICLE

Background and purpose

Fibroblast growth factor 23 (FGF23) is an osteogenic hormone associated with chronic kidney disease and is an emerging risk factor for several cardiovascular diseases. The association of FGF23 with stroke is unclear. The aim of this study was to investigate the association of FGF23 with incident intracerebral hemorrhage (ICH).

Methods

This was a nested case–control study of 220 ICH cases and 244 age‐ and sex‐matched controls from the population‐based Malmö Diet and Cancer Study ( = 28,449). Incident ICH cases were ascertained using national registers and classified by bleeding location. Logistic regression was used to study the association of plasma levels of FGF23 with incident ICH, adjusting for potential ICH risk factors. Subgroup analyses were performed for lobar and non‐lobar ICH, fatal ICH, ICH with large volume and ICH with poor functional outcome, respectively.

Results

Higher FGF23 levels at baseline were significantly associated with incident ICH. After multivariable adjustment, the odds ratio for the association with all ICH was 1.84 (95% confidence interval [CI] 1.25–2.71,  = 0.002) per doubling of FGF23 concentration. For lobar and non‐lobar ICH, odds ratios were 1.73 (95% CI 1.04–2.87,  = 0.035) and 2.13 (95% CI 1.32–3.45,  = 0.002), respectively. FGF23 was also significantly associated with fatal ICH, ICH with large volume and ICH with poor functional outcome.

Conclusions

Higher FGF23 was associated with incident ICH in this nested case–control study. Further studies are required to explore whether the association is causal.

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Authors:
Edith H. Svensson and Martin Söderholm
Article first published online:
31 Aug 2021 | DOI: 10.1111/ene.15060

ORIGINAL ARTICLE

Background and purpose

Although the majority of migraine with aura (MwA) patients experience simple visual aura, a discrete percentage also report somatosensory, dysphasic or motor symptoms (the so‐called complex auras). The wide aura clinical spectrum led to an investigation of whether the heterogeneity of the aura phenomenon could be produced by different neural correlates, suggesting an increased visual cortical excitability in complex MwA. The aim was to explore whether complex MwA patients are characterized by more pronounced connectivity changes of the visual network and whether functional abnormalities may extend beyond the visual network encompassing also the sensorimotor network in complex MwA patients compared to simple visual MwA patients.

Methods

By using a resting‐state functional magnetic resonance imaging approach, the resting‐state functional connectivity (RS‐Fc) of both visual and sensorimotor networks in 20 complex MwA patients was compared with 20 simple visual MwA patients and 20 migraine without aura patients.

Results

Complex MwA patients showed a significantly higher RS‐Fc of the left lingual gyrus, within the visual network, and of the right anterior insula, within the sensorimotor network, compared to both simple visual MwA and migraine without aura patients ( < 0.001). The abnormal right anterior insula RS‐Fc was able to discriminate complex MwA patients from simple aura MwA patients as demonstrated by logistic regression analysis (area under the curve 0.83).

Conclusion

Our findings suggest that higher extrastriate RS‐Fc might promote cortical spreading depression onset representing the neural correlate of simple visual aura that can propagate to sensorimotor regions if an increased insula RS‐Fc coexists, leading to complex aura phenotypes.

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Authors:
Marcello Silvestro, Alessandro Tessitore, Federica Di Nardo, Fabrizio Scotto di Clemente, Francesca Trojsi, Mario Cirillo, Fabrizio Esposito, Gioacchino Tedeschi and Antonio Russo
Article first published online:
03 Sep 2021 | DOI: 10.1111/ene.15061

ORIGINAL ARTICLE

Background

Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes in SuS.

Methods

A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion‐weighted imaging (DWI‐HL) were analyzed at diagnosis and during follow‐up. Outcomes involved descriptive characteristics of patients at onset and last follow‐up.

Results

Twenty‐three patients (38.1 [18.8–56.5] years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1–3.4) months after the first symptom. All patients had DWI‐HL at the acute phase. Patients were separated into two groups according to the number of DWI‐HL on first MRI: a first group of patients (=15) displaying low brain lesion load (<50 DWI‐HL per patient) and a second group of patients (=8) displaying high brain lesion load (≥100 DWI‐HL). The median follow‐up was 57.9 (9.7–98) months. Clinical features, treatment, relapse rate, time to disappearance of DWI‐HL, disabilities and professional outcome did not differ according to brain lesion load.

Conclusion

Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.

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Authors:
Carole Scheifer, Marie‐Cécile Henry Feugeas, Mélanie Roriz, Fleur Cohen Aubart, Serge Doan, Eric Jouvent, Isabelle Klein, Carla Machado, Diane Rouzaud, Thomas Papo and Karim Sacré
Article first published online:
23 Aug 2021 | DOI: 10.1111/ene.15062

ORIGINAL ARTICLE

Background and purpose

Creutzfeldt–Jakob disease (CJD) is a transmissible spongiform encephalopathy characterized by rapid onset and high mortality. Despite considerable progress in the treatment and diagnosis of CJD, patient prognosis remains poor. Many studies have found that the immune response is associated with the pathophysiology of CJD. However, few studies have reported coexpression correlations between genes associated with CJD and the immune response. This study was undertaken to construct a network of coexpressed immune‐ and CJD‐related genes that may reveal new biomarkers and therapeutic targets for CJD.

Methods

Gene expression data from 11 CJD patients and 10 nonneurological controls were obtained from the Gene Expression Omnibus database. High‐confidence protein–protein interaction (PPI) data were downloaded from the Human Protein Reference Database, and gene expression data of immune‐ and CJD‐associated genes were downloaded from the AmiGo16 and DisGeNET databases, respectively. An immune/CJD‐related expression network was constructed based on Pearson correlation coefficients and PPI networks, and a CJD‐directed neighbour coexpression network was extracted, in which we compared the gene expression patterns and correlations between different groups. The samples were classified using CJD‐specific modules, and differentially expressed genes (DEGs) between the CJD and nonneurological controls groups were identified within the CJD‐specific modules. Further functional analysis was performed using Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis of genes in each CJD‐specific module.

Results

We constructed an immune/CJD‐related coexpression gene network comprising 2007 nodes and 5268 edges, with immune‐associated genes occupying important positions in the network. In the CJD‐directed neighbour coexpression network, immune‐associated genes exhibited the highest coexpression level with their interacting genes. Results from Pearson correlation analysis showed that most of the CJD‐associated genes were positively correlated with immune‐associated genes. Screening for CJD‐specific modules identified MAPK1, CASP3, APP, MAPT, SNCA, and YWHAH, indicating a close connection between CJD and the immune response. Analyses of coexpression status and expression level of CJD‐specific genes revealed a very high coexpression pattern for any two genes, with most genes being DEGs. Finally, KEGG enrichment analyses of all CJD‐specific genes showed that the pathophysiology of CJD is closely related to infection and the immune response.

Conclusions

Our coexpression network analysis revealed a close connection between CJD‐ and immune‐associated genes, and we identified six CJD‐specific modules. Biological function analysis of CJD‐specific module genes revealed that immune responses are associated with CJD pathophysiology and may provide novel diagnostic and therapeutic biomarkers for this disease.

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Authors:
Xiaoou Hai, Jiaming Zhou and Guangyan Liu
Article first published online:
31 Aug 2021 | DOI: 10.1111/ene.15063

ORIGINAL ARTICLE

Background

In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without thunderclap headache (TCH), and tended to present more severe forms of RCVS than patients with TCH. We aimed to analyze the risk for complications of RCVS in patients with and without TCH at onset.

Methods

In a pooled cohort of 345 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of neurological complications, and the functional outcome at 3 months.

Results

As compared to the 281 patients with TCH at onset, the 64 patients without TCH had a higher risk for any neurological complication (61% vs. 24%, OR 4.9, 95% CI 2.8–8.7,  < 0.001). The association was strongest for cervical artery dissections (28% vs. 5%, OR 8.1, 95% CI 3.7–17.6,  < 0.001), followed by posterior reversible encephalopathy syndrome (17% vs. 3%, OR 7.1, 95% CI 2.7–18.4,  < 0.001), seizures (9% vs. 2.5%, OR 4.1, 95% CI 1.3–12.5,  = 0.019), and subarachnoid hemorrhage (41% vs. 16%, OR 3.5, 95% CI 1.9–6.3,  < 0.001). In multivariable analysis, the risk for any neurological complication remained significantly elevated in the absence of TCH (OR 3.5, 95% CI 1.8–6.8,  < 0.001). The functional outcome was equal in both groups, with a modified Rankin scale score of 0–1 in ≥90% of patients.

Conclusions

Absence of TCH at onset might predict a higher risk of complications in RCVS. Our results warrant further multicentric studies to prove this finding.

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Authors:
Kristin Sophie Lange, Ophélie Forster, Jérôme Mawet, Gabrielle Tuloup, Cécilia Burcin, Lucas Corti, Claire Duflos, Caroline Roos and Anne Ducros
Article first published online:
24 Aug 2021 | DOI: 10.1111/ene.15064

ORIGINAL ARTICLE

Background and purpose

Magnetic resonance imaging (MRI) is commonly used in the diagnostic work‐up for status epilepticus (SE). The purpose of this study was to characterize MRI features in SE patients and determine their association with clinical and electroencephalography (EEG) findings. The mid‐term consequences of baseline MRI features were also analysed.

Methods

This is a prospective study including consecutive patients with SE who underwent brain MRI within 240 h after SE onset. The MRI protocol included T1‐weighted (T1WI), T2‐weighted (T2W), fluid‐attenuated inversion recovery (FLAIR) and diffusion‐weighted imaging (DWI) sequences. Follow‐up MRI was performed after SE resolution in some patients.

Results

Sixty patients (56.7% men, mean age 58.3 years) were included. SE‐related MRI abnormalities were seen in 31 (51.7%), manifesting as hyperintensities on T2W/FLAIR imaging (58.1%) and DWI (74.2%) sequences. Hippocampal and pulvinar involvement was seen in 58.0% and 25.8% of patients, respectively. MRI abnormalities were associated with a longer SE duration ( = 0.013) and the presence of lateralized periodic discharges (LPDs) on EEG ( < 0.001). Amongst the 33 follow‐up MRIs, nine (27.3%) showed mesial temporal sclerosis (MTS), which was associated with severe clinical status ( = 0.031), hippocampal oedema ( = 0.001) and LPDs ( = 0.001) at baseline. A poorer clinical outcome was associated with baseline T2W/FLAIR imaging hyperintensities ( = 0.003).

Conclusion

MRI showed abnormalities in more than half of SE patients. A longer SE duration and LPDs on EEG were associated with SE‐related MRI abnormalities and the development of MTS.

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Authors:
Silvana Sarria‐Estrada, Estevo Santamarina, Manuel Quintana, Deborah Pareto, Maria Sueiras, Cristina Auger, Manuel Toledo and Alex Rovira
Article first published online:
03 Sep 2021 | DOI: 10.1111/ene.15065

ORIGINAL ARTICLE

Background and purpose

Modifiable lifestyle factors, including diet, may affect clinical outcomes in multiple sclerosis (MS). This study assessed the relationships between diet, and disability, fatigue, and depression risk in people with MS.

Methods

Participants from the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) international cohort were assessed over 2.5 years. Dietary data were obtained using a modified Diet Habits Questionnaire (DHQ), disability using the calculated Patient‐determined MS Severity Score (P‐MSSS), fatigue using the Fatigue Severity Scale, and depression risk using the Patient Health Questionnaire‐2. Participants reported whether they were experiencing symptoms due to a recent relapse. Cross‐sectional and prospective relationships of diet and disease outcomes were explored, adjusted for relevant confounders.

Results

Among 1,346 participants, higher DHQ scores showed significant dose‐dependent associations with lower frequencies of severe disability, fatigue, and depression risk, cross‐sectionally. Prospectively, higher baseline DHQ scores were associated with a lower risk of increasing disability, those above the median having 41% and 36% lower risk of increasing disability, and 0.30 P‐MSSS points less disability progression, but were not associated with fatigue or depression risk. Meat consumption was associated with 0.22 P‐MSSS points higher disability cross‐sectionally, while prospectively, baseline meat consumption was associated with 76% higher risk of increasing disability and 0.18 P‐MSSS points higher disability progression. Dairy consumption showed mixed associations cross‐sectionally and prospectively.

Conclusions

These results show that better quality of diet, as well as not consuming meat, were associated with reduced disability progression in people with MS. Substantiation of these findings in other settings may inform opportunities to manage disability progression in people with MS using dietary modifications.

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Authors:
Steve Simpson‐Yap, Nupur Nag, Yasmine Probst, George Jelinek and Sandra Neate
Article first published online:
26 Aug 2021 | DOI: 10.1111/ene.15066

ORIGINAL ARTICLE

Background

Magnetic resonance imaging (MRI) provides insight into various pathological processes in multiple sclerosis (MS) and may provide insight into patterns of damage among patients.

Objective

We sought to determine if MRI features have clinical discriminative power among a cohort of MS patients.

Methods

Ninety‐six relapsing remitting and seven progressive MS patients underwent myelin water fraction (MWF) imaging and conventional MRI for cortical thickness and thalamic volume. Patients were clustered based on lesion level MRI features using an agglomerative hierarchical clustering algorithm based on principal component analysis (PCA).

Results

One hundred and three patients with 1689 MS lesions were analyzed. PCA on MRI features demonstrated that lesion MWF and volume distributions (characterized by 25th, 50th, and 75th percentiles) accounted for 87% of the total variability based on four principal components. The best hierarchical cluster confirmed two distinct patient clusters. The clustering features in order of importance were lesion median MWF, MWF 25th, MWF 75th, volume 75th percentiles, median individual lesion volume, total lesion volume, cortical thickness, and thalamic volume (all values <0.01368). The clusters were associated with patient Expanded Disability Status Scale (EDSS) ( = 103, = 0.0338) at baseline and at 5 years ( = 72, = 0.0337).

Conclusions

These results demonstrate that individual MRI features can identify two patient clusters driven by lesion‐based values, and our unique approach is an analysis blinded to clinical variables. The two distinct clusters exhibit MWF differences, most likely representing individual remyelination capabilities among different patient groups. These findings support the concept of patient‐specific pathophysiological processes and may guide future therapeutic approaches.

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Authors:
Sandra M. Hurtado Rúa, Ulrike W. Kaunzner, Sneha Pandya, Elizabeth Sweeney, Ceren Tozlu, Amy Kuceyeski, Thanh D. Nguyen and Susan A. Gauthier
Article first published online:
29 Aug 2021 | DOI: 10.1111/ene.15067

ORIGINAL ARTICLE

Background and purpose

Sialorrhea often happens in patients with neurologic disorders, and botulinum toxin (BoNT), which inhibits acetylcholine activation, may be an effective treatment for drooling. This systematic review and meta‐analysis of randomized control trials aims to evaluate the efficacy and safety of BoNT in adults and children with sialorrhea due to neurological disorders.

Methods

The PubMed, Embase, and Cochrane databases were searched for relevant studies published before August 2021. The pooled estimate of outcomes was calculated using a random effect model.

Results

The review included 17 studies involving 981 patients. Compared with placebo, both BoNT type A (BoNT‐A) and BoNT type B (BoNT‐B) alleviated drooling frequency and severity (mean difference, 95% CI; BoNT‐A: −1.20, −1.89 to −0.51; BoNT‐B: −1.62, −2.07 to −1.17), reduced saliva weight (BoNT‐A: −1.70, −2.30 to −1.10; BoNT‐B: −1.12, −1.97 to −0.27), and improved global impression of change (BoNT‐A: −1.30, −1.73 to −0.86; BoNT‐B: −1.58, −1.95 to −1.21) in adults 4 weeks postinjection. BoNT‐B remained effective at 12 weeks. In children, BoNT‐A and BoNT‐B alleviated sialorrhea symptoms (BoNT‐A: −1.63, −2.42 to −0.85; BoNT‐B: −5.20, −6.03 to −4.37) and BoNT‐A reduced saliva weight (−0.77, −1.54 to 0.00) at 4 weeks postinjection. After 12 weeks, BoNT‐B remained efficacious. Most adverse effects (AEs) were mild to moderate and self‐limited.

Conclusions

There is moderate certainty of evidence (COE) that either BoNT‐A or BoNT‐B could relieve sialorrhea after 4 and 12 weeks of follow‐up without significantly more severe AEs in adults. However, the COE is very low to low in children.

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Authors:
Ya‐Chien Yu, Chen‐Chih Chung, Yu‐Kang Tu, Chien‐Tai Hong, Kee‐Hsin Chen, Ka‐Wai Tam and Yi‐Chun Kuan
Article first published online:
12 Sep 2021 | DOI: 10.1111/ene.15083

SHORT COMMUNICATION

Background and purpose

The European Federation of Neurological Associations (EFNA), in partnership with the NeuroCOVID‐19 taskforce of the European Academy of Neurology (EAN), has investigated the impact of the first wave of the COVID‐19 pandemic on individuals with neurological diseases, as well as the hopes and fears of these patients about the post‐pandemic phase.

Methods

An EFNA‐EAN survey was available online to any person living with a neurological disorder in Europe. It consisted of 18 items concerning the impact of the first wave of the COVID‐19 pandemic on the medical care of people with neurological disorders, and the hopes and fears of these individuals regarding the post‐pandemic phase.

Results

For 44.4% of the 443 survey participants, the overall care of their neurological disease during the pandemic was inappropriate. This perception was mainly due to significant delays in accessing medical care (25.7%), insufficiently reliable information received about the potential impact of COVID‐19 on their neurological disease (49.6%), and a substantial lack of involvement in their disease management decisions (54.3%). Participants indicated that their major concerns for the post‐pandemic phase were experiencing longer waiting times to see a specialist (24.1%), suffering from social isolation and deteriorating mental well‐being (23.1%), and facing delays in clinical trials with disinvestment in neuroscience research (13.1%).

Conclusions

Despite the great efforts of health services to cope with the first wave of the COVID‐19 pandemic, individuals with neurological conditions feel they have been left behind. These findings provide invaluable insights for improving the care of patients with neurological disorders in the further course of the COVID‐19 pandemic.

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Authors:
Benedetta Bodini, Elena Moro, Joke Jaarsma, Elizabeth Cunningham, Johann Sellner, Donna Walsh, Claudio L. Bassetti, Ettore Beghi, Daniel Bereczki, Benedetta Bodini, Anja Burlica, Francesco Cavallieri, Michael Crean, Giovanni Di Liberto, Raimund Helbok, Thomas M. Jenkins, Antonella Macerollo, Luis F. Maia, Elena Moro, Celia Oreja‐Guevara, Serefnur Özturk, Martin Rakusa, Anna Sauerbier, Johann Sellner, Riccardo Soffietti, Pille Taba, Antonio Pisani, Alberto Priori, Tim J. von Oertzen and Marialuisa Zedde
Article first published online:
05 Oct 2021 | DOI: 10.1111/ene.15087

ORIGINAL ARTICLE

Background and purpose

Knowledge about the seizure prevalence in the whole symptomatic course, from disease onset to death, in neurodegenerative diseases (ND) is lacking. Therefore, the aim was to investigate seizure prevalence and associated clinical implications in neuropathologically diagnosed ND.

Methods

Clinical records of cases from the Neurobiobank Munich, Germany, were analyzed. Neuropathological diagnoses of the assessed cases included Alzheimer disease (AD), corticobasal degeneration (CBD), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Seizure prevalence during the whole symptomatic disease phase was assessed and compared amongst ND. Associations between first clinical symptom and seizure prevalence and between seizures and disease duration were examined.

Results

In all, 454 patients with neuropathologically diagnosed ND and with available and meaningful clinical records were investigated (AD,  = 144; LBD,  = 103; PSP,  = 93; FTLD,  = 53; MSA,  = 36; CBD,  = 25). Seizure prevalence was 31.3% for AD, 20.0% for CBD, 12.6% for LBD, 11.3% for FTLD, 8.3% for MSA and 7.5% for PSP. Seizure prevalence was significantly higher in AD compared to FTLD ( = 0.005), LBD ( = 0.001), MSA ( = 0.005) and PSP ( < 0.001). No other significant differences regarding seizure prevalence were found between the studied ND. Cognitive first symptoms in ND were associated with an increased seizure prevalence (21.1% vs. 11.0% in patients without cognitive first symptoms) and motor first symptoms with a decreased seizure prevalence (10.3% vs. 20.5% in patients without motor first symptoms). Seizures were associated with a longer disease duration in MSA (12.3 vs. 7.0 years in patients without seizures;  = 0.017).

Conclusions

Seizures are a clinically relevant comorbidity in ND, particularly in AD. Knowledge of the first clinical symptom in ND may allow for estimation of seizure risk.

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Authors:
Jonathan Vöglein, Irena Kostova, Thomas Arzberger, Soheyl Noachtar, Marianne Dieterich, Jochen Herms, Peer Schmitz, Viktoria Ruf, Otto Windl, Sigrun Roeber, Mikael Simons, Günter U. Höglinger, Adrian Danek, Armin Giese and Johannes Levin
Article first published online:
17 Sep 2021 | DOI: 10.1111/ene.15089

SHORT COMMUNICATION

Background and purpose

Globular glial tauopathies (GGTs) have heterogeneous presentations; little evidence regarding typical clinical and magnetic resonance imaging (MRI) presentations are available.

Methods

We retrospectively assessed MRIs from three postmortem‐confirmed GGT cases, in two patients with atypical progressive aphasia and one with corticobasal syndrome.

Results

We suggest that four principal concomitant MRI findings characterize GGT type I: a sagittal callosal hyperintense band, marked focal callosal atrophy suggesting white matter degeneration originating in cortical areas responsible for symptoms (anterior atrophy in predominantly language manifestations and posterior atrophy in predominantly apraxia), periventricular white matter lesions, and mild‐to‐moderate brain stem atrophy.

Conclusions

We observed four concomitant MRI abnormalities in patients with atypical dementia, parkinsonism, and late incomplete supranuclear gaze palsy. Two patients had atypical progressive aphasia and one had corticobasal syndrome.

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Authors:
Jiri Keller, Anna Kavkova, Radoslav Matej, Zsolt Cséfalvay and Robert Rusina
Article first published online:
12 Sep 2021 | DOI: 10.1111/ene.15090

SHORT COMMUNICATION

Background

Although hereditary ataxias are a group of clinically and genetically heterogeneous disorders, specific clinical clues can sometimes incriminate certain genes. This can trigger genetic testing in sporadic patients or prompt dissecting certain genes more thoroughly when initial genetic testing is negative. Also for the assembly of gene panels and interpretation of the results, genotype−phenotype correlations remain important to establish.

Methods

We clinically evaluated a Belgian family with autosomal dominant inherited sensory ataxia and variable pyramidal involvement and performed targeted clinical exome sequencing. Secondly, we retrospectively screened sequencing data of an in‐house cohort of 404 patients with neuromuscular disorders for variants in the identified gene .

Results

All affected family members showed sensory ataxia on examination. Pyramidal involvement, and sometimes slow‐pursuit abnormalities and/or a sensory neuropathy, were more variable findings. We identified the heterozygous variant p.Arg199Cys in in all three affected siblings of our family. We did not find additional pathogenic variants in in our in‐house neuromuscular cohort.

Conclusions

We confirm the heterozygous variant p.Arg199Cys in in a Belgian family with autosomal dominant sensory ataxia and variable pyramidal involvement. This constitutes a rare but clinically recognizable phenotype that warrants testing of . Unlike the distinctive bi‐allelic loss of function variants in associated with hereditary spastic paraplegia (HSP), the p.Arg199Cys variant is the only one reported in sensory ataxia. It is important for neurologists to be aware of this characteristic phenotype and to include this gene in gene panels for ataxia and HSP.

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Authors:
Sien H. Van Daele, Matthieu Moisse, Valérie Race, Amélie Van Eesbeeck, Liesbeth Keldermans, Sascha Vermeer, Hilde Van Esch, Kristl G. Claeys and Philip Van Damme
Article first published online:
17 Sep 2021 | DOI: 10.1111/ene.15091

ORIGINAL ARTICLE

Background

The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care.

Methods

The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre‐ and post‐interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct‐to‐center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke‐specific in situ simulation training. Primary outcome measure was the ‘door‐to‐needle’ time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre‐existing treatment algorithm.

Results

The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre‐intervention (interquartile range [IQR] 25–43 min) to 33 min (IQR 23–39 min,  = 0.03) post‐intervention achieved by simulation‐experienced stroke teams. Concerning EVT, we found significantly shorter door‐to‐groin times in patients who were treated by teams with simulation experience as compared to simulation‐naive teams in the post‐interventional phase (−21 min, simulation‐naive: 95 min, IQR 69–111 vs. simulation‐experienced: 74 min, IQR 51–92,  = 0.04).

Conclusion

An intervention combining workflow refinement and simulation‐based stroke team training has the potential to improve process times in acute stroke care.

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Authors:
Ferdinand O. Bohmann, Katharina Gruber, Natalia Kurka, Laurent M. Willems, Eva Herrmann, Richard du Mesnil de Rochemont, Peter Scholz, Heike Rai, Philipp Zickler, Michael Ertl, Ansgar Berlis, Sven Poli, Annerose Mengel, Peter Ringleb, Simon Nagel, Johannes Pfaff, Frank A. Wollenweber, Lars Kellert, Moriz Herzberg, Luzie Koehler, Karl Georg Haeusler, Anna Alegiani, Charlotte Schubert, Caspar Brekenfeld, Christopher E. J. Doppler, Özgür A. Onur, Christoph Kabbasch, Tanja Manser, Helmuth Steinmetz and Waltraud Pfeilschifter
Article first published online:
21 Oct 2021 | DOI: 10.1111/ene.15093

ORIGINAL ARTICLE

Background

The mechanisms underlying speech abnormalities in Parkinson's disease (PD) remain poorly understood, with most of the available evidence based on male patients. This study aimed to estimate the occurrence and characteristics of speech disorder in early, drug‐naive PD patients with relation to gender and dopamine transporter imaging.

Methods

Speech samples from 60 male and 40 female de novo PD patients as well as 60 male and 40 female age‐matched healthy controls were analyzed. Quantitative acoustic vocal assessment of 10 distinct speech dimensions related to phonation, articulation, prosody, and speech timing was performed. All patients were evaluated using [123]I‐2b‐carbomethoxy‐3b‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane single‐photon emission computed tomography and Montreal Cognitive Assessment.

Results

The prevalence of speech abnormalities in the de novo PD cohort was 56% for male and 65% for female patients, mainly manifested with monopitch, monoloudness, and articulatory decay. Automated speech analysis enabled discrimination between PD and controls with an area under the curve of 0.86 in men and 0.93 in women. No gender‐specific speech dysfunction in de novo PD was found. Regardless of disease status, females generally showed better performance in voice quality, consonant articulation, and pauses production than males, who were better only in loudness variability. The extent of monopitch was correlated to nigro‐putaminal dopaminergic loss in men ( = 0.39,  = 0.003) and the severity of imprecise consonants was related to cognitive deficits in women ( = −0.44,  = 0.005).

Conclusions

Speech abnormalities represent a frequent and early marker of motor abnormalities in PD. Despite some gender differences, our findings demonstrate that speech difficulties are associated with nigro‐putaminal dopaminergic deficits.

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Authors:
Jan Rusz, Tereza Tykalová, Michal Novotný, David Zogala, Evžen Růžička and Petr Dušek
Article first published online:
17 Sep 2021 | DOI: 10.1111/ene.15099

SHORT COMMUNICATION

Background and purpose

Previous observational studies have reported that patients with migraine have an increased risk of stroke. We explored whether migraine has a causal effect on stroke using a two‐sample Mendelian randomization approach.

Methods

Genetic instruments were selected from large genome‐wide association studies of migraine and stroke. A two‐sample Mendelian randomization analysis was performed, along with sensitivity analysis. We used migraine subtypes (any migraine, migraine with aura, migraine without aura) as risk factors and stroke, ischemic stroke, and hemorrhagic stroke as outcomes for this analysis. Ischemic stroke subtypes were also included to explore the underlying pathogenesis linking migraine to stroke.

Results

Migraine did not show any association with stroke (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.87–1.03), ischemic stroke (OR, 0.93; 95% CI, 0.85–1.02), or hemorrhagic stroke (OR, 1.26; 95% CI, 0.84–1.91), suggesting that the observed association may not be causal. Neither migraine with aura nor without aura showed causal relationship with outcomes. The sensitivity analysis supported the results of the primary analysis. Regarding ischemic stroke subtypes, migraine seemed to have a negative association with large‐artery atherosclerosis (OR, 0.81; 95% CI, 0.68–0.95), whereas associations with small‐vessel occlusion or cardioembolism were not evident.

Conclusions

Contrary to previous observational studies, we were unable to find any causal relationship between migraine and stroke. However, the suggested negative association of migraine in large‐artery atherosclerosis warrants further research.

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Authors:
Keon‐Joo Lee, Soo Ji Lee, Hee‐Joon Bae and Joohon Sung
Article first published online:
26 Sep 2021 | DOI: 10.1111/ene.15101

ORIGINAL ARTICLE

Background and purpose

Atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long‐term rhythm monitoring. There is an unmet need for a pre‐selection of CS patients benefitting from such work‐up. A clinical risk score was therefore developed for the prediction of AF after CS and its performance was evaluated over 1 year of follow‐up.

Methods

Our proposed risk score ranges from 0 to 16 points and comprises variables known to be associated with occult AF in CS patients including age, N‐terminal pro‐brain natriuretic peptide, electrocardiographic and echocardiographic features (supraventricular premature beats, atrial runs, atrial enlargement, left ventricular ejection fraction) and brain imaging markers (multi‐territory/prior cortical infarction). All CS patients admitted to our Stroke Unit between March 2018 and August 2019 were prospectively followed for AF detection over 1 year after discharge.

Results

During the 1‐year follow‐up, 24 (16%) out of 150 CS patients with AF (detected via electrocardiogram controls, = 18; loop recorder monitoring, = 6) were diagnosed. Our predefined AF Risk Score (cutoff ≥4 points; highest Youden's index) had a sensitivity of 92% and a specificity of 67% for 1‐year prediction of AF. Notably, only two CS patients with <4 score points were diagnosed with AF later on (negative predictive value 98%).

Conclusions

A clinical risk score for 1‐year prediction of AF in CS with high sensitivity, reasonable specificity and excellent negative predictive value is presented. Generalizability of our score needs to be tested in external cohorts with continuous cardiac rhythm monitoring.

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Authors:
Markus Kneihsl, Egbert Bisping, Daniel Scherr, Harald Mangge, Simon Fandler‐Höfler, Isabella Colonna, Melanie Haidegger, Sebastian Eppinger, Edith Hofer, Franz Fazekas, Christian Enzinger and Thomas Gattringer
Article first published online:
23 Sep 2021 | DOI: 10.1111/ene.15102

REVIEW ARTICLE

Background and purpose

Many migraine patients rely on over‐the‐counter analgesics for the treatment of migraine attacks. Fixed‐dose combinations of aspirin, paracetamol and caffeine (APC) have been used for treating migraine in many countries for a long time. We performed a meta‐analysis for the comparison of APC versus placebo, which has not been done to date.

Methods

Randomized, blinded, placebo‐controlled, parallel‐group studies using APC to treat a migraine attack were included in a meta‐analysis. We calculated the rate ratio (RRs) associated with APC versus placebo.

Results

Seven studies were included, with 3306 participants (2147 treated with APC and 1159 treated with placebo). For the primary efficacy outcome, being pain‐free at 2 h, APC was superior to placebo (19.6% vs. 9.0%, RR 2.2, 95% confidence interval [CI] 1.4–3.3). For the co‐primary efficacy outcome, pain relief at 2 h, APC was superior to placebo (54.3% vs. 31.2%, RR 1.7, 95% CI 1.6–1.9). Adverse events were more frequent in the APC than the placebo groups (10.9% vs. 7.8%, RR 1.7, 95% CI 1.3–2.2).

Conclusions

Results showed that APC is superior to placebo in the treatment of acute migraine attacks. Efficacy, measured by pain‐free response and pain relief at 2 h, was clinically relevant.

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Authors:
Hans Christoph Diener, Charly Gaul, Walter Lehmacher and Thomas Weiser
Article first published online:
28 Sep 2021 | DOI: 10.1111/ene.15103

ORIGINAL ARTICLE

Background and purpose

Pitt–Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by deletions/variants in the gene. Seizures may be present in up to half of the patients, leading to a more severe disease burden. This study aims to analyse the electroclinical phenotype, treatment options, and long‐term outcomes of epilepsy in PTHS.

Methods

A multicentre observational cohort study was performed, and the electroclinical data of PTHS individuals affected by epileptic seizures were retrospectively reviewed and analysed.

Results

The series includes 21 patients (11 female) with a median age at seizure onset of 2 years (range = 0.5–8). The median time of follow‐up was 7.9 years (range = 2–27). Both generalized and focal epilepsies were present at the same prevalence (42.8%), whereas a minority of patients presented developmental and epileptic encephalopathies (14.4%). At the long‐term follow‐up, 42.8% achieved seizure freedom, whereas 42.8% developed drug‐resistant epilepsy (DRE). The age at seizure onset was found to be an independent predictor for seizure outcome; in this regard, patients having seizure onset after the age of 2 years were more prone to achieve seizure freedom (odds ratio = 0.04, 95% confidence interval = 0.003–0.53; = 0.01). During evolution, seizures tended to settle down, and even in patients with DRE, seizures tended to persist at a lower frequency and appeared to be more easily manageable over time.

Conclusions

This study provides new insight into the natural history of epilepsy in PTHS. Better characterization of epileptic phenotype and prompt tailored treatment improve overall management and quality of life.

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Authors:
Sara Matricardi, Paolo Bonanni, Giulia Iapadre, Maurizio Elia, Elisabetta Cesaroni, Alberto Danieli, Susanna Negrin, Luca Zagaroli, Francesca Felicia Operto, Marco Carotenuto, Francesco Pisani, Emanuela Claudia Turco, Alessandro Orsini, Alice Bonuccelli, Salvatore Savasta, Daniela Concolino, Giuseppe Di Cara, Pasquale Striano and Alberto Verrotti
Article first published online:
07 Oct 2021 | DOI: 10.1111/ene.15104

ORIGINAL ARTICLE

Background and purpose

To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia (TN) and to explore the predictive ability of MRI for initial surgical outcome and long‐term pain relief/recurrence after Gamma Knife radiosurgery (GKS).

Methods

Thirty patients with idiopathic or classic TN, who underwent GKS and were followed for at least 24 months, were retrospectively included. Pre‐treatment structural MRI and pre‐ and serial, postoperative clinical features were investigated. Fifteen age‐ and sex‐matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non‐responders, patients with pain recurrence/long‐lasting pain relief at the last follow‐up). Clinical and MRI predictors of treatment outcomes were explored.

Results

Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. No cortical thickness and GM volume differences were observed when TN initial responders and non‐responders were compared. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long‐lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKS at the last follow‐up (=0.57, <0.001).

Conclusion

The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.

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Authors:
Luigi Albano, Federica Agosta, Silvia Basaia, Antonella Castellano, Roberta Messina, Veronica Parisi, Lina Raffaella Barzaghi, Andrea Falini, Pietro Mortini and Massimo Filippi
Article first published online:
24 Sep 2021 | DOI: 10.1111/ene.15105

ORIGINAL ARTICLE

Background and purpose

The purpose was to evaluate whether intracranial interictal epileptiform discharges (IEDs) that are not visible on the scalp are associated with changes in the frequency spectrum on scalp electroencephalograms (EEGs).

Methods

Simultaneous scalp high‐density EEG and intracranial EEG recordings were recorded in nine patients undergoing pre‐surgical invasive recordings for pharmaco‐resistant temporal lobe epilepsy. Epochs with hippocampal IED visible on intracranial EEG (ic‐IED) but not on scalp EEG were selected, as well as control epochs without ic‐IED. Welch's power spectral density was computed for each scalp electrode and for each subject; the power spectral density was further averaged across the canonical frequency bands and compared between the two conditions with and without ic‐IED. For each patient the peak frequency in the delta band (the significantly strongest frequency band in all patients) was determined during periods of ic‐IED. The five electrodes showing strongest power at the peak frequency were also determined.

Results

It was found that intracranial IEDs are associated with an increase in delta power on scalp EEGs, in particular at a frequency ≥1.4 Hz. Electrodes showing slow frequency power changes associated with IEDs were consistent with the hemispheric lateralization of IEDs. Electrodes with maximum power of slow activity were not limited to temporal regions but also involved frontal (bilateral or unilateral) regions.

Conclusions

In patients with a clinical picture suggestive of temporal lobe epilepsy, the presence of delta slowing ≥1.4 Hz in anterior temporal regions can represent a scalp marker of hippocampal IEDs. To our best knowledge this is the first study that demonstrates the co‐occurrence of ic‐IED and increased delta power.

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Authors:
Pia De Stefano, Margherita Carboni, Renaud Marquis, Laurent Spinelli, Margitta Seeck and Serge Vulliemoz
Article first published online:
27 Sep 2021 | DOI: 10.1111/ene.15106

ORIGINAL ARTICLE

Background

Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH).

Methods

Participants of the Helsinki Small Vessel Disease Study ( = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation.

Results

Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single‐leg stance, timed up‐and‐go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant‐evaluated IADL, but not on self‐evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up‐and‐go performance.

Conclusion

The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.

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Authors:
Hanna Jokinen, Hanna M. Laakso, Matti Ahlström, Anne Arola, Juha Lempiäinen, Johanna Pitkänen, Teemu Paajanen, Sietske A. M. Sikkes, Juha Koikkalainen, Jyrki Lötjönen, Antti Korvenoja, Timo Erkinjuntti and Susanna Melkas
Article first published online:
26 Sep 2021 | DOI: 10.1111/ene.15108

ORIGINAL ARTICLE

Background and purpose

The spinal cord central echo complex (SCCEC) is a special ultrasonography‐based intramedullary structure, but its clinical significance in degenerative cervical myelopathy (DCM) is undefined. This study aimed to explore the potential of the SCCEC in predicting postoperative neurological recovery in DCM.

Methods

Thirty‐two DCM patients who underwent intraoperative ultrasonography‐guided French‐door laminoplasty were prospectively enrolled. The modified Japanese Orthopaedic Association (mJOA) score was evaluated preoperatively and 12 months postoperatively. SCCEC width (SCCEC‐W), and anteroposterior diameter (APD) and transverse diameter (TD) of the spinal cord were measured on transverse ultrasonographic images, while the tissue widths from anterior and posterior borders of the spinal cord to the SCCEC were measured on sagittal ultrasonographic images. The APD of the spinal cord and occupying rate of the spinal canal were measured on preoperative magnetic resonance imaging (MRI).

Results

All patients achieved improvements in mJOA scores, with an average recovery rate (RR) of 68.69 ± 20.22%. Spearman correlation analysis revealed that SCCEC‐W, and ratios between the SCCEC‐W and APD/TD based on ultrasonography, correlated moderately with mJOA score RR, with coefficients of −0.527, −0.605 and −0.514, respectively. The ratio between SCCEC‐W and ultrasonographic TD correlated moderately with preoperative APD of the spinal cord. The MRI measurements and ultrasonography‐based tissue widths showed no significant correlation with mJOA score RR.

Conclusions

The SCCEC may have predictive potential as an intraoperative indicator of neurological recovery in treating DCM. SCCEC‐W may be related to spinal cord compression in DCM.

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Authors:
Guoliang Chen, Huachuan Wu, Ningning Chen, Meng Wang, Liangyu Shi, Jiachun Li, Fuxin Wei, Zuofeng Xu, Xizhe Liu and Shaoyu Liu
Article first published online:
30 Sep 2021 | DOI: 10.1111/ene.15109

ORIGINAL ARTICLE

Background and purpose

The distribution of the major modifiable risk factors for intracerebral hemorrhage (ICH) changes rapidly. These changes call for contemporary data from large‐scale population‐based studies. The aim of the present study was to examine trends in incidence, risk factors, and mortality in ICH patients from 2004 to 2017.

Methods

In a population‐based cohort study, we calculated age‐ and sex‐standardized incidence rates (SIRs), incidence rates (IRs) stratified by age and sex per 100,000 person‐years, and trends in risk profiles. We estimated absolute mortality risk, and the Cox proportional hazards regression multivariable‐adjusted hazard ratios for 30‐day and 1‐year mortality.

Results

We included 16,902 patients (53% men; median age 75 years) from 2004 to 2017. The SIR of ICH decreased from 33 (95% confidence interval [CI] 32–34) in 2004/2005 to 28 (95% CI 27–29) in 2016/2017. Among patients aged ≥70 years, the IR decreased from 137 (95% CI 130–144) in 2004/2005 to 112 (95% CI 106–117) in 2016/2017. The IR in patients aged <70 years was unchanged. From 2004 to 2017, the proportion of patients with hypertension increased from 49% to 66%, the use of oral anticoagulants increased from 7% to 18%, and the use of platelet inhibitors decreased from 40% to 28%. The adjusted hazard ratio for 30‐day mortality in 2016/2017 was 0.94 (95% CI 0.89–1.01) and 1‐year mortality was 0.98 (95% CI 0.93–1.04) compared with 2004/2005.

Conclusion

The incidence of spontaneous ICH decreased from 2004 to 2017, with no clear trend in mortality. The risk profile of ICH patients changed substantially, with increasing proportions of hypertension and anticoagulant treatment. Given the high mortality rate of ICH, further advances in prevention and treatment are urgently needed.

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Authors:
Tine Glavind Bülow Pedersen, Nicklas Vinter, Morten Schmidt, Lars Frost, Pia Cordsen, Grethe Andersen and Søren Paaske Johnsen
Article first published online:
28 Sep 2021 | DOI: 10.1111/ene.15110

ORIGINAL ARTICLE

Background

SMASH‐U is a systematic aetiological classification system for intracerebral haemorrhage (ICH) proven to be a predictor of post‐ICH haematoma expansion and mortality. However, its role in predicting functional outcome remains elusive. Therefore, we aimed to investigate whether SMASH‐U is associated with long‐term functional outcome after ICH and improves the accuracy of prediction when added to max‐ICH score.

Methods

Consecutive acute ICH patients from 2012 to 2018 from the neurology department of Tongji Hospital were enrolled. ICH aetiology was classified according to the SMASH‐U system. The association of SMASH‐U with 12‐month functional outcome after ICH and the predictive value were evaluated.

Results

Of 1938 ICH patients, the aetiology of 1295 (66.8%) patients were classified as hypertension, followed by amyloid angiopathy ( = 250, 12.9%), undetermined ( = 159, 8.2%), structural lesions ( = 149, 7.7%), systemic disease ( = 74, 3.8%) and medication ( = 11, 0.6%). The baseline characteristics were different among the six aetiologies. In multivariate analysis, SMASH‐U was proven to be a predictor of 12‐month unfavourable functional outcome. When adding the SMASH‐U system, the predictive performance of max‐ICH score was improved (area under the receiver operating characteristic curve from 0.802 to 0.812,  = 0.010) and the predictive accuracy was enhanced (integrated discrimination improvement [IDI]: 1.60%,  < 0.001; continuous net reclassification improvement [NRI]: 28.16%,  < 0.001; categorical NRI: 3.34%,  = 0.004).

Conclusions

SMASH‐U predicted long‐term unfavourable functional outcomes after acute ICH and improved the accuracy of prediction when added to max‐ICH score. Integrating the aetiology to a score model to predict the post‐ICH outcome may be meaningful and worthy of further exploration.

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Authors:
Yuchao Jia, Guo Li, Guini Song, Xiaodong Ye, Yuyan Yang, Kai Lu, Shanshan Huang and Suiqiang Zhu
Article first published online:
30 Sep 2021 | DOI: 10.1111/ene.15111

SHORT COMMUNICATION

Background and purpose

High mortality rates have been reported in patients with cerebral venous sinus thrombosis (CVST) due to vaccine‐induced immune thrombotic thrombocytopenia (VITT) after vaccination with adenoviral vector SARS‐CoV‐2 vaccines. The aim of this study was to evaluate whether the mortality of patients with CVST‐VITT has decreased over time.

Methods

The EudraVigilance database of the European Medicines Agency was used to identify cases of CVST with concomitant thrombocytopenia occurring within 28 days of SARS‐CoV‐2 vaccination. Vaccines were grouped based on vaccine type (adenoviral or mRNA). Cases with CVST onset until 28 March were compared to cases after 28 March 2021, which was the day when the first scientific paper on VITT was published.

Results

In total, 270 cases of CVST with thrombocytopenia were identified, of which 266 (99%) occurred after adenoviral vector SARS‐CoV‐2 vaccination (ChAdOx1 nCoV‐19,  = 243; Ad26.COV2.S,  = 23). The reported mortality amongst adenoviral cases with onset up to 28 March 2021 was 47/99 (47%, 95% confidence interval 37%–58%) compared to 36/167 (22%, 95% confidence interval 16%–29%) in cases with onset after 28 March ( < 0.001). None of the four cases of CVST with thrombocytopenia occurring after mRNA vaccination died.

Conclusion

The reported mortality of CVST with thrombocytopenia after vaccination with adenoviral vector‐based SARS‐CoV‐2 vaccines has significantly decreased over time, which may indicate a beneficial effect of earlier recognition and/or improved treatment on outcome after VITT.

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Authors:
Anita van de Munckhof, Katarzyna Krzywicka, Diana Aguiar de Sousa, Mayte Sánchez van Kammen, Mirjam R. Heldner, Katarina Jood, Erik Lindgren, Turgut Tatlisumak, Jukka Putaala, Johanna A. Kremer Hovinga, Saskia Middeldorp, Marcel Levi, Marcel Arnold, José M. Ferro and Jonathan M. Coutinho
Article first published online:
01 Oct 2021 | DOI: 10.1111/ene.15113

ORIGINAL ARTICLE

Background and purpose

Accurate epidemiological information is essential for the improved understanding of dystonia syndromes, as well as better provisioning of clinical services and providing context for diagnostic decision‐making. Here, we determine epidemiological, social deprivation, and mortality characteristics of adult‐onset idiopathic dystonia in the Welsh population.

Methods

A retrospective population‐based cohort study using anonymized electronic health care data in Wales was conducted to identify individuals with dystonia between 1 January 1994 and 31 December 2017. We developed a case‐ascertainment algorithm to determine dystonia incidence and prevalence, as well as characterization of the dystonia cohort, based on social deprivation and mortality.

Results

The case‐ascertainment algorithm (79% sensitivity) identified 54,966 cases; of these cases, 41,660 had adult‐onset idiopathic dystonia (≥20 years). Amongst the adult‐onset form, the median age at diagnosis was 41 years, with males significantly older at time of diagnosis compared to females. Prevalence rates ranged from 0.02% in 1994 to 1.2% in 2017. The average annual incidence was 87.7/100,000/year, increasing from 49.9/100,000/year (1994) to 96.21/100,000/year (2017). In 2017, people with dystonia had a similar life expectancy to the Welsh population.

Conclusions

We have developed a case‐ascertainment algorithm, supported by the introduction of a neurologist‐reviewed validation cohort, providing a platform for future population‐based dystonia studies. We have established robust population‐level prevalence and incidence values for adult‐onset idiopathic forms of dystonia, with this reflecting increasing clinical recognition and identification of causal genes. Underlying causes of death mirrored those of the general population, including circulatory disorders, respiratory disorders, cancers, and dementia.

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Authors:
Grace A. Bailey, Anna Rawlings, Fatemeh Torabi, Owen Pickrell and Kathryn J. Peall
Article first published online:
15 Oct 2021 | DOI: 10.1111/ene.15114

SHORT COMMUNICATION

Background and purpose

Diagnostic criteria for adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony‐stimulating factor 1 receptor () mutation have recently been proposed. Our objective was to assess their accuracy in an independent multicenter cohort.

Methods

We evaluated the sensitivity and specificity of the diagnostic criteria for ALSP (including the “probable” and “possible” definitions) in a national cohort of 22 patients with mutation, and 59 patients with an alternative diagnosis of adult onset inherited leukoencephalopathy.

Results

Overall, the sensitivity of the diagnostic criteria for ALSP was 82%, including nine of 22 patients diagnosed as probable and nine of 22 diagnosed as possible. Twenty of the 59 mutation‐negative leukoencephalopathies fulfilled the diagnostic criteria, leading to a specificity of 66%.

Conclusions

Diagnostic criteria for ALSP have an overall limited sensitivity along with a modest specificity. We suggest that in patients suspected of genetic leukoencephalopathy, a comprehensive magnetic resonance imaging pattern‐based approach is warranted, together with white matter gene panel or whole exome sequencing.

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Authors:
Xavier Ayrignac, Clarisse Carra‐Dallière, Pekes Codjia, Kevin Mouzat, Giovanni Castelnovo, Emmanuel Ellie, Frédérique Etcharry‐Bouyx, Serge Belliard, Cecilia Marelli, Florence Portet, Isabelle Le Ber, Francoise Durand‐Dubief, Guillaume Mathey, Bruno Stankoff, Imen Dorboz, Severine Drunat, Odile Boespflug‐Tanguy, Nicolas Menjot de Champfleur, Serge Lumbroso, Fanny Mochel and Pierre Labauge
Article first published online:
28 Sep 2021 | DOI: 10.1111/ene.15115

ORIGINAL ARTICLE

Background and purpose

Multiple sclerosis (MS) is a chronic immune‐mediated disease of the central nervous system with an undetermined etiology. Retinoids may have immunomodulatory effects that favorably influence MS progression. We aimed to explore the yet unknown relationship between exposure to retinoids and the risk of acquiring MS.

Methods

We performed a nationwide cohort study in the Danish population in the period 1998–2016, comparing MS incidence in three groups: users of systemic retinoids; users of topical retinoids (negative control group); and users of non‐retinoid acne drugs (control group). We used data from the Danish Multiple Sclerosis Registry (DMSR), the Danish National Prescription Registry and the Danish National Patient Registry. Linkage was obtained through the personal identification number (CPR number). We addressed confounding by three‐way propensity score (PS)‐matching weights. Additionally, to evaluate a cumulative dose–response effect for systemic retinoids on MS incidence, we conducted a case–control study, nested within the cohort.

Results

A total of 257,193 users of non‐retinoid acne drugs, 130,560 users of topical retinoids, and 75,610 users of systemic retinoids were included. Systemic retinoid use was not associated with a reduced risk of MS compared to non‐retinoid acne drug use in crude (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61 to 1.05]) and weighted analyses (HR 0.89, 95% CI 0.67 to 1.20). There was no evidence of a cumulative dose–response association between systemic retinoids and MS incidence.

Conclusions

Use of systemic retinoids was not associated with a reduced incidence of MS compared to use of non‐retinoid acne drugs in this study.

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Authors:
Filipe Cortes‐Figueiredo, Nete Munk Nielsen, Egon Stenager, Friedemann Paul, Jesper Hallas and Kasper Bruun Kristensen
Article first published online:
30 Sep 2021 | DOI: 10.1111/ene.15116

ORIGINAL ARTICLE

Background

We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti‐IgLON5 disease.

Methods

We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow‐up outcomes.

Results

The median age of onset for symptoms was 60 (range: 33–73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein‐Barr virus (EBV)‐related anti‐IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow‐up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2).

Conclusions

The clinical spectrum of anti‐IgLON5 disease is variable. Our results highlight a boarder spectrum of anti‐IgLON5 disease.

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Authors:
You Ni, Dingding Shen, Ying Zhang, Yaying Song, Yining Gao, Qinming Zhou, Lu He, Dou Yin, Ying Wang, Fan Song, Meiyuan Chen, Yajun Lian, Yuan Chen, Xing Zhao, Xiang Zhang, Xiangjun Chen, Yuting Wang, Ling Zhang, Nanxun Mo, Dong Lv, Jun Liu, Zhifeng Mao, Lisheng Peng and Sheng Chen
Article first published online:
03 Oct 2021 | DOI: 10.1111/ene.15117

ORIGINAL ARTICLE

Background and purpose

Anti‐‐methyl‐‐aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti‐NMDAR encephalitis patients and its relationship with the executive function.

Methods

Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting‐state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups.

Results

Compared to controls, the patients had higher executive control scores ( < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83.

Conclusions

Our study provides evidence of abnormal cerebral function in anti‐NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti‐NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti‐NMDAR encephalitis patients from healthy controls.

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Authors:
Peirong Wu, Xiaomin Pang, Xiulin Liang, Wutong Wei, Xinrong Li, Jingyuan Zhao and Jinou Zheng
Article first published online:
03 Oct 2021 | DOI: 10.1111/ene.15119

ORIGINAL ARTICLE

Background and purpose

Real‐world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease‐modifying therapies (DMTs). Our aim was to provide real‐world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab.

Methods

Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation.

Results

We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow‐up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first‐line oral agents (56), first‐line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty‐five patients were treatment‐naïve. The pre‐alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment ( < 0.001). The number of previous‐year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38,  = 0.009). Progression‐free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re‐baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years.

Conclusions

Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.

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Authors:
Cinzia Valeria Russo, Francesco Saccà, Jessica Frau, Pietro Annovazzi, Elisabetta Signoriello, Simona Bonavita, Roberta Grasso, Marinella Clerico, Cinzia Cordioli, Alice Laroni, Marco Capobianco, Valentina Torri Clerici, Arianna Sartori, Paola Cavalla, Giorgia Teresa Maniscalco, Sara La Gioia, Francesca Caleri, Alessia Giugno, Rosa Iodice, Antonio Carotenuto, Eleonora Cocco, Giuseppe Fenu, Mauro Zaffaroni, Damiano Baroncini, Giacomo Lus, Antonio Gallo, Stefania Federica De Mercanti, Caterina Lapucci, Valeria Di Francescantonio, Laura Brambilla, Maria Pia Sormani and Alessio Signori
Article first published online:
05 Oct 2021 | DOI: 10.1111/ene.15121

REVIEW ARTICLE

Background and purpose

The effect of mirror therapy for unilateral neglect after stroke currently remains uncertain.

Methods

This systematic review investigated the effect of mirror therapy on neglect and daily living activities in patients with unilateral neglect after stroke when compared with no treatment, sham mirror therapy, or routinely applied therapies only. We performed a systematic electronic search of PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Data to identify relevant randomized control trials (RCTs).

Results

We included five RCTs in the data synthesis. Mirror therapy (combined or not with other treatments) was more effective in improving neglect as compared with sham mirror therapy or no treatment (combined or not with the other therapies; standard mean difference [SMD] = 1.62, 95% confidence interval [CI] = 1.03–2.21,  < 0.00001). Mirror therapy (combined or not with other therapies) was effective in improving daily living activities as compared with sham mirror therapy or no treatment (combined or not with the other therapies; SMD = 2.09, 95% CI = 0.63–3.56,  = 0.005).

Conclusions

Our results show that mirror therapy effectively improves neglect and daily living activities in patients with unilateral neglect after stroke. Future trials with high methodological quality and larger sample sizes are needed to determine the immediate and long‐term effect of appropriate mirror therapy protocol for unilateral neglect.

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Authors:
Yuqian Zhang, Ying Xing, Congqin Li, Yan Hua, Jian Hu, Yuyuan Wang, Ru Ya, Qiong Meng and Yulong Bai
Article first published online:
05 Oct 2021 | DOI: 10.1111/ene.15122

ORIGINAL ARTICLE

Background

Dementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia.

Methods

We applied a retrospective, nested case‐control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non‐dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method.

Results

The dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C‐statistic of the model was 0.71 (95% confidence interval [CI] 0.70–0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk ( = 0.99). At a cutoff value of 50 points, the high‐risk patients had an approximately three‐fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78–3.31). The DDRS performance, including discrimination (C‐statistic 0.71, 95% CI 0.69–0.73) and calibration ( value of Hosmer−Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37–3.35) was similar to those in the derivation set.

Conclusion

The DDRS system has the potential to serve as an easily accessible screening tool to determine the high‐risk groups who deserve subsequent neurological evaluation in daily clinical practice.

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Authors:
Tsai‐Chieh Ling, Chiung‐Chih Chang, Chung‐Yi Li, Junne‐Ming Sung, Chien‐Yao Sun, Kuen‐Jer Tsai, Ya‐Yun Cheng, Jia‐Ling Wu, Yi‐Ting Kuo and Yu‐Tzu Chang
Article first published online:
07 Oct 2021 | DOI: 10.1111/ene.15123

ORIGINAL ARTICLE

Background

Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size.

Methods

Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline‐recommended in‐hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3).

Results

Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline‐directed management measures, indicated by risk‐adjusted individual measures and the all‐or‐null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex‐related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%).

Conclusions

Compared to male patients, female patients had more vascular risk factors and received similar in‐hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

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Authors:
Hong‐Qiu Gu, Chun‐Juan Wang, Xin Yang, Chelsea Liu, Xia Wang, Xing‐Quan Zhao, Yi‐Long Wang, Li‐Ping Liu, Xia Meng, Yong Jiang, Hao Li, Yong‐Jun Wang and Zi‐Xiao Li
Article first published online:
03 Oct 2021 | DOI: 10.1111/ene.15124

ORIGINAL ARTICLE

Background and purpose

The aim of this study was to define the prevalence of pre‐eclampsia, gestational hypertension (HT), chronic HT, and gestational diabetes during pregnancy in a defined population of patients with saccular intracranial aneurysms (sIAs).

Methods

We included all patients with sIA, first admitted to the Neurosurgery Department of Kuopio University Hospital from its defined catchment population between 1990 and 2015, who had given birth for the first time in 1990 or later. The patients’ medical records were reviewed, and clinical data were linked with prescription drug usage, hospital diagnoses and causes of death, obtained from nationwide registries. The prevalences of pre‐eclampsia, other hypertensive disorders and gestational diabetes in patients were compared with a matched control population ( = 324). In addition, the characteristics of sIA disease in patients with pre‐eclampsia were compared to those of sIA patients without pre‐eclampsia.

Results

A total of 169 patients with sIA fulfilled the inclusion criteria. Of these, 22 (13%) had pre‐eclampsia and 32 (19%) had other hypertensive disorders during pregnancy. In 324 matched controls who had given birth, the prevalence of pre‐eclampsia was 5% ( = 15) and other hypertensive disorders were diagnosed in 10% ( = 34). There was no significant difference in prevalence of gestational diabetes (12% vs. 11%). Patients with sIA with pre‐eclampsia more frequently had irregularly shaped aneurysms (= 0·003).

Conclusions

Pre‐eclampsia was significantly more frequent in patients with sIA than in their population controls. Irregularly shaped aneurysms were more frequent in sIA patients with pre‐eclampsia. Further studies are required to determine whether history of pre‐eclampsia may indicate an elevated risk for sIA formation or rupture.

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Authors:
Satu Kotikoski, Arttu Kurtelius, Heidi J. Nurmonen, Juho Paavola, Virve Kärkkäinen, Terhi J. Huuskonen, Jukka Huttunen, Timo Koivisto, Mikael von und zu Fraunberg, Juha E. Jääskeläinen and Antti E. Lindgren
Article first published online:
12 Oct 2021 | DOI: 10.1111/ene.15125

ORIGINAL ARTICLE

Background and purpose

Previously it has been shown that patients with painful diabetic neuropathy (PDN) have greater corneal nerve loss compared to patients with painless diabetic neuropathy. This study investigated if the severity of corneal nerve loss was related to the severity of PDN.

Methods

Participants with diabetic neuropathy ( = 118) and healthy controls ( = 38) underwent clinical and neurological evaluation, quantitative sensory testing, nerve conduction testing and corneal confocal microscopy and were categorized into those with no ( = 43), mild ( = 34) and moderate‐to‐severe ( = 41) neuropathic pain.

Results

Corneal nerve fibre density ( = 0.003), corneal nerve fibre length ( < 0.0001) and cold perception threshold ( < 0.0001) were lower and warm perception threshold was higher ( = 0.002) in patients with more severe pain, but there was no significant difference in the neuropathy disability score ( = 0.5), vibration perception threshold ( = 0.5), sural nerve conduction velocity ( = 0.3) and amplitude ( = 0.7), corneal nerve branch density ( = 0.06) and deep breathing heart rate variability ( = 0.08) between patients with differing severity of PDN. The visual analogue scale correlated significantly with corneal nerve fibre density ( = −0.3,  = 0.0002), corneal nerve branch density ( = −0.3,  = 0.001) and corneal nerve fibre length ( = −0.4,  < 0.0001). Receiver operating curve analysis showed that corneal nerve fibre density had an area under the curve of 0.78 with a sensitivity of 0.73 and specificity of 0.72 for the diagnosis of PDN.

Conclusions

Corneal confocal microscopy reveals increasing corneal nerve fibre loss with increasing severity of neuropathic pain and a good diagnostic outcome for identifying patients with PDN.

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Authors:
Alise Kalteniece, Maryam Ferdousi, Shazli Azmi, Saif Ullah Khan, Anne Worthington, Andrew Marshall, Catharina G. Faber, Giuseppe Lauria, Andrew J. M. Boulton, Handrean Soran and Rayaz A. Malik
Article first published online:
13 Oct 2021 | DOI: 10.1111/ene.15129

ORIGINAL ARTICLE

Background

Telemedical services can be used to complement on‐site services when demand for specialists exceeds supply or when specialists are not evenly distributed across health systems. Using stroke as an example, this study aimed to explore how patients and staff experience telestroke cooperation in a stroke network in Germany.

Methods

We conducted a qualitative multi‐method and multi‐centre study combining 32 non‐participant observations at one hub and four spoke hospitals with 26 semi‐structured interviews with hub and spoke staff as well as stroke patients and relatives. Observation protocols and interview transcripts were analysed to identify barriers and facilitators to telestroke cooperation from the perspectives of staff, patients and relatives.

Results

In terms of barriers to telestroke cooperation, we found technological problems, providing the treatment for one patient from two sites, competing priorities between telestroke and in‐house duties in the spoke hospitals, as well as difficulties in participating in the teleneurological examination via a videoconferencing system for older and disabled patients. In terms of facilitators, we found an overall very positive perception of telestroke provision by patients, good professional relationships within the network, and sharing of neurological expertise to be experienced as helpful for telestroke cooperation.

Conclusions

We recommend better integration of telemedical services into the care pathway, fostering relationships within the network, improved technological support and resources, and more emphasis within networks, in public awareness efforts as well as in academia on the evaluation of telemedical services from the perspectives of patients and relatives, especially older patients and patients with disabilities.

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Authors:
Loraine Busetto, Melek Sert, Franziska Herzog, Johanna Hoffmann, Christina Stang, Hemasse Amiri, Fatih Seker, Jan Purrucker, Sibu Mundiyanapurath, Peter Arthur Ringleb, Simon Nagel, Martin Bendszus, Wolfgang Wick and Christoph Gumbinger
Article first published online:
28 Oct 2021 | DOI: 10.1111/ene.15130

LETTERS TO THE EDITOR

Comment on “Predictive factors for a severe course of COVID‐19 infection in myasthenia gravis patients with an overall impact on myasthenic status and survival” by Jakubíková et al.

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Authors:
Giuliana Galassi and Alessandro Marchioni
Article first published online:
12 Oct 2021 | DOI: 10.1111/ene.15131

LETTERS TO THE EDITOR

Reply to the letter from Gazulla et al.

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Authors:
Philippe Corcia, Christian Lunetta, Philippe Couratier, Patrick Vourc'h, Marta Gromicho, Claude Desnuelle, Marie‐Hélène Soriani, Susana Pinto and Mamede de Carvalho
Article first published online:
18 Oct 2021 | DOI: 10.1111/ene.15134

LETTERS TO THE EDITOR

Familial clustering of primary lateral sclerosis and amyotrophic lateral sclerosis: Supplementary evidence for a continuum

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Authors:
José Gazulla, Silvia Izquierdo‐Alvarez, Emilio Ruiz‐Fernández and José Berciano
Article first published online:
14 Nov 2021 | DOI: 10.1111/ene.15146

COMMENTARY

Cerebral venous sinus thrombosis associated with COVID‐19 vaccine‐induced thrombocytopenia: Improvement in mortality rate over time

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Authors:
Barbara Casolla and Charlotte Cordonnier
Article first published online:
31 Oct 2021 | DOI: 10.1111/ene.15151

LETTERS TO THE EDITOR

Predictive factors for a severe course of COVID‐19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival

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Authors:
Michala Jakubikova, Michaela Tyblova, Adam Tesar, Horakova Magda, Vlazna Daniela, Rysankova Irena, Novakova Iveta, Doleckova Kristyna, Dusek Pavel, Pitha Jiri, Vohanka Stanislav and Bednarik Josef
Article first published online:
09 Nov 2021 | DOI: 10.1111/ene.15158