cover image European Journal of Neurology

European Journal of Neurology

2024 - Volume 31
Issue 9 | September 2024

ISSUE INFORMATION

Issue Information

ORIGINAL ARTICLE

Background and purpose

A mobile stroke unit (MSU) reduces delays in stroke treatment by allowing thrombolysis on board and avoiding secondary transports. Due to the beneficial effect in comparison to conventional emergency medical services, current guidelines recommend regional evaluation of MSU implementation.

Methods

In a descriptive study, current pathways of patients requiring a secondary transport for mechanical thrombectomy were reconstructed from individual patient records within a Danish ( = 122) and an adjacent German region ( = 80). Relevant timestamps included arrival times (on site, primary hospital, thrombectomy centre) as well as the initiation of acute therapy. An optimal MSU location for each region was determined. The resulting time saving was translated into averted disability‐adjusted life years (DALYs).

Results

For each region, the optimal MSU location required a median driving time of 35 min to a stroke patient. Time savings in the German region (median [Q1; Q3]) were 7 min (−15; 31) for thrombolysis and 35 min (15; 61) for thrombectomy. In the Danish region, the corresponding time savings were 20 min (8; 30) and 43 min (25; 66). Assuming 28 thrombectomy cases and 52 thrombolysis cases this would translate to 9.4 averted DALYs per year justifying an annual net MSU budget of $0.8M purchasing power parity dollars (PPP‐$) in the German region. In the Danish region, the MSU would avert 17.7 DALYs, justifying an annual net budget of PPP‐$1.7M.

Conclusion

The effects of an MSU can be calculated from individual patient pathways and reflect differences in the hospital infrastructure between Denmark and Germany.

CASE REPORT

Abstract

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle‐term treatment benefit for patients with CLN2.

ORIGINAL ARTICLE

Background and purpose

Various electrodiagnostic criteria have been developed in Guillain–Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria.

Methods

From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally.

Results

Of the 1137 studies, 68.3% ( = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%.

Conclusions and discussion

This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

CASE REPORT

Abstract

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss, and rarely associated with extraocular manifestations including multiple sclerosis‐like lesions. The association of LHON and neuromyelitis optica spectrum disorders has rarely been reported. Here is reported a case of glial fibrillary acidic protein astrocytopathy presenting with area postrema syndrome in a patient with previously diagnosed recessive LHON due to mutations in the nuclear gene . This case emphasizes the necessity of extensive investigations for other treatable conditions in patients with LHON and otherwise unexplained extraocular involvement and the possibility that also visual symptoms can respond to immune therapy.

CASE REPORT

Background and purpose

‘Dancing‐like’ semiology is extremely rare and described in few case reports. It is characterized by rhythmic, oscillatory movements of the pelvis and/or limbs during which the subject appears to be dancing. It has been associated with both the frontal and temporal epileptic zone; however, the possible network involved in these fascinating seizures is unclear.

Methods

The case of a 45‐year‐old woman suffering from drug‐resistant focal epilepsy with multi‐day seizures of bizarre semiology is described. A structural and perfusion magnetic resonance imaging study (interictal and peri‐ictal) and video‐electroencephalograms were carried out, and several home videos were employed. A vagal stimulator was implanted.

Results

Home videos documented the ‘dancing’ semiology of seizures better than video‐ electroencephalogram recordings. The imaging study revealed a focal frontal polymicrogyria with a peri‐ictal cerebral blood flow increase at the perisylvian lesion foci. The combination of add‐on cenobamate and vagal nerve stimulation resulted in complete seizure freedom.

Conclusion

The unusual and complex dancing‐like semiology observed during our patient's seizures adds to the repertoire of fascinating complex motor manifestations of frontal lobe epilepsy.

ORIGINAL ARTICLE

Background and purpose

Human motor planning and control depend highly on optimal feedback control systems, such as the neocortex–cerebellum circuit. Here, diffusion tensor imaging was used to verify the disruption of the neocortex–cerebellum circuit in spinocerebellar ataxia type 3 (SCA3), and the circuit's disruption correlation with SCA3 motor dysfunction was investigated.

Methods

This study included 45 patients with familial SCA3, aged 17–67 years, and 49 age‐ and sex‐matched healthy controls, aged 21–64 years. Tract‐based spatial statistics and probabilistic tractography was conducted using magnetic resonance images of the patients and controls. The correlation between the local probability of probabilistic tractography traced from the cerebellum and clinical symptoms measured using specified symptom scales was also calculated.

Results

The cerebellum‐originated probabilistic tractography analysis showed that structural connectivity, mainly in the subcortical cerebellar–thalamo–cortical tract, was significantly reduced and the cortico–ponto–cerebellar tract was significantly stronger in the SCA3 group than in the control group. The enhanced tract was extended to the right lateral parietal region and the right primary motor cortex. The enhanced neocortex–cerebellum connections were highly associated with disease progression, including duration and symptomatic deterioration. Tractography probabilities from the cerebellar to parietal and sensorimotor areas were significantly negatively correlated with motor abilities in patients with SCA3.

Conclusion

To our knowledge, this study is the first to reveal that disrupting the neocortex–cerebellum loop can cause SCA3‐induced motor dysfunctions. The specific interaction between the cerebellar–thalamo–cortical and cortico–ponto–cerebellar pathways in patients with SCA3 and its relationship with ataxia symptoms provides a new direction for future research.

ORIGINAL ARTICLE

Background and purpose

A real‐time biomarker in chemotherapy‐induced peripheral neurotoxicity (CIPN) would be useful for clinical decision‐making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN.

Methods

This single‐center prospective observational longitudinal study included patients treated with paclitaxel (TX;  = 34), brentuximab vedotin (BV;  = 29), or oxaliplatin (PT;  = 19). All patients were assessed using the Total Neuropathy Score–clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6–12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2.

Results

Eighty‐two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR‐CIPN, respectively, without differences among them ( = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents ( < 0.001).

Conclusions

A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

ORIGINAL ARTICLE

Background and purpose

Dysphagia is an important feature of neurodegenerative diseases and potentially life‐threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control.

Methods

In a retrospective case–control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel‐based morphometry and region‐of‐interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence.

Results

Dysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9–100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate.

Conclusions

Dysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.

ORIGINAL ARTICLE

Background and purpose

Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta‐analysis of NFL in ALS and FTD was performed.

Methods

Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated.

Results

In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences.

Discussion

Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias.

ORIGINAL ARTICLE

Objective

To compare the real‐world effectiveness and tolerability of calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients.

Methods

This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult‐to‐treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS).

Results

The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (−13.0 vs. −8.7 days/month,  < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%,  < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (−13.0 vs. −9.1 MMDs,  < 0.001; ≥50% RR: 73.9% vs. 50.3%,  < 0.001) or those with medication‐overuse headache (MOH) (−13.3 vs. −9.0 MMDs,  < 0.001; ≥50% RR: 79.0% vs. 51.6%,  < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (−42.2 vs. −11.8,  < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%,  = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%,  < 0.001). However, none of the patients discontinued treatment due to AEs.

Conclusions

In this multicenter, real‐world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

CORRIGENDUM

Corrigendum to Cross‐sectional area reference values for peripheral nerve ultrasound in adults: A systematic review and meta‐analysis—Part I: Upper extremity nerves

ORIGINAL ARTICLE

Objective

Little is known about amyotrophic lateral sclerosis (ALS)‐nonspecific cognitive deficits – most notably memory disturbance – and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor and cerebrospinal fluid (CSF) biomarkers Aβ and tau proteins with cognitive and motor phenotype in ALS.

Methods

haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aβ42, Aβ40, total tau (T‐tau), and phosphorylated tau (P‐tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was employed to evaluate the neuropsychological phenotype.

Results

‐E4 allele was associated with worse ECAS memory score (median, 14.0 in carriers vs. 16.0 in non‐carriers) and lower CSF Aβ42 (−0.8 vs. 0.1, log‐transformed values) and Aβ42/40 ratio (−0.1 vs. 0.3). Some 37.1% of ALS patients showed low Aβ42 levels, possibly reflecting cerebral Aβ deposition. While lower Aβ42/40 correlated with lower memory score ( = 0.20), Aβ42 positively correlated with both ALS‐specific ( = 0.24) and ALS‐nonspecific ( = 0.24) scores. Although Aβ42/40 negatively correlated with T‐tau ( = −0.29) and P‐tau181 ( = −0.33), we found an unexpected positive association of Aβ42 and Aβ40 with both tau proteins. Regarding motor phenotype, lower levels of Aβ species were associated with lower motor neuron (LMN) signs (Aβ40:  = 0.34; Aβ42:  = 0.22).

Conclusions

haplotype and CSF Aβ biomarkers are associated with cognitive deficits in ALS and particularly with memory impairment. This might partly reflect AD‐like pathophysiological processes, but additional ALS‐specific mechanisms could be involved.

ORIGINAL ARTICLE

Background and purpose

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy mortality. All international guidance strongly advocates for clinicians working with people with epilepsy (PWE) to discuss SUDEP. Clinician views working with PWE in the UK and Norway on SUDEP counselling are compared.

Methods

A cross‐sectional online mixed methodology survey of 17 Likert and free‐text response questions using validated themes was circulated via International League against Epilepsy/Epilepsy Specialist Nurses Association in the UK and International League against Epilepsy/Epilepsinet in Norway using a non‐discriminatory exponential snowballing technique leading to non‐probability sampling. Quantitative data were analysed using descriptive statistics and Mann–Whitney, Kruskal–Wallis, chi‐squared and Fisher's exact tests. Significance was accepted at  < 0.05. Thematic analysis was conducted on free‐text responses.

Results

Of 309 (UK 197, Norway 112) responses, UK clinicians were more likely to have experienced an SUDEP ( < 0.001), put greater importance on SUDEP communication ( < 0.001), discuss SUDEP with all PWE particularly new patients ( < 0.001), have access and refer to bereavement support ( < 0.001) and were less likely to never discuss SUDEP ( < 0.001). Significant differences existed between both countries’ neurologists and nurses in SUDEP counselling with UK clinicians generally being more supportive. UK responders were more likely to be able to identify bereavement support ( < 0.001). Thematic analysis highlighted four shared themes and two specific to Norwegians.

Discussion

Despite all international guidelines stating the need/importance to discuss SUDEP with all PWE there remain hesitation, avoidance and subjectivity in clinicians having SUDEP‐related conversations, more so in Norway than the UK. Training and education are required to improve communication, engagement and decision making.

ORIGINAL ARTICLE

Background and purpose

Most neurological diseases have a chronic and progressive clinical course, with patients living for extended periods with complex healthcare needs. Evidence from other countries suggests that palliative care (PC) is insufficiently integrated in the care of these patients. This study aims to identify PC and advance care planning (ACP) knowledge and the perceived preparedness of Italian residents in neurology.

Methods

This is a cross‐sectional online survey of physicians attending the 36 Italian neurology residency programmes.

Results

Of 854 residents, 188 (22%) participated. Their mean age was 28.4 ± 2.0 years; 49% were women; 45% were from the north, 23% from the centre and 32% from the south of Italy. Few residents (6%) reported that a teaching course in PC was part of the graduate programme, and 3% of the postgraduate programme. During their residency, 9% of participants received PC training, and 18% ACP training. Only 13% reported to have participated in the ACP process, half within their neurology residency programme. Residents considered PC support very/extremely important in all the pre‐specified clinical situations, with values ranging between 78% and 96%. Over 70% of residents revealed education needs, particularly concerning ACP.

Conclusions

Our data confirm the need for improving PC training in the graduate and postgraduate curriculum. This, together with collaboration and joint training of neurology and PC, is essential to improve the quality and continuity of care and respond to the complex needs of people with neurological disorders causing severe disability.

ORIGINAL ARTICLE

Background and purpose

We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS).

Methods

A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging.

Results

Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS ( = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD ( = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%;  = 0.095 and  = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic–pituitary–adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%;  = 0.007 and  = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy.

Conclusions

MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

ORIGINAL ARTICLE

Objective

To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS).

s

In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail‐arm, flail‐leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival.

Results

Mean sNfL was ‐ compared to typMN (75.7 pg/mL,  = 1791) ‐ significantly lower in LMNp (45.1 pg/mL,  = 413), UMNp (58.7 pg/mL  = 206), and PLS (37.6 pg/mL,  = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL,  = 669), limb (64.1 pg/mL,  = 1305), flail‐arm (46.4 pg/mL,  = 283), flail‐leg (53.6 pg/mL,  = 141), and thoracic (74.5 pg/mL,  = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months,  = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed ( < 0.001).

Conclusions

This study underscored the correlation of ALS phenotypes – differentiated for motor neuron involvement and region of onset/propagation – with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice.

ORIGINAL ARTICLE

Background and Purpose

This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities.

Methods

Data from the ATTENTION cohort were used to perform a post‐hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90‐day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied.

Results

Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78–26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28–6.92;  = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44–2.81;  = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management ( = 0.042).

Conclusion

An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO.

CORRIGENDUM

Corrigendum to use of antihypertensive medication and formation of de novo intracranial aneurysms

ORIGINAL ARTICLE

Background and purpose

Hypertension significantly contributes to stroke. Previous research has indicated a connection between daytime napping and stroke. Research on the connection between daytime napping duration and first stroke in hypertensive individuals is lacking nevertheless.

Methods

This research, which ran from 24 August 2013 to 31 December 2022, recruited 11,252 individuals with hypertension and without a history of stroke from the China Stroke Primary Prevention Trial. To determine the relationship between daytime napping duration and stroke onset in hypertensive individuals, we conducted analyses for threshold effects, multivariate‐adjusted Cox proportional hazard regression models, and Kaplan–Meier survival curves.

Results

The duration of daytime napping (<75 min) was positively correlated with stroke risk; beyond 75 min, the risk did not increase further. When compared to hypertensive individuals who napped for 1–30 min, daytime napping 31–60 min (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.06–1.53) and >60 min (HR = 1.37, 95% CI = 1.14–1.65) were substantially related with a greater risk of first stroke. Additionally, this correlation was absent in cases of hemorrhagic stroke, but present in cases of ischemic stroke, specifically for hypertensive individuals who napped for 31–60 min or >60 min ( < 0.05). Kaplan–Meier survival curves displayed that hypertensive individuals who extended daytime napping had an elevated incidence of stroke.

Conclusions

Hypertensive individuals who take longer daytime naps (>30 min) are at an elevated risk of stroke onset, particularly ischemic stroke, irrespective of other factors.

POSITION PAPER

Background and purpose

Two novel enzyme replacement therapies (ERTs), studied in phase 3 trials in late‐onset Pompe patients, reached marketing authorization by the European Medicines Agency in 2022 and 2023. The European Pompe Consortium (EPOC) updates and extends the scope of the 2017 recommendations for starting, switching and stopping ERT.

Methods

The European Pompe Consortium consists of 25 neuromuscular and metabolic experts from eight European countries. This update was performed after an in‐person meeting, three rounds of discussion and voting to provide a consensus recommendation.

Results

The patient should be symptomatic, that is, should have skeletal muscle weakness or respiratory muscle involvement. Muscle magnetic resonance imaging findings showing substantial fat replacement can support the decision to start in a patient‐by‐patient scenario. Limited evidence supports switching ERT if there is no indication that skeletal muscle and/or respiratory function have stabilized or improved during standard ERT of 12 months or after severe infusion‐associated reactions. Switching of ERT should be discussed on a patient‐by‐patient shared‐decision basis. If there are severe, unmanageable infusion‐associated reactions and no stabilization in skeletal muscle function during the first 2 years after starting or switching treatment, stopping ERT should be considered. After stopping ERT for inefficacy, restarting ERT can be considered. Six‐monthly European Pompe Consortium muscle function assessments are recommended.

Conclusions

The triple‐S criteria on ERT start, switch and stop include muscle magnetic resonance imaging as a supportive finding and the potential option of home infusion therapy. Six‐monthly long‐term monitoring of muscle function is highly recommended to cover insights into the patient's trajectory under ERT.

ORIGINAL ARTICLE

Background and purpose

Hereditary transthyretin‐mediated amyloidosis with polyneuropathy (ATTRv‐PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real‐world outcomes of patients with ATTRv‐PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch.

Methods

This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv‐PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12‐month patisiran treatment period.

Results

Among the 24 patients with ATTRv‐PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy.

Conclusions

Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv‐PN.

ORIGINAL ARTICLE

Background

Acute headache may be the primary symptom of subarachnoid hemorrhage (SAH). Recent guidelines suggest that non‐contrast computed tomography (CT) is adequate to exclude aneurysmal SAH if performed within 6 h after symptom onset. However, most studies of acute headache including CT, lumbar puncture and SAH are multicenter studies from referral hospitals with highly selected patient populations. The main purpose of this study was to describe the diagnostic properties of head CT and cerebrospinal fluid (CSF) spectrophotometry for detecting SAH in an unselected primary hospital population with acute headache.

Methods

A retrospective cross‐sectional study conducted at a large primary hospital serving roughly 10% of the Norwegian population. Diagnostic workup from consecutive patients evaluated for acute headache in 2009–2020 were collected. All CSF‐spectrophotometry reports were standardized and the same CT scanner was used during the study.

Results

A total of 3227 patients were included. Median age was 45 years and 63% were women. In total, 170 (5.3% of all acute headache patients) had SAH. Of 3071 CT‐negative patients, 2852 (93%) underwent lumbar puncture. Of the CSF reports, 2796 (98%) were negative for xanthochromia. Overall, the rate for detection of aneurysmal SAH by positive xanthochromia was 9 in 2852 cases (3‰). The miss rate for the detection of an aneurysmal SAH with a CT scan within 6 h was 0 and within 12 h 1 in 2852 cases (0.3‰).

Conclusion

In acute headache, a CT scan taken within 6 h is practically 100% sensitive for detecting any SAH.

EDITORIAL

How many lives must be lost before we consider SUDEP counselling an obligation rather than a choice? The need for public policies