Neurological research and practice最新文献

Background: Tenecteplase (TNK) offers promising efficacy and safety data for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) and pharmacological advantages over alteplase (rt-PA), justifying its gradual adoption as primary thrombolytic agent. At our tertiary care center, we transitioned from rt-PA to TNK, providing valuable real-world insights into this process, including its use beyond the 4.5-hour time window.

Methods: We retrospectively analyzed our stroke registry to compare clinical and procedural data from AIS patients treated with rt-PA (up to 6 months before transition) and those treated with TNK (up to 6 months after transition, starting June 2024). Primary endpoints included treatment metrics, such as door-to-needle (DTN), door-to-imaging (DTI), imaging-to-needle (ITN), door-to-groin and door-to-recanalization times. Safety outcomes comprised rate of any intracranial hemorrhage (ICH), symptomatic ICH (sICH), parenchymatous hematoma type 2 (PH 2) and post-thrombolysis angioedema. A semiquantitative questionnaire evaluated satisfaction with TNK and changes in lysis behavior among nurses and physicians 3 months post-implementation.

Results: During the twelve-month period (December 1, 2023 - November 30, 2024), 276 patients underwent IVT. Median DTN times were significantly shorter with TNK (n = 138) compared to rt-PA (n = 138) (TNK 27 min [IQR 19-39] vs. rt-PA 34 min [IQR 25-62]; p = 0.011). No significant differences were observed in safety outcomes, including any ICH (TNK 9% vs. rt-PA 6%; p = 0.30), sICH (2% vs. 1%; p = 0.31), PH 2 rates (1% in both groups), or angioedema (3% vs. 1%; p = 0.18). Staff satisfaction with TNK was high, citing advantages in preparation, administration, and time efficiency. Importantly, no changes in lysis behavior were reported following the transition.

Conclusions: Transitioning to TNK in routine practice at a tertiary care center seems feasible with reduced ITN and consequently DTN times. Functional outcomes at discharge were comparable without significant difference in the rate of (s)ICH. Overall, the transition to TNK was well-received by medical staff, highlighting TNK's practical advantages in acute stroke care.

Trial registration: N.A.

Background: The recreational use of nitrous oxide (N₂O) has seen a worldwide rise in the recent years, resulting in an increased incidence of neurological complications due to N₂O-induced functional vitamin B₁₂ deficiency. Here, we report on a cohort of patients admitted to a tertiary care center with neurological symptoms in the context of recreational N₂O use between 2020 and 2024.

Methods: We screened the database of the University Hospital Frankfurt for patients ≥ 18 years of age who presented with neurological deficits and a history of N₂O consumption between January 2020 and December 2024. We analyzed the spectrum of neurological deficits as well as radiological and laboratory findings.

Results: We identified a total of 20 patients, 16 males and 4 females, with a median age of 21 years. We found a steady increase in the number of cases, with no cases in 2020 and 2021 and a definite peak in 2024. The mean daily N₂O consumption was 2500 g. All patients reported sensory deficits; 85% had gait disturbances and 70% had motor deficits. Less frequent symptoms included pain, bladder or bowel dysfunction, fatigue and spasticity. The median score on the modified Rankin scale (mRS) was 2, with some patients being wheelchair-bound. The most frequently observed lesion pattern was combined myelo-polyneuropathy. T2-hyperintense myelon lesions were observed in 11 of 15 patients (73.3%). Surprisingly, laboratory work-up revealed normal vitamin B₁₂ levels in nearly all patients (95%), whereas homocysteine and methylmalonic acid levels were prominently elevated in all patients (100%). In addition, 13 patients (65%) presented with hematological abnormalities. All of the patients who presented for follow-up (20%) reported continued use of N₂O. There was no neurological improvement in any of these cases.

Conclusions: Our study confirms that the increasing incidence of N₂O-induced neurotoxicity reported in other countries can also be observed in Germany. Therefore, it underlines the relevance of the current debate on health policies. In addition, our study highlights the pitfalls of vitamin B12 laboratory testing and emphasizes the need to address substance addiction in treatment.

Background: In amyotrophic lateral sclerosis (ALS), heterogeneity of motor phenotypes is a fundamental hallmark of the disease. Distinct ALS phenotypes were associated with a different progression and survival. Despite its relevance for clinical practice and research, there is no broader consensus on the classification of ALS phenotypes.

Methods: An expert consensus process for the classification of ALS motor phenotypes was performed from May 2023 to December 2024. A three-determinant anatomical classification was proposed which is based on the (1) region of onset (O), (2) the propagation of motor symptoms (P), and (3) the degree of upper (UMN) and/or lower motor neuron (LMN) dysfunction (M). Accordingly, this classification is referred to as the "OPM classification".

Results: Onset phenotypes differentiate the site of first motor symptoms: O1) head onset; O2d) distal arm onset; O2p) proximal arm onset; O3r) trunk respiratory onset; O3a) trunk axial onset; O4d) distal leg onset; O4p) proximal leg onset. Propagation phenotypes differentiate the temporal propagation of motor symptoms from the site of onset to another, vertically distant body region: PE) earlier propagation (within 12 months of symptom onset); PL) later propagation (without propagation within 12 months of symptom onset), including the established phenotypes of "progressive bulbar paralysis" (O1, PL), "flail-arm syndrome" (O2p, PL), and "flail-leg syndrome" (O4d, PL); PN) propagation not yet classifiable as time since symptom onset is less than 12 months. Phenotypes of motor neuron dysfunction differentiate the degree of UMN and/or LMN dysfunction: M0) balanced UMN and LMN dysfunction; M1d) dominant UMN dysfunction; M1p) pure UMN dysfunction ("primary lateral sclerosis", PLS); M2d) dominant LMN dysfunction; M2p) pure LMN dysfunction ("progressive muscle atrophy", PMA); M3) dissociated motor neuron dysfunction with dominant LMN and UMN dysfunction of the arms and legs ("brachial amyotrophic spastic paraparesis"), respectively.

Conclusion: This consensus process aimed to standardize the clinical description of ALS motor phenotypes in clinical practice and research - based on the onset region, propagation pattern, and motor neuron dysfunction. This "OPM classification" contributes to specifying the prognosis, to defining the inclusion or stratification criteria in clinical trials and to correlate phenotypes with the underlying disease mechanisms of ALS.

Background: Research of the past years has refined our perception of cerebral amyloid angiopathy-related inflammation (CAA-ri) as a subacute autoimmune encephalopathy, which is presumably caused by elevated CSF concentrations of anti-amyloid β (Aβ) autoantibodies. A broad understanding of the pathophysiological mechanisms and diagnostic criteria of CAA-ri may lay the foundation for improved immunosuppressive treatment of the disease.

Main text: Spontaneous CAA-ri mainly occurs in elderly patients but might also be evoked iatrogenically by modern treatment with amyloid-modifying therapies in Alzheimer's disease (AD). On a histopathological level, CAA-ri is characterized by microglial activation and the formation of vasogenic edemas. Clinically, the disease frequently presents with progressive cognitive decline, focal neurological deficits, headache and epileptic seizures. While brain biopsy has formerly represented the gold standard in the diagnosis of CAA-ri, its importance has been increasingly replaced by clinical as well as radiological diagnostic criteria and the relevance of anti-Aβ autoantibodies in the CSF of affected patients. Though relevant progress has been achieved in immunosuppressive treatment of CAA-ri, the protocols lack standardization as well as decision criteria for the choice of the respective immunosuppressive agent.

Conclusions: CAA-ri gains increasing interest as a spontaneous human model of iatrogenic edematous amyloid-related imaging abnormalities (ARIA-E) in the context of amyloid-modifying therapies. In near future, screening of AD patients for the presence of CAA-ri using CSF anti-Aβ autoantibodies might play a decisive role in the risk stratification as well as dosage finding of amyloid-modifying therapies, as they show high specificity for CAA-ri. The clinical and radiological diagnostic criteria by Auriel et al. allow diagnosis of probable resp. possible CAA-ri with high accuracy. Though only tested in small, specialized patient cohorts to date, additional imaging modalities (¹¹C-PK11195 PET) might play a future role in the clinical monitoring of CAA-ri. Therapy of CAA-ri frequently encompasses initial steroid treatment, whereby different schemes, dosages as well as substances are used. Choice of immunosuppressive agents with higher potency still requires objective decision criteria, which should be established in future studies involving larger CAA-ri patient cohorts.

Background: The decision to discontinue disease-modifying therapies (DMTs) in patients with multiple sclerosis (PwMS) is a critical clinical challenge. Historically, DMTs were discontinued due to side effects, treatment limitations, or progression to secondary progressive MS. However, advancements in MS therapies, particularly high-efficacy DMTs (HE-DMTs) and the increased knowledge on disease courses and phenotypes have resulted in more personalized treatment approaches and introduced discussion on scheduled DMT discontinuation. This review explores the current evidence on DMT discontinuation, focusing on its implications for aging populations and the interplay between cardiovascular diseases (CVD) and MS.

Current evidence and interplay with cvd: Randomized trials such as DISCOMS and DOT-MS have provided insights into discontinuing DMTs in stable patients. In summary, both randomized clinical trials highlight the risk of disease reactivation following treatment discontinuation. Due to the limited sample size, neither study was able to conduct subgroup analyses based on age groups. Additionally, DOT-MS was terminated prematurely, direct comparisons with other studies should be avoided. While older studies and observational data (e.g., OFSEP) have shown relapse risks associated with discontinuation, particularly for drugs like natalizumab and fingolimod, there is limited data on HE-DMT discontinuation outcomes. Comorbidities, particularly CVDs, further complicate decisions regarding the continuation of DMTs in older adults. MS patients bear a higher burden of CVD, which is also associated with unfavorable disease courses. While optimizing cardiovascular risk profiles appears advisable, it remains unclear whether DMTs themselves have a positive impact on CVDs.

Conclusion: Given the complexities associated with discontinuing DMTs in MS patients, it is essential to balance the avoidance of polypharmacy with the potential risks of disease reactivation and the impact of comorbidities, especially CVDs, on disease progression. The interplay between MS and CVD highlights the importance of a holistic risk assessment when considering DMT discontinuation.

Background: Atrial fibrillation (AF) is a common cause of cardioembolic stroke and can lead to severe and recurrent cerebrovascular events. Thus, identifying patients suffering from cardioembolic events caused by undetected AF is crucial. Previously, we found an association between increasing stroke severity and a decreasing left atrial appendage (LAA) blood flow velocity below 60 cm/s.

Methods: This was a prospective single-center cohort study including hospitalized patients who underwent a transesophageal echocardiography (TEE) in sinus rhythm. The participants were divided into two groups (≥ 60 cm/s;<60 cm/s) based on their maximum LAA blood flow velocity. The results of the cardiovascular risk assessment and 24- to 72-hour ECG Holter were recorded. Follow-up appointments were scheduled at 3, 6, 12, 24 and 36 months. The primary endpoint was new-onset AF. The statistics included a Cox-proportional-hazard-model and a binary logistic regression. Numerical data or categorical data were analyzed with the Mann-Whitney U test or chi-square test.

Results: A total of 166 patients were recruited. The median LAA blood flow velocity was 64 cm/s. New-onset AF was diagnosed in 22.9% of the patients. An LAA blood flow velocity ≤ 60 cm/s was associated with a threefold increased risk of new-onset AF (35.8% vs. 11.5%; HR3.56; CI95%1.70-7.46; p < 0.001), independently according to a multivariate analysis (p = 0.035). Furthermore, a decreasing LAA blood flow velocity was associated with an increased risk of new-onset AF (OR1.043; CI95%1.021-1.069; p < 0.001).

Conclusion: A low LAA blood flow velocity (≤ 60 cm/s) in sinus rhythm is prospectively associated with an increased risk of new-onset AF. Additional simple LAA-TEE examinations could help to identify patients who benefit from more accurate cardiac rhythm monitoring.

Background: Pharyngeal electrical stimulation (PES) is a neurostimulation intervention that can improve swallowing and facilitate decannulation in tracheotomised stroke patients with dysphagia. The PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) study found that PES can reduce dysphagia severity in patients with neurogenic (non-stroke) dysphagia who required mechanical ventilation and tracheotomy. However, the predictive factors for treatment success among these patients remain unclear.

Methods: We conducted a subgroup analysis using data from PHADER, with a focus on non-stroke participants who had required mechanical ventilation and tracheotomy. Multiple linear regression was performed to predict treatment success, as measured in improvement in dysphagia severity rating scale (DSRS) total score, accounting for age, sex, time from diagnosis to PES, PES perceptual threshold and PES stimulation intensity at the first session.

Results: Fifty-seven participants (mean[standard deviation] age: 63.6[15.5] years; male: 70.2%) were included in the analysis. These comprised traumatic brain injury (22[38.6%]), critical illness polyneuropathy (15[26.4%]), and other neurological conditions that caused dysphagia (20[35.0%]). Regression analyses identified that a lower PES perceptual threshold at the first session (p = 0.027) and early intervention (p = 0.004) were significant predictors associated with treatment success at Day 9 and 3 months post PES respectively.

Conclusions: We identified two predictive factors associated with successful PES treatment in patients with neurogenic (non-stroke) dysphagia requiring mechanical ventilation and tracheotomy: a lower PES perceptual threshold at the first session and early intervention. These predictors provide critical guidance for optimizing clinical decision-making in managing non-stroke neurogenic dysphagia patients in critical care settings.

Background: Congenital anomalies and neurodevelopmental disorders are complex conditions often requiring comprehensive diagnostic approaches. Next-generation sequencing (NGS), particularly whole-exome sequencing (WES), has greatly improved the detection of pathogenic variants, including copy number variations (CNVs), which account for up to 35% of genetic causes in neurological patients. Combining CNV and single nucleotide variant (SNV) analysis through WES enhances diagnostic accuracy, especially in cases with unclassified congenital anomalies.

Case presentation and literature review: This study reports a 14-year-old male patient with multiple congenital anomalies, including hypospadias, complete cleft palate, and recurrent pneumonia. His clinical presentation includes significant physical and intellectual developmental delays, autism-like symptoms, and spastic diplegia. Whole-exome sequencing (WES) was performed due to these complex symptoms, revealing a novel heterozygous deletion on chromosome 10q24.31-q24.33. Laboratory findings indicated agammaglobulinemia, leading to prophylactic antibiotic therapy and immunoglobulin replacement. Additional imaging studies showed cystic malformation of the middle lobe of the right lung, sliding hiatal hernia with prolapse of the gastric mucosa, and brain anomalies consistent with Joubert syndrome.

Conclusions: This case underscores the importance of genetic analysis in understanding the etiology of congenital anomalies and neurodevelopmental disorders, providing critical insights into the molecular mechanisms driving complex phenotypes. The identified chromosomal deletion contributes to the existing literature on genomic imbalances associated with similar phenotypes.

Background: Intracranial haemorrhage (ICH) is one of the most serious complications of anticoagulant therapy with oral factor Xa inhibitors (FXai). To meet an urgent medical need of optimising treatment pathways, we assessed the frequency of ICH during oral FXai treatment, as well as the associated burden on the German healthcare system.

Methods: Our study was based on a claims database comprising over 4 million people with statutory health insurance in Germany. The study included people initiating oral FXai treatment for the first time between 2016 and 2021, and who experienced ICH during a three-year treatment period. For a balanced comparison of hospitalisations, costs, and mortality, propensity score matching between patients with and without ICH was performed.

Results: During the study period, 78,086 patients had started oral FXai therapy, of which 530 experienced ICH during the therapy. The incidence rate of ICH was highest within the first 90 days after the start of oral FXai therapy during follow-up with 0.64 events per 100 patient-years (PY; 95% CI: 0.52-0.77%). Three-month mortality rates were significantly higher among patients who had experienced an ICH event (39.4%; 95% CI: 35.4-43.8%), as opposed to patients without ICH (5.9%; 95% CI: 4.2-8.3%). This difference prevailed during follow-up, while mortality increased at roughly equal rates in both patient groups. Patients with ICH were on average hospitalised for 40.4 days/PY (95% CI: 35.7 days - 45.2 days) in the first year after the event; comparable patients without ICH were hospitalised for 10.8 days/PY (95% CI: 8.3 days - 13.2 days). Annual total costs per patient were €37,328 (95% CI: €32,243-€42,412) for patients with ICH, and €10,564 (95% CI: €9,298-€11,831) for patients without ICH. Hospitalisation costs were the main driver with 86.1% versus 50.8%, respectively.

Conclusions: Incidence rates of ICH during oral FXai therapy were within the range of other published real-world data. Duration of hospitalisations, associated costs, and mortality were high and significantly higher for patients with ICH than for comparable patients without ICH. The high burden on the healthcare system highlights the need for preventive measures and more efficient treatment pathways for patients with ICH under oral FXai therapy.

Objective: Immunomodulatory treatment options for multiple sclerosis show an inverse risk‒benefit ratio of side effects and treatment efficacy. Although rare, anti-B-cell therapies can cause acute or late-onset neutropenia.

Methods: We report a case of severe recurrent fluctuating neutropenia after ofatumumab treatment.

Results: We observed four recurrences even after pausing with ofatumumab and repeated granulocyte stimulating factor (G-CSF) treatment. In total, neutropenia occurred five times and was associated with recurrent pulmonary, urinary tract, and skin infections. Bone marrow investigation revealed no signs of lymphoma or leukemia. Interestingly, routine molecular testing revealed two gene variants of unknown significance for BCORL1 and ASXL1, both of which play a role in hematopoiesis. The neutrophil count recovered spontaneously six months after the cessation of treatment with ofatumumab.

Discussion: This case highlights the necessity of identifying patients at risk and monitoring white blood cell counts regularly for up to 6 months after initial neutropenia.