Neurological research and practice最新文献

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.

Background: Decannulation in tracheotomized neurological patients is often complicated by severe dysphagia, which compromises airway safety and delays weaning. Additional challenges, including reduced cough strength, excessive bronchial secretions, and altered airway anatomy exacerbate weaning issues, thereby increasing morbidity and mortality. This review summarizes diagnostic procedures and therapeutic options crucial for the rehabilitation of tracheotomized patients.

Main body: Key diagnostic strategies for assessing decannulation readiness focus on airway protection, airway patency, bronchial secretion management, and cough function. These are collectively introduced as the A²BC criteria in this review. Advanced tools such as flexible endoscopic evaluation of swallowing, endoscopic assessment of airway anatomy, measurement of cough strength, and intrathoracic pressure are essential components of a systematic evaluation. Therapeutic interventions encompass restoring physiological airflow, behavioral swallowing treatment, secretion management, and pharyngeal electrical stimulation. The proposed decannulation algorithm integrates two pathways: the "fast-track" pathway, which facilitates rapid decannulation based on relevant predictors of decannulation-success, and the "standard-track" pathway, which progressively increases cuff deflation intervals to build tolerance over time.

Conclusion: Successful decannulation in neurological patients demands a multidisciplinary, patient-centered approach that combines advanced diagnostics, targeted therapies, and structured management pathways. The proposed algorithm integrates fast-track and standard-track pathways, balancing rapid diagnostics with gradual weaning strategies. This framework promotes flexibility, enabling clinicians to tailor interventions to individual patient needs while maintaining safety and optimizing outcomes.

Background: There is an emerging understanding of the increased risk of stroke in patients with immune thrombocytopenic purpura (ITP) and immune thrombotic thrombocytopenic purpura (iTTP). We aimed to determine the prevalence and characteristics of acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) in patients with ITP and iTTP in a systematic review and meta-analysis.

Methods: We used PubMed, Embase, Cochrane, Web of Science, and Scopus using text related to ITP, iTTP, stroke, AIS, and ICH from inception to 11/3/2023. Our primary outcome was to determine prevalence of AIS and/or ICH in a cohort of ITP or iTTP patients (age > 18). Our secondary outcomes were to determine stroke type associated with thrombopoietin receptor agonists (TPO-RAs) in ITP patients, as well as risk factors associated with stroke in ITP and iTTP patients.

Results: We included 42 studies with 118,019 patients (mean age = 50 years, 45% female). Of those, 27 studies (n = 116,334) investigated stroke in ITP patients, and 15 studies (n = 1,685) investigated stroke in iTTP patients. In all ITP patients, the prevalence of AIS and ICH was 2.1% [95% Confidence Interval (CI) 0.8-4.0%] and 1.5% (95% CI 0.9%-2.1%), respectively. ITP patients who experienced stroke as an adverse event (AE) from TPO-RAs had an AIS prevalence of 1.8% (95% CI 0.6%-3.4%) and an ICH prevalence of 2.0% (95% CI 0.2%-5.3%). Prevalence of stroke did not significantly differ between all ITP patients and those treated with TPO-RAs. iTTP patients had a prevalence of AIS and ICH of 13.9% (95% CI 10.2%-18.1%) and 3.9% (95% CI 0.2%-10.4%), respectively. Subgroup analysis revealed the prevalence of AIS and ICH was greater in iTTP patients vs. all ITP patients (p < 0.01 and p = 0.02, respectively). Meta-regression analysis revealed none of the collected variables (age, sex, history of diabetes or hypertension) were risk factors for stroke in all ITP patients, although there were high levels of data missingness.

Conclusions: Prevalence of different stroke types was lower in all ITP patients vs. iTTP patients. Additionally, ITP patients experienced a similar prevalence of stroke regardless of if they were specifically denoted to have been treated with TPO-RAs or not, supporting the continued use of TPO-RAs in management. Risk factors for stroke remain unclear, and future studies should continue to investigate this relationship.

Background: The majority of randomised controlled trials in acute stroke and many for prevention are neutral, i.e. they failed to reach statistical significance. However, many of these will find apparent benefit in a component of a subgroup, findings which may be 'chased' in a follow-up trial. The evidence to date is that these follow-on trials are very likely to be neutral.

Findings: We discuss the issue of chasing subgroups in neutral trials and illustrate the challenges in five pairs of exemplar acute stroke trials. Problems in the exemplar trials include failing to define the subgroup in advance or even changing its definition, failing to show that both the interaction test and the primary outcome in the component were statistically significant, failing to publish additional information on the positive subgroup component, having too many subgroups, failing to make the follow-on trial large enough and failing to report the findings of the follow-on trial.

Conclusion: When chasing a positive component in a subgroup, it is vital that the subgroup: should be plausible biologically, defined a priori and have a significant interaction test. Further the number of subgroups should be limited and the component of interest should be statistically significant. Explanations should be given as to why the component is positive and other components of the subgroup are negative. Other outcomes should also show potential benefit. Unless this guidance is followed, it is highly likely that follow-on trials will be neutral as has occurred previously.

Background: Animal studies suggest that high-density lipoprotein cholesterol (HDL-C) attenuates reperfusion injury. We aimed to assess whether higher serum HDL-C levels modulate the risk of intracranial haemorrhage (ICH) after thrombectomy in human stroke survivors.

Methods: We included consecutive patients from our prospective anterior circulation large vessel occlusion (acLVO) registry who underwent thrombectomy between 01/2017 and 01/2023 at the tertiary stroke centre of the University Hospital Carl Gustav Carus in Dresden, Germany in a propensity score-matched analysis. We assessed the association between serum HDL-C levels and post-interventional ICH as well as 90-day functional outcome quantified by the modified Rankin Scale (mRS). For sensitivity analysis, we used multivariable lasso logistic regression. Analyses were adjusted for demographics, cardiovascular risk profiles, stroke characteristics, and procedural times.

Results: Of 1702 patients screened, 807 (420 women, median age 77 years [66-84, IQR]) were included. Post-interventional ICH reduced the probability of a favourable functional outcome (90-day mRS 0-2) by 14.8% (ß = 0.15; 95% CI [0.06;0.24]; p = 0.001. An HDL-C level above the median (1.15 mmol/L) decreased the probability of ICH by 13.6% (ß = - 0.14; 95CI% [- 0.22; - 0.05]; p = 0.002) and increased the probability of favourable functional outcome by 13.2% (ß = - 0.13; 95CI% [- 0.22; - 0.05]; p = 0.003). In sensitivity analyses, higher HDL-C levels were independently associated with lower odds of ICH (adjusted OR 0.62; 95% CI [0.43;0.88]; p = 0.008) and higher odds of favourable functional outcome (adjusted OR 0.60; 95% CI [0.40; 0.90]; p = 0.015).

Conclusions: In patients undergoing thrombectomy for acLVO, higher HDL-C levels were associated with a reduced probability of post-interventional ICH and a favourable functional outcome. These observations could not be explained by conventional vascular risk profiles.

Due to its unspecific clinical presentation and the multitude of possible etiologies, chronic meningoencephalitis in immunosuppressed patients often represents a diagnostic challenge. Here, we report the clinical, radiological, cerebrospinal fluid, and microbiological findings of a 54-year-old male immunocompromised patient with mantle cell lymphoma and a 2-month history of brainstem and spinal meningoencephalitis. After unsuccessful treatment trials with antibiotics, a Candida albicans infection was confirmed by biopsy of a spinal cord lesion and large-volume cerebrospinal fluid culture. Therapy with liposomal amphotericin B/flucytosine and subsequent fluconazole resulted in significant clinical improvement. This case illustrates the importance of identifying the underlying cause of chronic meningoencephalitides in immunocompromised patients.

Background: The neuroprotective and proangiogenic potential of ghrelin in acute ischemic stroke has been demonstrated in experimental studies. However, the transferability of these results is limited as ghrelin was administered either before or very early after stroke onset and follow-up was limited to the first days after stroke. The aim of this study was therefore to close and extend this knowledge gap. To this end, we investigated the effect of ghrelin in two different translational animal models, one investigating acute and one investigating long-term structural and functional recovery after experimental stroke.

Methods: Middle cerebral artery occlusion (MCAO) or photothrombotic stroke was induced in 65 adult male Wistar rats. Eleven sham-operated animals served as controls. The rats were treated with either ghrelin, the ghrelin receptor antagonist [D-Lys]-GHRP-6 or a control substance. Up to four weeks after ischemia, behavioral tests such as the cylinder test, the tape removal test, and the rotarod test were performed to examine sensorimotor deficits, and the Morris water maze was performed to examine effects on the acquisition and consolidation of new memories. The structural outcome was determined by a differential analysis of neurogenesis in relation to survival and proliferation of newborn neurons in the post-ischemic brain, angiogenesis and determination of infarct size.

Results: Ghrelin treatment improved motor and somatosensory functions and preserved the consolidation of new memories after photothrombotic stroke. As a structural correlate, long-term survival and sustained proliferation of neuronal cells after stroke was significantly increased in ghrelin-treated rats, while angiogenesis remained unaffected. In contrast to these neuroregenerative mechanisms, ghrelin did not induce immediate neuroprotective effects after MCAO.

Conclusions: Our results suggest that ghrelin has a significant pro-neuroregenerative effect by enhancing long-term survival and sustained proliferation of neurons in the dentate gyrus and peri-infarct area, thus promoting functional recovery. Overall, ghrelin represents a promising target in the subacute and chronic phase after ischemic stroke.

Background: Patients with epileptic seizures represent a significant proportion of emergency department (ED) admissions and are often referred for cranial imaging due to suspected or observed trauma. Neurological guidelines provide limited advice on indications for imaging in this scenario, and traumatological clinical decision rules on the use of CT in mild traumatic brain injury explicitly exclude patients with seizures preceding the trauma. This gap in recommendations may contribute to overimaging for trauma rule-out after a seizure.

Methods: We analysed medical records of patients with known epilepsy admitted to our ED after a seizure between January 2022 and March 2024. Using clinical data including the findings from cranial CT and risk factors for traumatic brain injury, we re-assessed the need for CT imaging by application of the Canadian CT head rule (CCHR) or in the context of head trauma under anticoagulation.

Results: During the observational period, 683 patients with known epilepsy were referred to our hospital due to a seizure (mean age 48.8 years, 57.7% male). A head CT scan was obtained in 337 (49.3%) of all encounters. In only two patients, CT diagnosed an acute seizure-related traumatic lesion, one focal subarachnoid haemorrhage and one skull base fracture. Twenty-six cases (3.8%) with seizure-related trauma were reassessed as requiring a CT for trauma-related injury evaluation. Particularly in the absence of head impact or risk factors, a high degree of variability regarding CT ordering practice was observed.

Conclusions: Our results demonstrate frequent use and low diagnostic yield of CT in ED seizure patients with respect to trauma-related head injury. Circumstantial factors, clinical signs or symptoms and medical risk factors variedly impact on clinicians' decision to perform imaging. The absence of clear recommendations regarding imaging for trauma apparently provokes frequent diagnostic rule-out even in patients with low risk for traumatic brain injury. We suggest an approach to identify patients not requiring a head CT by considering the CCHR, presence of anticoagulation and appreciating the postictal state as a feature specific to patients with seizures.

Background: The low rate of organ donation in Germany has been linked to a deficit in the detection of patients with brain death (BD) in hospitals. It is unclear how crisis-related health system disruptions, such as the COVID-19 pandemic, affect this detection deficit.

Methods: Secondary data analysis of anonymized data from deceased patients with acute brain injury from Saxony, Saxony-Anhalt and Thuringia during the pre-pandemic and pandemic period (01/2019-12/2022). Pandemic phases were stratified according to the predominant SARS-CoV-2 variant. Logistic multilevel models were employed to assess outcomes including diagnosis of BD, deceased organ donations, missed cases with potential BD and organ donation-related interactions with the German Organ procurement organization. Models accounted for regional COVID-19 incidence and first-dose vaccination rates, as well as age, gender and types of brain injuries.

Results: A total of 11,100 deceased individuals from 136 hospitals were analyzed. An inverse association was observed between COVID-19 incidence and the determination of BD (adjusted odds ratio [aOR] 0.94, 95%CI [0.91; 0.97]; p < 0.001) as well as deceased organ donation (aOR 0.94, 95%CI [0.90; 0.98]; p = 0.001). When stratified by pandemic phases, this inverse association was evident for both BD determination (aOR 0.92, 95%CI [0.87; 0.99]; p = 0.02) and deceased organ donation (aOR 0.90, 95%CI [0.83; 0.97]; p = 0.01) during the initial wild-type phase. In the alpha phase, the association was observed only for BD determination (aOR 0.76, 95%CI [0.59; 0.98]; p = 0.03). No association was found in subsequent pandemic phases.

Conclusion: The initial impact on BD detection during the pandemic highlights the importance of the health system's adaptive capacity in times of crisis.