Neurological research and practice最新文献

This correspondence responds to Schoene et al.'s study on the impact of the COVID-19 pandemic on brain death (BD) detection in German hospitals. While their data-driven approach provides valuable insights, this response emphasizes the need to contextualize BD determination within the lived clinical and ethical realities of the pandemic. It argues that the reduction in BD assessments cannot solely be attributed to organizational lapses but must also account for ethical dilemmas, safety concerns, and triage pressures faced by healthcare providers. The author highlights the limitations of rigid BD protocols during public health emergencies and advocates for flexible, ethically guided practices. Drawing on international experience, including temporary adaptations in Cuba's BD policies, the letter underscores the importance of physician support, context-sensitive decision-making, and humanistic engagement with families. Ultimately, it calls for a reexamination of how BD determinations are understood and implemented under crisis conditions, urging reforms that integrate medical standards with compassionate care and ethical reflection.

Background: Digital mobility outcomes (DMOs) have emerged as novel biomarkers offering objective, quantitative, and examiner-independent outcome measures for clinical studies. Unfortunately, research efforts on DMOs have not yet investigated the domain of clinical utility in Parkinson's disease, i.e. providing evidence of improvements in health outcomes, diagnosis, decision-making, or prevention when compared to e.g. standard-of-care procedures. This manuscript, via a consensus building approach, aims to create a structured conceptual framework to map the knowledge generated by DMOs with clinical domains that could benefit from it.

Methods: We conducted a three-round consensus-building study with 12 experts recruited from the Mobilise-D consortium's Parkinson's Disease Working Group. The experts designed and ranked different aspects of the conceptual framework via a 5-level Likert scale for level of agreement. Consensus for the different points evaluated was based on a double threshold: the simultaneous presence of a high level of agreement had to be accompanied by a low level of disagreement. As secondary objectives, the experts were asked to rate the practical application of DMOs by evaluating the timeline to applicability, the foreseen challenges for their implementation in clinical settings, and their main role in the decision-making process.

Results: A full consensus on the clinical utility framework was achieved after three rounds. The final framework consisted of three main categories (Disease Diagnosis, Patient Evaluation, and Treatment Evaluation) and six underlying domains (Enhancing Diagnostic Procedure, Predicting Risk, Timely Detecting Deterioration, Enhancing Clinical Judgment, Selecting Treatment, and Monitoring Treatment Response). The experts believed in the next 1-5 years DMOs will play a relevant role in clinical decision making, complementing care knowledge with useful digital biomarkers information. However, the main challenge to address is the definition of clear reference value for DMOs interpretability.

Conclusions: This framework provides a structure for subsequent studies to build into by diversifying expert cohorts and expand our findings beyond PD. Additionally, our results support researchers planning future clinical trials where DMOs can play a valuable role for clinical decision support. Ultimately, this is the first step toward developing guidelines to assess DMOs' clinical utility and support their integration into Real World clinical practice.

Background: Hereditary transthyretin amyloidosis is a rapidly progressive and lethal disease. Thanks to the increasing number of disease-modifying treatments, prognosis has improved significantly. However, new challenges regarding treatment response and when to change treatment remain unanswered. The objective of this study was to evaluate rationales for treatment switches from the past and to formulate learnings for future management.

Methods: In this retrospective single center study, we analyzed real-world data of 13 patients with hereditary transthyretin amyloidosis undergoing single or multiple treatment switches before January 2024. Data involved demographic characteristics as well as reasons for treatment switches in a descriptive and exploratory manner. Available amyloid specific therapies during the study period included tafamidis 20 mg, tafamidis 61 mg, patisiran, inotersen and vutrisiran.

Results: Switches from tafamidis 20 mg were most frequently due to disease progression (83.3%). Patisiran transitions predominantly occurred following vutrisiran's approval, driven by preference for subcutaneous administration and extended dosing intervals (65.0%). Two cases of switches from inotersen were both associated with severe adverse effects.

Conclusions: In this study, reasons for treatment switches were manifold, encompassing disease progression, the occurrence of adverse events, patient preferences and/or the availability of newly approved drugs. Hence, multidimensional consideration of these reasons remains pivotal in guiding the subsequent choice of medication in particular and managing hereditary transthyretin amyloidosis in general.

Background: Recreational nitrous oxide (N₂O) abuse has become increasingly prevalent, raising concerns about associated health risks. In Germany, the lack of reliable data on N₂O consumption patterns limits the development of effective public health interventions. This study aims to address this knowledge gap by examining trends, determinants, and health consequences of N₂O abuse in Germany.

Methods: A two-phase online survey was conducted from July 17 to September 13, 2024 among members of the German Neurological Society (DGN). In the first phase (101 respondents), the frequency and trends of N₂O-related cases were assessed. In the second phase (17 respondents) detailed information on diagnostic and therapeutic approaches was collected.

Results: Occasional N₂O-related cases were reported in 60% and 5% noted regular occurrences, particularly in the cities of Berlin and Frankfurt/Main. A nation-wide increase in case numbers was observed. Most neurologists treated between 1 and 10 cases annually, with metropolitan regions reporting higher numbers exceeding 30 per year. Myelopathy (94%) and neuropathy (88%) were widely recognized complications, whereas hypercoagulability (24%) and skin alterations (12%) were less frequently acknowledged. Vitamin B₁₂ levels (94%) and differential blood counts (88%) were the most frequently assessed markers, while methylmalonic acid was most often regarded as the key parameter for detecting N₂O-related vitamin B₁₂ deficiency (78%). Treatment predominantly involved intramuscular vitamin B₁₂ (88%), occasionally in combination with methionine (24%). Neurological deficits improved (median modified Rankin Scale score from 3 to 2), but 75% of cases relapsed after renewed N₂O use.

Conclusion: This study provides evidence of widespread N₂O abuse in Germany, with hotspots in Berlin and Frankfurt/Main, and a concerning rise in rural areas. While myelopathy is well recognized among neurologists, other clinical manifestations are underreported. Improved communication, along with standardized diagnostics and treatment protocols, is urgently needed to address the heterogenous awareness of symptomatology, diagnostic sensitivity and specificity, and therapeutic strategies.

Awareness concerning iatrogenic cerebral amyloid angiopathy (iCAA) is increasing but its pathophysiology remains unclear. We discuss the implications of the clinical, imaging and neuropathological findings in two previously unpublished cases of probable iCAA: a 55-year-old female presenting with rapidly progressive cognitive impairment, showing imaging and histological evidence of CAA and having undergone neurosurgical treatment at the age of 6; and a 56-year-old male with a four-year history of recurring intracerebral hemorrhages (ICH) and neurosurgical intervention at the age of 5. In the first case, a brain biopsy was performed.Additionally, a systematic review of iCAA cases with neuropathological data suggests that most of the patients have concomitant amyloid parenchymal deposition and none or minimal tau pathology. The pathophysiological role of tau pathology in iCAA remains unclear. iCAA patients presenting with cognitive impairment without symptomatic ICH may be underdiagnosed.

Background: Parkinson's disease (PD) multimodal complex treatment (PD-MCT) is an inpatient therapeutic programme specifically designed for patients exhibiting parkinsonian symptoms. Established in Germany, this comprehensive approach addresses the multifaceted challenges associated with the management of PD, particularly in advanced stages or when complications such as motor fluctuations, dyskinesia, or non-motor symptoms become pronounced. The programme integrates pharmacological optimization, physiotherapy, occupational therapy, speech therapy, and psychological support, among other complementary therapies, to enhance patient outcomes holistically. Despite its availability for seventeen years, only seven studies evaluating the effectiveness of PD-MCT have been conducted. In this study we evaluated the effects of PD-MCT with a special focus on gait, hypothesizing an improvement after the treatment.

Methods: In this single-centre cohort study at a German university hospital we included patients with PD diagnosed by the Movement Disorder Society (MDS) criteria, aged 18-85 years, legal capacity to consent and admitted for treatment with PD-MCT. We assessed changes in motor and non-motor symptoms using Wilcoxon's signed rank test on pre/post measurements of part III of the motor part of the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Parkinson's Disease Questionnaire (PDQ-39) and the Timed Up and Go Test (TUG). As a particular emphasis was placed on gait analysis we objectively measured gait throughout the treatment period using advanced mobile sensor technology and analysed gait speed, stride length and lift height using linear mixed effects models.

Results: In our sample of 43 PD patients we found significant improvements in MDS-UPRDRS part III (V = 679, p = 0.001), PDQ-39 (V = 770, p < 0.001) and TUG (V = 753.5, p < 0.001) values. as well as in the assessed gait parameters gait speed (t = 66.44, p < 0.001), stride length (t = 62.67, p < 0.001) and lift height (t = 28.16, p < 0.001).

Conclusions: Our results underscore the added value of a multimodal inpatient approach, thereby supporting its role as a justified investment in the management of complex PD cases. This work contributes to the expanding body of evidence advocating for integrated, multidisciplinary care models in the treatment of neurodegenerative disorders.

Trial registration: This study has not been registered.

Objective: To assess the role of spectral domain Optical Coherence Tomography (OCT) as a biomarker in Huntington's disease (HD).

Methods: This cross-sectional study compared spectral domain OCT data, cognitive function, and olfactory function in HD patients and healthy controls (HC). HD patients were classified into Stage1 and Stage2 based on motor symptoms and functional capacity.

Results: We recruited a total of 68 participants including 39HD patients (22 stage1, 17 stage2) and 29 age-matched HC. There were no significant differences in age and gender between the groups. Stage2 HD patients showed worse motor function (UHDRS-TMS 28.44 ± 18.13 vs. 13.74 ± 8.78, p = 0.002), functional capacity (UHDRS-TFC 8.13 ± 2.03 vs. 12.44 ± 0.99, p < 0.001), and lower scores on MMSE (27.36 ± 1.64 vs. 28.73 ± 1.74, p = 0.005 vs. 29.45 ± 0.91, p < 0.001) compared to stage1 HD patients and HC, respectively. Both stage1 and stage2 HD groups displayed significantly reduced macular retinal nerve fibre layer thickness (mRNFL) (33.45 ± 4.70, 31.90 ± 3.47 vs. 38.45 ± 5.00; p < 0.001) and ganglion cell-inner plexiform layer thickness (GCIPL) (71.63 ± 6.38, p = 0.007; 60.42 ± 4.67, p < 0.001 vs. 77.03 ± 8.40) as compared to HC. The retinal OCT parameters mRNFL and GCIPL correlated moderately with PIN_HD (r=-0.424, r=-0.513; p < 0.001), CAP (r=-0.425, r=-0.482; p < 0.001) and olfactory dysfunction for both smell identification (r = 0.446, r = 0.500; p < 0.001) and smell discrimination (r = 0.563, r = 0.467; p < 0.001).

Conclusions: HD patients exhibit significantly thinner retinal ganglion cell inner plexiform layer and macular retinal nerve fibre layer compared to HC, even in the early phase of the disease. These findings suggest that OCT may serve as a valuable biomarker to monitor neurodegeneration at an early disease stage.

Background: Endovascular thrombectomy (EVT)-often combined with intravenous thrombolysis-is the standard of care for acute ischemic stroke (AIS) secondary to large vessel occlusions (LVO). While indications keep expanding, the feasibility and utility of intra-procedural neuromonitoring of the sedated patient has neither been clarified nor characterized.

Objective: To evaluate the feasibility of near-infrared spectroscopy (NIRS) for cortical oxygenation and bispectral index (BIS) for electroencephalographic function as non-invasive neuromonitoring tools for AIS patients undergoing EVT, and assess their utility in predicting successful recanalization.

Methods: We extracted data on all patients receiving continuous NIRS and/or BIS monitoring in the Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) clinical trial. SIESTA randomized AIS patients undergoing EVT for anterior proximal LVO to general anesthesia versus conscious sedation. For this analysis, the primary outcomes included changes in NIRS and BIS values pre- and post-recanalization and associations of parameter changes with successful or unsuccessful recanalization outcomes. Statistical analysis was performed using a Wilcoxon signed rank tests.

Results: Of the 150 patients, 66 were monitored continuously with NIRS, and 50 with BIS. An increased NIRS-derived cerebral tissue oxygenation (stated as tissue saturation index - TSI) was observed in affected hemisphere following successful recanalization, as well as a significant reduction in the difference between affected and unaffected hemispheres. In contrast, no significant changes were observed with BIS monitoring between pre- and post-recanalization status.

Conclusion: In this post-hoc analysis, changes in NIRS monitoring were associated with successful reperfusion. Non-invasive oximetry by NIRS may serve as a valuable tool during and after mechanical thrombectomy to detect and respond to an insufficient perfusion or re-occlusion.

Background: Kappa free light chains (KFLC), a byproduct of immunoglobulin (Ig) synthesis by B-lineage cells, can serve as an indicator for inflammatory activity. In multiple sclerosis (MS), especially the intrathecal KFLC production has gained increasing importance as a biomarker for central nervous system (CNS) inflammation and was included into the proposed 2024 revision of the McDonald criteria. In contrast, studies investigating the significance of KFLC in serum and the effects of disease-modifying therapies (DMT) on KFLC serum concentration in MS are rare. The aim of the present work was to investigate the impact of B cell depletion with ocrelizumab on KFLC concentrations in serum of MS patients and the ability of serum KFLC to monitor disease activity.

Methods: 50 MS patients were included in the present study- 38 with the diagnosis of relapsing MS (RMS) and 12 with diagnosis of primary-progressive MS (PPMS) -, who were treated with ocrelizumab for two years. Serum concentrations of albumin, immunoglobulins and KFLC as well as lymphocyte subsets were determined at baseline and after two years.

Results: Serum Ig and KFLC concentrations were found to be significantly lower after two years of ocrelizumab treatment (mean serum concentrations: KFLC: 9.5 mg/l vs. 7.8 mg/l, p = 0.0003; IgG: 9 g/l vs. 8 g/l, p = 0.0002; IgA: 2 g/l vs. 1.8 g/l, p = 0.0010; IgM: 1.8 g/l vs. 0.7 g/l, p < 0.0001). Serum KFLC concentration did not correlate with clinical and paraclinical parameters of disease activity.

Conclusions: Treatment with ocrelizumab reduces serum KFLC concentration in MS patients. However, serum KFLC concentration is not able to predict disease activity in these MS patients.