Neurological research and practice最新文献

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.

Background: Neurovascular networks (NVNs) in Germany are supra-regional care structures for patients with neurovascular diseases. Each NVN consists of a tertiary care center serving as the coordinating center-in some cases, two or three coordinating centers-and at least three partner hospitals. Since 2018, 19 neurovascular networks (NVNs) have been audited and certified. NVNs play a crucial role in stroke care in Germany, as first described and quantified in 2020.

Methods: The present article provides an update on interdisciplinary NVNs in Germany and outlines recent developments in neurovascular patient care. Audit reports from 19 NVNs, certified between 2021 and 2024, were analyzed, and compared to previously reported data from 2017 to 2019. Additionally, structural and quality-related parameters for coordinating centers and partner hospitals were compared.

Results: The number of NVNs increased from 15 to 19, with approximately 120,000 from an estimated 262,000 neurovascular patients in Germany now treated annually in certified NVN hospitals. In particular, annual thrombectomy rates at coordinating centers have increased over-proportionally (> 4400, as compared to previously < 2500), and surgical treatments for intracerebral hemorrhages have also increased. Process times-door-to-needle and door-to-groin times-remained stable or exhibited slight increases. Substantial variability was observed among NVN partner hospitals regarding procedural volumes.

Conclusions: The treatment of patients with neurovascular diseases in Germany has expanded considerably within certified NVN hospitals in recent years. The NVNs ensure comprehensive, high-quality stroke care nationwide.

White matter hyperintensities of presumed vascular origin (WMH) are associated with various clinical sequelae. In stroke patients, the total WMH burden is linked to recurrent cerebrovascular events and worse clinical outcomes. As WMH also affect the integrity of large-scale structural brain networks, we hypothesize that the extent of WMH-related network damage carries relevant information to explain outcome variability in addition to global WMH volume. Clinical and structural brain imaging data of 33 severely affected acute stroke patients were analyzed from two independent cohorts. Imaging data were acquired within the first two weeks after stroke. WMH-related localized and global network damage was derived. WMH network effects were differentially assessed for total, periventricular (pWMH), and deep WMH (dWMH). Using ordinal logistic regression analyses, network damage was associated with functional outcome at follow-up after three to six months. WMH were linked to a significant disconnection of multiple cortical and subcortical brain regions. Global and localized pWMH-related network damage affecting distinct brain regions of both hemispheres were independently associated with a worse outcome after adjustment for baseline symptom burden, age, brain infarct volume, and total WMH volume. Total and dWMH-related network disturbances did not show similar associations. This study indicates that pWMH-related network damage affecting specific brain regions is linked to functional outcome in acute stroke patients. It underscores the potential significance of pre-existing WMH-related network damage as a crucial factor in comprehending outcome variability after severe stroke.

Introduction: The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need.

Methods: A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a presymptomatic and early ALS signature. Perspective The premodiALS study aim to identify a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early diagnosis and future clinical practice for ALS disease.