Katrin Hahn

Epidemiology and treatment of HIV changed substantially within the last three decades. However, HIV-associated neurological disorders such as mild forms of HIV-associated neurocognitive disorder (HAND) as well as HIV-associated distal symmetrical sensory polyneuropathy are amongst the most frequent complications in patients with longstanding HIV infection. Opportunistic infections occur less frequently compared to former years, but especially in patients with late presentation of HIV progressive multifocal leukoencephalopathy (PML) (0.7 per 1,000 patient-years), toxoplasma encephalitis (0.4 per 1,000 patient-years) and cryptococcal meningitis (0.2 per 1,000 patient-years) remain the most common opportunistic infections. The guidelines for diagnosis and treatment of HIV-associated neurological disorders of the German Society of Neurology were revised addressing recent changes in treatment opportunities of HAND, HIV associated complications of the peripheral nervous system and muscles and opportunistic infections of the central nervous system (CNS).

Hereditary transthyretin (ATTRv) amyloidosis is a rare, progressive multisystem disease caused by pathogenic variants in the transthyretin ( TTR ) gene. ATTRv-associated Polyneuropathy (ATTRv-PN) manifests in a length-dependent sensorimotor and autonomic pattern, commonly accompanied by cardiomyopathy. In recent years, clinical trials have introduced two classes of disease modifying treatments (DMT), TTR stabilizers and gene silencers. Across populations and outcome parameters, all trials share one result disease progression was significantly slowed and patients’ span and quality of life substantially improved compared to placebo, even though a function once lost would not be retrieved. This expert consensus paper provides recommendations for the treatment of ATTRv-PN in Germany and was jointly developed by experts from the German Society of Amyloid Diseases (DGAK) and the German Neurological Society (DGN). In addition to evidence from pivotal clinical trials, the recommendations incorporate benefit assessments of the German Federal Joint Committee (G-BA). For first-line treatment, the DGAK/DGN recommends one of the two second-generation TTR gene-silencing agents, vutrisiran or eplontersen, for most patients with symptomatic ATTRv-PN. For patients showing even minor signs of disease progression under a TTR stabilizer, the authors recommend immediate switch to a gene silencer. Evidence is limited for or against switching between silencers or combining different agents. Informed patient participation is crucial upon initiation and adaptation of DMT. For central nervous system (CNS) involvement, none of the approved agents sufficiently crosses the blood-brain barrier. Aligned with that, there are no observed or expected CNS side effects of any of the DMTs. In the future, next-generation RNA-interference therapies, gene-editing approaches, and amyloid-depleting antibodies are expected to further expand therapeutic options.

Introduction: Vaccination against COVID-19 has been crucial in controlling the pandemic. While side effects are typically mild, rare neurological complications have been reported. This is a case series of ten patients who reported of persistent fasciculations after COVID-19 vaccination. Methods: We describe the clinical presentation and diagnostic work-up of ten patients with new-onset fasciculations in temporal proximity to COVID-19 vaccination. Patients with prior SARS-CoV-2 infection or known alternative causes of fasciculations were excluded. Routine clinical data, including neurological examination, laboratory results, and electrophysiology (electromyography and nerve conduction studies), were analyzed. Results: Ten patients (5 male, 5 female; mean age 42.4 years) reported fasciculations beginning within 6 h to 13 days post-vaccination and persisting for 2–12 months at the time of presentation. Fasciculations were accompanied by additional symptoms such as paresthesia and fatigue. Laboratory results were mostly unremarkable; two patients had positive myositis antibodies without clinical correlates. Electrophysiology was unremarkable in six patients, while fasciculation potentials were detected in four patients. Nine were diagnosed with probable benign fasciculation syndrome (BFS), and one met diagnostic criteria for amyotrophic lateral sclerosis (ALS). Discussion: In this small, retrospective case series, most cases of post-vaccination fasciculations were benign and compatible with BFS. Whether BFS onset was causally linked to vaccination or due to a nocebo effect remains unclear. One patient was diagnosed with ALS, though a causal link remains speculative given the study’s limitations and rarity of similar reports. Larger, prospective studies are needed to validate these observations and explore underlying pathophysiological mechanisms.

Background: Systemic amyloidosis comprises a heterogeneous group of rare diseases characterised by extracellular deposition of misfolded protein fibrils, leading to progressive organ dysfunction. Due to the variability in clinical presentation and course, collection of system-specific and longitudinal data is essential for understanding disease progression, treatment response and patient outcomes. At the Amyloidosis Center Charité Berlin (ACCB), a prospective amyloidosis registry has been established to systematically collect clinical, laboratory, imaging and patient-reported data with the aim of improving the characterization of the diseases and facilitating translational research. Methods: This is a single-center prospective registry study that enrols patients diagnosed with systemic amyloidosis. The registry includes demographic data, multidisciplinary clinical phenotyping, biomarkers, biobanking, genetic information, imaging studies, and patient reported outcomes. Here, we describe the standardised protocol for diagnostic workup, baseline and longitudinal data collection, and disease-specific follow-up algorithms. Data will be collected digitally in interoperable data formats to ensure shareability in accordance with GDPR-policies. Discussion: This registry will serve as a resource for characterizing amyloidosis as a rare disease model in a real-world setting and identifying patterns in disease progression and treatment efficacy. By prospectively collecting high-quality longitudinal data, the study aims to generate insights that can inform clinical decision-making, improve risk stratification and support future intervention studies. In addition, the registry enables collaboration in the discovery of biomarkers and new therapeutic approaches. Ongoing analysis of this cohort will provide a basis for the further development of personalised treatment strategies and the improvement of patient care. Ethics and dissemination: Ethical approval was given by the local ethic committee. Dissemination of data in publications with different scientific observational and correlational questions is planned. Clinical trial registration : DRKS00032002

Wearable sensors enable continuous recording of electrocardiographic, photoplethysmographic, and inertial signals and have accelerated the development of digital biomarkers in cardiovascular medicine. Transthyretin amyloidosis (ATTR) is a progressive multisystem disease characterized by arrhythmia, conduction disturbances, hemodynamic impairment, autonomic dysfunction, and gait abnormalities, making it theoretically suitable for multimodal wearable monitoring. This review summarizes current knowledge on wearable applications in amyloidosis with ATTR serving as an illustrative case, evaluates the plausibility of extrapolating signal-based biomarkers from related cardiovascular and neurological cohorts, and outlines methodological and implementation challenges. ATTR-specific data remain limited to small observational studies, mainly on long-term rhythm monitoring and supervised functional assessment. More comprehensive findings support the extraction of metrics such as atrial fibrillation burden, activity patterns, gait variability, and heart rate variability. However, ATTR-related structural remodeling and high arrhythmia burden may distort conventional digital biomarkers, necessitating disease-specific preprocessing and prospective validation. Wearable monitoring in ATTR is technically feasible and biologically plausible but remains investigational. Before routine integration into care pathways can be recommended, standardized, phenotype-stratified studies are needed that link wearable-derived characteristics to assessed clinical outcomes.

Cardiac amyloidosis (CA), a fatal and progressive cardiomyopathy is characterized by amyloid deposition within the myocardium. The main forms of CA include transthyretin amyloidosis (ATTR-CM; distinguished into a hereditary and wildtype form [ATTRv and ATTRwt]) and light-chain amyloidosis (AL). Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is increasingly recognized among heart failure (HF) patients, despite its underestimated prevalence as a rare disease. ATTR-CM is challenging to diagnose due to its broad phenotypic overlap with HF, yet a timely differentiation of CA is crucial, as effective treatment can significantly improve quality of life. Machine learning (ML) approaches could enable earlier detection of ATTR-CM in routine care data. Data of ATTR-CM patients from the Amyloidosis Center Charité Berlin (2002-2023) and data from a cohort with heart failure and aortic stenosis screened for ATTR-CM were mapped from ICD-10-GM to ICD-10-CM and evaluated with an open-source random forest (RF) model based on ICD-10-CM codes which was previously validated in multiple external cohorts in the US and UK. In the cohort of patients with HF and aortic stenosis, cases of ATTR-CM were recognized using the algorithm, although it was not possible to distinguish between ATTRv-CM and ATTRwt-CM. Sensitivity and specificity were significantly lower than in the external validations in the US and UK. Model performance depended strongly on coding granularity and feature availability and contributed to the diminished predictive power. While the RF model showed moderate transferability under enriched conditions, reliance of geographically specific ICD-10 systems limits broader applicability due to coding discrepancies and information loss. These findings underscore the need for improved semantic harmonization of routine data, as well as the integration of rare disease specific ontologies such as the Human Phenotype Ontology (HPO) and ORPHAcodes to enhance cross-border ML-based assistance for timely diagnosing patients with rare diseases.

Introduction: Monitoring individuals with peripheral neuropathies is challenging due to limited availability and time resources of neurologists, especially for rare genetic forms. This highlights the need for innovative methods to quantify disease severity efficiently and enable telemedical settings. In this study, we explored the feasibility of visual grading of gait disability as a novel approach for remote disease monitoring, using genetic neuropathies (Charcot Marie Tooth Disease, short CMT) as a model. Methods: We prospectively evaluated 53 participants with CMT using a battery of clinical examination scores, and patient reported outcome measures (PROMs), as well as semi‐standardized sagittal‐plane videos of participants walking a 4‐m runway for 5 ± 2 min cross‐sectionally, and developed the Visual Gait Assessment Scale in Polyneuropathy (vGASP) to grade the severity of gait abnormality. Results: Three independent raters evaluated the score as easily understandable and quick. The vGASP was internally consistent (inter‐class coefficient of 0.9) and valid when correlating with validated clinical outcome measures (Spearman's ρ = 0.6–0.8). Conclusions: The vGASP may offer a time‐effective solution for remote monitoring of patients in CMT and potentially other gait‐affecting polyneuropathies.

Wearable sensors enable continuous recording of electrocardiographic, photoplethys-mographic, and inertial signals and have accelerated the development of digital bi-omarkers in cardiovascular medicine. Transthyretin amyloidosis (ATTR) is a progressive multisystem disease characterized by arrhythmia, conduction disturbances, hemody-namic impairment, autonomic dysfunction, and gait abnormalities, making it theoreti-cally suitable for multimodal wearable monitoring. This review summarizes current knowledge on wearable applications in ATTR, evaluates the plausibility of extrapolating signal-based biomarkers from related cardiovascular and neurological cohorts, and out-lines methodological and implementation challenges. ATTR-specific data remain limited to small observational studies, mainly on long-term rhythm monitoring and supervised functional assessment. More comprehensive findings support the extraction of metrics such as atrial fibrillation burden, activity patterns, gait variability, and heart rate var-iability. However, ATTR-related structural remodeling and high arrhythmia burden may distort conventional digital biomarkers, necessitating disease-specific preprocessing and prospective validation. Wearable monitoring in ATTR is technically feasible and biologically plausible but remains investigational. Before routine integration into care pathways can be recommended, standardized, phenotype-stratified studies are needed that link wearable-derived characteristics to assessed clinical outcomes.

To comprehensively characterize complement pathway activation in chronic inflammatory demyelinating polyneuropathy (CIDP) and its association with clinical disease features using advanced complement profiling. Complement protein levels indicative of classical, lectin, and alternative pathway activation were quantified by multiplex ELISA and compared between 28 patients with typical CIDP, 24 patients with Charcot-Marie Tooth neuropathy (CMT), and 24 demographically matched healthy controls (HD). Serum levels of activated complement proteins-C3a, C4a, Ba, Bb, C5a, and the soluble terminal complement complex sC5b-9 (sTCC)-were significantly elevated in CIDP patients compared to healthy donors (HD) (p < 0.001). Except for C3a, these protein levels were also significantly higher in CIDP patients than in those with Charcot-Marie-Tooth disease (CMT). Among CIDP patients, those with active, unstable disease exhibited significantly higher levels of terminal complement components (C5a and sTCC) compared to patients with stable disease or in remission (p < 0.001). These findings highlight the critical involvement of aberrant complement activation in the pathophysiology of CIDP and provide a rationale for further investigation into targeted complement inhibition as a therapeutic approach.

Background: This manuscript presents the study protocol for a planned mixed-methods study on the transition to an opt-out approach for the electronic health record (elektronische Patientenakte, ePA) in Germany in 2025. This change represents a paradigm shift in the healthcare system and aims to promote broad adoption. While the ePA has the potential to improve cross-sectoral care and patient empowerment, structural and individual barriers may hinder successful implementation. Understanding these factors is crucial to developing strategies for effective integration and long-term utilization of the ePA. Objective: This study aims to systematically investigate the barriers and facilitators influencing the adoption and use of the ePA among various user groups, including both patients and healthcare providers, in Germany. It seeks to identify sociodemographic and contextual factors affecting acceptance and usage while also exploring the ePAs potential to optimize healthcare processes, patient satisfaction, and empowerment. Methods: This mixed-methods exploratory study employs the Consolidated Framework for Implementation Research to examine the structural, organizational, and individual determinants of ePA implementation. Data will be collected in four modules: (1) patient interviews and surveys with ePA users and nonusers, (2) analysis of aggregated usage data from all ePAs in Germany, (3) interviews and surveys with stakeholders in outpatient and emergency care, and (4) focus groups for validation and synthesis of findings. Quantitative analyses include descriptive statistics and regression models, whereas qualitative data will be analyzed using structured content analysis. Discussion: This study is expected to provide a comprehensive understanding of the factors that affect ePA adoption and use in Germany. Insights from different perspectives will inform targeted strategies to overcome barriers, strengthen health literacy, and enhance system usability. These insights will contribute to recommendations for optimizing the implementation of the ePA in Germany and promoting the digital transformation of the German healthcare system.