Background and Objectives Reliable biomarkers for autoimmune encephalitis (AE) are limited, and emerging CSF markers are not incorporated into current diagnostic criteria. Prognostic tools remain insufficient, highlighting the need for biomarkers that support both early diagnosis and assessment of disease severity and prognosis. Methods In this multicenter prospective cohort study, we analyzed clinical data and paired CSF-serum samples from adults with definite AE enrolled in the German Network for Research on Autoimmune Encephalitis registry and the CSF biobank of Hannover Medical School. Of 2,330 screened individuals, 92 patients with anti–N-methyl-d-aspartate receptor (NMDAR, n = 53), anti–leucine-rich glioma-inactivated 1 (LGI1, n = 20), or anti–contactin-associated protein-like 2 (CASPR2, n = 19) encephalitis were included and followed longitudinally for a median of 38 months. Control groups comprised patients with relapsing multiple sclerosis, varicella-zoster virus encephalitis, and noninflammatory neurologic conditions (each n = 30), as well as antibody-positive patients without AE (n = 15), with the groups frequency-matched for age and sex. Kappa free light chain (KFLC), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokines were measured in paired CSF-serum samples obtained at baseline and during follow-up. Disease severity and disability were assessed using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score and the modified Rankin Scale (mRS). Results Intrathecal synthesis of KFLC was detected in 94% of anti-NMDAR, 50% of anti-LGI1, and 53% of anti-CASPR2 encephalitis cases, demonstrating higher diagnostic sensitivity than CSF-restricted oligoclonal bands or pleocytosis. Diagnostic specificity across pooled control groups was moderate at 44% but reached 90% when compared with noninflammatory neurologic controls. CSF NfL z-score levels were strongly associated with baseline disease severity, with each 1-standard deviation increase corresponding to an approximately 10-point higher CASE score, independent of clinical covariates (β = 0.61). Longitudinal changes in NfL concentrations in CSF and serum were associated with disease severity and neurologic disability at follow-up (CASE score: adjusted R2 = 0.401; mRS score: adjusted R2 = 0.203). GFAP and cytokines showed limited diagnostic or prognostic utility. Discussion Intrathecal KFLC synthesis represents a highly sensitive CSF marker that supports early suspicion of autoimmune encephalitis and prompts antibody testing. NfL provides robust biochemical information on baseline disease severity and longitudinal changes that may aid prognostic assessment across AE subtypes.
F. Konen, E. Bucak, F. Bachhuber et al.· Neurology(R) neuroimmunology...· 0 citations
BackgroundDistinguishing Alzheimer's disease (AD) from frontotemporal dementia (FTD) remains a major clinical challenge, particularly in early disease stages due to overlapping symptoms. Although neuropsychological assessment is central to diagnosis, brief cognitive screening instruments often emphasize episodic memory, whereas comprehensive neuropsychological assessment encompasses multiple cognitive domains. Nevertheless, social cognition and other relevant functions may remain underrepresented in routine clinical assessment.ObjectiveTo identify neuropsychological domains and test procedures that reliably differentiate AD from FTD and support differential diagnosis.MethodsA systematic PubMed literature search was conducted using predefined inclusion and exclusion criteria. Original studies directly comparing neuropsychological performance in patients with AD and FTD were included. Owing to methodological heterogeneity, findings were synthesized narratively.ResultsA total of 322 records were identified, of which 80 studies met the inclusion criteria. A clear domain-specific pattern emerged. Episodic memory impairment, particularly delayed recall deficits, consistently distinguished AD from FTD, with poorer performance in AD. In contrast, deficits in social cognition, including theory of mind and emotion recognition, were more pronounced in FTD and were often detectable early in the disease course. Executive functions and language showed heterogeneous findings, with discriminative value depending on specific subdomains and FTD subtypes. Visuospatial functions and attention provided supportive but less consistent differentiation, while global screening instruments showed limited diagnostic specificity.ConclusionsDifferentiation between AD and FTD should not rely on single cognitive domains. The most clinically meaningful distinction is achieved through a multidimensional assessment integrating episodic memory, social cognition, and selected executive and behavioral measures.
Jana Marie Freitag, F. Konen, J. Heck et al.· Journal of Alzheimer's Disea...· 0 citations
Early and reliable diagnosis of multiple sclerosis (MS) is critical for initiating an appropriate disease-modifying therapy (DMT). The 2024 revisions of the McDonald diagnostic criteria incorporate novel fluid and imaging biomarkers aiming to facilitate an accurate and timely diagnosis. The aim of this point-of-view paper is to discuss the implementation of the 2024 McDonald criteria in the clinical routine setting in context of the German Health care system and provide consensus recommendations by an interdisciplinary expert panel. A multidisciplinary panel of nine experts in the field of diagnosis and treatment of MS convened to discuss the potential advances and challenges of the clinical implementation of the 2024 McDonald criteria and develop consensus recommendations. The panel identified implementation challenges regarding limited specialized resources for the suggested additional imaging markers such as the detection of optic nerve (ON) lesions, paramagnetic rim lesions (PRLs) and the demonstration of lesions with a central vein sign (CVS) as well as the implementation of kappa free light chains (kFLC) in Germany. We advocate a stratified diagnostic approach: cerebrospinal fluid (CSF) analysis remains essential. The consideration of ON lesions, PRLs and lesions with a CVS should be reserved for diagnostic situations in which the diagnosis cannot be established with conventional MRI protocols or other methods for examination of the optic nerve. To minimize misdiagnosis and to address the complexity of treating radiologically isolated syndrome, there is a necessity of continuous professional training and nuanced, patient-centered therapeutic strategies, especially for individuals with radiologically isolated syndrome but also for atypical presentations. In conclusion, the 2024 revisions of the McDonald criteria aim to facilitate an accurate and early diagnosis of MS potentially enabling earlier MS therapy initiation. However, the routine implementation, particularly regarding the new imaging markers, requires an expansion of resources and expertise limiting the general applicability in the German healthcare system.
M. P. Wattjes, A. Bayas, Stefan Bittner et al.· Therapeutic Advances in Neur...· 0 citations
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