This review provides an overview on different antibody test methods that can be applied in cases of suspected paraneoplastic neurological syndromes (PNS) and anti-neuronal autoimmune encephalitis (AIE) in order to explain their diagnostic value, describe potential pitfalls and limitations, and discuss novel approaches aimed at discovering further autoantibodies. Onconeuronal antibodies are well-established biomarkers for PNS and may serve as specific tumor markers. The recommended procedure to detect onconeuronal antibodies is a combination of indirect immunohistochemistry on fixed rodent cerebellum and confirmation of the specificity by line assays. Simplification of this approach by only using line assays with recombinant proteins bears the risk to miss antibody-positive samples. Anti-neuronal surface antibodies are sensitive and specific biomarkers for AIE. Their identification requires the use of test methods that allow the recognition of conformation dependent epitopes. These commonly include cell-based assays and tissue based assays with unfixed rodent brain tissue. Tissue based assays can detect most of the currently known neuronal surface antibodies and thus enable broad screening of biological samples. A complementary testing on live neuronal cell cultures may confirm that the antibody recognizes a surface epitope. In patients with peripheral neuropathy, the screening may be expanded to teased nerve fibers to identify antibodies against the node of Ranvier. This method helps to identify a novel subgroup of peripheral autoimmune neuropathies, resulting in improved immunotherapy of these patients. Tissue based assays are useful to discover additional autoantibody targets that play a role in diverse autoimmune neurological syndromes. Antibody screening assays represent promising avenues of research to improve the diagnostic yield of current assays for antibody-associated autoimmune encephalitis.

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome. Methods: Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary. Results: The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r s = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability. Conclusions: sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.

Objective To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. Methods Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. Results Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. Conclusions This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

Over the last years the clinical picture of autoimmune encephalitis has gained importance in neurology. The broad field of symptoms and syndromes poses a great challenge in diagnosis for clinicians. Early diagnosis and the initiation of the appropriate treatment is the most relevant step in the management of the patients. Over the last years advances in neuroimmunology have elucidated pathophysiological basis and improved treatment concepts. In this monocentric study we compare demographics, diagnostics, treatment options and outcomes with knowledge from literature. We present 38 patients suffering from autoimmune encephalitis. Antibodies were detected against NMDAR and LGI1 in seven patients, against GAD in 6 patients) one patient had coexisting antibodies against GABAA and GABAB), against CASPR2, IGLON5, YO, Glycine in 3 patients, against Ma-2 in 2 patients, against CV2 and AMPAR in 1 patient; two patients were diagnosed with hashimoto encephalitis with antibodies against TPO/TG. First, we compare baseline data of patients who were consecutively diagnosed with autoimmune encephalitis from a retrospective view. Further, we discuss when to stop immunosuppressive therapy since how long treatment should be performed after clinical stabilization or an acute relapse is still a matter of debate. Our experiences are comparable with data from literature. However, in contrary to other experts in the field we stop treatment and monitor patients very closely after tumor removal and after rehabilitation from first attack.