Dubey, Divyanshu

Abstract Objectives γ‐Aminobutyric acid B receptor (GABA B R)‐IgG (immunoglobulin G) is an intermediate‐risk paraneoplastic autoantibody often associated with seizures. We aimed to assess the clinical and oncological features of GABA B R‐IgG autoimmune encephalitis (AE) and evaluate the performance of antibody testing. Methods Patients testing positive for GABA B R‐IgG in serum/cerebrospinal fluid (CSF) at Mayo Clinic Neuroimmunology Laboratory were identified. Archived sera were retested by cell‐based assay (CBA) at 1:100 and 1:200 dilutions. A live‐cell flow cytometry–based assay (LCFBA) was developed and validated using archived sera and CSF. True positivity included patients with classic presentations of GABA B R‐IgG AE or oncological explanations for antibody presence. Results Eighty‐six patients (median age 63 years; 43 female) presented with classic presentations of GABA B R‐IgG AE: encephalopathy with prominent seizures ( n = 55), status epilepticus ( n = 23), and rapidly progressive dementia ( n = 8). In addition, 44 patients (33%) had a false‐positive result for GABA B R‐IgG characterized by non‐specific symptoms/alternate diagnoses. Malignancy was identified in 78% of true‐positive patients, predominantly small cell lung carcinoma (SCLC). Testing serum at 1:100 dilution on CBA and using tissue immunofluorescence assay (IFA) in serum and CSF improved the identification of true‐positive patients ( p < 0.001). CBA at 1:100 dilution performed better than conventional CBA (at 1:10 dilution, p < 0.001) and tissue IFA ( p = 0.031). An in‐house LCFBA showed 100% sensitivity and specificity in CSF, performing similarly to conventional CBA ( p = 0.125) in CSF, but better than tissue IFA ( p = 0.031). Furthermore, serum LCFBA performed better than conventional CBA ( p = 0.022) and tissue IFA ( p = 0.006). LCFBA had the highest diagnostic accuracy and was closely followed by CBA at 1:100 dilution. Significance GABA B R‐IgG AE often presents as encephalopathy with seizures or status epilepticus in the context of an underlying SCLC. Multimodal evaluation using tissue IFA and fixed CBA at higher dilutions improves detection of true cases. LCFBA performs very well as a diagnostic test with very high sensitivity and specificity.

ABSTRACT Objectives To investigate the value of cytokine, chemokine, and neurofilament light chain (NfL) concentrations in predicting relapse risk, chronic epilepsy, and functional impairment in LGI1 autoimmune encephalitis (AE). Methods Cytokines/chemokines (IL‐1‐beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8/CXCL8, IL‐10, IL‐12p70, IL‐13, IL‐17A, GM‐CSF, TNF‐alpha, IFN‐gamma, CXCL9, CXCL10, CXCL13, BAFF) and NfL concentrations were measured in CSF and paired serum from LGI1‐AE patients evaluated at Mayo Clinic (01/2015–02/2024), using a multiplex immunoassay system (ELLA, Bio‐Techne) and correlated with clinical outcomes. A laboratory‐based cohort of LGI1‐IgG‐positive patients and control cohorts, including patients with mixed non‐inflammatory disorders (MNID), Alzheimer's disease (AD), and temporal lobe epilepsy (TLE) were analyzed. Results Forty‐four patients with LGI1‐AE were included; 29 (66%) were male, with a median age of 68.5 years (range, 8–85). Median time from symptom onset to CSF sampling was eight months (IQR, 3–17); 19/42 (45%) experienced a clinical relapse and 27% developed chronic epilepsy. Serum IL‐6, serum and CSF IL‐8/CXCL8, and IL‐17A were higher in LGI1‐IgG positive patients than MNID ( p < 0.05). TLE cytokine/chemokine profiles were similar to LGI1 AE; AD patients had lower serum IL‐6 and CSF IL‐8/CXCL8 ( p = 0.04; p = 0.01), and higher serum IL‐17A and GM‐CSF ( p = 0.004; p = 0.01) than LGI1‐AE. Higher CSF IL‐6 and IL‐8/CXCL8 in LGI1‐AE associated with clinical relapse ( p < 0.05) and higher CSF NfL associated with chronic epilepsy ( p = 0.01). Conclusion Elevations in IL‐6, IL‐8/CXCL8, and IL‐17A were identified in this LGI1‐AE cohort. CSF IL‐6, IL‐8/CXCL8, and NfL levels are potential prognostic biomarkers for risk of relapse and chronic epilepsy in LGI1‐AE.

Similar to the general population, people with epilepsy (PWE) will often have multiple medical issues that may impact their care. It is therefore important for epilepsy clinicians to be aware of these issues to optimize treatment and quality of life outcomes. In this review, we discuss cardiovascular and respiratory as well as infectious disorders in PWE. We also examine autoimmune disorders and outline reproductive and sexual health issues.

This case series describes a distinctive inspiratory noise observed during sleep in patients with IgLON5-antibody disease.

This case report discusses a man who tested positive for IgLON5-IgG antibody after intermittent episodes of paresthetic feeling involving the throat and jaw, associated with subtle dysarthria and dysphagia, and upper-extremity paresthesia with piloerection of the forearms.

ABSTRACTBackground and AimsNerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow‐up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time.MethodsNewly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow‐up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first‐line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange).ResultsOf 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow‐up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (R = −0.8 to −0.6, p ≤ 0.004) and INCAT disability score improvements (R = −0.6 to −0.3, p ≤ 0.032) across all follow‐up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude.InterpretationThe first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.

ABSTRACTBackground and AimsLeucine Zipper 4 (LUZP4)‐immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor‐related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4‐IgG seropositivity.Case ReportA 51‐year‐old male presented with a 5‐week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4‐month follow‐up, the patient had significant improvement in hand strength and had transitioned from walker to cane.InterpretationLUZP4‐IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T‐cell‐mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.