Gupta, Rajesh

Leucine-rich glioma-inactivated-1 (LGI1) IgG-associated autoimmune encephalitis typically presents with faciobrachial dystonic seizures, hyponatremia, and temporal lobe MRI abnormalities. However, the clinical spectrum of LGI1 IgG-associated AE extends beyond these classical features, with reports of diverse seizure semiologies and atypical presentations challenging traditional diagnostic paradigms. This study reports a male in his late 60s presenting with recurrent episodes of right foot cramping and electric shock-like pain, progressing to generalized tonic-clonic seizures. Initial workup suggested chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but LGI1 IgG antibodies were subsequently detected. Despite treatment with intravenous immunoglobulin (IVIG), the seizures persisted. This case highlights the heterogeneity in LGI1 encephalitis presentations. The patient’s proprioceptive-induced reflex seizures represent a rare manifestation of the disease. Treatment with rituximab, a B-cell depleting therapy, resulted in significant improvement, suggesting its potential effectiveness in LGI1 encephalitis with a resistant seizure course. The case also emphasizes the intricate interplay between the mesial temporal lobe, basal ganglia, and frontal regions in LGI1 encephalitis pathophysiology.

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298