Background: Epilepsia partialis continua (EPC) is a form of focal status epilepticus, often requiring multiple anti-seizure medications (ASM). There are no established guidelines for pharmacological management. Perampanel (PER), an AMPA receptor antagonist, has gained attention in treating status epilepticus based on limited case reports. This study evaluates the efficacy of PER in treating EPC. Methods: We retrospectively analyzed the treatment response and adverse effects of PER in patients with EPC at our local hospital from January 2024 to January 2025. Seven patients with EPC were included. The loading dose of PER ranged from 6 mg to 20 mg. The etiology of EPC was intracranial hemorrhage (70%) and glioblastoma (30%). A clinical response was defined as seizure freedom within 72 hours of initiating PER, with PER being the last ASM added. Results: PER resulted in seizure termination in 6 of 7 patients. Time to response ranged from 24 to 72 hours. Oral PER, up to a dose of 16 mg, was well-tolerated in conscious patients. Common side effects included sedation, delirium, agitation, and nausea. Conclusions: Our real-world data suggest that PER can be an effective and well-tolerated early adjunct therapy in EPC, particularly at higher oral loading doses in conscious patients.

Background: Over 28% of people with epilepsy (PwE) experience anxiety related to their seizures, yet research on interventions for epilepsy-specific (ES) interictal anxiety remains limited. The community-based pilot, ’AnxEpi-VR,’ tested virtual reality exposure therapy (VR-ET), showing potential effectiveness and laying the groundwork for evaluating its impact on ES-anxiety in the present randomized controlled trial. Methods: Fourteen PwE admitted to the Epilepsy Monitoring Unit at Toronto Western Hospital used a 360-degree VR-intervention twice daily for five minutes up to ten days. The control group (n=7) viewed neutral VR environments (e.g., beach, forest scenes), while the experimental group (n=7) experienced VR-ET targeting ES anxiety (e.g., subway seizure scenarios). Data was collected at baseline, pre and post-VR exposure, post-intervention, and one-month follow-up using self-report questionnaires, semi-structured interviews, and VR-usage metrics. Clinicaltrials.gov NCT06028945. Results: At baseline, 71% of the control group and 83% of the exposure group had a brEASI score ≥7, indicative of an anxiety disorder. Post-intervention, this decreased to 57% and 50%, respectively. The average Fast Motion Sickness rating was 1.29, indicating minimal motion sickness. Of the exposure participants, 71% felt the scenarios simulated their real-world anxiety triggers. Conclusions: VR-ET was well-tolerated in PwE. Future recommendations include diversifying scenarios, adding interactive features, and improving software connectivity.

Background: Routine electroencephalography (EEG) provides excellent temporal resolution for evaluation of focal epilepsy, but lacks spatial resolution. High-density-EEG (HDEEG)-based source-localization significantly enhances spatial resolution, but requires greater standardization. We systematically review HDEEG systems, methods, and metrics utilized for evaluating focal epilepsy. Methods: A systematic search was conducted in PubMed using PRISMA guidelines with keywords “HDEEG” or “high-density EEG”, “source localization and “focal epilepsy”. Inclusion criteria: studies from the last 20 years, human subjects with focal epilepsy, sample size ≥ 10 and HDEEG with source localization methods clearly described. Results: 37 of 65 studies fulfilled inclusion criteria, with most reporting N<50. Most studies (14) used a 256-electrode HDEEG setup; 10 used 128-electrode configurations, and 6 used 76–83 electrodes. EEG source localization most commonly used Cartool (N=12) and Curry (N=5) softwares. Standard MRIs were used in 25 studies, and customized MRIs in 12. Metrics like clustering coefficient were reported to represent dipole distribution (10 studies); while functional connectivity analysis was reported in 7 studies. Conclusions: Variations in software choice, metrics for dipole distribution assessment, and MRI integration are evident from the current literature. Clustering methods and functional connectivity metrics are most commonly employed to represent dipole distribution, reflecting their increasing utility in understanding brain networks.

Background: Mesial temporal lobe epilepsy (mTLE) is a heterogenous condition with variable post-surgical outcomes. Combining high resolution magnetic resonance imaging (MRI), stereoelectroencephalography (SEEG) and histology may establish different subtypes of mTLE. Methods: Retrospective analysis of patients with mTLE with 1) SEEG Patterns 2) MRI 3) Post temporal lobectomy tissue analysis 4) Engel Classification. HippUnfold method was used to segment hippocampus on MRI. Results: Of 109 patients investigated with SEEG, 11 patients were analyzed so far. Low voltage fast activity was seen in 215 seizures, low-frequency periodic spikes in 21, sharp activity at <13 Hz in 58, rhythmic spike sharp wave activity in 86, and other types were less frequent. MRI revealed unilateral mesial temporal sclerosis (MTS) in 6 (54.55%), bilateral MTS in 2 (18.18%), and was normal in 3 (27.27%) patients. Histopathology showed ILAE grade I in 3 (37.5 %), II in 4 (50 %), IV in 1 (12.5%) patient. 63.63% had Engel Class I at 6 months. HippUnfold analysis and SEEG electrode coregistration was done in one patient and will be attempted in the rest. Conclusions: Our study highlights a strong correlation between SEEG findings and histological analysis in mTLE. A multidimensional classification will help predict long term outcomes.

Background: Drug-resistant epilepsy (DRE), defined by persistent seizures despite appropriate anti-seizure medication trials, affects about one-third of individuals with epilepsy. Deep brain stimulation (DBS) has emerged as a promising avenue for improved seizure control. This project reviews existing publications to better understand the neuromodulation parameters used in DBS, aiming to inform clinical decisions on optimizing treatment parameters in patients living with DRE. Methods: A comprehensive literature search of PubMed and Google Scholar was conducted using the keywords “DBS,” “epilepsy,” and “parameters.” Only original studies reporting specific stimulation parameters were included, with meta-analyses and review papers excluded. A weighted Pearson correlation, using study sample size as the weight, examined frequency, pulse width, seizure reduction, and responder rate. Results: So far, 28 studies (1997-2024) have been reviewed, encompassing a total of 1,054 patients, with study size ranging from 1-250 patients. Electrode targets included the hippocampus, ANT, amygdala, centromedian nucleus, and STN. DBS frequencies ranged from 60–333 Hz, and pulse widths from 40–450 µs. Pearson correlation results suggest moderate frequencies (130–145 Hz) and wider pulse widths (300–450 µs) correlate with better seizure reduction and higher responder rates. Conclusions: These results support a formal meta-analysis to further investigate neuromodulation parameters to improve outcomes for DRE patients.

Background: Predicting neurological recovery in patients with severe brain injury remains challenging. Continuous EEG monitoring can detect malignant patterns but is resource-intensive, and its role in long-term functional outcome prediction is unclear. This study evaluates the utility of parameterized short-segment EEG, acquired via EEG cap, in predicting neurological recovery. Methods: We analyzed short-segment high-density EEGs from 42 patients in the NET-ICU cohort with acute neurological injury. EEGs were pre-processed into standard clinical formats and parameterized using five visual EEG features associated with outcome prediction. Random Forest Classifier (RFC) models were trained and cross-validated to predict recovery of responsiveness (following 1-2 step commands during or after ICU admission) using: EEG features alone; clinician prediction combined with EEG features. Results: EEG-based prediction outperformed clinician bedside assessment (AUC ROC: 0.80 vs. 0.67) under the RFC model. Combining clinician Glasgow Outcome Scale–Extended (GOSE) scores with EEG features improved overall predictive performance (AUC ROC: 0.91). Conclusions: Standardized EEG features obtained using EEG caps can improve the accuracy of neurological recovery predictions in patients with acute severe brain injury. This suggests that automated extraction of background brain signals has the potential to provide clinically meaningful prognostic information in critical care settings, enhancing accessibility and resource efficiency.

Background: CIDP is a rare immune-mediated demyelinating neuropathy that has significant phenotypic variability. A unifying immunopathological mechanism remains elusive, likely due to etiological heterogeneity among the variant presentations. This is best exemplified by the identification of nodal/paranodal antibodies, such as neurofascin 155, in a subgroup of CIDP patients who present with a distinct phenotype. Methods: We present the case of a 39-year-old male who presented with a 2-year history of progressive stocking-glove sensory loss and sensory ataxia. Electrodiagnostics confirmed an acquired demyelinating neuropathy, with serum anti-NF155 IgG4. His case was refractory to standard immunomodulatory therapy, including adequate trials of IVIG, steroids, azathioprine, and rituximab. He also had a non-therapeutic trial of PLEX, methotrexate, and tacrolimus. Results: After cessation of all immunomodulatory therapy for 2 years, he had spontaneous remission of his CIDP and near-complete resolution of electrodiagnostic/clinical abnormalities. Conclusions: This case provides insights into the natural history of NF155 “paranodalopathy” and highlights a unique case of supra-refractory CIDP which underwent spontaneous remission with near-complete resolution. Delayed effect from rituximab was posited as a contributor, however, the patient had no clinical or electrophysiological improvement 20-months after initiation of anti-CD20 therapy. Current data suggests the majority of CIDP patients respond to rituximab within 6-12 months.

Background: Axonal degeneration has been recognized as a key early contributor to the clinical presentation and pathogenesis of amyotrophic lateral sclerosis (ALS). Activation of the calcium-dependent cysteine protease calpain-2 is considered a critical effector of axonal degeneration. Based on evidence supporting a potential benefit of calpain-2 modulation in ALS and other neurodegenerative diseases, Amylyx developed AMX0114, an antisense oligonucleotide (ASO) inhibitor of calpain-2. This phase 1 study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMX0114 in people with ALS. Methods: LUMINA is planned to be conducted at ~15 sites in North America enrolling approximately 48 participants randomized 3:1 to receive AMX0114 or placebo. After study completion, an open-label extension study of AMX0114 will be implemented if data supports a positive benefit-risk profile. Results: The primary endpoints of the study include the incidence of adverse events (AEs), serious AEs, and dose-limiting toxicities. Secondary and tertiary endpoints include PK measurements (plasma and cerebrospinal fluid [CSF] levels of AMX0114), PD biomarkers, and functional measures of ALS progression. Conclusions: LUMINA is a first-in-human study evaluating the safety, tolerability, PK, and PD of AMX0114, the first ASO targeting calpain-2 in adult participants with ALS. Enrollment is planned to begin in Canada in early 2025.

Background: In the Phase 3 MycarinG study (MG0003/NCT03971422), one 6-week cycle of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo. After MycarinG, patients could enrol in open-label extension studies (MG0004 then MG0007, or MG0007 directly). Methods: In MG0004 (NCT04124965), patients received once-weekly rozanolixizumab 7mg/kg or 10mg/kg for ≤52 weeks. In MG0007 (NCT04650854), after a cycle of rozanolixizumab 7mg/kg or 10mg/kg, subsequent cycles were based on symptom worsening at the investigator’s discretion. Pooled data are reported across MycarinG, MG0004 (first 6 weeks) and MG0007 (final data) for patients receiving ≥2 symptom-driven cycles (efficacy; ≤13 cycles) or ≥1 cycle (safety). Results: 196 patients received ≥1 rozanolixizumab dose of whom 129 received ≥2 symptom-driven cycles (7mg/kg: n=70; 10mg/kg: n=59). Treatment response was maintained from Cycles 1–13: mean change from baseline to Day 43 in MG-Activities of Daily Living score ranged from -3.2 to -4.9 (7mg/kg) and -3.2 to -6.7 (10mg/kg). Quantitative MG and MG Composite scores also improved. Treatment-emergent adverse events (TEAEs) did not increase with repeated cyclic treatment, and most were mild/moderate; the most common event was headache. Conclusions: Rozanolixizumab showed consistent improvements across MG-specific outcomes up to 13 cycles and repeated cyclic treatment was generally well tolerated. Funding: UCB.

Background: Analysis of 20 pairs is the traditional standard when using SFEMG to diagnose MG. Some studies show that fewer pairs are needed if results are normal. We examined what impact this might have on long-term outcomes. Methods: Hospital charts of 239 consecutive patients who underwent SFEMG between January 2011, and July 18th, 2024, were reviewed. Results: 201 patients were identified; 128 had normal SFEMGs. Of the patients with normal SFEMGs, 58 (45.31%) had 12 pairs observed and 69 (53.91%) had 20 or more pairs observed. In the 12 pair group, 1(1.72%) patient had delayed MG diagnosis, and 2 (3.45%) patients were referred for repeat SFEMGs; in the 20 or more group, 2 (2.90%) patients belong in each aforementioned category. No patients from either group were hospitalized for MG after SFMEG. Conclusions: Preliminary results demonstrate no difference in frequency of poor outcomes between patients who had 20 or more pairs observed and those who had 12 pairs observed, supporting the safety of shortening the test in appropriate situations.

Background: In generalized myasthenia gravis (gMG), there remains an unmet need for treatments providing meaningful symptom control. Methods: Mean changes in MG-ADL were compared between nipocalimab + standard-of-care (SoC) and placebo+SoC. The proportion of patients achieving: Minimal Symptom Expression (MSE), MG-ADL score 0/1, time with MSE, sustained within person meaningful change (WPMC) starting from Week 4, and time spent with WPMC were compared. Results: Nipocalimab+SoC demonstrated significant improvement in MG-ADL compared to placebo+SOC, LS-mean-change[SE] -4.7[0.329] vs -3.25[0.335]; Difference in means[SE]=-1.45 [0.470], p=0.002. The mean difference favoured nipocalimab+SoC, and was significant as early as week 1: LS-mean-change[SE]: -2.72[2.979] vs -1.77[2.426]; Difference in means[SE] -0.82[0.410], p=0.046. Nipocalimab+SoC patients were three times more likely to achieve MSE at any point during the study vs placebo; Odds Ratio[95% CI]: 3.0[1.3, 6.8]; 31.2% vs. 13.2%. For the 25 patients reaching MSE, the time sustaining MSE [percent time with MSE] was 101.5 days, (60.4%, nipocalimab+SOC) vs 55 days, (32.7%, placebo+SOC). Similarly, the proportion of patients with sustained WPMC favored nipocalimab+SOC, 55.8% vs 26.3%, placebo+SOC, p<0.001. The median percent time spent with WPMC was 84.5%, nipocalimab+SOC vs 39.9%, placebo+SOC, p=0.007. Conclusions: Based on MG-ADL data from Phase 3, nipocalimab an FcRn blocker, demonstrated rapid, substantial, and sustained symptom control.

Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

Background: Late-onset Pompe disease (LOPD) is caused by a deficiency of acid α-glucosidase (GAA), leading to progressive muscle and respiratory decline. Cipaglucosidase alfa (cipa), a recombinant human GAA naturally enriched with bis-mannose-6-phosphate, exhibits improved muscle uptake but is limited by inactivation at near-neutral blood pH. Miglustat (mig), an enzyme stabiliser, binds competitively and reversibly to cipa, enhancing its stability and activity. Methods: In dose-finding studies, Gaa-/- mice were treated with cipa (20 mg/kg) +/- mig (10 mg/kg; equivalent human dose ~260 mg). Clinical study methodologies have been published (Schoser et al. Lancet Neurol 2021:20;1027–37; Schoser et al. J Neurol 2024:271;2810–23). Results: In Gaa-/- mice, cipa+mig improved muscle glycogen reduction more than cipa alone and grip strength to levels approaching wild-type mice. LOPD patients (n=11) treated with cipa alone showed dose-dependent decreases in hexose tetrasaccharide (Hex4) levels by ~15% from baseline, decreasing another ~10% with added mig (260 mg). In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. Among 151 patients (three trials), mig-related adverse events occurred in 21 (13.9%), none serious. Conclusions: Mig stabilised cipa in circulation, improving cipa exposure, further reducing Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Sponsored by Amicus Therapeutics, Inc.

Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.

Background: The complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.

Background: Generalized myasthenia gravis (gMG) is a rare, chronic, autoimmune disease characterized by muscle weakness and fatigue. This study aims to describe the natural history, disease burden and treatment patterns of gMG patients in Canada. Methods: Data was analyzed from the Adelphi MG II DSP™, a gMG patient-level cross-sectional database, collected through surveys between February-June 2024. Neurologists provided sociodemographic, symptomatology, and treatments data. Results: Fifteen neurologists provided data for 46 gMG patients. The cohort’s mean (SD) age was 58.1 (14.7) years, 52.2% male, 82.6% White/Caucasian and 89.1% were anti-AChR Ab positive. Mean time since diagnosis was 3.4 (3.1) years, 22% reported a change in employment status due to gMG. Most had public insurance (68.9%). Disease severity was mostly MGFA class II (78.2%) patients. Common symptoms included eyelid ptosis (76.1%), dysarthria (50.0%), and dyspnea (54.3%) – mean MG-ADL was 5.6 (5.1). During their disease course, 34.9% experienced ≥1 myasthenic crisis, while 25.6% reported symptom exacerbation. At time of survey, patients had used 1.8 (0.9) lines of maintenance treatment. Most prescribed treatments (alone or in combinations) were pyridostigmine (95.6%), corticosteroids (48.9%), non-steroidal immunosuppressants (42.2%), Immunoglobulins (31.1%), and biologics (22.2%). Conclusions: gMG patients continue to experience symptoms burden and crisis/exacerbations. These findings highlight an unmet need for new, safe and effective therapeutics that are publicly covered to manage gMG-related clinical manifestations.

Background: Generalized myasthenia gravis (gMG) is a potentially life threatening chronic autoimmune disease that can impair patients’ ability to work effectively and increase reliance on public support benefits. A public economic framework was used to explore how treatment influences patients’ and caregivers’ economic activity, including tax revenues and public support in Canada. Methods: Natural history of gMG was simulated using a multi-state Markov cohort model. Health states were based on MG Activities of Daily Living (MG-ADL) total score in patients with AChR-Ab+ refractory gMG. Treatment, costs, and economic outcomes of patients taking efgartigimod were compared with alternative therapeutic options. Canadian public support benefits were based on official government sources. Results: Improved MG-ADL states predict higher workforce participation, lower rates of disability and less caregiving needs, resulting in higher tax revenues and less public support costs. Compared to alternative therapeutic options, efgartigimod is estimated to yield lifetime fiscal gains of $458,755 that exceed the incremental cost of $291,073, suggesting the Canadian government receives $1.6 for every $1.0 spent on efgartigimod for the treatment of gMG. Conclusions: Compared with alternative options, efgartigimod generated a positive fiscal return for the Canadian governments with additional savings from disease management, public benefits, and averted tax revenue losses.

Background: Efgartigimod, a human immunoglobulin G1 (IgG1) antibody Fc fragment, reduces IgG levels through neonatal Fc receptor blockade. Efgartigimod PH20 SC (1000-mg fixed dose, coformulated with recombinant human hyaluronidase PH20) is provided in a vial administered via a separate syringe (V+S). Here, we investigate bioequivalence, safety, and tolerability of efgartigimod PH20 SC administered via prefilled syringe (PFS) vs V+S in healthy participants. Methods: Bioequivalence was assessed in a phase 1, open-label study. Healthy participants (n=72) were randomized to receive one injection of efgartigimod PH20 SC via PFS or V+S in a crossover design. Separate studies evaluated feasibility of different injection speeds and usability of the PFS. Results: Bioequivalence between efgartigimod PH20 SC via PFS or V+S was established, as the 90% CI around the geometric least-squares mean ratio of Cmax and AUC0-inf was within predefined criteria (80.00%-125.00%). Most adverse events were mild to moderate. No observed differences in incidence of reported injection site reactions emerged. No serious adverse events or deaths occurred. Rapid (20-second) administration was feasible and the PFS could be safely prepared and administered by participants/caregivers. Conclusions: Efgartigimod PH20 SC administered via PFS is bioequivalent to efgartigimod PH20 SC administered via V+S, which may provide an additional convenient treatment option.

Background: RAISE-XT (NCT04225871; Phase 3 study) showed clinically meaningful and sustained improvements in myasthenia gravis (MG)-specific outcomes with zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with acetylcholine receptor autoantibody-positive generalised MG. Methods: Adults self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. This post hoc analysis assessed durability of response to Week 120 in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) responders at Week 1 of two double-blind studies (NCT03315130, NCT04115293). Responder definitions: improvements of ≥3-points (MG-ADL) or ≥5-points (QMG) (interim data cut: 11 November 2023). Results: 93 patients were randomised to zilucoplan 0.3mg/kg in the double-blind studies; 43.0% (n=40/93) and 33.3% (n=31/93) were MG-ADL and QMG responders, respectively, at Week 1. Week 1 responders spent a median #of 98.9% (5.8–99.2) and 99.0% (2.5–99.2) time in response up to Week 120 for MG-ADL and QMG. Week 1 non-responders spent# a median #of 84.6% (0.0–98.3) and 66.7% (0.0–98.9) time in response up to Week 120 for MG-ADL and QMG, with most responding later in the study. Conclusions: Among early (Week 1) zilucoplan responders, time in response remained high (99%) up to Week 120. These data demonstrate rapid and sustained efficacy with long-term zilucoplan treatment.#

Background: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) is a rare, acquired polyneuropathy, especially in children, affecting the peripheral nervous system. It most commonly presents in a symmetric, proximal and distal, sensorimotor fashion. Immunosuppression and immunomanipulation are treatment modalities. This is an update of the 14-year-old male presented, at the 2024 CNSF meeting, with severe progressive CIDP who became refractory to steroid and IVIg but responded to Rituximab. Methods: At the age of 16, at a stage of recovery where he had regained MRC grade 5 strength diffusely, all therapies were sequentially tapered (prednisone & IVIg) or withdrawn (rituximab). He did well for approximately 6 months at which point he relapsed severely to the point of needing a walker. Repeat electrodiagnostics confirmed latency, amplitude, and conduction velocity deteriorations as compared to previous. As a result, prednisone, IVIg, and rituximab were reinstated. Results: As per the first exposure to rituximab, the patient began to respond roughly 3 months after the retreatment with targeted anti-CD20 therapy. He has again made a complete recovery physically but not electrophysiologically. This is the same pattern of response that was originally manifested. Conclusions: Rituximab appears to be an effective treatment for severe IVIg-refractory pediatric CIDP.