Long-term safety and efficacy of Eculizumab in Aquaporin-4 IgG-positive NMOSD

Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. Methods Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. Interpretation This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088–109

Tongue somatosensory-evoked potentials in microvascular decompression treated trigeminal neuralgia

Somatosensory-evoked potentials of the tongue (tSSEP) provide useful information about trigeminal-afferent pathway. The aim of this study was to evaluate tSSEP in trigeminal neuralgia (TN) treatment with microvascular decompression. Two patients with trigeminal neuralgia refractory to conservative treatment underwent microvascular decompression of the trigeminal nerve. tSSEP was performed a month prior to surgery and in the month after the surgery in both patients. Pain frequency and tSSEP were analyzed before and after surgery. In both patients, a complete resolution of pain occurred. In patient 1, tSSEP latencies became shorter than before surgery and wave N1 appeared. The intensity of stimulation necessary to reach the threshold was 4 mA before the surgery and 1 mA after the surgery. A complete recovery of tSSEP after the operation was achieved in patient 2. The results of present study demonstrate potential value of tSSEP in pre-surgery evaluation and post-surgery follow-up of TN patients

Anomalies Characteristic of Central Nervous System Demyelination

Radiologically isolated syndrome (RIS) was defined in 2009 for asymptomatic patients who presented incidentally identified white matter anomalies within the central nervous system suggestive of multiple sclerosis (MS). Approximately one-third of RIS subjects will have a seminal clinical demyelinating event within 5 years of the identification of their abnormal MRI. Clinical evolution mirrors relapsing remitting or progressive forms of MS. Pejorative factors for clinical conversion are male gender, age younger than 35 years, and spinal cord lesions

The role of iron and myelin in orientation dependent R2* of white matter

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R2 * relaxation rate. However, their quantification based on R2 * maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R2 * shows a linear increase with increasing iron content. In white matter, R2 * is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R2 * decay in white matter. Applying our model to fibre orientation-dependent in vivo R2 * data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non-lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin-induced orientation-dependent and iron-induced orientation-independent components is able to fit in vivo R2 * data