Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.

Background: Only limited data exist on the potential benefit of prehospital video-based teletriage for patients with acute stroke. Methods: During a 6-month period, all patients from a defined geographical catchment area with a 911 call for acute stroke were screened by the paramedic team on site. Those with known symptom onset of <6h underwent video-based teletriage for transfer to either the closest tertiary (for suspected LVO occlusion) or to the closest secondary stroke centers. Patients referred for thrombectomy by same the secondary stroke centers without teletriage during the same period served as control. Results: Overall, 33 patients were teletriaged and 23 (70%) were bypassed to the tertiary center. Of the latter, 13 (median NIHSS 19) underwent thrombectomy (+/- iv thrombolysis). During the same period, 22 patients (median NIHSS 17) were referred for thrombectomy without teletriage. The median time from 911 to thrombectomy was 129 [IQR 51] min after teletriage, as compared to 196 [74] min in controls (p=0.015). The median NIHSS at 24h was 6 in the teletriage group versus 14.5 in controls (p=0.07). Conclusions: Video-based prehospital teletriage for acute stroke is feasible, reliably identifies patients without LVO stroke and significantly improves the delay between stroke alert and thrombectomy in eligible LVO stroke patients.

Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.

Background: Low back pain (LBP) is a common cause of disability and decreased quality of life. The Saskatchewan Spine Pathway classification (SSPc) is a method for triaging patients who are candidates for surgery. Methods: Consecutive patients who underwent lumbosacral instrumented fusion for degenerative spinal pathology from Jan 1, 2012, to Sept 20, 2018, by a single surgeon at our institution were retrospectively reviewed. Patients were stratified by SSPc into 4 groups based on pain pattern. Demographic and clinical data were collected. Outcomes were compared between cohorts both for absolute values and achieving MCID. Results: 169 consecutive patients were included in our study. After stratifying by SSPc grouping, there were 61 SSPc I patients, 45 SSPc III patients, and 63 SSPc IV patients. Patients in all groups had clinical improvement following surgery. Patients classified as SSPc III had superior outcomes in ODI, EQ-5D and EQ-VAS, and were more likely to achieve the MCID for ED-5D. Multivariate analysis demonstrated that SSPc grouping is an independent predictor of final VAS back, ODI, EQ-5D, and EQ-VAS as well as achieving the MCID for EQ-5D. Conclusions: The SSPc classification is associated with outcomes following lumbosacral fusion. In particular, patients with SSPc pattern 3 had better outcomes and improved QALY.

Background: The formation of pial-pial collateral network aneurysms due to carotid occlusion is a rare neurological phenomenon. This case details a 69-year-old male who developed a pial-pial collateral network aneurysm secondary to left internal carotid artery occlusion, leading to intracranial hemorrhage. Methods: The patient presented with altered consciousness due to left temporal intracerebral hemorrhage, subdural hematoma, and intraventricular hemorrhage. Cerebral angiography revealed an occluded left internal carotid artery, with superficial temporal artery (STA) and superior orbital artery anastomosis, and extensive pial-pial collaterals from the posterior temporal artery. A 4 mm aneurysm arising from this collateral network was identified. Surgical intervention involved a left temporal craniectomy and excision of the aneurysm, prioritizing the preservation of the STA. N.B., Informed patient consent was obtained in this study. Results: Successful aneurysm removal and preservation of collateral pathways were confirmed by postoperative imaging. The patient exhibited rapid neurological improvement; by postoperative day (POD) one, the patient showed limited response to stimuli. He was extubated by POD4 and discharged on POD27, where he conversed well, was independently ambulatory, and needed minimal to no assistance in activities of daily living. Conclusions: This case highlights the need for careful preoperative planning and intraoperative precision, especially in preserving vital collateral vascular pathways.

Background: The use of patient reported and functional outcome measures in routine practice enhances shared decision making and supports patient-centred care. This study compared the perspectives of Chronic Inflammatory Neuropathy (CIN) patients and providers regarding their experience using an outcome measure panel. Methods: A one year study was conducted to evaluate a nine measure outcome set in routine clinical practice for CIN. The panel included patient-reported outcome measures (e.g., I-RODS and EQ-5D-5L) and functional measures (e.g., grip strength). At the conclusion of the study, participants and providers completed an online questionnaire on their experience. Results: 25 patients and five providers completed the questionnaire. Both patients and providers reported benefit in tracking disease progression, supporting treatment-related decisions, and broadening views of health. Both groups agreed patient involvement in care was enhanced. Preference for specific measures, frequency, and data presentation differed. Providers emphasized integration into electronic medical records and streamlining processes. 100% of providers and 80% of patients wanted to continue completing outcome measures. Conclusions: CIN patients and providers recognize the value of integrating outcome measures into routine care. To effectively implement these measures in clinical settings, it is important to understand the patient and provider perspective and prevent unnecessary burdens to ensure sustainability of use.

Background: The complement component 5 inhibitor therapies (C5ITs) eculizumab and ravulizumab have been approved or submitted for regulatory approval in several regions for AQP4+ NMOSD. Methods: This global, long-term, prospective, multicenter, observational registry will enroll adult patients with AQP4+ NMOSD being treated with eculizumab or ravulizumab and who have received ≥1 dose of eculizumab or ravulizumab within 4 or 12 weeks prior to enrollment, respectively. Inclusion criteria include available historical data on C5IT dosing since initiation and the number and types of relapses from 1 year prior to C5IT initiation through enrollment. The primary outcome is annualized relapse rate. Safety outcomes will include serious adverse events, meningococcal infections, and pregnancy, breastfeeding, and neonatal outcomes. Data will be collected prospectively for up to 5 years. Approximately 130 patients will be enrolled, with a maximum of around 200 patients in up to 10 countries globally. Results: N/A Conclusions: This registry will collect data to characterize the long-term effectiveness and safety of the C5ITs eculizumab and ravulizumab in patients with AQP4+ NMOSD to provide evidence on the real-world impact of C5ITs in this patient population.

Background: Neurological complications following vaccinations have been described before, but the rates of neurological complications, and their variation by ethnicity, following COVID-19 vaccine are not well-known. Methods: We conducted a population-based cohort study of Ontarians aged 18 years and over who received their first COVID-19 vaccine, and followed them for six weeks to estimate the incidence of neurological events, ascertained using validated case definitions based on ICD-10 codes. Ethnicity was defined using last name surname algorithm. We used multivariable logistic regression models, adjusting for age, sex, and vaccine-type to evaluate ethnic differences. Results: In the included 10,063,466 Ontario residents, incidence of GBS (n=72), CVST (n=52) and transverse myelitis (n=25) after first COVID-19 vaccine was rare. The crude rate of ischemic stroke (240/1,000,000 people) was the highest followed by Bell’s palsy (54/1,000,000). Compared to the general population, the adjusted odds of ischemic stroke and Bell’s palsy were lower in Chinese (aORBell’s 0.62; 0.39-0.98 and a ORischemic stroke 0.74; 0.59-0.91) and South Asians (aORBell’s 0.83; 0.52-1.31 and aORischemic stroke 0.84; 0.65-1.08). Conclusions: The incidence of neurological events following COVID-19 vaccine is low, and it varies by ethnicity. Our findings should encourage vaccination against COVID-19 in all ethnic groups.

Background: Research consistently shows that adolescents transitioning from pediatric to adult care struggle. Although data looking at young adults with epilepsy is limited, research suggests that these adults tend to have higher rates of depression and anxiety, lower rates of medication compliance, and lower education. Methods: To better understand this population and their struggles, a retrospective chart review of 58 patients transferred from pediatric to adult care was done. Results: 39.7% of participants were lost to follow-up; 12 were temporarily lost (average 1.3 years) and 11 were permanently lost. Twenty-three participants admitted to medication non-compliance, with fifteen having break-through seizures. Of the 45 patients that filled out mental health assessments at initial visit, 28.9% met the threshold for major depressive disorder, and 56.6% of patients had symptoms of anxiety. Data found that at one-year follow-up, 60% of these patients had similar or worsened depression scores, and 64% had similar or worsened anxiety scores. Conclusions: The findings of this study are concerning and highlight the need for greater education and support for these adolescents. Specifically, patients need more education on the importance of consistent follow-ups and consistently taking medication. Findings also suggest the importance of assessing and addressing mental health concerns.

A decoupling method is proposed for the elastic stiffness modeling of hybrid robots based on the rigidity principle, screw theory, strain energy, and Castigliano’s second theorem. It enables the decoupling of parallel and serial modules, as well as the individual contributions of each elastic component to the mechanism’s stiffness performance. The method is implemented as follows: (1) formulate limb constraint wrenches and corresponding limb stiffness matrix based on the screw theory and strain energy, (2) formulate the overall stiffness matrix of parallel and serial modules corresponding to end of the hybrid robots based on the rigidity principle, principle of virtual work, the wrench transfer formula, and strain energy methods, and (3) obtain and decouple the overall stiffness matrix and deflection of the robot based on the Castigliano’s second theorem. Finally, A planar hybrid structure and the 4SRRR + 6R hybrid robot are used as illustrative examples to implement the proposed method. The results indicate that selectively enhancing the stiffness performance of the mechanism is the most effective approach.

Background: Vestibular schwannomas are the most common tumour of the CPA with an annual incidence of 17.4/1 million. Approximately 5-10% of these tumours demonstrate spontaneous regression without intervention while under observation. Previous research studies have assessed patient factors and imaging characteristics through chart review to attempt to identify predictive factors of spontaneous regression. There have not been any studies where patient questionnaires are used to assess patient lifestyle factors or characteristics which may predict spontaneous regression. Methods: Using a clinical database of acoustic schwannomas treated by one team at our institution, we have identified approximately 40 patients, of a database of 900 patients, who have demonstrated significant spontaneous regression (>5mm in size reduction in one dimension) or complete resolution of their acoustic schwannoma. Clinical, radiological, and lifestyle factors are reviewed though clinical records and patient questionnaire. Regression analysis is performed. Results: Using patients who have tumors with significant spontaneous regression, we attempt to create a model that predicts regression of these tumours. Conclusions: In conclusion, this is the first study to consider patient lifestyle factors obtained through patient survey in addition to clinical and radiographic factors to attempt to create a predictive model of spontaneous regression of acoustic schwannoma.

Background: Sleep-wake states (SWS) affect the expression of interictal epileptiform discharges (“spikes”), which affects resultant source localization calculations used in epilepsy evaluation. We hypothesize that spike localizations from non-REM sleep 1-3 are most concordant with one another. Methods: We used Standardized low-resolution brain electromagnetic tomography (sLORETA) in Curry 8 software to calculate source localization voxels of spikes in N1-3, REM, or wakefulness (W). We assessed voxel concordance between N1-N2-N3/N1-N2-W/N1-N3-W/N2-N3-W/REM-N1-N2/REM-N1-N3/REM-N2-N3/REM-N1-W/REM-N2-W/REM-N3-W. We classified concordances into those containing and not containing a SWS (e.g. N1 vs. not-N1 = N1-N2-N3/N1-N2-W/N1-N3-W/REM-N1-N2/REM-N1-N3/REM-N1-W vs. REM-N2-W/REM-N3-W/REM-N2-N3/N2-N3-W) for comparison. Results: Concordances did not differ for N1-3 or W. However, concordances with REM were lower than those without REM as a fraction of source localization space (median 32.1% vs. 56.1%, p<0.001) and cortical grey matter (median 20.4% vs. 27.3%, p=0.003). Conclusions: As expected, source localizations from spikes in N1, N2, and N3 did not significantly differ from one another because these three states are constituent members of non-REM sleep. Surprisingly, however, source localizations derived from awake spikes – not a constituent of non-REM sleep – also did not differ. In contrast, REM was most different by reproducibly exhibiting the least three-way concordance. These findings reinforce the unique localizing ability of REM sleep.

Background: Treatment of generalized myasthenia gravis (gMG) with reduced steroid dosages may minimize steroid-associated AEs. Corticosteroid dosage changes were not permitted during the 26-week, CHAMPION MG study of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG. Participants who completed the study could receive ravulizumab in the open-label extension (OLE; NCT03920293); corticosteroid adjustments were permitted. Methods: Patients could receive intravenous ravulizumab (blind induction or bridging dose at Week 26 [OLE start] for those previously receiving placebo or ravulizumab, respectively, then 3000–3600 mg at Week 28 and every 8 weeks thereafter) for ≤4 years. Results: Among 161 patients (78 ravulizumab, 83 placebo) who entered the OLE and received ravulizumab for ≤164 weeks, 113 received oral or enteral corticosteroids during the OLE; the proportion treated with >10 mg/day corticosteroids decreased from 58% (n=66) at first OLE dose to 37% (n=42) (35 [31%] received ≤5 mg/day and 71 [63%] received ≤10 mg/day) at last reported dose. Fourteen patients (12%) discontinued corticosteroids. The mean (SD) corticosteroid dosage/patient decreased from 17.5 (11.9) mg/day at first OLE dose to 11.7 (10.9) mg/day at last assessment. Conclusions: Ravulizumab decreased corticosteroid use in patients with AChRAb+ gMG, suggesting a steroid-sparing role for ravulizumab.

Background: Blood loss quantification and management are important facets of cranial surgery, having been linked with adverse outcomes if management is inadequate. While many studies report estimated blood loss (EBL) as an outcome measure, inconsistencies exist in EBL quantification and management strategies Methods: A systematic review of cranial surgery literature on blood loss measurement and management was conducted according to PRISMA guidelines utilizing a novel software platform, Nested Knowledge Results: Initial search yielded 1029 non-duplicated. 107 full-text studies were included. 70% of studies were retrospective. Most common treatment conditions were 41% craniosynostosis (44/107) and 36% tumor (39/107). Most common EBL measurement methods were comparison of pre-operative and post-operative hemoglobin/hematocrit in 46.7% (50/107), anesthesia record in 26.2% (28/107), and surgeon estimation in 9.3% (10/107). 53.3% of studies did not specify a quantification methodology. Blood loss management strategies also varied, with transfusion being the most common method in 64.5% (69/107) of studies Conclusions: EBL quantification and blood loss management remain important clinical and research metrics. Despite this, significant heterogeneity exists in blood loss quantification and management strategies, with most studies providing no data on EBL quantification. Standardization of EBL quantification/reporting should be undertaken to improve comparability and consistency across studies.

Markwelchite, ideally TlPbSbS3, is a new mineral from the hydrothermal deposit of Jas Roux, Hautes-Alpes, France. It occurs as a black anhedral crystal associated closely with protochabournéite. Microhardness measurements (VHN15) gave a mean value of 197 kg/mm2 corresponding to a Mohs hardness of ~3–4. In plane-polarised incident light, markwelchite is grey in colour. Under crossed polars, it is distinctly anisotropic with greyish white to bluish rotation tints, with bright red internal reflections. Reflectance percentages (Rmin and Rmax) are: 28.5, 31.5 (471.1 nm); 28.3, 30.7 (548.3 nm); 27.9, 30.3 (586.6 nm); and 27.6, 29.8 (652.3 nm). The mean of 5 electron microprobe spot analyses gave Tl 34.67(45), Pb 31.86(25), Sb 15.06(15), As 2.37(5), S 15.35(20), total 99.31 wt.%, corresponding, on the basis of a total of 6 atoms per formula unit and structural results, to Tl1.063Pb0.964(Sb0.775As0.198)Σ0.973S3.000. Single-crystal X-ray diffraction studies revealed that markwelchite is isotypic with richardsollyite, TlPbAsS3. It is monoclinic, space group P21/c, with the following unit-cell parameters: a = 8.9144(3), b = 8.4513(3), c = 8.6511(3) Å, β = 108.723(4)°, V = 617.27(4) Å3 and Z = 4. The five strongest observed powder-diffraction lines [d in Å (Irel)(hkl)] are: 3.88 (100)($\bar{2}$11); 3.78 (90)(210); 3.29 (90)(102); 2.73 (85)($\bar{1}$13); and 2.93 (75)(022). The crystal structure can be described as formed by (100) [Me2(SbS3)]– layers sandwiching the Me1+ cations. The Me1 site has a seven-fold coordination, whereas the Me2 site has an 6+2 coordination corresponding to a distorted, bicapped trigonal prismatic coordination, and the Sb site displays a trigonal pyramidal coordination with three S atoms and Sb at the apex.

The name markwelchite honours Dr Mark D. Welch of the Natural History Museum, London, UK.

The new mineral has been approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA2024–001). A discussion on the relationships between markwelchite and synthetic TlPbSbS3 is also provided.

Background: Pilocytic astrocytoma and other circumscribed low-grade brain tumors can exhibit spontaneous enhancement changes despite stable size and clinical status. We aimed to describe this phenomenon in adults. Methods: We performed a retrospective review of our MRI database (2011-2021) to identify cases with enhancement changes in otherwise stable tumors. We searched for reports containing: “pilocytic”, “pilomyxoid”, “RGNT”, “rosette”, “glioneuronal”, “DNET”, and “dysembryoplastic”. Exclusion criteria included WHO grade 3/4 tumors, patients <19 years, equivocal diagnostic findings, and no serial MRIs. We reviewed 238 patients. Results: We identified 12 adult patients with the desired phenomenon: 6 pilocytic astrocytoma, 1 pilomyxoid astrocytoma, 2 rosette-forming glioneuronal tumor, 1 unverified low-grade glioma, and 2 cases without biopsy. Seven were untreated, while five were residual or recurrent tumors. Six showed a pattern of new/increasing and subsequent decreasing/disappearing enhancement over 1-4 years. One exhibited spontaneous regression of enhancement over 1 year. Five showed repeating cycles of increasing and decreasing enhancement over longer monitoring periods of 7-15 years, with mean duration of increasing enhancement prior to decline of 21.4 months (SD 5.9). Conclusions: Spontaneous contrast enhancement fluctuation in adult pilocytic astrocytoma and other circumscribed low-grade brain tumors can occur, and on its own should not be misconstrued as evidence of tumor progression/regression.

This study identified 26 late invasive primary surgical site infection (IP-SSI) within 4–12 months of transplantation among 2073 SOT recipients at Duke University Hospital over the period 2015–2019. Thoracic organ transplants accounted for 25 late IP-SSI. Surveillance for late IP-SSI should be maintained for at least one year following transplant.