Accuracy of serum neurofilament light to identify contrast-enhancing lesions in multiple sclerosis.

BACKGROUND: Contrast-enhancing magnetic resonance imaging (MRI) lesions (CELs) indicate acute multiple sclerosis inflammation. Serum biomarkers, neurofilament light (sNfL), and glial fibrillary acidic protein (sGFAP) may increase in the presence of CELs, and indicate a need to perform MRI. OBJECTIVE: We assessed the accuracy of biomarkers to detect CELs. METHODS: Patients with two gadolinium-enhanced MRIs and serum biomarkers tested within 3 months were included (N = 557, 66% female). Optimal cut-points from Bland-Altman analysis for spot biomarker level and Youden's index for delta-change from remission were evaluated. RESULTS: A total of 116 patients (21%) had CELs. A spot sNfL measurement >23.0 pg/mL corresponded to 7.0 times higher odds of CEL presence (95% CI: 3.8, 12.8), with 25.9% sensitivity, 95.2% specificity, operating characteristic curve (AUC) 0.61; while sNfL delta-change >30.8% from remission corresponded to 5.0 times higher odds (95% CI: 3.2, 7.8), 52.6% sensitivity, 81.9% specificity, AUC 0.67. sGFAP had poor CEL detection. In patients > 50 years, neither cut-point remained significant. sNfL delta-change outperformed spot levels at identifying asymptomatic CELs (AUC 0.67 vs 0.59) and in patients without treatment escalation between samples (AUC 0.67 vs 0.57). CONCLUSION: Spot sNfL >23.0 pg/mL or a 30.8% increase from remission provides modest prediction of CELs in patients <50 years; however, low sNfL does not obviate the need for MRI.

A possible case of serum sickness after ocrelizumab infusion.

A 41-year-old female diagnosed with multiple sclerosis began ocrelizumab treatment. She received her first treatment course without significant complication. After receiving the first maintenance dose 6 months later, she developed weakness, myalgias, gastrointestinal symptoms, headache, and intermittent fever persisting for 4 weeks. A working diagnosis of serum sickness was determined after excluding other probable entities. She received 3 days of 1 g methylprednisolone intravenously and five plasma exchanges, experiencing gradual improvement. Serum sickness has occurred with monoclonal antibodies including rituximab. This case of possible ocrelizumab-associated serum sickness suggests that clinicians should remain vigilant about this possibility with this medication.

Peripheral nerve injuries: A retrospective survey of 1124 cases.

BACKGROUND: Peripheral nerve injuries (PNIs) remain an important health problem often leading to severe motor disabilities predominantly in the younger population. OBJECTIVE: To analyze our experience of clinical and electrodiagnostic evaluation (EDX) of PNIs over a 26-year period. MATERIALS AND METHODS: Between 1989 and 2014, 1124 consecutive patients with 1418 PNIs were referred for clinical as well as EDX evaluation. These PNIs involved upper and lower limbs as well as the facial nerves. Patients with iatrogenic lesions and spinal cord/spinal root lesions were excluded from this analysis. Brachial plexus (BP) injuries with associated or not with root avulsions were considered as one particular nerve and was include in the study as BP. The etiological categories of the sustained trauma included vehicular accidents, penetrating injuries, falls, gunshot wounds, car accidents involving pedestrians, sports injuries, and miscellaneous injuries. RESULTS: The mean age of our patients was 34.2 years and most were males (76.7%). Majority (80.9%) of the PNIs were isolated injuries. Combined lesions most commonly involved the ulnar and median nerves. Upper-limb PNIs accounted for 72.6% of our patients. The ulnar nerve was injured most often, either singly or in combination. Vehicular accidents were the most common causes of injury (46.4%), affecting the brachial BP or the radial, fibular, or sciatic nerves. Penetrating trauma (23.9%) commonly affected the ulnar and the median nerves. Falls and gunshot wounds frequently affected the ulnar, radial, and median nerves. Sports injuries, mostly soccer related, affected predominantly the fibular nerves. BP injuries were considerably more common in accidents involving motorcycles than those involving cars (46.1% vs. 17.1%), and root avulsions was more frequently associated in these cases. CONCLUSIONS: Most PNIs were caused by vehicular accidents and penetrating trauma, and affected young men. Overall, ulnar nerve, primary BP, and median nerve PNIs were the most prevalent lesions.

Effectiveness and safety of dimethyl fumarate in progressive multiple sclerosis.

BACKGROUND: There is limited data analyzing the safety and effectiveness of dimethyl fumarate (DMF) in the progressive multiple sclerosis (PMS) population. OBJECTIVE: To analyze the safety and effectiveness of DMF in patients with PMS. METHODS: We used Cox proportional hazards models to compare the time to confirmed worsening and improvement on the Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) between patients treated with DMF and glatiramer acetate (GA) for at least one year. RESULTS: We included 46 patients treated with DMF and 42 patients treated with GA. The safety and tolerability of GA and DMF were consistent with established profiles. There was no difference in confirmed EDSS progression. A trend towards reduced T25FW was seen in the DMF compared to GA after adjustment (HR = 0.86; 95% CI:0.37, 1.98; p = 0.72 and HR = 0.60; 95% CI:0.27, 1.34; p = 0.21, respectively). CONCLUSION: Dimethyl fumarate showed a trend towards reduction in T25FW but no evidence of clinically significant impact on EDSS. The small sample precluded definitive determination.

Teriflunomide Safety and Efficacy in Advanced Progressive Multiple Sclerosis.

OBJECTIVES: To explore the safety and efficacy profile of teriflunomide in progressive multiple sclerosis. METHODS: We conducted a single-center retrospective observational analysis of a progressive multiple sclerosis population, assessing safety and efficacy in patients treated at least one year with teriflunomide or glatiramer acetate. Sustained progression of expanded disability status scale and sustained worsening of timed 25-foot walk were compared using a Cox proportional hazards model. RESULTS: Teriflunomide group (n = 29) mean characteristics: age = 58 years (SD ± 7.6), disease duration = 16.7 years (SD ± 9.5), expanded disability status score = 5.9 (SD ± 1.3), and follow - up = 32.4 months (SD ± 13.6). Glatiramer acetate group (n = 30) mean characteristics: age = 52.4 years (SD ± 11.3), disease duration = 15.1 years (SD ± 10.4), expanded disability status score = 5.7 (SD ± 1.6), and follow - up = 46.9 months (SD ± 43.9). Both treatments were well tolerated without serious side effects. After adjustment for age, sex, and baseline expanded disability status score, sustained expanded disability status score progression did not differ between groups (hazard ratio = 1.17; 95% confidence interval: 0.45, 3.08; p = 0.75). Sustained timed 25-foot walk worsening after adjustment also did not differ (hazard ratio = 0.56; 95% confidence interval: 0.2, 1.53; p = 0.26). CONCLUSION: In an advanced progressive multiple sclerosis population, no substantial differences in tolerability, safety, sustained EDSS progression, or sustained T25FW worsening over time were observed between glatiramer acetate and teriflunomide-treated groups. The small sample precluded definitive determination.

Gold(III) complexes with ONS-Tridentate thiosemicarbazones: Toward selective trypanocidal drugs.

Tridentate thiosemicarbazone ligands with an ONS donor set, H2L(R) (R = Me and Et) were prepared by reactions of 1-phenyl-1,3-butanedione with 4-R-3-thiosemicarbazides. H2L(R) reacts with Na[AuCl4]·2H2O in MeOH in a 1:1 M ratio under formation of green gold(III) complexes of composition [AuCl(L(R))]. These compounds represent the first examples of gold(III) complexes with ONS chelate-bonded thiosemicarbazones. The in vitro anti-Trypanosoma cruzi activity against both trypomastigote and amastigote forms (IC50try/ama) of CL Brener strains as well as the cytotoxicity against LLC-MK2 cells of the free ligands and complexes was evaluated. The complex [AuCl(L(Me))] was found to be more active and more selective than its precursor ligand and the standard drug benznidazole with a SItry/ama value higher than 200, being considered as a lead candidate for Chagas disease treatment. Moreover the in vitro activity against the replicative amastigote form (IC50ama) of T. cruzi was additionally investigated revealing that [AuCl(L(Me))] was also more potent than benznidazole still with a similar selectivity index. Finally, docking studies showed that free ligands and complexes interact with the same residues of the parasite protease cruzain but with different intensities, suggesting that this protease could be a possible target for the trypanocidal action of the obtained compounds.