We investigated the therapeutic potential of the interleukin‐6 receptor inhibitor tocilizumab in 7 patients with new onset refractory status epilepticus (NORSE) who remained refractory to conventional immunotherapy with rituximab (n = 5) or without rituximab (n = 2). Status epilepticus (SE) was terminated after 1 or 2 doses of tocilizumab in 6 patients with a median interval of 3 days from the initiation. They had no recurrence of SE during the observation. However, 2 patients experienced severe adverse events related to infection during the tocilizumab therapy. Further prospective controlled studies are warranted to validate the efficacy and safety of tocilizumab in patients with NORSE. Ann Neurol 2018;84:940–945

The optic nerve sheath diameter (ONSD) is considered as an indirect marker for intracranial pressure (ICP). However, the optimal cut-off value for an abnormal ONSD indicating elevated ICP and its associated factors have been unclear. Thus, we investigated normative values for the ONSD using ultrasonography and investigate the potential factors affecting it. We prospectively recruited healthy volunteers between September 2016 and March 2017. A total of 585 individuals were included, in which the mean ONSD was 4.11 mm [95% confidence interval (CI), 4.09–4.14 mm]. Although ONSD was correlated with sex (p = 0.015), height (p = 0.003), and eyeball transverse diameter (ETD) (p < 0.001) in simple linear regression analyses, multiple linear regression analysis revealed that only ETD was independently associated with ONSD (p < 0.001). Accordingly, we further established a normative value for the ONSD/ETD ratio and its associated factors. The mean ONSD/ETD ratio was 0.18 (95% CI, 0.18–0.18), but the ONSD/ETD ratio was not correlated with sex, height, weight, body mass index, and head circumference. Our findings suggest that the ONSD had a strong correlation with ETD, and ONSD/ETD ratio might provide more reliable data than ONSD itself as a marker of ICP.

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BackgroundWe aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway.MethodsTwo cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells.ResultsSeven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1+ TILs were significantly decreased in BM (P = 0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3+ (P = 0.078), CD8+ (P = 0.055), FOXP3+ (P = 0.016), and PD-1+ (P = 0.016) TILs.ConclusionsThere may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1+ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti–PD-1 antibody in BM.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5214-8) contains supplementary material, which is available to authorized users.

Background and PurposeThe optic nerve sheath diameter (ONSD) is an indirect marker of the intracranial pressure, but the normal range of ONSD as measured using magnetic resonance imaging (MRI) and its associations with clinical parameters and the eyeball transverse diameter (ETD) remain unclear.MethodsWe included 314 healthy adults who underwent brain MRI examinations for health screening between June 2014 and September 2017. The ONSD and ETD of each eye were calculated using time-of-flight magnetic resonance angiography. Linear regression analyses were performed to assess the relationships between ONSD and variables including age, sex, height, weight, body mass index (BMI), mean arterial blood pressure (MABP), intraocular pressure (IOP), and ETD. We further investigated a normative value for the ONSD/ETD ratio and its associated factors.ResultsThe mean ONSD and ETD were 4.71 mm [95% confidence interval (CI), 4.66–4.75 mm] and 21.24 mm (95% CI, 21.13–21.35 mm), respectively. Multiple linear regression analysis showed that ONSD was only associated with ETD (p<0.001), with it being independent of age, sex, height, weight, BMI, MABP, and IOP. The ONSD/ETD ratio had a mean value of 0.22 (95% CI, 0.22–0.22), and was not correlated with age, sex, height, weight, BMI, MABP, or IOP.ConclusionsThis study determined the normative value of MRI-based ONSD in healthy Korean adults. There was a strong correlation between the ETD and ONSD, which can be presented as the ONSD/ETD ratio. This parameter needs to be investigated further in disease populations.

ObjectiveTo determine whether CSF biomarkers can be used as a predictor of freezing of gait (FOG) in Parkinson disease (PD) and to investigate the predictive value of clinical, dopamine transporter (DAT) imaging, and CSF parameters both separately and in combination.MethodsThis study using the PPMI data included 393 patients with newly diagnosed PD without FOG at baseline. We evaluated CSF for β-amyloid 1-42 (Aβ42), α-synuclein, total tau, phosphorylated tau181, and the calculated ratio of Aβ42 to total tau at baseline. Demographic and clinical data and DAT imaging results were also investigated. Cox proportional-hazards regression analyses were performed to identify the factors predictive of FOG. From these results, we constructed a predictive model for the development of FOG.ResultsDuring a median follow-up of 4.0 years, only Aβ42 among the CSF biomarkers was associated with the development of FOG (hazard ratio 0.997, 95% confidence interval [CI] 0.996–0.999, p = 0.009). Postural instability gait difficulty (PIGD) score, caudate DAT uptake, and, to a lesser extent, male sex, Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score, and Montreal Cognitive Assessment score were also predictive of FOG. The combined model integrating the PIGD score, caudate DAT uptake, and CSF Aβ42 achieved a better discriminative ability (area under the curve 0.755, 95% CI 0.700–0.810) than any factor alone.ConclusionWe found CSF Aβ42 to be a predictor of FOG in patients with early PD. Furthermore, the development of FOG within 4 years after diagnosis of PD can be predicted with acceptable accuracy with our risk model.

Objective We investigated the effects of prolonged‐release melatonin (PRM) on idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Methods In this 4‐week, randomized, double–blind, placebo–controlled pilot study, 30 participants with polysomnography–confirmed iRBD were assigned to receive PRM 2 mg per day, PRM 6 mg per day, or placebo. Medication was administered orally 30 min before bedtime. Primary outcomes included scores from the Clinical Global Impression‐Improvement (CGI‐I) and the Korean version of the RBD questionnaire‐Hong Kong (RBDQ‐KR). The secondary outcomes included RBDQ‐KR factor 1 and factor 2 subscores, the Pittsburgh Sleep Quality Index score, the Epworth Sleepiness Scale score, the Short Form Health Survey version 2 score, and the frequency of dream–enacting behaviors assessed using a sleep diary. Results After 4 weeks, there were no differences in the proportions of patients with a CGI‐I score of much improved or very much improved among the study groups. In addition, RBDQ‐KR scores and secondary outcomes were not improved in all groups at 4 weeks, and there were no differences between the groups. Conclusion Our findings suggest that PRM may not be effective in treating RBD–related symptoms within the dose range used in this study. Further studies using doses higher than 6 mg per day are warranted.

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