Observation has been a mainstay in asymptomatic meningiomas, but it may increase the risk associated with treatment due to tumor enlargement and the aging of patients. Understanding the natural course of meningiomas is important to provide appropriate treatment. The majority of previous studies investigated factors related to their growth, but failed to demonstrate their relationship with symptomatic progression (sympP) because of its rarity. We reviewed and meta-analyzed 27 studies that investigated natural courses in asymptomatic or untreated meningiomas to find clinico-radiological factors predictive of radiological progression (radioP), growth speed, and sympP. In results of time-growth analysis, two-thirds of meningiomas showed radioP defined by a volume criterion and the rate approached a plateau at 4–5 years. In growth curve analyses, about half of incidental meningiomas presented decelerating or no growth, while less than one-quarter of them grew exponentially. RadioP, growth speed [annual volume change (AVC) or relative growth rate], and sympP each had different factors related to them. Younger age, non-calcification, and high intensity on T2-weighted image were related to radioP and rapid growth speed, but not to sympP. Tumors in males and those of larger size were likely to be symptomatic in the meta-analysis. AVC (≥2.1 cm3/year) was the strongest indicator of sympP. Apart from perifocal edema, radiological features at up-front imaging may not be useful for predicting sympP. This may be due to dynamic changes of those radiological markers in the long term. Quantified tumor size and growth speed, especially AVC, are important markers for deciding on treatment.
The long-term prophylactic effect of carotid artery stenting (CAS) remains incompletely elucidated. We evaluated outcomes of CAS at our institution to determine the safety and efficacy of CAS in real-world settings. We retrospectively analyzed 73 patients who underwent CAS from 2006 to 2013. Periprocedural results were compared between asymptomatic and symptomatic carotid stenosis groups. The primary endpoint was a composite of ipsilateral stroke, death, and carotid artery restenosis beyond 30 days and within 5 years after the first procedure. The average age was 72.2 years with a majority of male subjects (84.9%). Twenty-seven patients (37%) were asymptomatic. Incidence of periprocedural adverse events and mRS ≤2 at 30 days after CAS were not significantly different between groups (P = 0.14 and 0.07, respectively). CAS was unsuccessful in three patients and one post-procedural minor stroke occurred. Therefore, 69 patients were included in the long-term study. The rate of occurrence of the primary endpoint was 21.7%. Ipsilateral ischemic stroke occurred in one patient, which was due to cardiogenic embolus. Nine patients died, and cancer was the most frequent cause. Five in-stent restenoses were observed. All patients with restenosis underwent additional CAS without any occurrence of stroke. This study revealed the safety and long-term efficacy of CAS in a real-world setting. Routine follow-up is also important for detecting carotid artery restenosis.
Endoscopic treatment for chronic subdural hematoma (CSDH) has been reported, but endoscopic findings of CSDH have not been thoroughly investigated. This study aimed to elucidate the relationship between endoscopic findings and CSDH recurrence. Furthermore, it examined the association between Nagahori’s histopathological staging of CSDH and outer membrane color. Here, we retrospectively analyzed the operative videos of 70 patients with CSDH. The endoscopic findings were investigated, and their correlations with CSDH recurrence, the reduction ratio of the midline shift, and hematoma thickness on day 30 after the operation were analyzed. The outer membrane was white in 21 cases, yellow in 25 cases, and red in 24 cases. CSDH recurred in three (4.2%) patients, all of whom had a white outer membrane (adjusted odds ratio, 18; 95% confidence interval, 1.6–20.6; P = 0.007). The other endoscopic findings were not significantly related to CSDH recurrence, extent of the reduction ratio of the midline shift, or hematoma thickness. The outer membrane colors of white, red, yellow, and white almost corresponded to the histopathological staging from type I to IV in order. Our findings suggest that a white outer membrane is a risk factor for recurrence; these colors may represent the extent of inflammation related to the evolution of CSDH estimated from the histopathological findings.
The histone H3K27M-mutant diffuse midline glioma is often seen in children and has a very poor prognosis regardless of its histological grade. Although it can occur in adults, few studies on adult cases have been reported. We examined adult midline glioma cases for their histological grade, presence of H3K27M mutation, and expression of related factors—enhancer of zeste homolog 2 (EZH2), H3K27me3, p16, and methylthioadenosine phosphorylase. These tumor characteristics were also evaluated for their prognostic value in adult midline glioma. High histological grade, H3K27M-mutant, high EZH2 expression, and high H3K27me3 expression was detected in 12/23 (53%), 11/23 (48%), 9/23 (39%), and 12/23 (52%) cases, respectively. Histological grade and prognosis were significantly correlated (P <0.01). The high expression of EZH2 and the low expression of H3K27me3 correlated with histological malignancy (P = 0.019 and 0.009) and prognosis (P = 0.048 and 0.047). To broaden the scope of our analysis, a review of cases reported in the literature (2014–2019) was performed. In the 171 cases, H3K27M-mutant showed poor prognosis in the young adult group (P = 0.001), whereas H3K27 status had no effect on prognosis in the older age group (P = 0.141). Histological grade was correlated with prognosis in both young adults and older groups (P <0.001, P = 0.003, respectively). We demonstrate differences in prognostic factors for diffuse gliomas in the midline region for children and adults. Importantly, the H3K27M mutation significantly influences prognosis in children, but not necessarily in adults. Contrarily, histological grading and immunostaining are important prognostic tools in adults.
Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135–218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.
Intravenous (i.v.) phenytoin/fosphenytoin is recommended as the second-line therapy of antiepileptic drugs in patients with status epilepticus (SE). i.v. Levetiracetam is regarded as an effective and safe equivalent with i.v. phenytoin/fosphenytoin. However, i.v. levetiracetam is not covered by public health insurance for SE in most countries. For this study, we performed the real-world practice pattern survey of antiepileptic drugs for status epilepticus using the nationwide inpatient database. We used the Japanese Diagnosis Procedure Combination inpatient database in Japan and identified all cases of emergency admission attributable to status epilepticus from March 2011 through March 2018. We described the patient characteristics and practice pattern of antiepileptic drugs. The analysis conducted for this study examined 31,472 cases. As the second-line therapy, the use of i.v. levetiracetam increased rapidly from 2016; 35% of cases received i.v. levetiracetam in 2017. By contrast, the use of i.v. phenytoin/fosphenytoin decreased from 2016. In-hospital mortality decreased year-by-year. No year-by-year change was observed for deaths within 24 h, length of hospital stay, drug-induced hepatitis, or drug-induced eruption. Although the use of levetiracetam for treatment of SE is not compensated by public health insurance in Japan, i.v. levetiracetam use is increasing dramatically as the second-line SE therapy. We propose that health insurance coverage be extended to include i.v. levetiracetam treatment for SE.