The administration of antiepileptic drugs (AEDs) is the first treatment of epilepsy, one of the most common neurological diseases. Therapeutic guidelines include newer AEDs as front-line drugs; ...monotherapy with new AEDs is delivered in Japan. While about 70% of patients obtain good seizure control by taking one to three AEDs, about 60% experience adverse effects and 33% have to change drugs. Compared to traditional AEDs, the prolonged administration of new AEDs elicits fewer adverse effects and fewer drug interactions and their teratogenicity may be lower. These characteristics increase drug compliance and allow combination therapy for drug-resistant epilepsy, although the antiepileptic effects of the new AEDs are not greater than of traditional AEDs. Comorbidities are not rare in epileptics; many adult patients present with stroke and brain tumors. In stroke patients requiring risk control and in chemotherapy-treated brain tumor patients, their fewer drug interactions render the new AEDs advantageous. Also, new AEDs offer favorable side benefits for concurrent diseases and conditions. Patients with stroke and traumatic brain injury often present with psychiatric/behavioral symptoms and cognitive impairment and some new AEDs alleviate such symptoms. This review presents an outline of the new AEDs used to treat adult patients based on the pharmacological activity of the drugs and discusses possible clinical indications from the perspective of underlying causative diseases and comorbidities.
Recovery from adult growth hormone deficiency (AGHD) after transsphenoidal surgery (TSS) has not been well discussed because of the lack of examinations including pituitary provocation tests (PPTs) ...before and after the procedure. This study aimed to evaluate the growth hormone (GH) axis function of patients with nonfunctioning pituitary adenoma (NFPA) via pre- and postoperative PPTs. Moreover, the predictive factors for recovery from AGHD after TSS were validated to facilitate surgery for AGHD in patients with NFPA.
In total, 276 patients (median age 60.0 years) who underwent TSS for NFPA were included in this study. PPTs were performed before and 3 months after TSS. Then, the relationships between recovery from AGHD after TSS and clinical, surgical, and hormonal factors, including peak GH level based on PPTs, were evaluated statistically.
In this study, 114 patients were diagnosed with preoperative AGHD. Approximately 25.4% recovered from AGHD after TSS. In contrast, among the 162 patients without preoperative AGHD, 13 (8.0%) had newly developed postoperative AGHD. The predictive factors for recovery from AGHD were younger age, female sex, initial TSS, and high peak GH level based on preoperative PPT. According to the receiver operating characteristic curve analysis, patients who were aged ≤ 62.2 years and had a peak GH level of ≥ 0.74 μg/L based on preoperative PPT were likely to recover from AGHD (sensitivity: 82.8%, specificity: 72.9%, and area under the curve: 0.8229).
AGHD caused by NFPA can improve after initial TSS among young patients with certain peak GH levels assessed by preoperative PPT. Whether TSS for NFPA can promote recovery from AGHD is worth considering in some patients.
Rathke's cleft cysts (RCCs) are relatively common and often detected incidentally. They are usually asymptomatic and managed conservatively. However, little is known about their natural history. ...Thus, the authors aimed to examine the natural course of RCCs and identify the risk factors for their progression.
This retrospective study examined 229 patients (median age 43.0 years) diagnosed with RCCs by MRI and followed up without surgery (median period 36.6 months). The median cyst height on the initial MRI was 10 mm. Progression or regression of RCC was defined as cyst height changes of ≥ 1 mm.
In total, 23 (10.0%) RCCs progressed, whereas 73 (31.9%) RCCs spontaneously regressed. The remaining 133 were noted to be stable throughout the follow-up period. Patients with progressed RCCs were significantly older than those with stable RCCs. In patients with acute headache as an initial symptom, RCCs were significantly more likely to spontaneously regress. New symptoms occurred in 6 patients, 5 of whom underwent surgery for RCC progression. Of these 6 patients, 1 patient had persistent adrenocorticotropic hormone deficiency and 1 patient developed diabetes insipidus. Kaplan-Meier analysis results showed RCC progression and new symptom development rates to be 12.0% and 4.1% at 5 years and 13.7% and 5.7% at 10 years, respectively.
RCCs rarely progress or cause new symptoms in the long term. Patients with asymptomatic RCC should be followed up for at least 5 years to ensure RCC inactivity. RCCs in older adults may require greater surveillance.
Purpose
Diabetes insipidus (DI) following transsphenoidal surgery (TSS) is a common complication. Although postoperative DI often occurs in patients with craniopharyngioma and Rathke’s cleft cyst, ...postoperative DI in patients with non-functioning pituitary adenoma (NFPA) has not been fully examined. We clarified the clinical characteristics and magnetic resonance imaging (MRI) findings predicting postoperative DI in NFPAs.
Methods
A total of 333 patients undergoing initial TSS for NFPA were included in this retrospective study. Hyperintensity (HI) in the posterior pituitary lobe was evaluated on preoperative T1-weighted MRI. Based on the findings of HI patients were divided into three groups as follows: HI was not detected (Disappearance group), HI located intrasellarly (Intrasellar group), and HI located suprasellarly (Suprasellar group).
Results
The overall rate of DI was 21.9%, including permanent DI in 0.6%. DI occurred at postoperative day 1 (72.6%) or day 2 (19.2%) and improved within 7 days in most cases (87.7%). Univariable and multivariable analyses showed that the predictive factors of DI were a younger age (odds ratio OR 0.97, 95% confidence interval CI 0.95–0.99,
P
= 0.0037) and larger tumor diameter (OR 1.04, 95% CI 1.01–1.08,
P
= 0.0155). The rate of DI was highest in the Disappearance group (43.8%) followed by the Intrasellar group (26.0%). The OR was 2.17 in the Intrasellar group compared with the Suprasellar group (95% CI 1.17–4.02,
P
= 0.0141).
Conclusions
Factors predicting DI following TSS for NFPA were a younger age, larger tumor size, and the location of intrasellar HI on preoperative T1-weighted MRI.
Purpose
Thyrotropin-secreting pituitary adenomas (TSPA) are extremely rare pituitary adenomas; their perioperative thyroid hormone dynamics have not been completely elucidated. Here, we investigated ...the clinical characteristics, perioperative findings, and thyroid hormone dynamics of TSPA at a single institution.
Methods
We enrolled 11 patients who underwent transsphenoidal surgery (TSS) for TSPA during 2005–2019 at Hiroshima University Hospital (TSPA group) and 24 patients who underwent TSS for nonfunctioning pituitary adenomas (NFPA) in 2019 (NFPA group; for comparison). Their clinical characteristics, operative findings, and thyroid hormone dynamics, including serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were retrospectively analyzed.
Results
The NFPA group demonstrated a slight temporary decrease in serum TSH/ FT3/ FT4 levels on day 1 postoperatively and improvement in the levels on day 4 postoperatively. In contrast, the serum TSH level in the TSPA group demonstrated a marked decrease on day 1 postoperatively but improved on day 7 postoperatively. The serum FT3 level was also markedly decreased on day 1 postoperatively but remained within the normal range. The serum FT4 level revealed a gradual decrease until day 21 postoperatively and then recovered within the normal range 3 months postoperatively. There was no significant difference in the frequency of decline in serum FT4 level between the two groups; no patients required thyroid hormonal replacement 3 months postoperatively.
Conclusions
Despite a variable degree of transient hypothyroidism, all patients had a normal thyroid function after 3 months follow-up.
Glioblastoma multiforme (GBM), the most common brain malignancy in adults, is generally aggressive and incurable, even with multiple treatment modalities and agents. Filamins (FLNs) are a group of ...actin-binding proteins that regulate the actin cytoskeleton in cells. However, the role of FLNs in malignancies-particularly in GBM-is unclear.
The relation between FLNC expression and overall survival in GBM was evaluated by the Kaplan-Meier analysis using GBM patients from the Kagoshima University Hospital (n = 90) and data from the Cancer Genome Atlas (TCGA) (n = 153). To assess FLNC function in GBM, cell migration and invasion were examined with Transwell and Matrigel invasion assays using FLNC-overexpressing U251MG and LN299 GBM cells, and ShRNA-mediated FLNC knocked-down KNS81 and U87MG cells. The gelatin zymography assay was used to estimate matrix metalloproteinase (MMP) 2 activity.
In silico analysis of GBM patient data from TCGA and immunohistochemical analyses of clinical GBM specimens revealed that increased FLNC expression was associated with poor patient prognosis. FLNC overexpression in GBM cell lines was positively correlated with enhanced invasiveness, but not migration, and was accompanied by upregulation of MMP2.
FLNC is a potential therapeutic target and biomarker for GBM progression.
The hallmark of most cancer cells is the metabolic shift from mitochondrial to glycolytic metabolism for adapting to the surrounding environment. Although epigenetic modification is intimately linked ...to cancer, the molecular mechanism, by which epigenetic factors regulate cancer metabolism, is poorly understood. Here, we show that lysine-specific demethylase-1 (LSD1, KDM1A) has an essential role in maintaining the metabolic shift in human hepatocellular carcinoma cells. Inhibition of LSD1 reduced glucose uptake and glycolytic activity, with a concurrent activation of mitochondrial respiration. These metabolic changes coexisted with the inactivation of the hypoxia-inducible factor HIF1α, resulting in a decreased expression of GLUT1 and glycolytic enzymes. In contrast, during LSD1 inhibition, a set of mitochondrial metabolism genes was activated with the concomitant increase of methylated histone H3 at lysine 4 in the promoter regions. Consistently, both LSD1 and GLUT1 were significantly overexpressed in carcinoma tissues. These findings demonstrate the epigenetic plasticity of cancer cell metabolism, which involves an LSD1-mediated mechanism.
Mylonitic orthogneisses in the Kathmandu area, central Nepal have been investigated using whole-rock and mineral chemistry, Rb-Sr isotopes, and zircon U-Pb age dating. Zircon REE patterns determined ...from orthogneisses are characterized by enriched HREE patterns and the prominent Eu anomalies, consistent with a magmatic origin. The U-Pb zircon age dating and Ti-in-zircon thermometry revealed crystallization took place ca. 1.74 Ga at temperatures of 705-765℃; typical of felsic magmatism in the crust. Whole-rock data from most orthogneisses in this study and from similar rocks in previous studies span the 'syn-collisional' and 'post-collisional' fields on various tectonic discrimination diagrams, while some data also plot in rift-related magmatism fields. The peraluminous compositions, very high Sr isotopic ratios (0.865-3.585) and high Th and U concentrations for all orthogneisses in this study indicate that mylonitic orthogneisses are largely of S-type crustal origins. The new data presented herein, combined with that of previous studies, outline at least two Palaeoproterozoic magmatic episodes: 1) ca. 1.92-1.90 Ga rift-related magmatism derived from mantle melting and 2) 1.84-1.74 Ga crustal melting, resulting from burial of the Indian basement during thermal subsidence after rifting. This two-stage Palaeoproterozoic magmatism in Nepal occurred along the northern passive margin of the Indian basement during and/or after the breakup of the Columbia supercontinent.
Abstract
BACKGROUND
Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are ...inherently biased, and there are currently no prospective, multicenter studies.
OBJECTIVE
To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions.
METHODS
We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively.
RESULTS
There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively.
CONCLUSION
In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.
Graphical Abstract
Graphical Abstract
To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), ...when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.
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