Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.

Touch imprint cytology is useful for the intraoperative pathological diagnosis of PitNETs' surgical margins.

Touch imprint cytology (TIC) and frozen section (FS) procedures are essential for intraoperative pathological diagnosis (IPD). They are invaluable tools for therapeutic decision-making, helping surgeons avoid under or overtreatment of patients. Pituitary neuroendocrine tumors (PitNETs) are generally small, slow-growing tumors with low-grade malignancy located at the base of the skull where it is impossible to maintain a wide tumor margin. Therefore, transsphenoidal surgery (TSS) should be performed with necessary caution, and with sufficient and minimal resection. Thus, this study aimed to evaluate the diagnostic accuracy of TIC for the diagnosis of PitNET and determine its ability to accurately evaluate the surgical margin compared to the FS procedure. A total of 104 fresh specimens from 28 patients who underwent TSS for PitNETs were examined using TIC and FS. TIC specimens were categorized according to the cell imprinting pattern. All specimens with a large number of neuroendocrine cells diffusely attached to the glass surfaces had PitNET components. Contrarily, no rich or diffuse cell attachments were observed in any non-tumoral endocrine cells. In conclusion, recognizing a pattern of endocrine cell adherence to glass is highly effective in IPD to certify the existence of a PitNET component.

Comparative physiology of canopy tree leaves in evergreen and deciduous forests in lowland Thailand.

The typical seasonally dry forests in Southeast Asia are the mixed deciduous forest (MDF), dry dipterocarp (deciduous) forest (DDF), and dry evergreen forest (DEF). We obtained 21 physiological traits in the top/sunlit leaves of 107, 65 and 51 tree species in MDF, DEF and DDF, respectively. Approximately 70%, 95% and 95% of canopy tree species which consist of MDF, DEF and DDF are sampled, respectively. Light-saturated photosynthetic rates (Asat) exhibit a positive correlation with foliar nitrogen (N) and phosphorus (P) on leaf mass and area bases across tree species. Decreased leaf mass-based P reduces the positive slope of the mass-based N and Asat relationship across species and habitats. The differences in nutrient and water use and leaf habits are well matched to the variation in soil properties among the forest types, highlighting the reliability of this comprehensive database for revealing the mechanism of niche segregation based on edaphic factors.

Clinical decision-making based on 11C-methionine PET in recurrent Cushing's disease with equivocal MRI findings.

OBJECTIVE: Diagnosis and accurate localization of recurrent tumors in Cushing's disease (CD) are challenging, especially after multiple transsphenoidal surgeries (TSSs) or radiosurgery. Even experts face difficulties in detecting these recurrent tumors, and a favorable surgical outcome is not guaranteed. In this report, the authors aimed to determine the usefulness of 11C-methionine positron emission tomography (MET-PET) for evaluating patients with recurrent CD with inconclusive magnetic resonance imaging (MRI) lesions and to develop a treatment protocol for these cases. METHODS: In this retrospective study of patients with recurrent CD in the period between April 2018 and December 2022, the authors assessed the usefulness of MET-PET in determining whether equivocal MRI findings were recurrent tumors or postsurgical cavities and deciding further treatment options. All patients had undergone at least one TSS, and most had undergone multiple TSSs and had pathologically confirmed corticotroph tumors with hypercortisolemia. RESULTS: Overall, 15 patients with recurrent CD (10 females and 5 males) were included, all of whom had undergone MET-PET. All patients had been subjected to multiple treatments, including TSSs or radiosurgeries. Their MRI scans demonstrated less-enhanced lesions that were not confirmed as recurrences even with cutting-edge MRI because they could not be distinguished from postsurgical changes with confidence. MET uptake was positive in 8 patients (9 examinations) and negative in 7. Following MET-PET, repeat TSS was performed in 5 patients. Corticotroph tumors were identified in all 5 patients, even though one of them had negative MET uptake. The MET uptake precisely identified a tumor location on the opposite side of the MRI-suspected lesion in 2 patients. Meanwhile, patients with negative uptake and mild hypercortisolism were only observed. Nonsurgical options were also used in other patients: temozolomide (TMZ) was administered in 2 patients owing to a prior history of multiple TSSs and radiosurgery and the drug-resistant nature of the disease. TMZ was highly effective in these patients; their Cushing's symptoms ameliorated, and their adrenocorticotropic hormone and cortisol levels continued to decline. Interestingly, MET uptake disappeared following TMZ treatment. CONCLUSIONS: MET-PET is extremely useful for confirming equivocal lesions on MRI in patients with recurrent CD and for deciding further treatment options. The authors propose a novel protocol based on MET-PET results for treating patients with relapsing CD in whom the recurrent tumors cannot be confirmed with MRI.

Muscle magnetic resonance imaging abnormality in neuroleptic malignant syndrome: a case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and occasionally fatal undesirable reaction to dopamine antagonists, and its phenotype is diverse owing to causative drugs. Classically, elevation of serum creatine kinase is described in NMS. Some reports have described muscular pathological findings; however, muscle magnetic resonance imaging (MRI) has not been reported previously. CASE PRESENTATION: A 63-year-old woman with a history of schizophrenia presented to our hospital with a high fever, excessive sweating, muscle weakness, and elevated serum creatine kinase levels. Muscle MRI revealed T2 high-intensity lesions in several muscles with gadolinium enhancement, and the pathology of the muscle biopsy showed a very mild presence of muscle fiber necrosis and regeneration with type 2c fibers without inflammation. Her symptoms resolved by treatment with levodopa/carbidopa, dantrolene. Finally, the patient was diagnosed with NMS. CONCLUSIONS: This is the first report of muscle MRI abnormalities in a patient with NMS. Muscle MRI abnormalities in NMS may be associated with non-inflammatory myopathic changes. The cause of creatine kinase elevation cannot be explained by abnormal strong muscle contraction nor inflammation.

Resection of the Cavernous Sinus Medial Wall Improves Remission Rate in Functioning Pituitary Tumors: Retrospective Analysis of 248 Consecutive Cases.

BACKGROUND: The purpose of transsphenoidal surgery (TSS) for a functioning pituitary tumor (FPT) is to achieve endocrinological remission. The biggest challenge is aggressive tumor resection invading the cavernous sinus (CS). OBJECTIVE: To evaluate the effects of the medial wall of CS (MWCS) resection during FPT surgery. METHODS: Consecutive FPTs were reviewed for CS invasion (CSI) between April 2018 and December 2021. We operated on more than 250 FPTs, including 134 somatotroph tumors, 70 corticotroph tumors, 35 lactotroph tumors, and 9 thyrotroph tumors. RESULTS: The patients were classified into 3 groups based on the relationship between the tumor and the CS: group A (no clear wall invasion), in which MWCS was not removed because of no tumorous direct contact with MWCS (N = 92) and group B (possible wall invasion), where MWCS was removed because we were not confident of MWCS invasion (N = 102). Among these 102 patients, histological tumor invasion was confirmed in 45 of 79 patients (57%) for whom histology findings were available. Tumors invading the CS clearly during surgery were classified into the "clear CS invasion" (group C: N = 55) group. The overall complete remission rate in group B was 94%, which was as high as that in group A (87%). Moreover, we clarified that microscopic invasion of MWCS could not always be predicted from Knosp grading. CONCLUSION: MWCS invasion occurred in 57% of cases confirmed histologically where it was unclear during surgery, and its resection can improve the overall complete remission rate in FPT cases.

Fresh-marketable tomato yields enhanced by moderate weed control and suppressed fruit dehiscence with woodchip mulching.

The use of plastic film imposes various environmental risks in agroecosystems. The replacement of plastics with organic materials for mulching has been suggested to enhance the sustainability of agroecosystems. However, whether woodchip mulch can be used for annual crops needs to be verified. We examined the effects of mulberry woodchip mulches on tomato-fruit yields over two successive years. Mulberry is the unique food plant of silkworms, and it will be better if its pruned shoots can be recycled rather than incinerated as waste. Setting three treatments, including woodchip mulch, weed-free and weedy (i.e., unweeded) treatments, we compared the amounts of fresh-marketable and unmarketable tomato fruits. The yields of fresh-marketable tomato fruits in the woodchip mulch treatment were significantly 16-57% higher than those in the weed-free treatment and comparable to those in the weedy treatment. The yields of unmarketable dehiscent tomato fruits in the weed-free treatment were significantly 46-86% higher than those of the other two treatments. The woodchip mulches extensively suppressed the weed density, while the grown weeds became large, preventing strong sunlight exposure and dehiscence of tomato fruits. Current results suggest that woodchips could be a possible alternative to plastics, facilitating climate change mitigation with agroforestry practices.

Apoplexy in sellar metastasis from papillary thyroid cancer: A case report and literature review.

Background: Pituitary metastasis from papillary thyroid cancer (PTC) is rare and only a few cases have been reported. Case Description: We report the case of a patient who presented with visual dysfunction and panhypopituitarism. Magnetic resonance imaging revealed a pituitary tumor and hydrocephalus. Transsphenoidal surgery had been indicated, but his surgery had been postponed due to COVID-19 pandemic. During that waiting period, he showed pituitary apoplexy with consciousness disturbance, resulting in acute adrenal insufficiency and diabetes insipidus. He was urgently hospitalized and underwent transsphenoidal surgery. Rapid and permanent pathological examinations have confirmed metastasis of PTC to the pituitary. The patient also underwent serial thyroidectomy. He was also suspected to have secondary hydrocephalus and underwent lumboperitoneal shunting after excluding cerebrospinal fluid metastasis. Thereafter, his cognitive dysfunction and performance status improved dramatically. Conclusion: To the best of our knowledge, this is the first patient with PTC who developed pituitary apoplexy secondary to metastasis.

Temozolomide and Capecitabine Treatment for an Aggressive Somatotroph Pituitary Tumor: A Case Report and Literature Review.

Aggressive somatotroph pituitary tumor that causes acromegaly is extremely rare and resists conventional treatments such as multiple surgeries, radiotherapies, and various types of somatostatin analogs. Here, we propose a novel treatment option for these rare cases by discussing our case and reviewing the literature. We experienced an aggressive somatotroph tumor in a 52-year-old woman with acromegaly. Not only could a complete remission of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) not be obtained, but the tumor continued to grow and eventually recurred around the brainstem despite multidisciplinary treatments. We employed immunohistochemistry and a three-dimensional (3D) spheroid ex vivo assay to determine the best treatment option for this case. Although histology showed strong O 6-methylguanine DNA methyltransferase expression and high Ki-67 labeling index (22%), temozolomide (TMZ) combined with capecitabine (CAPTEM) treatment was performed based on the results of the patient-derived 3D spheroid ex vivo assay, which predicted more effective treatment with CAPTEM than with TMZ alone. Consequently, GH and IGF-1 levels were restored to normal range with remarkable tumor shrinkage after CAPTEM treatment. To the best of our knowledge, there have been even very few reports describing successful treatment for such aggressive and refractory somatotroph tumors and this is the first report showing the effectiveness of CAPTEM on refractory somatotroph tumor both ex vivo and in vivo.

Partial nephrogenic diabetes insipidus with a novel arginine vasopressin receptor 2 gene variant.

X-linked nephrogenic diabetes insipidus (NDI) is caused by variations in arginine vasopressin receptor 2 (AVPR2). Some patients show partial resistance to arginine vasopressin (AVP). A 19-month-old Japanese boy presented with polydipsia since infancy. His mother had a history of polydipsia during pregnancy, and his maternal granduncle also had polydipsia. Intermediate urine osmolality and markedly high plasma AVP levels were observed in the water deprivation test. Subsequent pitressin administration caused no further elevation in urine osmolality. We diagnosed the patient with partial NDI, initiated therapy with hydrochlorothiazide, and placed him on a low-sodium diet. Although his urine volume decreased by 20-30% after the initiation of therapy, progressive hydronephrosis and growth retardation developed 2 years later. We investigated his genetic background by multiplex targeted sequencing of genes associated with inherited renal diseases, including AVPR2 and aquaporin-2 (AQP2). We identified a hemizygous missense variant in AVPR2 NM_000054:c.371A>G,p.(Tyr124Cys) in the boy and a heterozygous variant in the mother at the same locus. Distinguishing partial NDI from primary polydipsia is difficult because of its mild symptoms. Markedly elevated plasma AVP levels with intermediate urine osmolality may suggest partial NDI, and genetic analysis can be useful for such patients.

Parenchyma underlies the interspecific variation of xylem hydraulics and carbon storage across 15 woody species on a subtropical island in Japan.

Parenchyma is an important component of the secondary xylem. It has multiple functions and its fraction is known to vary substantially across angiosperm species. However, the physiological significance of this variation is not yet fully understood. Here, we examined how different types of parenchyma (ray parenchyma [RP], axial parenchyma [AP] and AP in direct contact with vessels [APV]) are coordinated with three essential xylem functions: water conduction, storage of non-structural carbohydrate (NSC) and mechanical support. Using branch sapwood of 15 co-occurring drought-adapted woody species from the subtropical Bonin Islands, Japan, we quantified 10 xylem anatomical traits and examined their linkages to hydraulic properties, storage of soluble sugars and starch and sapwood density. The fractions of APV and AP in the xylem transverse sections were positively correlated with the percentage loss of conductivity in the native condition, whereas that of RP was negatively correlated with the maximum conductivity across species. Axial and ray parenchyma fractions were positively associated with concentrations of starch and NSC. The fraction of parenchyma was independent of sapwood density, regardless of parenchyma type. We also identified a negative relationship between hydraulic conductivity and NSC storage and sapwood density, mirroring the negative relationship between the fractions of parenchyma and vessels. These results suggest that parenchyma fraction underlies species variation in xylem hydraulic and carbon use strategies, wherein xylem with a high fraction of AP may adopt an embolism repair strategy through an increased starch storage with low cavitation resistance.

Efficacy of temozolomide combined with capecitabine (CAPTEM) on refractory prolactinomas as assessed using an ex vivo 3D spheroid assay.

PURPOSE: Refractory prolactinomas resistant to dopamine agonists (DAs) pose a clinical challenge. Temozolomide (TMZ) is a recommended treatment option, but its effects are difficult to predict, and the alternatives are limited. Recent reports suggested that TMZ combined with capecitabine (CAPTEM) can be effective for the treatment of aggressive pituitary tumors. This study sought to evaluate the effect of TMZ in an ex vivo three-dimensional (3D) spheroid culture assay and determine if this assay could be used to predict the therapeutic effect of CAPTEM in actual refractory prolactinomas. METHODS: Surgically resected tumor tissues from two patients with refractory prolactinoma were cultured as 3D spheroids. The effects of TMZ were assessed based on its suppression of cell viability and reduction of prolactin (PRL) levels. RESULTS: In Case 1, the 3D culture assay showed no effect of TMZ on cell viability or PRL suppression. Clinically, TMZ treatment did not reduce PRL levels (8870→8274 ng/mL) and the tumor progression. However, CAPTEM partially reduced PRL levels (9070→4046 ng/mL) and suppressed the tumor growth. In Case 2, TMZ in the 3D culture assay showed a 50% reduction of cell viability and 40% reduction of PRL levels. Clinically, CAPTEM was highly effective, with a considerable reduction in PRL level (17,500→210 ng/mL), and MRI showed almost no residual tumor. CONCLUSIONS: This is the first report to describe the effects of CAPTEM treatment on refractory prolactinomas. The ex vivo 3D spheroid culture assay reliably predicted TMZ sensitivity and informed the selection between TMZ or CAPTEM treatment for refractory prolactinomas.

Zn tolerance in the evergreen shrub, Aucuba japonica, naturally growing at a mine site: Cell wall immobilization, aucubin production, and Zn adsorption on fungal mycelia.

Aucuba japonica Thunb. is an evergreen understory shrub that grows naturally at a mine site. The mine soil contains high concentrations of heavy metals, and A. japonica appears to maintain detoxification mechanisms against heavy metals in the study site's understory. This study aimed to investigate the heavy metal tolerance mechanisms in A. japonica, considering the possible roles of arbuscular mycorrhizal and root-endophytic fungi. We conducted fieldwork in summer (canopy-foliation season) and winter (canopy-defoliation season) to measure the heavy metal concentrations in leaves, branches, and roots and analyze possible detoxicants in the roots. The infection rates of arbuscular mycorrhizal and root-endophytic fungi were evaluated via microscopic observation, and heavy metal (Zn) localization in A. japonica roots was observed using confocal laser scanning microscopy. Field analysis showed that A. japonica accumulated excessive Zn and produced aucubin and citric acid in the roots in both summer and winter. Zn localization observations clarified that Zn was distributed in thickened epidermal and cortical cell walls, suggesting that the cell walls functioned as Zn deposition sites, reducing Zn toxicity. It was further clarified that Zn was contained within cortical cells, indicating that Zn might be detoxified by aucubin and citric acid. Arbuscular mycorrhizal and root-endophytic fungi within cortical cells adsorbed Zn on fungal cell walls, indicating that these fungi would reduce Zn content within root cells and might alleviate Zn toxicity. Our results indicated that A. japonica would maintain Zn tolerance in both summer and winter via Zn immobilization in the cell walls and production of aucubin and citric acid, and that arbuscular mycorrhizal and root-endophytic fungi might play important roles in the Zn tolerance of A. japonica.

Evolutionary loss of thermal acclimation accompanied by periodic monocarpic mass flowering in Strobilanthes flexicaulis.

While life history, physiology and molecular phylogeny in plants have been widely studied, understanding how physiology changes with the evolution of life history change remains largely unknown. In two closely related understory Strobilanthes plants, the molecular phylogeny has previously shown that the monocarpic 6-year masting S. flexicaulis have evolved from a polycarpic perennial, represented by the basal clade S. tashiroi. The polycarpic S. tashiroi exhibited seasonal thermal acclimation with increased leaf respiratory and photosynthetic metabolism in winter, whereas the monocarpic S. flexicaulis showed no thermal acclimation. The monocarpic S. flexicaulis required rapid height growth after germination under high intraspecific competition, and the respiration and N allocation were biased toward nonphotosynthetic tissues. By contrast, in the long-lived polycarpic S. tashiroi, these allocations were biased toward photosynthetic tissues. The life-history differences between the monocarpic S. flexicaulis and the polycarpic S. tashiroi are represented by the "height growth" and "assimilation" paradigms, respectively, which are controlled by different patterns of respiration and nitrogen regulation in leaves. The obtained data indicate that the monocarpic S. flexicaulis with the evolutionary loss of thermal acclimation may exhibit increased vulnerability to global warming.

Tumor Shrinkage by Metyrapone in Cushing Disease Exhibiting Glucocorticoid-Induced Positive Feedback.

CONTEXT: Paradoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing disease (CD). Its pathophysiology and prevalence remain unclear. CASE DESCRIPTION: A 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma adrenocorticotropic hormone (ACTH) levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment. EX VIVO EXPERIMENTS: The resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (P < 0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather a 20% to 40% suppression (P < 0.05). CLINICAL STUDY: A cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low-dose and high-dose DST from 2014 to 2020 was performed. Eight cases (8.7%) showed an increase in serum cortisol after both low-dose and high-dose DST. CONCLUSION: This is the first report of a patient with glucocorticoid (GC)-driven positive feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive-feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive feedback in CD and the therapeutic approach for these patients remain to be investigated.

Tree hazards compounded by successive climate extremes after masting in a small endemic tree, Distylium lepidotum, on subtropical islands in Japan.

Ongoing global warming increases the frequency and severity of tropical typhoons and prolonged drought, leading to forest degradation. Simultaneous and/or successive masting events and climatic extremes may thus occur frequently in the near future. If these climatic extremes occur immediately after mass seed reproduction, their effects on individual trees are expected to be very severe because mass reproduction decreases carbohydrate reserves. While the effects of either a single climate extreme or masting alone on tree resilience/growth have received past research attention, understanding the cumulative effects of such multiple events remains challenging and is crucial for predicting future forest changes. Here, we report tree hazards compound by two successive climate extremes, a tropical typhoon and prolonged drought, after mass reproduction in an endemic tree species (Distylium lepidotum Nakai) on oceanic islands. Across individual trees, the starch stored within the sapwood of branchlets significantly decreased with reproductive efforts (fruit mass/shoot mass ratio). Typhoon damage significantly decreased not only the total leaf area of apical shoots but also the maximum photosynthetic rates. During the 5-month period after the typhoon, the mortality of large branchlets (8-10-mm diameter) increased with decreasing stored starch when the typhoon hit. During the prolonged summer drought in the next year, the recovery of total leaf area, stored starch, and hydraulic conductivity was negatively correlated with the stored starch at the typhoon. These data indicate that the level of stored starch within branchlets is the driving factor determining tree regrowth or dieback, and the restoration of carbohydrates after mass reproduction is synergistically delayed by such climate extremes. Stored carbohydrates are the major cumulative factor affecting individual tree resilience, resulting in their historical effects. Because of highly variable carbohydrate levels among individual trees, the resultant impacts of such successive events on forest dieback will be fundamentally different among trees.

Revalidation of inferior petrosal sinus sampling: the latest results from a single-center experience.

Cushing's disease (CD), which manifests as excess cortisol secretion, is caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Such adenomas are occasionally difficult to identify on magnetic resonance imaging (MRI), and thorough endocrinological examination may be required to detect them. Inferior petrosal sinus (IPS) sampling (IPSS) has been the gold standard test for distinguishing CD from ectopic ACTH syndrome (EAS). However, IPSS is an invasive procedure, and proper catheterization is occasionally challenging due to anatomical variations. Thus, there have been ongoing debates regarding the necessity of this procedure. Here, we present our recent IPSS data derived from the analysis of 65 patients who were referred to us for possible CD between April 2018 and December 2020 after undergoing meticulous endocrinological testing. Even with detailed MRI, no obvious lesions were identified in 19 patients. IPSS performed on these 19 individuals identified an IPS-to-peripheral ACTH gradient in 15 of them. The four patients who lacked this gradient were subjected to a classical algorithm using concurrently measured prolactin levels, the results of which were consistent with their ultimately confirmed diagnoses: two true-positive and two true-negative diagnoses. These findings support the validity of the algorithm and demonstrate that the prolactin-adjusted IPS-to-peripheral ACTH ratio can improve the differentiation between CD and EAS. We had no false-negative results, but three patients were false-positive. Consequently, those three patients in which no apparent tumor was clarified during surgery could not have any endocrinological improvement postoperatively.

SCN8A-related developmental and epileptic encephalopathy with ictal asystole requiring cardiac pacemaker implantation.

INTRODUCTION: SCN8A-related epilepsy has various phenotypes. In particular, patients with developmental and epileptic encephalopathy (DEE) are resistant to antiepileptic drugs and may present with autonomic symptoms, such as marked bradycardia and apnea during seizures, and thus have an increased risk of sudden death. Herein, we report a case of very severe SCN8A-related epilepsy necessitating cardiac pacemaker implantation because of repetitive ictal asystole. CASE REPORT: The patient was a 14-month-old girl. Tremor and generalized tonic seizure occurred after birth. During seizures, bradycardia and perioral cyanosis occurred, and then, after developing tachycardia and apnea, marked bradycardia and generalized cyanosis occurred, which sometimes resulted in ictal asystole requiring cardiopulmonary resuscitation. Her seizures were refractory to antiepileptic drugs. As the seizures requiring resuscitation did not decrease, cardiac pacemaker implantation was performed four months after birth. Exome sequencing revealed a heterozygous de novo variant in SCN8A (NM_014191.3:c.4934T>C,p.(Met1645Thr)). Even though phenytoin was effective, seizures with bradycardia remained approximately once a month, and pacemaker activity was observed. CONCLUSIONS: This is, to our knowledge, the first reported case of SCN8A-related DEE in whom pacemaker implantation was performed. Pacemaker implantation should be considered as a treatment option for critical patients with SCN8A-related DEE as in the present case, because the incidence of sudden unexpected death in epilepsy is reported to be approximately 10% in patients with SCN8A-related DEE.

Treatment of an anterior cerebral artery pseudoaneurysm secondary to a transsphenoidal surgery using stent-assisted coiling.

BACKGROUND: Injury of the internal carotid artery (ICA) during transsphenoidal surgery (TSS) is a rare but critical complication. There are several reports on endovascular treatment of ICA injury during TSS. With the recent flourishing of extended TSS, injuries to the distal arteries such as the anterior cerebral artery (ACA) are more likely to occur. CASE DESCRIPTION: In the present case, we report a pseudoaneurysm of the right ACA due to injury during extended TSS for aggressive prolactinoma. Due to the absence of collateral vessels, the pseudoaneurysm had to be obliterated while preserving the parent artery. Hence, we decided to treat the pseudoaneurysm using stent-assisted coiling (SAC). The pseudoaneurysm was completely obliterated and he was discharged without any complications. CONCLUSION: To the best of our knowledge, this is the first case in which an ACA pseudoaneurysm caused by injury during the TSS was treated with SAC and the parent artery was preserved.

Hemostasis through Extended Transsphenoidal Route for Subarachnoid Hemorrhage after Conventional Transsphenoidal Surgery for a Pituitary Adenoma.

This report describes a 49-year-old male patient who presented with a pituitary adenoma extending to the suprasellar region. Subarachnoid hemorrhage (SAH) occurred after conventional transnasal transsphenoidal surgery for a non-functioning pituitary adenoma despite no suprasellar arachnoid membrane breakdown. Through extended transsphenoidal route, the suprasellar hematoma was removed and bleeding from a small vessel thought to be the branch of left superior hypophyseal artery was successfully controlled. Indeed, several case reports regarding this rare complication have been published, but the mechanism of SAH has never been identified and the prognosis was poor in most cases. This report illustrates the origin and mechanism of the bleeding clearly using the intraoperative video. This case suggests that immediate therapeutic intervention is necessary and extended transnasal transsphenoidal repeat surgery is useful for an appropriate hemostasis and removal of hematoma located in the suprasellar region.