Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis.

INTRODUCTION: Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA). METHODS: Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from 3 patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA. RESULTS: Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs. CONCLUSION: This study provides a comprehensive transcriptomic profile of lactotroph PitNETs and highlights the potential involvement of lincRNAs and specific signaling pathways in tumor pathogenesis. The identified upstream regulators may be potential therapeutic targets for future investigations.

Is oral Streptococcus mutans with collagen-binding protein a risk factor for intracranial aneurysm rupture or formation?

OBJECTIVE: Streptococcus mutans (SM) with the collagen-binding protein Cnm is a unique member of the oral resident flora because it causes hemorrhagic vascular disorders. In the multicenter study, we examined the relationship between Cnm-positive SM (CP-SM) and intracranial aneurysm (IA) rupture, which remains unknown. METHODS: Between May 2013 and June 2018, we collected whole saliva samples from 431 patients with ruptured IAs (RIAs) and 470 patients with unruptured IAs (UIAs). Data were collected on age, sex, smoking and drinking habits, family history of subarachnoid hemorrhage, aneurysm size, number of teeth, and comorbidities of lifestyle disease. RESULTS: There was no difference in the positivity rate of patients with CP-SM between the patients with RIAs (17.2%) and those with UIAs (19.4%). The rate of positivity for CP-SM was significantly higher in all IAs <5 mm than in those ≥10 mm in diameter (P=0.0304). In the entire cohort, the rate of positivity for CP-SM was lower in larger aneurysms than in smaller aneurysms (P=0.0393). CONCLUSIONS: The rate of positivity for CP-SM was lower among patients with large UIAs. These findings are consistent with the hypothesis that CP-SM plays a role in the formation of vulnerable IAs that tend to rupture before becoming larger.

Lung adenocarcinoma metastasis within a pituitary neuroendocrine tumor: a case report with review of literature.

Collision tumors involving the metastasis of malignant neoplasms to pituitary neuroendocrine tumors (PitNETs) are extremely rare. We herein report a case involving a patient with lung adenocarcinoma metastasis within a PitNET who exhibited relatively rapid progression of neurological symptoms. A 75-year-old man who underwent tumor resection 36 and 18 years prior to presentation for bladder and colon cancer, respectively, without recurrence presented with bitemporal hemianopsia, ptosis, and diplopia of the right eye. Subsequent magnetic resonance imaging (MRI) revealed a tumor 3.2 cm in diameter that extended from the anterior pituitary gland to the suprasellar region. Gadolinium-enhanced MRI of the tumor showed heterogeneous contrast enhancement. Considering the relatively rapid progression of neurological symptoms, semi-emergency endoscopic endonasal transsphenoidal surgery was performed. Histopathological examination revealed a group of thyroid transcription factor-1- and napsin A-positive papillary proliferating cells intermingled with α-subunit- and steroidogenic factor-1-positive PitNET cells. Thus, the patient was diagnosed with lung adenocarcinoma metastasis within a gonadotroph PitNET. Genetic testing revealed the presence of an EGFR (Ex-19del) mutation, after which chemotherapy was initiated. Additional stereotactic radiotherapy was performed for the residual tumor in the sella turcica. With continued chemotherapy, good control of both the primary and metastatic tumors was noted after 24 months after surgery. Cases of malignant neoplasm metastasis within a PitNET are difficult to diagnose. In the case of a sella turcica tumor with relatively rapid progression of neurological symptoms, early surgical intervention is recommended given the possibility of a highly proliferative tumor and the need to obtain pathologic specimens.

A clinicopathological study of low back pain due to middle cluneal nerve entrapment: case series.

PURPOSE: The middle cluneal nerve (MCN) is a pure sensory nerve around the middle buttock. Its entrapment between the iliac crest and the long posterior sacroiliac ligament elicits low back pain (LBP) that can be treated by MCN neurolysis or neurectomy. Because few studies examined the pathology of MCN entrapment (MCN-E) we subjected 7 neurectomized specimens from 6 LBP patients to pathologic study. METHODS: We present 6 consecutive patients (7 sides) with intractable LBP who underwent successful MCN neurectomy. Their symptom duration ranged from 6 to 96 months (average 47.3 months); the follow-up period ranged from 6 to 17 months (average 11.7 months). The surgical outcomes were evaluated using the numerical rating scale (NRS) for LBP and the Roland-Morris Disability Questionnaire (RDQ) score. The resected MCNs underwent neuropathological analysis. RESULTS: Postoperatively, all 6 patients reported immediate LBP amelioration; their NRS and RDQ scores were improved significantly. Pathological study of the 7 resected nerves showed that the myelinated fiber density was decreased in 6 nerves; we observed marked enlargement (n = 5), perineurial thickening and disruption (n = 6), intrafascicular fibrous changes (n = 5), myelinated fibers separated by fibrous cells under the perineurium (n = 4), and Renaut bodies (n = 3). The 7th nerve appeared normal with respect to the density and size of the myelinated fibers, however, the perineurium was slightly thickened. CONCLUSION: We present pathological evidence at the MCN compression site of 7 nerves from 6 patients whose LBP was alleviated by MCN neurectomy, indicating that MCN entrapment can elicit LBP.

Comparison of prophylactic antibiotics for endonasal transsphenoidal surgery using a national inpatient database in Japan.

BACKGROUND: The choice of prophylactic antibiotics for use in endonasal transsphenoidal surgery (ETSS) lacks universal standards. This study aimed to investigate the effectiveness of cefazolin, ampicillin and third-generation cephalosporins for preventing postoperative meningitis and secondary outcomes (in-hospital death and the combination of pneumonia and urinary tract infection) in patients who have undergone ETSS. METHODS: The study used data from the Diagnosis Procedure Combination database in Japan. Data from 10 688 patients who underwent ETSS between April 2016 and March 2021 were included. Matching weight analysis based on propensity scores was conducted to compare the outcomes of patients receiving cefazolin, ampicillin or third-generation cephalosporins as prophylactic antibiotics. RESULTS: Of the 10 688 patients, 9013, 102 and 1573 received cefazolin, ampicillin and third-generation cephalosporins, respectively. The incidence of postoperative meningitis did not significantly differ between the cefazolin group and the ampicillin group (OR, 1.02; 95% CI, 0.14-7.43) or third-generation cephalosporins group (OR, 0.81; 95% CI, 0.10-6.44). Similarly, in-hospital death and the composite incidence of pneumonia and urinary tract infection did not differ between the cefazolin group and the ampicillin or third-generation cephalosporins group. CONCLUSIONS: Cefazolin, ampicillin and third-generation cephalosporins as perioperative prophylactic antibiotics for ETSS do not differ significantly in terms of preventing meningitis.

Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor.

BACKGROUND: Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. CASE PRESENTATION: A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-ß and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. DISCUSSION AND CONCLUSIONS: This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.

Endoscopic spinal cord untethering using a 1 cm skin incision technique in pediatrics: a technical case report.

BACKGROUND: Spinal cord untethering by sectioning the filum terminale is commonly performed in tethered cord syndrome patients with minor abnormalities such as filar lipoma, thickened filum terminale, and low conus medullaris. Our endoscopic surgical technique, using the interlaminar approach, allows for sectioning the filum terminale through a very small skin incision. To our knowledge, this procedure has not been previously reported. This is the first case report involving a 1 cm skin incision. CASE PRESENTATION: A 9-month-old male patient was referred to our neurosurgical department due to a coccygeal dimple. MRI revealed a thickened fatty filum. After considering the treatment options for this patient, the parents agreed to spinal cord untethering. A midline 1 cm skin incision was made at the L4/5 vertebral level. Untethering by sectioning the filum terminale was performed by full endoscopic surgery using the interlaminar approach. The procedure was uneventful and there were no postoperative complications. CONCLUSIONS: In terms of visibility and minimizing invasiveness, our surgical technique of using the interlaminar approach with endoscopy allows for untethering by sectioning the filum terminale through a very small skin incision.

Spontaneous middle cerebral artery dissection: a series of six cases and literature review.

Middle cerebral artery (MCA) dissection is rare, and various clinical presentations, including hemorrhage, ischemia, or comorbidities, and the changes in imaging findings over time hinder treatment decisions. The European Stroke Organization guidelines exclude MCA dissection. Few cases have been reported with no review of the relevant literature. Therefore, we reviewed the relevant literature and our own experience with non-traumatic MCA dissection cases to determine appropriate treatment strategies. At our institution and affiliated institutions, we encountered six cases of MCA dissection-five with infarction and one with hemorrhage. Two patients underwent revascularization, and one underwent an aneurysmectomy. We reviewed English and Japanese articles in PubMed and Medical Journal Web and summarized the results based on the relationships among age, sex, location, the presence of an aneurysm, the presence of angiography, history, treatment, and mode of onset. The clinical course, changes in imaging, treatment strategies, and prognosis were discussed. Eighty cases were included in the review. Cerebral aneurysms were more common distal to the M2 area (p = 0.00) and were correlated with hemorrhage (p < 0.001). Most hemorrhagic cases with aneurysms were treated surgically, while ischemic cases were treated with antithrombotic agents, and both had a similar neurological prognosis. There were some cases of rebleeding after antithrombotic therapy, especially in older adults.Surgical treatment is recommended in cases of hemorrhage and confirmed aneurysms, particularly for lesions distal to the M2 area. Patients with aneurysm-associated ischemia should be followed up, and antithrombotic treatment should be considered with particular care in older adults.

Outcomes After Endoscopic Evacuation Versus Evacuation Using Craniotomy or Stereotactic Aspiration for Spontaneous Intracerebral Hemorrhage: Analysis Using a Japanese Nationwide Database.

BACKGROUND: Various surgical methods are available for managing large intracerebral hemorrhage. This study compared the prognosis of patients with spontaneous intracerebral hemorrhage who underwent endoscopic evacuation, stereotactic aspiration, and craniotomy by using a nationwide inpatient database in Japan. METHODS: Using the Diagnosis Procedure Combination database, we identified patients who underwent surgery for spontaneous intracerebral hemorrhage within 48 h after admission between April 2014 and March 2018. Eligible patients were classified into three groups according to the type of surgery (endoscopic surgery, stereotactic surgery, and craniotomy). Propensity score matching weight analysis was conducted to compare poor modified Rankin Scale score at discharge (severe disability or death) and hospitalization cost among the groups. RESULTS: Among 17,860 eligible patients, craniotomy, stereotactic surgery, and endoscopic surgery were performed in 14,354, 474, and 3,032 patients, respectively. In the matching weight analysis, all covariates were well balanced. Compared with the endoscopic surgery group, the proportion of poor prognosis (modified Rankin Scale score at discharge of 5 or 6) was significantly higher in craniotomy groups (odds ratio 2.51, 95% confidence interval 1.11-5.68; p = 0.028). Subgroup analysis based on hemorrhage location and consciousness level at the time of admission showed no significant difference between the surgical procedures. Hospitalization costs were significantly higher in the craniotomy group than in the endoscopic surgery group (difference US $9,724, 95% confidence interval 2,169-17,259; p = 0.011). CONCLUSIONS: Endoscopic surgery for spontaneous intracerebral hemorrhage was associated with improved prognosis compared with craniotomy at the hospital discharge. Future large-scale clinical trials are needed to evaluate the optimal surgical techniques for intracerebral hemorrhage.

Endoscopic surgery versus craniotomy for spontaneous intracerebral hemorrhage in the late elderly patients.

OBJECTIVES: To compare the prognosis of late elderly patients with spontaneous intracerebral hemorrhage (ICH) treated by endoscopic evacuation and craniotomy MATERIALS AND METHODS: Using the Diagnosis Procedure Combination database, we identified patients aged ≥ 75 years who underwent surgery for spontaneous ICH within 48 hours after admission between April 2014 and March 2018. Eligible patients were classified into two groups according to the type of surgery (endoscopic surgery and craniotomy). Propensity-score matching weight analysis was conducted to compare the good neurological outcome modified Rankin Scale (mRS) score (0-4) at discharge as the primary endpoint between the two groups. Secondary endpoints were postoperative meningitis, tracheostomy, reoperation within 3 days and total hospitalization costs. RESULTS: Among the 5,396 eligible patients, endoscopic surgery and craniotomy were performed in 895 and 4,501 patients, respectively. In the propensity-score matching weight analysis, all covariates were well balanced. The proportions of patients with a good prognosis (mRS score at discharge: 0-4) did not significantly differ between the surgical procedures (42.1% vs. 42.8%, p = 0.828). The proportions of meningitis, tracheostomy and reoperation were not significantly different between the two groups. Hospitalization costs were significantly higher in the craniotomy group than in the endoscopic surgery group (25,536 vs. 29,603 US dollars, p = 0.012). CONCLUSIONS: Inhospital outcomes did not differ between endoscopic and open surgeries for spontaneous ICH in the late-stage elderly patients aged ≥75 years. Hospitalization costs were significantly higher in the craniotomy group, suggesting that endoscopic surgery may be more acceptable.

Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Patient satisfaction with cluneal nerve entrapment surgery.

INTRODUCTION: Low back pain (LBP) from superior or middle cluneal nerve entrapment has been addressed surgically. We recorded patient satisfaction with this treatment. METHODS: We included 22 consecutive patients who had undergone surgery for unilateral cluneal nerve entrapment (superior: n = 17, middle: n = 5). The numerical rating scale (NRS) for LBP, the Oswestry Disability Index (ODI) score, and the EuroQOL 5-dimension, 5-level (EQ-5D-5L) scale before and 6 months after the operation were compared. Using these scores, the treatment outcome was compared with the patients' preoperative expectations. RESULTS: LBP was ameliorated in all 22 patients; their NRS, ODI, and EQ-5D-5L were significantly improved after surgery. Surgical satisfaction based on the postoperative NRS scores was recorded as 8.8 ± 1.1 (range 7-10). While the postoperative was significantly better than the expected NRS, the postoperative ODI was significantly higher than expected by the patients (both: p < 0.05). There was a moderate correlation between the postoperative NRS and ODI and postoperative patient satisfaction. CONCLUSION: Patient satisfaction with the surgical result was rated as acceptable.

Morphological changes in vertebral artery dissections observed on 4D flow magnetic resonance images: case report.

The morphology of vertebral artery (VA) dissections can change in the clinical course. A 58-year-old female with a 2-week headache was diagnosed with left VA dissection. Hemodynamic stress on the right VA detected on 4D flow MRI scans resulted in increased wall shear stress but the vessel was morphologically unchanged. Subsequent MRA revealed right VA dissection. Her bilateral dissections were treated conservatively and no neurological abnormality developed. Serial 4D flow MRI may be useful for observing morphological changes in VA dissections and help to clarify the mechanism(s) underlying VA dissections.

Vertebral artery V3 portion-radial artery-distal common carotid artery (V3-RA-dCCA) bypass for large basilar trunk aneurysm with bilateral proximal common carotid artery occlusion-technical note.

BACKGROUND: Large basilar trunk aneurysm caused by bilateral occlusion of the proximal common carotid artery is rare. We treated one case with vertebral V3 portion-radial artery-distal common carotid artery (V3-RA-dCCA) bypass. CASE DESCRIPTION: Basilar trunk aneurysm and bilateral occlusion of the proximal CCA were found incidentally in a 70-year-old woman. During the next 5 years, the aneurysm gradually enlarged to 12 mm, and blood flow of the anterior circulation was supplied through the posterior communicating artery. V3-RA-dCCA bypass was performed to reduce the stress of blood flow and prevent aneurysm growth and rupture. After exposing the neck portion, forearm of RA, and V3 portion of the vertebral artery, we created a space just below the sternocleidomastoid muscle to bypass the RA. We flushed the RA with albumin to stiffen the artery and temporarily clamped the bilateral sides of the RA to prevent twisting. We anastomosed the V3 and RA with a 9-0 thread and temporarily clamped the V3. After flushing the RA with albumin to prevent twisting, we clamped the external and internal carotid arteries, opened the dCCA with a vascular punch to prevent arterial dissection, and anastomosed the RA to the dCCA. The patency of the bypass was confirmed with Doppler and indocyanine green video angiography. The postoperative course was uneventful, bypass patency was good, and the aneurysm did not expand further. CONCLUSION: V3-RA-dCCA bypass may be an effective and low-risk treatment for large basilar trunk aneurysms with bilateral occlusion of the proximal common carotid artery.

Trends in surgical procedures for spontaneous intracerebral hemorrhage in Japan.

OBJECTIVES: Minimally invasive surgery for spontaneous intracerebral hemorrhage (ICH) has become increasingly popular in recent years. However, there are no reports on the recent trends in surgical procedures for spontaneous ICH. To investigate current trends in surgical methods for spontaneous ICH using a nationwide inpatient database from Japan. MATERIALS AND METHODS: Patients who underwent surgery for spontaneous ICH between April 2014 and March 2018 were identified in a nationwide inpatient database from Japan. We examined patient characteristics, diagnoses, types of surgery, complications, and discharge status. RESULTS: We identified 21,129 inpatients who underwent surgery for spontaneous ICH. The procedures were as follows: 16,256 (76.9%) transcranial hemorrhage evacuations, 3722 (17.6%) endoscopic hemorrhage evacuations, and 1151 (5.4%) stereotactic aspirations of hemorrhage. Patients tended to receive transcranial hemorrhage evacuations in hospitals with fewer surgical cases. The proportions of endoscopic hemorrhage evacuations increased annually, whereas those of stereotactic surgery decreased. The proportions of transcranial surgery remained almost unchanged. Tracheostomy and hospitalization costs were lower in the stereotactic aspirations of hemorrhage group, and the proportions of reoperation were higher in the endoscopic hemorrhage evacuations group. CONCLUSIONS: The use of endoscopic surgery for spontaneous ICH has increased in Japan. This study can form the basis of future clinical investigations into spontaneous ICH surgery.

[History of Skull Base Surgery].

Skull base surgery is a surgical field that involves the cooperation of multiple surgical and medical specialties, including neurosurgery, head-neck surgery, plastic-reconstructive surgery, radiation oncology, as well as multiple medical supporting teams. This field has been developed with the collaborative efforts of these medical specialties, and its history can be divided into five phases: Beginning of surgery(Prior to 1940); Early skull base surgery driven by the ENT-HN surgery group(1940-70); Conventional skull base surgery development based on anatomical, physiological knowledge and microsurgical equipment and technique(1970-90); Reflection and consolidation of the surgical dimension(1995-2005); and Evolution of endoscopic and new skull base surgical techniques(2005-). Several topics and advancements have improved this surgical field, such as access to the cavernous sinus, petrosal-temporal bone, and foramen magnum; concepts of minimally invasive surgical techniques; advanced endoscopic instruments; knowledge of biological assessments; and development of surgical robotics. To achieve a safe and effective surgery for cases of difficult cranial base lesions, clinicians must understand the origin of the surgical field, the detailed anatomy and physiology of the skull base, and the basic microsurgical techniques.

Differences Between Subarachnoid Hemorrhage Seen in Daily Practice and Aneurysms That Rupture During Follow-Up.

[Figure: see text].

Rapidly progressive brain atrophy in septic ICU patients: a retrospective descriptive study using semiautomatic CT volumetry.

BACKGROUND: Sepsis is often associated with multiple organ failure; however, changes in brain volume with sepsis are not well understood. We assessed brain atrophy in the acute phase of sepsis using brain computed tomography (CT) scans, and their findings' relationship to risk factors and outcomes. METHODS: Patients with sepsis admitted to an intensive care unit (ICU) and who underwent at least two head CT scans during hospitalization were included (n = 48). The first brain CT scan was routinely performed on admission, and the second and further brain CT scans were obtained whenever prolonged disturbance of consciousness or abnormal neurological findings were observed. Brain volume was estimated using an automatic segmentation method and any changes in brain volume between the two scans were recorded. Patients with a brain volume change < 0% from the first CT scan to the second CT scan were defined as the "brain atrophy group (n = 42)", and those with ≥ 0% were defined as the "no brain atrophy group (n = 6)." Use and duration of mechanical ventilation, length of ICU stay, length of hospital stay, and mortality were compared between the groups. RESULTS: Analysis of all 42 cases in the brain atrophy group showed a significant decrease in brain volume (first CT scan: 1.041 ± 0.123 L vs. second CT scan: 1.002 ± 0.121 L, t (41) = 9.436, p < 0.001). The mean percentage change in brain volume between CT scans in the brain atrophy group was -3.7% over a median of 31 days, which is equivalent to a brain volume of 38.5 cm3. The proportion of cases on mechanical ventilation (95.2% vs. 66.7%; p = 0.02) and median time on mechanical ventilation (28 [IQR 15-57] days vs. 15 [IQR 0-25] days, p = 0.04) were significantly higher in the brain atrophy group than in the no brain atrophy group. CONCLUSIONS: Many ICU patients with severe sepsis who developed prolonged mental status changes and neurological sequelae showed signs of brain atrophy. Patients with rapidly progressive brain atrophy were more likely to have required mechanical ventilation.

A survey of surgically resected pituitary incidentalomas and a comparison of the clinical features and surgical outcomes of non-functioning pituitary adenomas discovered incidentally versus symptomatically.

Pituitary tumors are discovered either incidentally by imaging studies (incidentalomas) or via evaluation of certain clinical symptoms (symptomatic tumors). In this study, we first surveyed patients with incidentalomas who underwent surgery. Cases included 62.3% non-functioning adenomas (NFPAs), 14.5% functioning adenomas, and 13.8% Rathke's cleft cysts. Next, we compared the clinical features and surgical outcomes of 145 patients whose preoperative diagnosis was NFPA (incidentalomas [n = 79] vs. symptomatic tumors [n = 66]). The patients with incidentalomas were older (59.9 vs. 55.3 years, p < 0.05) and had smaller tumors compared with the patients with symptomatic tumors (mean maximum diameter: 23.1 vs. 27.5 mm, p < 0.01). The main reason for undergoing imaging studies was headache (n = 25) in the incidentaloma group and visual disturbance (n = 46) in the symptomatic tumor group. The incidence of preoperative pituitary hormone deficiencies was lower in the incidentaloma than symptomatic tumor group (growth hormone deficiency: 37.7% vs. 66.7%, p < 0.01; gonadotropin deficiency: 19.0% vs. 39.4%, p < 0.01; adrenocorticotropic hormone deficiency: 3.8% vs. 18.2%, p < 0.01; thyroid stimulating hormone deficiency: 6.3% vs. 12.1%, p = 0.25). Postoperative pituitary function was better preserved in the incidentaloma than symptomatic tumor group (no deficiency: 58.2% vs. 28.8%, p < 0.01). The difference in postoperative complications between groups was not statistically significant (incidentalomas vs. symptomatic tumors: 21.5% vs. 19.7%, p = 0.84). In conclusion, incidentalomas were detected while smaller size and lower incidence of hormone deficiency than symptomatic tumors, and the pituitary hormones were also preserved after surgery. It is important to observe incidentalomas carefully and to judge whether to operate appropriately before they become symptomatic tumors.

Role of RNF213 polymorphism in defining quasi-moyamoya disease and definitive moyamoya disease.

OBJECTIVE: Quasi-moyamoya disease (QMMD) is moyamoya disease (MMD) associated with additional underlying diseases. Although the ring finger protein 213 (RNF213) c.14576G>A mutation is highly correlated with MMD in the Asian population, its relationship to QMMD is unclear. Therefore, in this study the authors sought to investigate the RNF213 c.14576G>A mutation in the genetic diagnosis and classification of QMMD. METHODS: This case-control study was conducted among four core hospitals. A screening system for the RNF213 c.14576G>A mutation based on high-resolution melting curve analysis was designed. The prevalence of RNF213 c.14576G>A was investigated in 76 patients with MMD and 10 patients with QMMD. RESULTS: There were no significant differences in age, sex, family history, and mode of onset between the two groups. Underlying diseases presenting in patients with QMMD were hyperthyroidism (n = 6), neurofibromatosis type 1 (n = 2), Sjögren's syndrome (n = 1), and meningitis (n =1). The RNF213 c.14576G>A mutation was found in 64 patients (84.2%) with MMD and 8 patients (80%) with QMMD; no significant difference in mutation frequency was observed between cohorts. CONCLUSIONS: There are two forms of QMMD, one in which the vascular abnormality is associated with an underlying disease, and the other in which MMD is coincidentally complicated by an unrelated underlying disease. It has been suggested that the presence or absence of the RNF213 c.14576G>A mutation may be useful in distinguishing between these disease types.