[Image Diagnosis of Trigeminal Neuralgia].

Classic trigeminal neuralgia is mainly caused by arterial compression; most cases involve the superior cerebellar artery, followed by the anterior cerebellar, basilar, and vertebral arteries. The detection of neurovascular conflicts in trigeminal neuralgia requires special magnetic resonance imaging(MRI)modalities, including high-resolution three-dimensional(3D)-T2 sequence, 3D-time of flight angiography, 3D-T1 sequencing with gadolinium injection, and merged images of these sequences. The conflicting sites are not necessarily restricted to the root entry zone of the trigeminal nerve root and can be located more distally, proximal to the Meckel's cavum. Arterial compression and its severity, including displacement, angulation, distortion, and atrophy of the trigeminal root, are good predictors of the long-term efficacy of decompression surgery. Veins, primarily the transverse pontine vein, comprise 10%-20% of all causative vessels in trigeminal neuralgia. Gadolinium-enhanced 3D-T1 MRI and high-resolution 3D-T2 MRI merged with computed tomographic angiography are useful for detecting venous compression.

Optic tract edema in craniopharyngioma as a predictor of BRAFV600E mutation presence.

OBJECTIVE: the advent of BRAF inhibitors for preoperative treatment of craniopharyngioma has necessitated the identification of BRAFV600E status. Hence, we investigated predictors of BRAFV600E mutation in craniopharyngiomas. METHODS: this retrospective study utilized data from 30 patients who were newly diagnosed with craniopharyngioma between 2011 and 2021. Magnetic resonance imaging (MRI) and computed tomography were performed within 1 week prior to surgery. Genetic analysis for BRAF mutation was performed using the Oncomine next-generation sequencing panel or Sanger sequencing. The relationship between BRAF mutation and demographic data, endocrinological function and tumour characteristics on imaging was assessed. RESULTS: tumour tissue carried the BRAFV600E mutation in nine patients. There was no significant difference in age, sex, or presence of hormonal dysfunction amongst patients with and without the BRAFV600E mutation in the tumour. Most tumours with the BRAFV600E mutation were histologically categorized as papillary craniopharyngioma (P = 0.0005), and were solid (P = 0.0002) and supra-diaphragmatic (P = 0.0033) on MRI. BRAFV600E tumours were more frequently associated with optic tract edema than wild-type tumour s (55.6 vs. 0%, P = 0.0009) and all tumour s with optic tract edema carried the BRAFV600E mutation. Optic tract edema was not associated with tumour volume, cysts, or preoperative pituitary function. CONCLUSIONS: in craniopharyngiomas, the presence of optic tract edema can predict the presence of BRAFV600E mutation with a positive predictive value of 100%. The finding should be verified in larger prospective cohorts and multivariate regression analysis.

Delayed postoperative hyponatremia in patients with acromegaly: incidence and predictive factors.

PURPOSE: Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS. METHODS: Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134 mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups. RESULTS: DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the two groups. CONCLUSION: The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.

Predictive factors of postoperative diabetes insipidus in 333 patients undergoing transsphenoidal surgery for non-functioning pituitary adenoma.

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.

Influence of growth hormone therapy on germinoma survivors.

PURPOSE: Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. METHODS: This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. RESULTS: In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. CONCLUSIONS: GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.

Dural sac shrinkage signs on magnetic resonance imaging at the thoracic level in spontaneous intracranial hypotension-its clinical significance.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. METHODS: Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. RESULTS: The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913-0.931). CONCLUSIONS: Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.

1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis.

Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson's disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD.

Preoperative sensory aura predicts risk for seizure in temporal lobe epilepsy surgery.

BACKGROUND: Patients with temporal lobe epilepsy (TLE) often report viscerosensory and experiential auras, with substantial epilepsy localization. However, few previous studies have investigated the epileptic preoperative aura, particularly with regard to its effect on surgical outcomes in patients with drug-resistant epilepsy. OBJECTIVE: This study investigated the potential role of preoperative aura in predicting outcomes after surgery for TLE. MATERIAL AND METHODS: This study included consecutive patients diagnosed with TLE who underwent anterior temporal lobectomy (ATL) for drug-resistant TLE during the period from January 1999 to December 2017. Data pertaining to patient age at the time of surgery, sex, age at initial seizure onset, duration of epilepsy, presence of preoperative aura, comprehensive clinical semiology, side of surgery, and type of pathology were analyzed. Preoperative auras were classified as autonomic, sensory, mental and affective, or multiple manifestations. Patients were followed at 3 and 12 months after surgery and at regular intervals thereafter. RESULTS AND CONCLUSIONS: A total of 498 patients were included in the study. Positive preoperative aura was observed in 386 patients (77.51%). The correlation of each variable with seizure outcomes was analyzed, and the only variable found to correlate with seizure outcome was the presence of preoperative aura. Compared with those with negative preoperative aura, those with positive preoperative aura were 1.74-fold more likely to be seizure-free after surgery for TLE. The analysis of patient data suggested a later onset of initial seizure in those with positive preoperative aura, compared with those without (p = 0.04, 95% confidence interval (CI): 0.55-3.24). Patients with a shorter duration of disease prior to TLE surgery were more likely to achieve seizure-free status postoperatively. Preoperative sensory aura was a good predictor that a patient would be seizure-free during follow-up (p = 0.022).

High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: FLNC is a potential therapeutic target and biomarker for GBM progression.

Is additional mesial temporal resection necessary for intractable epilepsy with cavernous malformations in the temporal neocortex?

PURPOSE: Cavernous malformation (CM) in the temporal neocortex causes intractable epilepsy. Whether to resect additional mesial temporal structures in addition to the lesionectomy is a still controversial issue. To clarify the need for the procedure, we retrospectively analyzed pre- and postoperative clinical data of patients with surgically removed CM. SUBJECTS AND METHODS: We included data from 18 patients with CM in the temporal neocortex who presented with intractable epilepsy. Eleven patients of our early series were treated with extended resection, i.e., lesionectomy and the resection of additional mesial temporal structures. Seven patients underwent lesionectomy, i.e., removal of the CM and of hemosiderin-stained surrounding brain tissue. Pathological assessments of the resected hippocampus were performed. Chronic intracranial electroencephalography (EEG) recordings were obtained in 6 patients. We performed perioperative neuropsychological assessments in all patients. RESULTS: The seizure outcome was recorded as Engel class I in 17 patients (94.4%); Ia = 12 (66.7%) Ib = 2 (11.1%), Ic = 1 (5.6%), Id = 2 (11.1%), and class IIb in one patient (5.6%). Adding resection of the mesial temporal structures to lesionectomy did not alter the seizure outcome. Pathology of hippocampus revealed limited neuronal loss in CA4. Ictal onsets in the ipsilateral lateral cortex were detected in all 6 patients who underwent intracranial EEG. In 4 patients each, we also detected ictal onsets from the ipsilateral mesial temporal structures and from the contralateral temporal lobe. Postoperatively, in the patients where their CM was located in the language-dominant hemisphere (n = 10), the full-scale intelligence quotient (IQ) and the performance IQ increased (p < 0.05), whereas the verbal memory (WMS-R) deteriorated in two of 5 patients. CONCLUSION: Excellent seizure outcomes were obtained even the lesionectomy alone. To confirm appropriate surgical strategy for lateral temporal CM with intractable epilepsy, further studies in large sample size are needed.

Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis.

Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is characterized by rapid proliferation, aggressive migration, and invasion into normal brain tissue. Formin proteins have been implicated in these processes. However, the role of formin-like 1 (FMNL1) in cancer remains unclear. We studied FMNL1 expression in glioblastoma samples using immunohistochemistry. We sought to analyze the correlation between FMNL1 expression, clinicopathologic variables, and patient survival. Migration and invasion assays were used to verify the effect of FMNL1 on glioblastoma cell lines. Microarray data were downloaded from The Cancer Genome Atlas and analyzed using gene set enrichment analysis (GSEA). FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (p < 0.001). FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in the neural-to-mesenchymal transition. Conversely, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fiber assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.

Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma.

Multicentric gliomas are very rare. Due to differences in their tumor types they remain enigmatic. We focused on the pathogenesis of multicentric gliomas and compared their immunoprofile with that of solitary gliomas. This retrospective study included 6 males and 8 females with multicentric glioma (8 glioblastomas, 2 anaplastic astrocytomas, 4 diffuse astrocytomas). Their age ranged from 27 to 75 years and all were treated between 2004 and June 2015. The expression of mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, phosphatase and tensin homolog (PTEN), and epidermal growth factor receptor (EGFR) was examined immunohistochemically; for 1p19q analysis we used fluorescence in situ hybridization (FISH). In all patients, immunohistochemical staining was negative for mutant IDH1 and cytoplasmic PTEN; only 1 patient (7.1%) manifested nuclear PTEN positivity. FISH for 1p19q codeletion was negative in all 9 examined samples; 5 of 14 specimens (35.7%) were p53-positive, 9 (64.3%) were EGFR-positive, and 4 (28.6%) were ATRX-negative. The MIB-1 labeling index was 0.9-15.6% for grades II and III, and ranged between 17.3 and 52.4% for glioblastoma. Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. More studies are needed to confirm the molecular mechanisms underlying the pathogenesis of multicentric glioma.

Changes in quality of life in patients with acromegaly after surgical remission - A prospective study using SF-36 questionnaire.

Patients with acromegaly have a compromised quality of life (QOL). Modern surgical techniques have improved the surgical cure rate. However, there are no prospective studies reporting postoperative changes in QOL among patients cured solely by surgery. The aim of the present study was to determine the effect of surgery on QOL using the 36-item short form health survey (SF-36) questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS). Included in this prospective cohort were 41 patients with acromegaly who underwent surgery alone and achieved postoperative normalization of insulin-like growth factor-1. All participants completed the SF-36 preoperatively and 1 year postoperatively. Preoperatively, RCS and 4 subscale scores (role physical, social functioning, role emotional, mental health) were below the set standards for the normal population. Postoperatively, the PCS and RCS scores did not change significantly, but the MCS score improved significantly (from 48.1 ± 11.3 to 51.7 ± 8.9, p=0.03). Further we compared the QOL of 26 patients whose nadir GH level was < 0.4 µg/L during postoperative oral glucose tolerance testing (complete remission group) with that of 15 patients whose nadir GH level was ≥ 0.4 µg/L (partial remission group). There were no significant differences between these groups in terms of PCS, MCS, RCS, or any subscale scores. In conclusion, surgical remission mostly improved the participants' mental condition. There was no difference in QOL between patients who achieved the new remission criteria and those who did not.

Calcifying pseudoneoplasm of the neuraxis in direct continuity with a low-grade glioma: A case report and review of the literature.

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are presumed to be a non-neoplastic reactive pathology, based on the frequent finding of granulomatous inflammation. To our knowledge, there are few reports of CAPNON in association with a neoplasm. Here, we report the case of a 62-year-old man presenting with headache, which was caused by CAPNON in the left cingulate gyrus. CT scan revealed a calcified mass exhibiting gradual growth and increasing peritumoral edema. MRI showed an intra-axial hypointense mass on T1- and T2-weighted images. Development of a peri-lesional hyperintense lesion on T2-weighted images suggested local edema or tumoral invasion. Gadolinium-enhanced T1-weighted images revealed mild peripheral enhancement of the calcified nodule. L-methyl-11 C methionine-positron emission tomography revealed the uptake of tracer in the calcified nodule. The calcified mass and its enveloping brain tissue were removed using a parietal craniotomy. The calcified tissue was surrounded by spindle-shaped cells positive for GFAP and nestin. The MIB-1 labeling index of spindle cells was around 10% (i.e. a hot spot). Fourteen months after surgery, gadolinium-enhanced MRI evidenced growth of a tiny residual lesion. Therefore, this report illustrates a potential case of CAPNON arising from low-grade glial neoplasm.

Long-term outcome after endovascular treatment of cavernous sinus dural arteriovenous fistula and a literature review.

BACKGROUND: The long-term efficacy of endovascular treatment (EVT) for cavernous sinus dural arteriovenous fistulae (CS-dAVF) was assessed with a special focus on residual shunts after initial EVT. PATIENTS AND METHODS: This retrospective survey included 50 patients who had undergone EVT and were followed for 1 month or longer (median follow-up 56 months). RESULTS: Common preoperative symptoms were chemosis (78%), extra-ocular motor palsy (72%), exophthalmos (66%), and tinnitus (26%). CS-dAVF were addressed by transvenous embolization (tVE, n = 48), tVE only was used in 43 instances and tVE plus transarterial embolization (tAE) in five. Two patients underwent tAE only. Procedure-related morbidity (brainstem infarction) was recorded in one patient (2%) and transient symptom exacerbation (paradoxical worsening) in 12 patients (24%). Postoperative digital subtraction angiography showed no major retrograde shunt or cortical venous reflux in any of the 50 patients. Anterograde or minor retrograde residual shunt was observed in 17 patients (34%); three of these underwent additional tVE and four had Gamma Knife surgery. The shunt flow disappeared in all 17 patients 12.6 ± 13.4 (mean ± SD) months after initial EVT. At the latest follow-up, 65.7 ± 52.6 months after the initial operation, no shunt flow was observed in any of the 50 patients. None had remaining or newly developed chemosis or tinnitus on follow-up. The rate of persistent cavernous sinus symptoms at the latest follow-up was higher in patients with than without post-procedural paradoxical worsening (5/12, 41.7% vs. 2/38, 5.3%, p = 0.0059 by Fisher's exact test). CONCLUSIONS: Long-term follow-up showed that EVT, especially tVE, is an efficient and safe treatment for CS-dAVF. It resulted in the eventual disappearance of shunt flow. Residual shunt without major retrograde flow or cortical venous reflux can be monitored without additional treatment.

Expression of the JAK/STAT signaling pathway in the ligamentum flavum of patients with lumbar spinal canal stenosis.

BACKGROUND: Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF. METHODS: The LF of 10 LSS patients was analyzed and the expression of JAK1, STAT3, phosphorylated (p)-STAT3, and actin was examined by Western blot analysis. The expression of p-STAT3 was also examined by immunostaining and its positive cell ratio was compared between LSS and non-LSS samples. We measured the thickness of the LF on magnetic resonance images and studied the relationship between its thickness and the expression of p-STAT3. RESULTS: JAK1, STAT3, and p-STAT3 were detected in almost all samples by Western blot analysis. Immunoreactivity against p-STAT3 was observed mainly in endothelial- and fibroblast-like cells. The expression of p-STAT3 was significantly higher in LSS than non-LSS samples; it was significantly stronger on the dorsal than the dural side of the LF and positively correlated with the thickness of the LF on the dorsal side. CONCLUSIONS: The JAK/STAT signaling pathway is positively correlated with the thickness of the LF. Our findings suggest that JAK1 and STAT3 molecules are involved in and regulate LF hypertrophy.

Investigation of the clinical significance of the growth hormone-releasing peptide-2 test for the diagnosis of secondary adrenal failure.

The aim of this study was to evaluate the ability of the growth hormone-releasing peptide-2 (GHRP-2) test to clinically diagnose hypothalamo-pituitary-adrenal (HPA) axis failure. We performed an insulin tolerance test (ITT), CRH stimulation test, and GHRP-2 test on 47 patients suspected of having a hypothalamo-pituitary disorder. Patients with pituitary disorders had significantly lower ACTH responses to the GHRP-2 test compared to patients with hypothalamic disorders and the control group. In contrast, peak cortisol levels in response to the GHRP-2 test were significantly lower in both hypothalamic and pituitary disorder cases compared with the control group. Assignment of a cut-off value of 11.6 µg/dL for the peak serum cortisol level demonstrated that the GHRP-2 test was able to predict secondary hypoadrenalism with 88.9% specificity and 89.7% sensitivity. The responses of ACTH and cortisol to the GHRP-2 test had no correlation to the CRH test, suggesting the involvement of a different mechanism of ACTH secretion. These results indicate that the GHRP-2 test may induce ACTH secretion from the pituitary gland through direct stimulation. Although the GHRP-2 test does not have the same predictive value as the insulin tolerance test (ITT), it has similar diagnostic potential as the CRH stimulation test for evaluating HPA axis failure.

Diffusion-weighted imaging and the apparent diffusion coefficient on 3T MR imaging in the differentiation of craniopharyngiomas and germ cell tumors.

The apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) plays an important role in diagnosing intracranial tumors and predicting the histopathological grade of the tumor. However, the differences in the ADC values between craniopharyngiomas and germ cell tumors (GCTs) have not been clarified. We therefore evaluated the DWI and ADC values at b = 1000 and b = 4000 s/mm(2) on 3T magnetic resonance (MR) imaging and assessed the possibility of differentiating between craniopharyngiomas and GCTs. We retrospectively reviewed 19 patients with craniopharyngioma and 24 patients with GCT who underwent surgery and received a histopathological diagnosis. Thirty-four patients underwent DWI with b = 1000 and b = 4000 s/mm(2) and nine patients underwent periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DWI with b = 1000 s/mm(2). The ADC was determined by manually placing regions of interests (ROIs) in the respective tumor regions on the ADC maps and is expressed as the minimum (ADC(MIN)), mean (ADC(MEAN)), and maximum (ADC(MAX)) absolute values. The craniopharyngiomas showed lower intensity on DWI at b = 1000 and b = 4000 s/mm(2) than the GCTs. Furthermore, the craniopharyngiomas demonstrated significantly high ADC values (ADC(MIN), ADC(MEAN), and ADC(MAX)) in comparison with the GCTs on DWI at b = 1000 and b = 4000 s/mm(2). The logistic discriminant analysis clarified the advantage of ADC(MIN) at b = 4000 s/mm(2) in differentiating between craniopharyngiomas and GCTs compared with the other ADC values. DWI and the ADC values may help clinicians to differentiate between craniopharyngiomas and GCTs. The ADC(MIN) at b = 4000 s/mm(2) is particularly useful for differentiation.

Clinical features and natural course of acromegaly in patients with discordance in the nadir GH level on the oral glucose test and the IGF-1 value at 3 months after adenomectomy.

Discordant GH and IGF-1 levels after adenomectomy are well recognized in acromegalics. The aim of this study was to evaluate the clinical features and natural course of postoperative acromegaly associated with discordant GH and IGF-1 levels over a postoperative period. A total of 69 acromegalics underwent surgery with at least 1 year of follow-up and received 75-g oral glucose tolerance tests (OGTTs) at 3 months postoperatively. The patients were categorized into four groups according to the postoperative nadir GH levels and IGF-1 levels: controlled group (normal GH and normal IGF-1), high-IGF-1 group (normal GH and high IGF-1), high-GH group (high GH and normal IGF-1), and uncontrolled group (high GH and high IGF-1). The incidence of discordant GH and IGF-1 levels was 27.5%: high-IGF-1 group = 10.1% (n = 7) and high-GH group = 17.4% (n = 12). All patients in the high-IGF-1 group exhibited a decline in the IGF-1 level after surgery, with normalization observed in 71.4% of the patients without additional treatment (median 23 months). These subjects had preoperatively high IGF-1 levels despite not demonstrating higher GH levels than the patients in the controlled group. On the other hand, four patients in the high-GH group exhibited an elevated nadir GH level higher than 1.0 µg/L on repeated OGTTs after 3 months, and one patient experienced a recurrence of acromegaly. Patients in the high-IGF-1 group require no additional treatments, and their IGF-1 levels are likely to normalize within a few years. However, patients in the high-GH group should be carefully followed due to the possibility of recurrence.

Combined surgical intervention with vagus nerve stimulation following corpus callosotomy in patients with Lennox-Gastaut syndrome.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a drug-resistant pediatric epilepsy characterized by multiple seizure types, including drop attacks (DAs). Palliative procedures such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) may be effective for adequate seizure control in LGS patients who are not candidates for resective surgery. We evaluated the efficacy of the combination of these two procedures for LGS-related seizures. METHOD: Ten patients with LGS (age 3-30 years at VNS implantation) underwent CC and subsequent VNS. We evaluated surgical outcomes, particularly with respect to the efficacy of VNS on seizure reduction rates for different residual seizure types after CC. We compared clinical parameters, including sex, age, seizure duration, history, MRI findings, extent of CC, number of antiepileptic drugs, and neuropsychological states, between VNS responders and non-responders to predict satisfactory seizure outcomes with respect to residual seizures after CC. FINDINGS: VNS was effective for residual seizures regardless of seizure type (except for DAs) after CC in patients with LGS. Six of ten (60%) patients had a satisfactory seizure outcome (≥50% seizure reduction) for all residual seizure types after VNS. Two of ten (20%) patients were seizure-free at 12 months post-VNS. Even those patients that were non-responders, with respect to all seizures including DAs, after prior CC showed favorable responses to subsequent VNS. Compared to VNS, excellent seizure outcomes for DAs were achieved after CC in seven of nine (77.8%) patients with DAs. Among the clinical parameters, only conversation ability before VNS was significantly different between responders and non-responders (p = 0.033). CONCLUSION: Combined VNS and prior CC produced satisfactory seizure outcomes in LGS patients with different seizure types, including DAs. Even non-responders to prior CC responded to subsequent VNS for residual seizures, except for DAs. There is a greater likelihood that these procedures may be more feasible in patients who possess conversation ability prior to VNS.