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.

Indocyanine green endoscopic evaluation of pituitary stalk and gland blood flow in craniopharyngiomas.

To assess the use of indocyanine green (ICG) fluorescence endoscopy to evaluate pituitary blood flow in craniopharyngioma resection and its possible impact on intraoperative decisions regarding pituitary stalk processing. Patients with craniopharyngiomas who had undergone transsphenoidal surgery since March 2021, when an ICG endoscope was introduced at the Kagoshima University Hospital, were included in the study. When targeted tumor removal was approaching completion, 10 mg of ICG was administered intravenously to evaluate blood flow in the pituitary stalk and gland. ICG signals and endocrinological status before and after surgery were evaluated retrospectively. Pituitary stalk and gland blood flow were evaluated as positive (++), weakly positive (+), and no signal (-).Ten patients with craniopharyngiomas underwent transsphenoidal surgery using an ICG endoscope (mean age 56.6 ± 14.2 years; 40% male). Among the eight patients in whom the pituitary stalk was preserved, pituitary function with positive signal on the stalk was intact in two. Two other patients with weakly positive stalk and positive pituitary gland signals showed intact function or minimal pituitary dysfunction. Four patients had impairments in more than three axes with poor ICG signals in the stalk or pituitary gland. Two patients underwent pituitary amputation because of high tumor invasion and lack of ICG signal in the stalk after tumor removal, resulting in panhypopituitarism. A negative ICG signal in the pituitary stalk is likely to indicate postoperative pituitary function loss. Craniopharyngioma surgery using ICG endoscopy may be useful for predicting endocrine prognosis and improving tumor outcomes.

A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas.

Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma-tailored 48-gene next-generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma-tailored 48-gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH-wildtype glioblastomas. Within these IDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp-wildtype glioblastomas (43%) than in TERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma-tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH- and TERTp-wildtype glioblastomas with frequent PDGFRA alterations.

[Bilateral Pallidotomy for Tardive Dystonia:A Case Report].

Tardive dystonia is a movement disorder related to the use of dopamine-receptor-blocking drugs. Several reports have shown that deep brain stimulation of the globus pallidus internus(GPi-DBS)is effective in treating tardive dystonia. However, a few reports demonstrated the efficacy of ablation of the GPi(pallidotomy). We herein report a case of tardive dystonia successfully treated with bilateral pallidotomy. A 32-year-old man developed severe tardive dystonia 10 years after the chronic use of antipsychotic drugs. Withdrawal of the drugs and botulinum toxin injections were ineffective. The patient underwent bilateral pallidotomy for tardive dystonia because of rejection of the implanted DBS devices. Significant improvement was observed, with a 95% decrease in the Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS)movement score, and no severe adverse events occurred. Symptomatic relief persisted for nine months. Pallidotomy is a feasible and efficacious procedure for tardive dystonia treatment without the use of hardware implantations.

Rapid malignant transformation of low-grade astrocytoma in a pregnant woman.

We report rapid malignant transformation of diffuse astrocytoma to glioblastoma during pregnancy in a young woman. A 21-year-old woman was found to have a non-enhancing right frontal lesion, supposed to be a low-grade astrocytoma according to magnetic resonance imaging (MRI) studied for chronic headache. Due to the absence of clinical symptoms, the patient refused further investigations and delivered a baby and then became pregnant with a second baby. At first, she refused the biopsy because she was afraid, although the size of the lesion on MRI was increasing; however, due to repeated persuasion, she underwent a biopsy during the 4th month of her second gestation, with a result of diffuse astrocytoma (WHO grade II). At 1 month after the second delivery and 6 months after the biopsy, MRI revealed further enlargement of the tumor and a heterogeneous kenhancement effect. A gross tumor removal was carried out, and the tumor was histologically diagnosed as glioblastoma (WHO grade IV). This is the quickest ever malignant transformation of diffuse astrocytoma during pregnancy in the published reports.

Secondary hypophysitis associated with Rathke's cleft cyst resembling a pituitary abscess.

Background: Although rare, cases of hypophysitis resembling a pituitary abscess (PA) have been reported. Differential diagnosis between hypophysitis and PA is crucial as the two diseases require different treatments. Case Description: A 38-year-old woman with headaches underwent head magnetic resonance imaging (MRI), which revealed an 11-mm mass lesion in the sella turcica. Due to breastfeeding, contrast-enhanced MRI was avoided. Pituitary adenomas and Rathke's cleft cyst (RCC) were suspected, and she was initially treated conservatively. Five months later, she acquired syndrome coronavirus two infections, and while the fever subsided with acetaminophen, the headache persisted. One month later, the headache worsened, followed by fever and diabetes insipidus. MRI revealed a pituitary cystic mass with ring-shaped contrast enhancement on T1-weighted MRI and increased signal intensity on diffusion-weighted imaging (DWI). PA was suspected, and emergency endoscopic transsphenoidal surgery was performed. The microbiological examination of the yellowish-brown content drained from the cystic mass was negative. Microscopically, the cystic lesion was covered with ciliated columnar epithelium and stratified squamous epithelium, with a dense inflammatory cell infiltrate consisting mainly of lymphocytes and plasma cells observed around the cyst. This supported the diagnosis of secondary hypophysitis associated with RCC without PA. Conclusion: We report a case of hypophysitis secondary to RCC resembling PA with ring-shaped contrast enhancement on MRI and increased signal intensity on DWI. This case emphasizes the need for cautious diagnosis of secondary hypophysitis due to RCC in individuals with MRIs and clinical manifestations resembling an abscess.

Gamma Knife Thalamotomy for Essential Tremor: A Retrospective Analysis.

BACKGROUND: Gamma knife (GK) thalamotomy has been used as a treatment option for essential tremor (ET). Numerous studies on GK use in ET treatment have reported more varied responses and complication rates. METHODS: Data from 27 patients with ET who underwent GK thalamotomy were retrospectively analyzed. The Fahn-Tolosa-Marin Clinical Rating Scale for Tremor, handwriting, and spiral drawing were evaluated. Postoperative adverse events and magnetic resonance imaging findings were also evaluated. RESULTS: The mean age at GK thalamotomy was 78.1 ± 4.2 years. The mean follow-up period was 32.5 ± 19.4 months. The preoperative postural tremor, handwriting, and spiral drawing scores were 3.4 ± 0.6, 3.3 ± 1.0, and 3.2 ± 0.8, respectively, all of which showed significant improvements to 1.5 ± 1.2 (55.9% improvement, P < 0.001), 1.4 ± 1.1 (57.6% improvement, P < 0.001), and 1.6 ± 1.3 (50% improvement, P < 0.001), respectively, at the available final follow-up evaluations. Three patients presented with no improvement in tremor. Six patients presented with adverse effects, including complete hemiparesis, foot weakness, dysarthria, dysphagia, lip numbness, and finger numbness, at the final follow-up period. Two patients presented with serious complications, including complete hemiparesis due to massive widespread edema and chronic encapsulated expanding hematoma. One patient died of aspiration pneumonia following severe dysphagia secondary to chronic encapsulated expanding hematoma. CONCLUSIONS: GK thalamotomy is an efficient procedure for treating ET. Careful treatment planning is necessary to reduce complication rates. The prediction of radiation complications will increase the safety and effectiveness of GK treatment.

Surgical aspects in craniopharyngioma treatment.

OBJECTIVES: Total surgical resection is the gold standard in the treatment of craniopharyngioma. However, there is concern that aggressive surgical resection might result in high rates of endocrinologic, metabolic, and behavioral morbidities. Subtotal resection (SR) with subsequent radiation therapy (RT) may reduce surgical complications, but it may also increase the risk of tumor recurrence and radiation-induced side effects. Therefore, the optimal surgical strategy remains debatable. METHODS: To determine the optimal surgical strategy, we assessed the clinical courses of 39 patients (19 male patients and 20 female patients) with newly diagnosed craniopharyngioma who were treated at our institute. The median age at diagnosis was 34 years (range: 0-76 years). The median follow-up period was 8.5 years (range: 3-160 months). Our treatment strategy comprised gross total resection (GTR) for craniopharyngioma in patients that were not at surgical risk. Conversely, after adequate tumor decompression, we used RT, mainly Gamma Knife radiosurgery, in patients at risk. We divided the patients into the following three groups depending on the treatment course: GTR, SR with RT, and SR with staged surgery. We compared tumor characteristics, as well as patients' conditions at the preoperative stage and last follow-up, among the three groups. RESULTS: There were 8, 21, and 10 patients in the GTR, SR with RT, and SR with staged surgery groups, respectively. There were no differences in the maximum tumor diameter, tumor volume, composition, and presence of calcification among the groups. Among the 39 patients, 24 underwent transcranial microsurgery and 15 underwent trans-sphenoidal surgery as the initial treatment. No cases involving surgical mortality, cerebrospinal fluid leakage, severely deteriorated visual function, or severe hypothalamic damage were observed. No tumor recurrence was noted in the GTR group. One patient required additional RT, and one patient underwent second surgery for tumor recurrence in the SR with RT group. In the SR with staged surgery group, 8 of the 10 patients eventually underwent RT, but tumor control was achieved in all patients at the latest follow-up. In this group, the third trans-sphenoidal surgery caused a severe vascular injury in one patient. At the final follow-up, 33 (85%) patients were undergoing anterior pituitary hormone replacement, and the rate of diabetes insipidus was 51%. There was no significant difference in the pituitary dysfunction rate among the groups. CONCLUSIONS: We observed a low rate of surgical complications and a sufficient tumor control rate in response to our treatment strategy. Despite attempting preservation of the pituitary stalk, we found it difficult to rescue anterior pituitary function.

Navigation-Guided Measurement of the Inferior Limit Through the Endonasal Route to the Craniovertebral Junction.

BACKGROUND: The endoscopic endonasal approach (EEA) has been accepted as an alternative option for diseases at the craniovertebral junction. However, the inferior destination through the endoscopic endonasal approach is anatomically higher than that of the transoral approach. Therefore, preoperative assessment of accessibility is mandatory for appropriate selection of indication. Using a navigation system, we examined the inferior limit through the endonasal route and evaluated the relationships between surrounding anatomicl structures and the lowest point. METHODS: This study included patients who underwent endoscopic transsphenoidal surgery for intrasellar lesions at our hospital (N = 23). At the start of surgery, the lowest point (target point [TP]) was marked with a straight probe under guidance of the navigation system. We measured 4 parameters on preoperative computed tomography: nasal length, hard palate length, anterior-posterior diameter of the nasopharynx, and nasopalatine angle. Patients were classified into groups depending on whether the TP was at or above (group A) or below (group B) the hard palatine line. RESULTS: TPs were above the hard palatine line in 15 patients (group A) and below the hard palatine line in 8 patients (group B). No TPs reached the nasopalatine line. Nasal length (P = 0.03) and nasopalatine angle (P = 0.01) were larger in group B than in group A. There were no significant differences in anterior-posterior diameter of the nasopharynx or hard palate length. CONCLUSIONS: The hard palatine line is a reliable parameter for assessing the inferior limit of the endoscopic endonasal approach. Nostril size affects accessibility with surgical instruments.

Histopathological variation in the demyelinating sentinel lesion of primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is one of the least common malignant brain tumors. It is usually diagnosed initially as diffuse large B cell lymphoma (DLBCL). In rare cases, however, a demyelinating lesion referred to as a "sentinel lesion" precedes the actual diagnosis, which usually depicts two distinct patterns of inflammatory cells during histological analysis. This case report describes a unique histological finding and describes the recognized variations in sentinel lesion histopathology. CASE DESCRIPTION: A 78-year-old female patient was found to have multiple white matter lesions of various degrees of enhancement on post-contrast T1-weighted magnetic resonance imaging. A stereotactic biopsy of a heterogeneous lesion in the left occipital lobe was performed, which revealed demyelination along with lymphocytic infiltration, reactive astrocytosis, abundant T cells, and foamy macrophages. There was no evidence of monoclonality, rapid regression of all lesions occurred, and the patient was thus treated for tumefactive demyelination. Three months later, all of the residual lesions had enlarged and were homogeneously enhancing. An endoscopic-guided biopsy of the right periventricular lesion showed diffuse atypical lymphoid cells. CONCLUSION: The sentinel lesion of PCNSL expresses a variable histological pattern of inflammatory cells. This case demonstrates a unique and rare picture of mixed perivascular and parenchymal infiltration of inflammatory cells, highlighting the importance of repeated biopsies and/or radiological examinations to obtain an accurate diagnosis.

Combined Transcranial-supraorbital and Transconjunctival Approach for Optic Nerve Coloboma with Ophthalmic Dysplasia Associated with Rheumatoid Arthritis.

We report a 59-year-old woman with optic nerve coloboma and ophthalmic dysplasia associated with rheumatoid arthritis. She experienced progressive visual dysfunction over the course of several years and presented with headache and pain in the left eye. Since infancy the visual acuity of her left eye had been compromised and her eyesight worsened gradually until she was blind in the left eye. Macroscopic observation showed a reddish lesion on the sclera thought to be due to rheumatoid arthritis (RA). Magnetic resonance imaging and computed tomography disclosed a well-defined cystic lesion at the left retro-bulbar optic nerve within the optic nerve sheath. We selected the combined transcranial-supraorbital and transconjunctival approach to remove the eyeball after detaching the optic nerve. This technique was successful and the placement of an ocular prosthetic was cosmetically acceptable.

Microvascular Decompression in Patients Aged 30 Years or Younger.

OBJECTIVE: The aim of this study was to identify the etiology of hemifacial spasm (HFS) and trigeminal neuralgia (TN) in patients aged 30 years or younger and to examine the efficacy of microvascular decompression (MVD). PATIENTS AND METHODS: Between 1996 and 2012, 228 HFS and 190 TN patients underwent MVD at Atsuchi Neurosurgical Hospital. Of these, 7 patients were 30 years of age or younger at the time of treatment (HFS: n = 6, TN: n = 1). Assessments were based on their medical history and on magnetic resonance imaging, magnetic resonance angiography, surgical, and follow-up findings. RESULTS: The age of the 6 HFS patients ranged from 23 to 30 years (mean 27.8 ± 1.8 [standard deviation] years) at the time of surgery; the earliest symptom onset was in an 11-year-old boy. We noted vascular variations in 5 patients, a duplicate posterior inferior cerebellar artery in 2 patients, a short basilar artery in 1 patient, and an aberrant arterial course in 2 patients. At the latest follow-up, 1-69 months after MVD, 5 of the HFS patients were asymptomatic and the 6th had mild residual symptoms. A 23-year-old TN female underwent straightening of the trigeminal nerve by separation of a thickened arachnoid membrane from the nerve and dislocation of a small branch of the superior cerebellar artery from the distal end of the root exit zone. While she continued to experience occasional facial pain 48 months after the operation, she required no medication because surgery yielded significant pain amelioration. CONCLUSION: Although the pathogenesis of early-onset HFS and TN remains unclear, our findings suggest that vascular variations may be related to the etiology of vascular compression symptoms in patients with HFS or TN. MVD was useful for the treatment of neurovascular compression symptoms in young patients.

Safety and long-term efficacy of ventro-oral thalamotomy for focal hand dystonia: A retrospective study of 171 patients.

OBJECTIVE: To report the safety and long-term efficacy of ventro-oral thalamotomy for 171 consecutive patients with task-specific focal hand dystonia. METHODS: Between October 2003 and February 2017, 171 consecutive patients with task-specific focal hand dystonia underwent unilateral ventro-oral thalamotomy. Etiologies included writer's cramps (n = 92), musician's dystonias (n = 58), and other occupational task-related dystonias (n = 21). The task-specific focal hand dystonia scale was used to evaluate patients' neurologic conditions (range 1-5, high score indicated a better condition). The scores before surgery; at 1 week, 3 months, and 12 months postoperatively; and the last available follow-up period were determined. Postoperative complications and postoperative recurrence were also evaluated. RESULTS: The scores before surgery; at 1 week (1.72 ± 0.57, 4.33 ± 0.85 [p < 0.001]), 3 months (4.30 ± 1.06 [p < 0.001]), and 12 months (4.30 ± 1.13 [p < 0.001]); and the last available follow-up (4.39 ± 1.07 [p < 0.001]) postoperatively improved. The mean clinical follow-up period was 25.4 ± 32.1 months (range: 3-165). Permanent adverse events developed in 6 patients (3.5%). Eighteen patients developed recurrent dystonic symptoms postoperatively. Of these 18 patients, 9 underwent ventro-oral thalamotomy again, of which 7 achieved improvement. CONCLUSION: Ventro-oral thalamotomy is a feasible and reasonable treatment for patients with refractory task-specific focal hand dystonias. Prospective, randomized, and blinded studies are warranted to clarify more accurate assessment of the safety and efficacy of ventro-oral thalamotomy for task-specific focal hand dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with task-specific focal hand dystonia, ventro-oral thalamotomy improves dystonia.

Bilateral lateral ventricular subependymoma with extensive multiplicity presenting with hemorrhage.

This 48-year-old-man who had undergone right thyroid lobectomy for undifferentiated thyroid carcinoma nine years earlier developed generalized seizures. His cerebrospinal fluid was xanthochromic with elevation of total protein. Computed tomography (CT) showed mixed-density bilateral ventricular masses. Magnetic resonance imaging (MRI) revealed multiple nodules in both lateral ventricles; they were heterogeneously enhanced by gadolinium. Diffuse hyperintensity in the right medial temporal lobe and bilateral subependymal area was noted on fluid-attenuated inversion recovery images. Susceptibility-weighted imaging showed low intensity in the masses and cerebellar sulci suggesting hemorrhage and hemosiderin deposition. The preoperative diagnosis was disseminated malignant tumor with recurring hemorrhage. Histological examination of biopsy specimens showed clusters of cells with small uniform nuclei embedded in a dense fibrillary matrix of glial cells and microcystic degeneration. Pseudo-rosettes indicating ependymoma were absent. Microhemorrhages and hemosiderin deposits were noted. Immunohistochemically, the background fibrillary matrix and neoplastic cells were positive for glial fibrillary acidic protein. Mutated isocitrate dehydrogenase-1 was negative. The MIB-1 index was 1.5%. The tumor was pathologically diagnosed as subependymoma containing microhemorrhages and hemosiderin deposits. The extensive multiplicity and hemorrhage encountered in this case have rarely been reported in patients with subependymoma.

Preoperative and Postoperative Pituitary Function in Patients with Tuberculum Sellae Meningioma -Based on Pituitary Provocation Tests.

Given the anatomical proximity of tuberculum sellae meningioma (TSM) to the hypothalamo-pituitary system, pituitary function impairments are of great concern. We retrospectively investigated pituitary function changes following surgery in patients with TSM using pituitary provocation tests (PPTs). Thirty-one patients (27 females and 4 males) with TSM underwent initial transcranial surgery (29 patients) or transsphenoidal surgery (two patients); surgeries were performed carefully to avoid injuring the pituitary stalk. In 24 patients, the PPTs were performed via a triple bolus injection with regular insulin, thyrotropin-releasing hormone (TRH), and luteinizing hormone releasing hormone (LH-RH). Seven patients underwent a quadruple test (growth-hormone-releasing factor, corticotrophin-releasing hormone, TRH, and LH-RH). The preoperative and postoperative target hormone levels of the anterior pituitary were normal in 93.5% and 96.8% of patients, respectively. At least one hormonal axis demonstrated impaired PPT responses in two patients (6.5%) preoperatively and in one patient (3.2%) postoperatively. The growth hormone (GH) response was also well preserved. A compromised GH peak level was only observed in one patient (3.2%) preoperatively. Postoperatively, transient diabetes insipidus and transient hyponatremia were observed in four (12.9%) and eight (25.8%) patients, respectively. No patients needed permanent postoperative hormone replacement. The preoperative pituitary function was well preserved in most patients, including those with large tumors pushing against the pituitary stalk considerably or embedded in it. After careful surgery to avoid damaging the pituitary stalk, pituitary function was preserved. However, transient postoperative hyponatremia occurred in 25.8% of patients; thus, surgeons should pay careful attention to this issue.

Efficacy of bevacizumab therapy for unresectable malignant glioma: A retrospective analysis.

Bevacizumab (BEV), an inhibitor of vascular endothelial growth factor A, has been used for primary and recurrent malignant gliomas in Japan since June, 2013. Previous randomized controlled studies demonstrated that BEV prolonged the progression-free survival, but not the overall survival (OS) of patients with newly diagnosed glioblastoma. The aim of the present study was to elucidate the effect of BEV on the OS of patients with unresectable malignant gliomas. Of the 440 cases of malignant glioma initially treated in our institute between 2000 and 2015, 88 were not suitable for maximal resection due to patient age, physical condition, tumor location and extent, or the patient's wishes. Based on the biopsy results, the pathological diagnosis was glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma in 60, 19 and 9 patients, respectively. Kaplan-Meier and log-rank analyses were performed to investigate the effect of BEV on OS. OS was longer in the BEV group (n=24) compared with that in the non-BEV group [n=64; median survival time (MST), 566 vs. 243 days, respectively; hazard ratio (HR)=0.413; 95% confidence interval (CI): 0.216-0.787; P=0.003]. In the 41 patients who received temozolomide (TMZ) and radiotherapy and the 31 patients with glioblastoma who received TMZ and radiotherapy, OS was longer in the BEV group compared with that in the non-BEV group (MST, 568 vs. 334 days, HR=0.404, 95% CI: 0.175-0.933, P=0.016; and MST, 566 vs. 160 days, HR=0.253, 95% CI: 0.099-0.646, P=0.001, respectively). In the Cox hazard model analysis of 41 patients who underwent TMZ-based chemoradiotherapy after biopsy, the use of BEV was the strongest independent beneficial factor associated with prolonged OS (HR=0.101; P=0.0002). Our retrospective survey suggested that BEV prolongs the OS of patients with unresectable malignant gliomas. However, these results must be verified by a well-designed prospective randomized controlled trial.

Cutaneous Mechanical Stimulation Regulates Ovarian Blood Flow via Activation of Spinal and Supraspinal Reflex Pathways in Anesthetized Rats.

The reflex effects of noxious mechanical stimulation of a hindpaw or abdominal skin on ovarian blood flow, and the reflex pathways involved in those responses were examined in anesthetized rats. Blood flow in the left ovary was measured using a laser Doppler flowmeter, and the activity of the left ovarian sympathetic nerve and mean arterial pressure (MAP) of the common carotid artery were recorded. Stimulation of the left or right hindpaw for 30 s produced marked increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the left ovarian sympathetic nerves were severed, the same stimulus produced a remarkable monophasic increase in ovarian blood flow that was explained by passive vasodilation due to a marked increase in MAP. After spinal transection at the third thoracic (T3) level, the responses of MAP, ovarian sympathetic nerve activity, and ovarian blood flow to hindpaw stimulation were nearly abolished. Stimulation of the abdomen at the right or left side for 30 s produced slight increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the ovarian sympathetic nerves were severed, the response of the ovarian blood flow changed to a monophasic increase due to an increase in MAP. After spinal transection, stimulation of the left abdomen produced a moderate increase in MAP, a remarkable increase in ovarian sympathetic nerve activity and a slight decrease in ovarian blood flow during the stimulation. In contrast, stimulation of the right abdomen produced a smaller response in ovarian sympathetic nerve activity during the stimulation while it increased the MAP to a similar degree. Ovarian blood flow slightly increased after the end of stimulation, which was explained as passive vasodilation due to the increase in MAP. In conclusion, stimulation of somatic afferents affects ovarian blood flow by inducing changes in ovarian sympathetic nerve activities and blood pressure. When stimulation was applied to a hindpaw whose segment of afferent input is far from the segment of the ovarian sympathetic nerves, it took a supraspinal reflex pathway. However, when stimulation was applied to the abdomen whose spinal segment of the afferent is close to the segment of the ovarian sympathetic nerve output, there are spinal segmental reflex pathways. The present results demonstrate that spinal reflexes depend on the laterality of the stimulus, while supraspinal reflexes do not depend on the laterality of the stimulus.

Development and pharmacological verification of a new mouse model of central post-stroke pain.

Central post-stroke pain (CPSP) including thalamic pain is one of the most troublesome sequelae that can occur after a cerebrovascular accident. Although the prevalence of CPSP among stroke patients is relatively low, the persistent, often treatment-refractory, painful sensations can be a major problem and decrease the affected patient's quality of life. To better understand of the pathophysiological basis of CPSP, we developed and characterized a new mouse model of thalamic CPSP. This model is based on a hemorrhagic stroke lesion with collagenase in the ventral posterolateral nucleus of the thalamus. Histopathological analysis indicated that the thalamic hemorrhage produced a relatively confined lesion that destroys the tissue within the initial bleed, and also showed the presence of activated microglia adjacent to the core of hemorrhagic lesions. Behavioral analysis demonstrated that the animals displayed diclofenac-, morphine- or pregabalin-resistant mechanical allodynia and thermal hyperalgesia of the hind paw contralateral to the lesion for over 112 days. However, we found that minocycline, a microglial inhibitor, significantly ameliorated mechanical allodynia and thermal hyperalgesia. These results suggest that this model might be proved as a useful animal model for studying the neuropathology of thalamic syndrome, and developing improved therapeutics for CPSP.

Primary malignant melanoma in the pineal region treated without chemotherapy.

BACKGROUND: Primary pineal malignant melanomas are uncommon intracranial tumor. Here we discuss and review a case of primary pineal malignant melanoma over its feature of imaging studies, pathological findings, and management. CASE DESCRIPTION: A 49-year-old woman receiving renal dialysis underwent computed tomography due to a 4-month history of tinnitus and hearing disturbance. A high-density 35-mm diameter tumor was detected in the pineal region; there was obstructive hydrocephalus. The tumor was heterogeneously hyperintense on T1-weighted magnetic resonance images, iso- and low-mixed intense on T2-weighted images with hemorrhagic components, and very low-intense on T2(*) images. A tumor was subtotally removed via the occipital transtentorial approach. Histologically, it consisted of densely proliferated spindle-shaped or polygonal cells with rich cytoplasmic melanin. The neoplastic cells manifested cellular pleomorphism, nuclear atypia, and mitosis (3/10 high-power fields) and were immunopositive for HMB45, Melan-A, and S100 protein. The MIB-1 index was 17.4%. Whole-body 18-fluoro-deoxyglucose positron emission tomography did not demonstrate any sites with hyper uptake. Examination of the skin and mucosa identified no lesions suggestive of melanoma. She underwent treatment with the whole brain and extended local boost irradiation. Chemotherapy was not delivered due to renal failure. Follow-up imaging studies showed no recurrence or distant lesions 56 weeks after surgery. CONCLUSION: We report a rare case of primary pineal malignant melanoma with prolonged survival of more than 56 weeks after subtotal tumor resection followed by whole-brain and extended local irradiation without chemotherapy. Radiotherapy without chemotherapy might be sufficient for the treatment of this tumor.