Helmet therapy efficacy and its prediction in Japanese infants with positional plagio- and brachycephaly.

PURPOSE: To provide additional information on optimal start times and therapeutic effectiveness based on treatment outcome of Japanese infants with positional plagio- and brachycephaly (PPB) receiving cranial molding helmet therapy (CMHT). METHODS: In this retrospective cohort study, data from a 3D head scanning system was analyzed from 2173 Japanese infants who completed CMHT. Anterior and posterior symmetry ratio (ASR and PSR) and longitudinal to transverse diagonal ratios (LD/TDR) were calculated based on skull shape at helmet design and at completion of therapy. The outcomes were evaluated using the regression analysis and a predictive model using cranial parameters was developed. RESULTS: The earlier the start of therapy, the greater the therapeutic effect on ASR, PSR, and LD/TDR (ASR, -0.134 percent points (ppt)/day; PSR, -0.086 ppt/day; and LD/TDR, -0.131 ppt/day). In the predictive model, in addition to starting age of the therapy, sex (male), the degree of deformity of the head (DoD) (moderate and severe), quadrant volume, PSR, and head circumference at the start of treatment also had a positive effect on changes in ASR, DoD (moderate and severe), ASR, LD/TDR and transverse diameter for PSR, sex (male), DoD (moderate), quadrant volume, PSR, and head circumference for LD/TDR. CONCLUSION: The starting age of therapy had a relatively smaller contribution to outcome effects. Applying the cranial parameter obtained at the start of treatment to the predictive model helps to predict the effect of CMHT and whether PPB can be treated with CMHT in infants of older age.

Pediatric craniopharyngioma with significantly increased intraoperative visual evoked potential amplitude and postoperative visual acuity improvement: a case report.

Visual evoked potential (VEP) is an established modality that allows safe brain tumor resection and preservation of optical function. We herein present a case of a pediatric craniopharyngioma with significant improvement in the VEP amplitude detected during endoscopic transsphenoidal surgery (ETS) and obvious postoperative improvement in visual acuity. A 13-year-old boy presented with visual acuity disturbance in his right eye and was followed up for 5 months by an ophthalmologist. His visual acuity rapidly worsened, and a suprasellar lesion with calcification was found on brain computed tomography. The patient underwent tumor resection during ETS with intraoperative transcranial VEP monitoring. Gross total tumor resection was achieved without injury to the perforators, including the superior hypophyseal arteries. The VEP amplitude was unstable, and significant waves were not detectable before tumor resection; however, a positive wave was detected after removing most of the tumor and exposing the bilateral optic nerves and optic chiasm. Subsequently, negative and positive VEP waves were continuously detected. Visual acuity improved remarkably on postoperative day 10. This case demonstrated both a significant increase in the intraoperative VEP amplitude and rapid postoperative improvement in visual acuity. We surmised that the preoperative rapid worsening of visual dysfunction, intraoperative increase in the VEP amplitude, and significant postoperative improvement in visual acuity were associated with the compression of the optic nerves by the internal carotid artery, anterior cerebral artery, and tumor.

A case of a pineal parenchymal tumor of intermediate differentiation with bifocal lesions differentiated by negative placental alkaline phosphatase in the spinal fluid.

Placental alkaline phosphatase (PLAP) in the spinal fluid is helpful for the diagnosis of intracranial germinomas. Bifocal lesions involving the pineal and pituitary regions have also been reported as characteristic findings of intracranial germinomas. We present a rare case of a 15-year-old boy with a pineal parenchymal tumor of intermediate differentiation (PPTID) with bifocal lesions negative for PLAP. Magnetic resonance imaging of the brain revealed bifocal mass lesions in the pineal and suprasellar regions and non-communicating hydrocephalus. We initially suspected a germinoma based on imaging findings, but all tumor markers, including PLAP, in the spinal fluid were negative. Based on these results, germinoma was considered less likely, and an endoscopic third ventriculostomy and endoscopic tumor biopsy were performed for diagnosis. The histopathological diagnosis was PPTID, corresponding to World Health Organization grade 3, in both pineal and suprasellar specimens. A craniotomy for tumor removal was performed, resulting in total resection. PLAP is known to have high sensitivity and extremely high negative predictive value for germinomas. Although bifocal lesions highly suggest germ cell tumors, there are exceptions, as in the present case. This case suggests that PLAP measurements are useful for differentiation, leading to appropriate treatment strategies.

Brainstem cavernous hemangioma with improvement of Holmes tremor on excision.

An 8-year-old boy presenting with left-angle paralysis, tremor in upper and lower extremities, and diplopia was diagnosed with hemorrhage from a mesencephalic cavernous hemangioma. He underwent hemangiomectomy through the occipital transtentorial approach 4 weeks post-hemorrhage, after which Holmes tremor (HT) markedly reduced. A year later, hemangioma has not recurred; he is now independent in his daily activities. Early intervention in the subacute stage allows for the complete removal of brainstem cavernomas (BSCs), with minimal risk of complications or sequelae. Proper timing and surgical approach for BSCs can prevent re-bleeding and improve HT after an initial hemorrhage, without any lasting negative consequences.

Selective surgical mamillo-thalamic tract disconnection in hypothalamic hamartoma results in complete disappearance of gelastic seizures.

Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications.

Efficacy of the pedicle trapezius muscle flap for the multisurgical removal of pediatric posterior fossa anaplastic ependymoma.

OBJECTIVE: Exceedingly refractory, pediatric anaplastic ependymoma in many cases requires multisurgical removal. The high risk of poor wound healing and CSF leakage especially at the posterior fossa make this tumor difficult to treat. CASE: A 9-year-old girl has had 4th ventricular anaplastic ependymoma since the age of 3. She experienced tumor removal 8 times including 4 posterior fossa craniotomies because tumors were disseminated not only to the posterior fossa but also to the cerebral hemispheres. She also underwent a dermal graft using a free flap. She experienced CSF leaks and meningitis frequently because the wound healing was poor. We performed a dermal flap closure using a pedicle trapezius muscle flap with a plastic surgeon when we performed the 5th tumor removal. RESULT: We achieved complete wound closure in spite of broad deficiencies in subcutaneous and epidermal tissues. After that, recurrences of posterior fossa tumors presented within a short term, and tumor removal via an incision of a pedicle trapezius muscle flap was performed without recurrence of CSF leaks and meningitis. DISCUSSION AND CONCLUSION: For the first time, we are able to report on the efficacy of using the pedicle trapezius muscle flap for multisurgical removal of pediatric posterior fossa anaplastic ependymoma. The muscle flap was found to be effective because of the multiple surgeries expected, and the pedicle trapezius muscle flap was found to be resilient to multiple surgical procedures. Although advantageous, the dorsal scapular artery which is required for flap creation is actually difficult to harvest. Compared to a flee flap, the pedicle trapezius muscle flap maintains vascular supply. Furthermore, this technique has the possibility of being applied to defective dura mater closure that cannot be watertight due to multiple surgeries. However, it is very important to inform the patient's family not only about the improved efficacy of surgery, but also to raise awareness on consequential cosmetic issues.

Breath-holding spells after endoscopic third ventriculostomy in a post-ventriculoperitoneal shunted patient.

Breath-holding spells (BHS) are commonly observed in children as a result of an autonomic nervous system disorder triggered by crying, emotional distress, or pain. There are several types of BHS and cyanotic type is one of them. We encountered a case of 3-year-old girl who presented with a delayed adaptation period and BHS 2 weeks after an endoscopic third ventriculostomy (ETV). She experienced severe headache due to increased intracranial pressure (ICP) during the delayed adaptation period, which may have contributed to the onset of BHS. Management of BHS warrants treatment of the symptoms and removal of the causative factors; in our case, intensive pain control and resolution of the increased ICP after the adaptation period were effective. While BHS are usually described as a benign condition that improves spontaneously, we highlighted the importance of recognizing and monitoring atypical symptoms such as BHS in pediatric cases.

One-Piece Frontoorbital Osteotomy With a Small Supraorbital Burr-Hole to Protect Against Intraoperative Dural Lacerations.

ABSTRACT: This paper aims to describe a new technique of 1-piece frontoorbital osteotomy with a small supraorbital burr hole, which resulted in improved safety during osteotomy of the anterior skull base. An 11 × 4 mm burr hole was created at the center of the orbit above the superior orbital rim using an "eyebrow key-window approach." Extradural dissection from the nasion to the medial side of the sphenoid ridge was performed through this hole, and dissection of the lateral side of the sphenoid ridge was completed from the edge of the coronal osteotomy. Osteotomy along the zygomaticofrontal and sphenofrontal sutures were performed using an oscillating saw with secure protection of the dura. Between December 2019 and June 2020, 3 patients with unilateral coronal craniosynostosis underwent 1-piece frontoorbital advancement with the eyebrow key-window approach. The median age was 11 months (8-15 months), median operation time was 249 minutes (244-255 minutes), and the average blood transfusion was 10.8 ml/kg (0-18 ml/kg). No complications were observed, and the technique was associated with improved safety of osteotomy around the anterior skull base for 1-piece frontoorbital advancement.

Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid.

PURPOSE: The disadvantages of biopsy for lesions in the basal ganglia and thalamus include a risk of various complications, difficulty in selecting the target tissue in some cases due to indistinct neuroimaging findings and limited availability of sample tissue. Placental alkaline phosphatase (PLAP) plays a decisive role in the diagnosis and management of intracranial germ cell tumors (IGCTs) in the basal ganglia and thalamus. The present study aimed to demonstrate the ability, specificity, and optimal use of PLAP values obtained from cerebrospinal fluid (CSF). METHODS: Twenty patients with lesions in the basal ganglia and thalamus were enrolled in this study: 11 had IGCTs and 9 had non-IGCTs. The values of PLAP and other established tumor markers in the CSF were measured in all patients before treatment. RESULTS: The mean follow-up period was 76.0 months (range, 3-168) for all lesions. PLAP was elevated in all 11 patients with IGCTs in the basal ganglia or thalamus, whereas none of the patients with non-IGCT exhibited elevated PLAP. Thus, the sensitivity and specificity of PLAP were both 100%. CONCLUSION: Our data demonstrated that the PLAP value can specifically identify the germinomatous component even in cases of IGCTs in the basal ganglia or thalamus with high sensitivity and specificity. PLAP is undoubtedly beneficial for the safe and timely detection of the germinomatous component of IGCTs in the basal ganglia and thalamus, because reliance on PLAP measurement enables us to avoid invasive surgical procedures and facilitates the prompt initiation of chemoradiation therapy.

Aspirin use and platelet aggregation in ischemic onset-type pediatric moyamoya patients with intractable headaches (moya-ache).

BACKGROUND: NSAIDs (nonsteroidal anti-inflammatory drugs) were administered to patients with ischemic onset-type moyamoya disease who experience headaches, but their therapeutic effect was very poor and resulted in a drop in quality of life (QOL). On the other hand, patients who were administered aspirin initially to prevent transient ischemic attacks (TIA) were observed to have a better QOL with the absence of headaches. Here, we report on patients with ischemic onset-type moyamoya disease experiencing headaches who received aspirin in order to verify its safety and effectiveness. METHODS: From October 2012 to July 2014, 35 patients (male: 19, female: 16 average age: 10.5 ± 3.9) with ischemic onset-type pediatric moyamoya disease and who were admitted or commuted to hospital and had surgical treatment were evaluated for background, moyamoya staging (Suzuki), presence/absence of TIA, and platelet aggregation activity by adenosine diphosphate (ADP)/collagen turbidity test. The patients were divided into four groups depending on the intensity of headache prior to being administered aspirin, and the Kruskal-Wallis test was carried out for platelet aggregation activity and moyamoya staging. Also, the 4 × 2 χ2 test was carried out for the presence/absence of TIA. Next, the items which were significant in these tests were used as independent variables to analyze the risk of headache onset, using logistic regression analysis. RESULTS: One item with statistical significance was the platelet aggregation test(PAT) value (on collagen) (P < 0.0001). A logistic regression analysis was carried out, using this value as an independent variable and headache intensity-as a dependent variable. As a result, an increase in PAT value by 1 translated into 4.43 times higher risk of the onset of intractable headache, and the onset of intractable headaches was predicted at 58.8% with collagen. The risk of developing a headache decreased as a result of aspirin administration, and the decrease was dependent on the collagen-induced aggregation suppression effect of aspirin. Aspirin was administered in the range of 1.6~9.5 mg/kg/day, and the PAT value decreasing rate was 42.9% on average. One case alone experienced nasal bleeding, and all cases showed an improvement in the intractable headaches. CONCLUSIONS: In patients with ischemic onset-type pediatric moyamoya disease who experience headaches, the platelet aggregation activity is accelerated, and aspirin administration is effective in alleviating headaches by inhibiting platelet activation, detected by the collagen PAT.

Clinical experience of growth hormone replacement for pediatric intracranial germ cell tumor.

PURPOSE: Intracranial germ cell tumors (IGCTs) account for 8-15% of brain tumors in children in Eastern Asia and typically occur at the age of puberty. Recently, adjuvant therapy has been modified to ameliorate post-treatment complications such as cognitive dysfunction, in patients with IGCT. However, endocrine problems remain to be resolved. There is reluctance to use growth hormone (GH) at an early stage after treatment for IGCT because of the risk of tumor recurrence; however, GH replacement must be administered before the onset of puberty in children with short stature. There is little guidance on this issue due to a lack of literature on the risks of GH replacement therapy in patients with IGCT. This study aimed to evaluate the safety of GH replacement. METHODS: In this retrospective study, 6 patients with IGCT who were under the age of 18 years when they started GH replacement therapy were reviewed. Histopathological analysis and/or analysis of tumor markers was used to confirm a diagnosis. RESULTS: All six cases who underwent GH replacement therapy showed no recurrence. GH replacement therapy was administered in 5 patients for short stature and all achieved a height within ± 2.0 standard deviation. CONCLUSION: GH replacement for children with IGCT was safe in our case series. Placental alkaline phosphatase levels in cerebrospinal fluid can be used to facilitate the decision on when to initiate GH replacement.

Intrinsic Well-Demarcated Midline Brainstem Lesion Successfully Resected through a Midline Pontine Splitting Approach.

INTRODUCTION: Surgical approaches to intrinsic pontine lesions are technically difficult and prone to complications. The surgical approach to the brainstem through midline pontine splitting is regarded as safe since there are no crossing vital fibers in the midline between the abducens nuclei at the facial colliculi in the pons and the oculomotor nucleus in the midbrain, although its actual utilization has not been reported previously. CASE PRESENTATION: A 6-year-old boy presented with a large intrinsic cystic lesion in the pons. We successfully achieved gross total removal via the median sulcus of the fourth ventricle. The fixation in adduction and limitation of abduction were newly observed in the left eye after surgery. DISCUSSION: The advantage of the surgical approach through the median sulcus is the longer line of dissection in an axial direction and the gain of a wider operative view. On the other hand, the disadvantage of this approach is the limited orientation and view toward lateral side and a possible impairment of the medial longitudinal fasciculi and paramedian pontine reticular formation, which are located lateral to the midline sulcus bilaterally and are easily affected via the median sulcus of the fourth ventricular floor. Ongoing developments in intraoperative neuro-monitoring and navigation systems are expected to enhance this promising approach, resulting in a safer and less complicated procedure in the future. CONCLUSION: The surgical approach through midline pontine splitting is suitable for midline and deep locations of relatively large pontine lesions that necessitate a wider surgical window.

Do Direct Bypasses Really Resolve Capillary Vessels in Moyamoya Disease? Delayed Hemorrhage Potentially Relevant to Direct Bypasses: A Pathological Investigation.

OBJECTIVE: Moyamoya disease is a chronic but progressive obliterative cerebrovascular disease of bilateral internal carotid arteries (ICAs) causing hemorrhagic or ischemic cerebral strokes. Surgical revascularization has the potential for resolving the capillary vessels, but the effect on the occlusive ICA and the moyamoya vessels after a direct bypass remains unclear. PATIENT: A 2-year-old girl with a history of repeated transient ischemic attacks and direct bypasses but demonstrating improvement and associated anomaly is reported. A year and a half later, after a bilateral revascularization, an intracerebral capsulized hematoma growth was identified, and it was removed surgically. Neovascularization including many microvessels similar to capillary telangiectasia were identified by pathological investigation despite the reduction of moyamoya vessels on the repeated angiograms after the revascularization surgeries. In the present case, proliferation of capillary vessels was clearly confirmed by direct bypasses. CONCLUSION: There is no doubt that direct bypasses prevent further ischemic stroke by improving cerebral blood flow. However, they may result in failure in reducing the load of moyamoya vessels, albeit decreasing the potential risk of hemorrhagic strokes.

Craniosynostosis Treatment Using Distraction Devices.

BACKGROUND: The authors report on surgical treatment for 20 patients with craniosynostosis in Japan in collaboration with neurosurgery department since 2007. They could safely expand the skull using distraction devices. METHODS: Total number of patients with craniosynostosis joint surgery was 20 (23 surgeries) at the time of this report. All patients were referred from the neurosurgery department. Neurosurgeons decided the patient selection and the surgical indications, and performed osteotomy, intraoperative measurement of intracranial pressure, and perioperative management. The plastic and reconstructive surgeons set in bone models and simulate bone cutting line preoperatively, and performed skin incisions with flap, set bone distractors or bone absorption plate fitted with flap closure during surgery. Postoperative systemic management was undertaken in the neurosurgery intensive care unit. In the plastic and reconstructive surgery department, postoperative wound care and bone lengthening, and removal of the bone distractors were done. RESULTS: All patients showed good bone forms, and there were no patients of serious complications such as meningitis. CONCLUSION: With these roles shared, safe surgery and perioperative management could be performed. Use of the craniosynostosis distraction devices is safe and excellent way, and the authors will continue to explore that direction further.

Can Moyamoya Disease Susceptibility Gene Affect Extracranial Systemic Artery Stenosis?

Diseases associated with the RNF213 gene include moyamoya disease, with the p.R4810K (c.14429G>A, rs112735431) homozygous variant thought to be the most pathogenic and significantly associated with severe manifestation such as early onset or cerebral infarction at onset. We report a case of a unique Japanese pedigree associated with RNF213. A 53-year-old woman with no arteriosclerotic risk factors experienced coronary artery disease, followed by coronary artery bypass surgery. In 8 years, she suffered sudden abdominal pain. Her abdominal contrast computed tomography revealed stenosis of abdominal artery and superior mesenteric artery. Though her 2 children and uncle had a typical moyamoya disease with RNF213 p.R4810K heterozygous variant, she has had no clinical and radiological evidence of moyamoya disease. Due to a family history of moyamoya disease, a genetic investigation was performed and revealed RNF213 p.R4810K homozygous variant. A possible role of RNF213 influencing systemic artery stenosis can be further be understood from this rare case harboring the homozygous variant carrier.

Genotype-Phenotype Correlation in Long-Term Cohort of Japanese Patients with Moyamoya Disease.

BACKGROUND: Homozygosity of this p.R4810K founder variant of RNF213moyamoya disease (MMD) susceptibility gene is known to influence the severity of the clinical disease phenotype at disease onset. However, the association between this genotype and long-term clinical manifestations has remained unclear. OBJECTIVES: The principal goal of this study was to investigate whether and how the p.R4810K variant of RNF213influences the long-term phenotype in Japanese patients with MMD. METHOD: This retrospective cohort study included 94 Japanese patients with MMD who underwent direct or combined bypass for revascularization with the p.R4810K genotype determined in our hospital. The following phenotypic parameters were analyzed at disease onset and over a long-term period: age and initial presentation at onset, recurrent stroke after initial revascularization, and final modified Rankin Scale. RESULTS: The p.R4810K genotype was significantly associated with the phenotype at onset, especially in younger patients. Over a median follow-up period of 100 months, recurrent stroke occurred in 6 out of 94 patients: none out of 5 patients with the homozygous variant, 5 out of 64 with the heterozygous variant, and 1 out of 25 in the wild-type group. There were no significant differences among the genotypes. In particular, recurrent cerebral hemorrhage occurred in 5 patients, all possessing the heterozygous variant. The log-rank test showed no difference between the genotypes in the stroke-free survival rate. Furthermore, the p.R4810K genotype was not associated with a poor functional condition. CONCLUSIONS: The p.R4810K founder variant of RNF213 affects the phenotype at disease onset. However, the optimal revascularization may be effective, regardless of the genotype, even for the homozygous variant, which has been thought to be the most pathogenic. This genotype may not strongly influence the long-term clinical manifestations or poor prognosis in MMD.

Basilar invagination in a child with atlanto-occipital subluxation and suspected prenatal Dandy-Walker malformation.

BACKGROUND AND PURPOSE: Although advances in imaging have allowed earlier and more accurate diagnosis of various fetal anomalies, Dandy-Walker malformation (DWM) remains one of the more challenging central nervous system anomalies to diagnose accurately before birth. Basilar invagination (BI), which is a dislocation of the dens in an upward direction, is occasionally accompanied by Klippel-Feil syndrome (KFS). We report a pediatric case of BI caused by atlanto-occipital subluxation (AOS) in KFS, suspected of having DWM prenatally but head magnetic resonance images (MRI) showed no evidence of that at 7 months of age. CASE: At 28 weeks of gestation, fetal MRI study revealed a small cerebellar vermis, leading us to suspect a DWM. The patient was born at 40 weeks of gestation. Head CT showed inferior vermian hypoplasia without findings of hydrocephalus. Cervicothoracic CT showed cervical lamina assimilations, thoracic hemivertebrae, and cervicothoracic scoliosis. He was diagnosed with Dandy-Walker variant and KFS. At 7 months of age, head MRI showed near normal cerebellum and vermis and there was no evidence of the DWM. He did not have intellectual or developmental delay and imaging studies were performed periodically. At 9 years of age, an already existing cough headache deteriorated. Three-dimensional reconstructed images from CT scan showed C1 hypoplasia, fusion of C1 and C2, BI, and AOS. Sagittal T2-weighted MRI showed protrusion of cerebellar tonsils inferiorly to the level of the posterior arch of C2. Serum calcium, phosphate, and parathyroid hormone levels were normal. The diagnosis was tonsillar herniation related to BI following AOS in KFS. Posterior occipitocervical fixation was performed under traction. CONCLUSIONS: We found out two important clinical issues: DWM findings after birth can be disappearing and BI can present sequential deterioration because of AOS in KFS. Our observation indicated the possible prognosis of pediatric BI with long follow-up and can help us decide on its surgical treatment timing when associated with AOS.

Application of indocyanine green fluorescence endoscopic system in transsphenoidal surgery for pituitary tumors.

BACKGROUND: For the precise removal of pituitary tumors, preserving the surrounding normal structures, we need real-time intraoperative information on tumor location, margins, and surrounding structures. The aim of this study was to evaluate the benefits of a new intraoperative real-time imaging modality using indocyanine green (ICG) fluorescence through an endoscopic system during transsphenoidal surgery (TSS) for pituitary tumors. METHODS: Between August 2013 and October 2014, 20 patients with pituitary and parasellar region tumors underwent TSS using the ICG fluorescence endoscopic system. We used a peripheral vein bolus dose of 6.25 mg/injection of ICG, started with a time counter, and examined how each tissue type increased and decreased in fluorescence through time. RESULTS: A total of 33 investigations were performed for 20 patients: 9 had growth hormone secreting adenomas, 6 non-functioning pituitary adenomas, 3 Rathke's cleft cysts, 1 meningioma, and 1 pituicytoma. After the injection of ICG, the intensity of fluorescence of tumor and normal tissues under near-infrared light showed clear differences. We could differentiate tumor margins from adjacent normal tissues and define clearly the surrounding normal structures using the different fluorescent intensities time changes and tissue-specific fluorescence patterns. CONCLUSIONS: The ICG endoscopic system is simple, user-friendly, quick, cost-effective, and reliable. The method offered real-time information during TSS to delimit pituitary and parasellar region tumor tissue from surrounding normal structures. This method can contribute to the improvement of total removal rates of tumors, reduction of complications after TSS, saving surgical time, and preserving endocrinological functions.

Platelet Aggregability as a Predictor of Restenosis Following Carotid Endarterectomy.

BACKGROUND: Antiplatelet drugs are administered before and after carotid endarterectomies (CEAs), but their efficacy for preventing restenosis remains unclear. Hence, this study aimed to identify associations between postoperative restenosis and platelet aggregability in CEA patients. METHODS: Thirty-six consecutive CEA patients treated at Tokyo Women's Medical University from May 2013 to March 2015 were included in this retrospective study. Restenosis was defined as a stenosis ratio greater than or equal to 50% per the European Carotid Surgery Trial criteria or peak systolic velocity of 150 cm/s on carotid ultrasound. Platelet aggregability was measured turbidimetrically using a light-transmission platelet aggregometer and analyzed in terms of aggregation profiles for 2 concentrations of collagen used to induce aggregation (.25 and 2.0 µg/mL). Patients were automatically divided into 9 classes (Class 1-9, from the lowest to the highest aggregability) using a software program according to area under their platelet aggregation curves. Each class was subdivided into 10 further gradations for a total of 90 possible scores (10-99) using a software program. Patients were divided into high- and low-platelet aggregability score groups (cut-off = 49). RESULTS: Data were analyzed for 36 of the 99 patients. Restenosis was observed in 10 (28%) patients. Restenosis incidence was significantly higher in patients with high-platelet aggregability score than in those with low-platelet aggregability score (50.0% [7/14] versus 13.6% [3 of 22]: P = .0176, odds ratio = 6.34, 95% CI: 1.27-31.57). CONCLUSIONS: Platelet aggregability is a useful metric for predicting and preventing restenosis after CEA. It has potential as an indicator for determining the optimal dose of antiplatelet drugs.

Exome Sequencing Identified CCER2 as a Novel Candidate Gene for Moyamoya Disease.

The etiology of Moyamoya disease (MMD) is still largely unclear, despite identification of RNF213 as the most significant susceptibility gene in East Asian patients. Following up our previous study confirming genetic heterogeneity in Japanese patients with MMD, we extensively surveyed novel candidate genes for a new perspective on the etiology of this disease. Two characteristic pedigrees without susceptibility variants in RNF213 were selected for whole-exome sequencing; 1 harbored 3 affected members, and the other included discordant monozygotic twins. In the former pedigree, 12 rare mutations in 12 genes were co-segregated with MMD. One of the most deleterious amino acid changes among these was p.T76_G80delinsPS in CCER2, which was also mutated in the latter pedigree (p.E242K), although the unaffected twin sister shared the same mutation reflecting reduced penetrance. These CCER2 mutations were predicted to promote aggregation or oligomerization of their protein product, using in silico functional analysis. Subsequent CCER2 re-sequencing in an additional 135 MMD probands identified 1 recurrent and an additional 2 in-frame insertion-deletion mutations, recurrent p.T76_G80delinsPS, p.H218_H220del, and p.E299del. Although CCER2 molecular function is not well characterized, it is a secretory protein expressed in the brain; therefore, it constitutes a potential biomarker of MMD.