[Genetic Analysis of Cerebrovascular Diseases].

With advances in genetic analysis technology, the genetic and molecular backgrounds of cerebrovascular diseases have become clearer. In moyamoya disease and intracranial artery stenosis, RNF213 p.Arg4810Lys has been identified as a disease susceptibility gene variant(germline variant), and various analyses have been conducted. PDGFRB mutations have been identified as characteristic somatic variants in cerebral aneurysms and are attracting attention. In addition, PIK3CA and MAP3K3 mutaions have been identified in cerebral cavernous malformations as somatic variants. Moreover, KRAS and BRAF mutations have been identified in arteriovenous malformations as somatic variants, respectively. Further studies are in progress. We reviewed the results of recent genetic analyses of cerebrovascular diseases, focusing particularly on genetic mutations.

Indirect revascularization for pediatric moyamoya disease.

OBJECTIVE: Indirect revascularization is a common and effective treatment for pediatric moyamoya disease. However, in several cases postoperative angiogenesis is not sufficient. It is not fully understood which factors are involved in the development of postoperative collateral circulation. In this study, the authors aimed to elucidate the factors related to postoperative angiogenesis in indirect revascularization. METHODS: Among the patients who underwent indirect revascularization for moyamoya disease from January 2015 to December 2022, those whose angiogenesis was evaluated using angiography were included. Age, onset symptoms, comorbidities, preoperative imaging findings, surgical details, perioperative complications, postoperative imaging findings, and modified Rankin Scale (mRS) score at the last outpatient visit were retrospectively examined. RESULTS: Ninety cases (53 patients; 37 bilateral, 16 unilateral) were included. Sixty-eight cases (75.6%) were symptomatic. The mean age at surgery was 7.9 years, and the mean postoperative follow-up duration was 48.5 months. Frontotemporal encephalo-duro-arterio-synangiosis (EDAS) was performed in all cases, and simultaneous frontal encephalo-galeo-synangiosis (EGS) was performed in 34 cases. Postoperative angiography revealed insufficient angiogenesis in 14 of 90 cases (15.6%) after frontotemporal EDAS and in 8 of 34 cases (23.5%) after frontal EGS. A high degree of ivy sign depicted on preoperative MRI was found to be significantly correlated with good angiogenesis after both surgical procedures (p = 0.00030 for EDAS and p = 0.0039 for frontal EGS). In addition, an advanced preoperative Suzuki stage was significantly correlated with good postoperative angiogenesis after EDAS (p = 0.00040). Good angiogenesis was significantly correlated with postoperative improvement of the ivy sign in both procedures (p = 0.0005 in EDAS and p = 0.030 in frontal EGS) as well as correlated with a better mRS score at long-term follow-up after EDAS (p = 0.018). CONCLUSIONS: Preoperative ivy sign and Suzuki classification are related to the degree of angiogenesis achieved after indirect revascularization for pediatric moyamoya disease.

Suzuki Stage VI Unilateral Moyamoya Disease Presenting With Massive Intraventricular Hemorrhage.

Moyamoya disease (MMD) is characterized by stenosis of the terminal portion of the internal carotid artery (ICA) and the development of collateral vessels. In late Suzuki stage MMD, ICA almost disappears, and the moyamoya vessels gradually regress. We report a case of late Suzuki stage unilateral MMD presenting with intraventricular hemorrhage. A 76-year-old woman who had previously been diagnosed with right ICA occlusive disease was referred to our hospital due to impaired consciousness. Radiological evaluation revealed massive intraventricular hemorrhage. After endoscopic hematoma removal, digital subtraction angiography (DSA) was performed to examine the vascular anatomy, which revealed numerous basal moyamoya vessels originating from the posterior cerebral artery. Three-dimensional rotational angiography identified a choroidal anastomosis originating from the posterior choroidal artery as the hemorrhage source. The patient had an RNF213 p.Arg4810Lys heterozygous variant in the germline. Based on the DSA findings, MMD was diagnosed, and the patient was transferred to a rehabilitation hospital with good postoperative consciousness. In conclusion, patients diagnosed with ICA occlusive disease may have late Suzuki stage MMD, potentially leading to major hemorrhage; therefore, antithrombotic medications should be administered with caution. In diagnosing ICA occlusive disease, the assessment of periventricular anastomosis should be considered, taking into account the possibility of MMD.

Association of rare variants in RNF213 with severe progression of intracranial artery stenosis in quasi-moyamoya disease.

OBJECTIVE: The genetic basis underlying the pathophysiology of quasi-moyamoya disease (qMMD) is unclear. Herein, the authors aimed to comprehensively analyze genetic variants in qMMD and investigate their association with clinical phenotypes, focusing on RNF213 and other moyamoya angiopathy (MMA)-related genes. METHODS: The authors evaluated 14 consecutive cases of qMMD, whose underlying conditions included autoimmune disease, head irradiation, meningitis/pachymeningitis, and Turner syndrome, and 9 cases of hyperthyroidism-associated MMD (hMMD). The frequencies of RNF213 p.Arg4810Lys in qMMD and hMMD were each compared to those in healthy controls and in patients with MMD. Whole-exome sequencing was performed, and rare variants (RVs) or damaging variants were analyzed in RNF213 and 36 MMA-related genes. RESULTS: The frequencies of p.Arg4810Lys were significantly higher in patients with qMMD (28.6%) and hMMD (33.3%) than in controls (1.1%; p < 0.001) and lower in the two former groups than in the MMD group (67.6%; p = 0.003 and 0.065, respectively). In qMMD, no significant clinical differences were observed based on the presence of p.Arg4810Lys. A novel RNF213 RV was identified in four cases with qMMD. These same cases also presented with significant worsening of intracranial main artery stenosis, which suggests a possible association between RNF213 RVs and the severe progression of qMMD. Among the 36 MMA-related genes, no variants correlated with specific phenotypes. CONCLUSIONS: While the clinical implications of p.Arg4810Lys in cases with qMMD were not identified, the study findings suggest a potential association between RNF213 RVs and the significant progression of intracranial artery stenosis. Genetic analysis should not focus solely on p.Arg4810Lys but instead consider a comprehensive analysis of RNF213 for more accurate clinical prognostication of qMMD.

Association of Genetic Variants with Postoperative Donor Artery Development in Moyamoya Disease: RNF213 and Other Moyamoya Angiopathy-Related Gene Analysis.

Robust postoperative bypass development is a characteristic of moyamoya disease (MMD); however, genetic factors mediating this phenomenon remain incompletely understood. Therefore, we aimed to elucidate the relationship between postoperative donor artery development and genetic variants. We retrospectively enrolled 63 patients (79 hemispheres) who underwent combined revascularization surgery. Postoperative development of the superficial temporal artery (STA), middle meningeal artery, and deep temporal artery (DTA) was assessed using the caliber-change ratio determined from magnetic resonance angiography measurements. We analyzed RNF213 and 36 other moyamoya angiopathy-related genes by whole-exome sequencing and extracted rare or damaging variants. Thirty-five participants carried RNF213 p.Arg4810Lys (all heterozygotes), whereas 5 had RNF213 rare variants (RVs). p.Arg4810Lys was significantly associated with postoperative DTA development, while age at surgery, hypertension, and hyperlipidemia were inversely associated. Multiple regression analysis revealed that age and p.Arg4810Lys held statistical significance (P = 0.044, coefficient - 0.015, 95% confidence interval (CI) - 0.029 to 0.000 and P = 0.001, coefficient 0.670, 95% CI 0.269 to 1.072, respectively). Those with RNF213 RV without p.Arg4810Lys exhibited a significant trend toward poor DTA development (P = 0.001). Hypertension demonstrated a significant positive association with STA development, which remained significant even after multiple regression analysis (P = 0.001, coefficient 0.303, 95% CI 0.123 to 0.482). Following Bonferroni correction for multiple comparisons, targeted analyses of RNF213 and 36 moyamoya angiopathy-related genes showed a significant association of only RNF213 p.Arg4810Lys with favorable DTA development (P = 0.001). A comprehensive analysis of RNF213, considering both p.Arg4810Lys and RVs, may provide a clearer prediction of postoperative DTA development.

Cranial distraction osteogenesis for craniosynostosis associated with osteopetrosis: A case report.

Background: Osteopetrosis is a rare disease characterized by systemic osteosclerosis and hematopoietic disturbances. Childhood-onset cases are often accompanied by hydrocephalus and craniosynostosis; however, there have been no established treatments. We performed cranial distraction in a child with osteopetrosis who presented with craniosynostosis and intracranial hypertension. Case Description: The patient was a 4-year-1-month-old boy. His pregnancy and birth were normal, but at 4 months of age, he was diagnosed with osteopetrosis based on generalized osteosclerosis and family history. A computed tomography scan of the head revealed early sagittal suture fusion and ventricular enlargement. A ventriculoperitoneal shunt was placed for intracranial hypertension; however, slit ventricle syndrome ensued and pansynostosis developed. To improve uncontrolled high intracranial pressure, cranial distraction was performed for intracranial volume expansion. No perioperative hemorrhagic or infectious complications were observed. After the start of distraction, the intracranial pressure gradually decreased, and clinical findings such as disturbance of consciousness and bradycardia disappeared. Bone regeneration in the defect site was good, and the extension device was removed 6 months after the operation. Conclusion: For osteopetrosis with poorly controlled intracranial hypertension, cranial distraction was considered to be an effective treatment.

Prevention of retethering in untethering surgery of a tight filum terminale.

OBJECTIVE: Untethering surgery for a tight filum terminale is a common treatment with considerable efficacy and safety. On the other hand, retethering has been reported to occur. One of the major mechanisms of retethering is adherence of the cut end of the sectioned filum to the midline dorsal dural surface. To prevent retethering, the authors sectioned a filum terminale at the rostral level to the dural incision to keep the distance between the cut end of the sectioned filum and the dural incision and investigated whether this procedure decreased the occurrence of retethering. METHODS: Among the patients who underwent untethering surgery for a tight filum terminale between 2012 and 2016, patients followed up more than 5 years were included in the study. Symptoms, comorbid malformations, preoperative imaging, surgical details, perioperative complications, and long-term outcomes were reviewed retrospectively. RESULTS: Retrospective data for a total of 342 cases were included. The median age at surgery was 11 months (range 3-156 months). Preoperative MRI revealed 254 patients (74.3%) had a low-set conus. There were 142 patients (41.5%) with filar lipoma and 42 patients (12.3%) with terminal cyst. Syringomyelia was found in 29 patients (8.5%). In total, 246 patients (71.9%) were symptomatic and 96 patients (28.1%) were asymptomatic. There were no perioperative complications that required surgical intervention or prolonged hospitalization. The mean postoperative follow-up was 88 months (range 60-127 months). There were 4 patients (1.2%) with retethering who presented with bladder and bowel dysfunction. The mean time from initial untethering to retethering was 54 months (range 36-80 months). All 4 patients underwent untethering surgery, and preoperative symptoms resolved in 3 patients. CONCLUSIONS: The retethering rate after untethering surgery for a tight filum terminale in our series was lower than those in previously reported studies. Sectioning the filum terminale at the rostral level to the dural incision was considered an effective way to prevent retethering.

Sequential Middle Meningeal Artery Embolization after Burr Hole Surgery for Recurrent Chronic Subdural Hematoma.

Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) is a novel, minimally invasive treatment. The indications and treatment practices for MMAE are variable and remain controversial. This study aimed to evaluate a strategy involving sequential MMAE after burr hole surgery for treating recurrent CSDH. We performed a retrospective analysis of data from consecutive patients who had undergone MMAE using liquid embolic agents within approximately 2 weeks after burr hole surgery for recurrent CSDH from September 2020 to March 2022. We analyzed patient characteristics, procedural details, CSDH recurrence after MMAE, surgical rescue, and complications. Six of the nine patients who underwent MMAE for CSDH recurrence were male, and the median age was 85 (range, 70-94) years. Five of the nine patients were being administered antithrombotic agents. The median duration between the burr hole surgery and MMAE procedure was 10 (range, 3-25) days. Anterior and posterior convexity branches were targeted for embolization using low-concentration N-butyl cyanoacrylate (NBCA), and the abnormal vascular networks with a cotton wool appearance disappeared after embolization in all cases. The NBCA distribution was observed by high-resolution computed tomography during the procedure; in three of nine cases, the NBCA penetrated not only the MMA but also the inner membrane. No recurrence, surgical rescue, or complications were observed in any patient during the median follow-up period of 3 months. As a minimally invasive treatment for recurrent CSDH, sequential MMAE after burr hole surgery may be a safe and effective option for preventing recurrence.

Cerebrovascular Events During Treatment for Systemic Malignant Tumors in Patients with Moyamoya Disease.

OBJECTIVE: With the increasing incidence of malignancies, the importance of cancer-associated stroke is emphasized. Although moyamoya disease is a leading cause of stroke, no reports have documented cancer-associated stroke in patients with this condition. We aimed to investigate cerebrovascular events during malignancy treatments in patients with moyamoya disease. METHODS: A total of 405 patients with moyamoya disease who visited our hospital between January 2000 and March 2022 were retrospectively examined. We evaluated the management of moyamoya disease, presence of the ring finger protein 213 p.Arg4810Lys variant, treatments for malignant tumors, presence of cerebrovascular events during treatment, and follow-up periods and outcomes. RESULTS: Among the 405 patients, 17 patients with moyamoya disease (4.2%) were diagnosed with malignancies. Among patients aged 60 years and over, 7 out of 67 (10.4%) had malignancies. Of the 17 patients, 11 (64.7%) were symptomatic, and 7 (41.2%) had revascularization surgery. 9 patients were treated with oral antiplatelet drugs. There was no significant difference between the groups with and without malignancy regarding the presence of the ring finger protein 213 p.Arg4810Lys variant (80.0% vs. 62.7%, P = 0.33). All patients underwent surgical treatment, and 7 (41.2%) received chemotherapy. One death due to tumor progression was reported. No cerebrovascular event was observed during malignancy treatments and follow-up periods, which had a mean duration of 6 years. CONCLUSIONS: In our cohort, malignancy treatments in patients with moyamoya disease were safely conducted without cerebrovascular events. However, it is advisable to avoid hypotension, dehydration, hyperventilation, and long-term discontinuation of antiplatelet drugs during the treatment of malignant tumors.

Intentional Staged Clipping Following Previous Coil Embolization of Ruptured Aneurysm with a Branch Arising from the Neck: Technical Note.

AIM: To present a substitute strategy for clipping: coil embolization of the ruptured aneurysm followed by intentional, staged clipping. CASE DESCRIPTION: We treated five cases of ruptured intracranial aneurysms with branches arising from the neck. The mean aneurysm diameter was 4.4 mm. In the acute rupture phase, coiling was performed without adjunctive endovascular techniques with intentional preservation of the neck in all cases. To treat recurrence during follow-up, the previously coiled aneurysm was clipped, which did not occasion any complications. Postoperative imaging showed completely obliterated aneurysms and preserved branches. No rebleeding occurred during the interval between coiling and clipping, and no rebleeding or recurrence occurred after clipping. No treatment-related complications occurred after coiling and clipping. CONCLUSION: This two-stage strategy may be effective for hemostasis and branch preservation for small- and medium-sized ruptured aneurysms with a branch arising from the neck. This intentional two-stage strategy can be a substitute strategy for clipping in the acute rupture phase with an acceptable outcome if the patient cannot undergo clipping as the first-line treatment.

Evaluation of Middle Cerebral Artery Symmetry: A Pilot Study for Clinical Application in Mechanical Thrombectomy.

BACKGROUND: Endovascular mechanical thrombectomy (MT) has now evolved to become the standard treatment for acute ischemic stroke due to large vessel occlusion. Arterial perforation is a potential complication of MT, and the risk of this event during blind crossing the occlusion site has been elucidated. The intracranial arterial system shows morphological structural symmetry, so we investigated the utility of the bilateral symmetry of the proximal middle cerebral artery (MCA) as a preprocedural evaluation to predict hidden running course distal to the thrombus. METHODS: This study retrospectively analyzed 191 consecutive patients (mean age, 67.5 ± 15.5 years; 100 women) who underwent time-of-flight-magnetic resonance angiography in our institution. Four landmarks of the MCA were assessed: division pattern, early branching pattern, length, and course pattern. Each geometric property was compared between cerebral hemispheres. Frequencies of symmetry and symmetry breaking were assessed. RESULTS: In 91% (bifurcation type, 87%; trifurcation type, 4%), branching patterns of the left and right M1 were symmetrical. Early frontal and/or temporal branches were observed in 31%, and the presence/absence of early branches was symmetrical in 70% cases. In 19%, M1 was classified as short M1, and classifications were identical between hemispheres in 74%. Running course of the M1 was symmetrical in 63%. Two or more parameters were symmetrical in 181 cases (95%). CONCLUSIONS: The symmetry of bilateral M1-2 structures was demonstrated in most cases from the perspectives of 4 parameters. The MCA symmetry can predict the running course of the MCA before crossing the occlusion site and shows potential benefits for neurointerventionalists.

Acute Thrombectomy for Contralateral Internal Carotid Artery Occlusion after Revascularization Surgery for Quasi-moyamoya Disease: A Case Report.

Ischemic complications can occur after revascularization surgery for moyamoya disease, but acute contralateral internal carotid artery (ICA) occlusion is an extremely rare complication. The patient was a 51-year-old woman with no medical history. Left frontal lobe infarction and bilateral ICA terminal stenosis were identified by repeated transient right paresis and aphasia. We diagnosed her with quasi-moyamoya disease associated with hyperthyroidism and performed revascularization surgery for the symptomatic left side. Although neurological symptoms did not worsen immediately after the surgery, disturbance of consciousness, right conjugate deviation, and left paresis appeared 4 hr after the surgery. New infarction appeared in the right frontal lobe, and the blood signal beyond the right middle cerebral artery (MCA) disappeared on MRI and MRA. Mechanical thrombectomy (MT) using a suction catheter improved antegrade blood flow in the MCA. The left paresis remained at discharge (modified Rankin Scale score = 4), but she was able to walk independently 3 months after the operation and was independent at home. Acute contralateral ICA occlusion after revascularization for moyamoya disease is an extremely rare complication, but the symptoms can be severe and treatment should be considered. To the best of our knowledge, there have been no reports of MT for postoperative acute contralateral ICA occlusion. Since the results of endovascular treatment such as percutaneous transluminal angioplasty and stent placement for patients with moyamoya disease are poor, MT using an aspiration catheter could be a good treatment option.

Carotid Endarterectomy for Intractable Repetitive Stenosis Following Carotid Artery Stenting.

BACKGROUND: Restenosis after carotid artery stenting has raised concerns regarding the long-term durability of carotid stenting. Recurrent restenosis after multiple endovascular interventions may pose a challenge for clinicians. CASE DESCRIPTION: We encountered 2 cases of intractable restenosis after redo-carotid artery stenting and performed carotid endarterectomy. We removed the embedded stent and plaque simultaneously, used the internal shunting system, and performed patch angioplasty with no further recurrence. CONCLUSION: Carotid endarterectomy could be considered as a first-line treatment for recurrent stenosis that proves refractory to multiple endovascular interventions.

Trans-cell Approach through Closed-cell Stent for Middle Meningeal Artery Embolization in Recurrent Chronic Subdural Hematoma.

We report a case of recurrent chronic subdural hematoma (CSDH) treated using the trans-cell approach through a closed-cell stent for middle meningeal artery embolization (MMAE). A 77-year-old man with acute ischemic stroke due to anterior circulation tandem occlusion was treated with intracranial thrombectomy and carotid artery stenting using a closed-cell stent 5 years ago. He experienced head trauma after a fall, which then developed into a CSDH. Burr hole surgery was performed twice, followed by MMAE considering the high possibility of recurrence due to antiplatelet therapy and brain atrophy after ischemic stroke. A distal access catheter was inserted into the external carotid artery through the closed-cell stent, and a microcatheter was navigated in the middle meningeal artery. The anterior and posterior convexity branches were embolized with 16.7% N-butyl cyanoacrylate. The postoperative course was favorable, and CT at 3-month follow-up showed a decrease in the hematoma. Even after the placement of the closed-cell stent, endovascular treatment of the external carotid artery is possible and can be a therapeutic option using the trans-cell approach.

Initial Report of the Perioperative Platelet Aggregation Test Using Hematracer ZEN in Neuroendovascular Therapy.

Objective: We report the characteristics of the platelet aggregation test using Hematracer ZEN (HTZ; DS medical, Tokyo, Japan) during the perioperative period. Methods: Among patients undergoing neuroendovascular treatment (EVT) at our hospital between June 2019 and June 2020, 42 consecutive patients with preoperative dual antiplatelet therapy (DAPT) were included. Oral administration of aspirin (ASA) at 81 mg and clopidogrel (CLP) at 75 mg was started 7 days before treatment (Flow Diverter [FD]: 14 days before). We evaluated platelet aggregation activity the day before treatment (FD: 2 days before) using HTZ. We adjusted the CLP dose according to the platelet aggregation test in each patient. We evaluated the platelet aggregating activity after EVT in patients requiring an intracranial stent or in which CLP was adjusted before EVT. Results: Platelet aggregating activity was able to be evaluated in all patients. In the preoperative examination, the efficacy of CLP was insufficient in one patient (2.4%), optimal medical effects were confirmed in 16 (38.1%), mildly excessive effects were noted in 10 (23.8%), and highly excessive effects were noted in 15 (35.7%). Reassessment was performed postoperatively in 20 patients. We switched CLP to prasugrel in one patient in which the CLP efficacy was considered insufficient in the preoperative evaluation. We reduced the CLP dose in seven patients with marked overdose, and the optimum range was reached in all. We did not adjust the CLP dose in 12 patients judged to have optimal or mildly excessive effects preoperatively, but 4 exhibited highly excessive drug efficacy and required CLP reduction. No postoperative symptomatic cerebral infarction or intracranial hemorrhage was observed (mean observation period: 11 months, range: 4-16 months). Conclusion: The platelet aggregation test using HTZ was simple and inexpensive, and was useful for adjusting the dose of antiplatelet drugs, but its utility should be evaluated in more patients.

Extracranial carotid artery aneurysm with myeloproliferative neoplastic cell invasion.

The major causes of rare extracranial carotid artery aneurysms are arteriosclerosis, trauma, and radiation therapy. Here, we describe a patient with an extracranial carotid artery aneurysm caused by a myeloproliferative neoplasm. A 67-year-old woman underwent excision of an irregularly shaped aneurysm in the left common carotid artery and a saphenous vein graft without major complications. The pathologic findings revealed abscess formation and atypical megakaryocyte infiltration, which was also seen in her bone marrow, indicating that the aneurysm was caused by a myeloproliferative neoplasm.

Two cases of symptomatic common carotid artery occlusion treated by carotid endarterectomy with L-shaped ministernotomy.

BACKGROUND: Common carotid artery occlusion (CCAO) is rare. Symptomatic lesions are resistant to medical treatment and revascularization are often required, but there is no consensus on the treatment of CCAO. In this paper, two cases of symptomatic CCAO treated by carotid endarterectomy (CEA) with L-shaped ministernotomy, in which the lesions extended to the beginning part of the CCA, are reported. CASE DESCRIPTION: Case 1 involved a 74-year-old man who presented with transient left limb numbness and an abnormal right visual field. Cerebrovascular angiography showed that the right CCA was occluded immediately after its origin and blood was supplied from the posterior circulation. CEA was performed with an L-shaped ministernotomy that allowed exposure of the CCA origin with minimal invasion. There were no complications associated with the sternal incision and he was discharged with a modified Rankin Scale (mRS) score of 0. Case 2 involved a 70-year-old man who presented with left half-blindness. Magnetic resonance imaging showed infarction in the right posterior cerebral artery region and neck echo showed CCA pseudo occlusion just before the carotid bulb. A new infarction in the right middle cerebral artery region developed during hospitalization. CEA with partial sternotomy was performed. The patient was rehabilitated with no deterioration of neurological findings and transferred with an mRS score of 3. CONCLUSION: There were no complications resulting from partial sternotomy in the two cases presented. CEA with partial sternotomy could be an effective treatment option for CCAO in which the internal carotid artery is patent and thrombus extends to the proximal CCA.

Imaging of transgenic cricket embryos reveals cell movements consistent with a syncytial patterning mechanism.

The mode of insect embryogenesis varies among species, reflecting adaptations to different life history strategies [1, 2]. In holometabolous insects, which include the model systems, such as the fruit fly and the red flour beetle, a large proportion of the blastoderm produces an embryo, whereas hemimetabolous embryos generally arise from a small region of the blastoderm [3]. Despite their importance in evolutionary studies, information of early developmental dynamics of hemimetabolous insects remains limited. Here, to clarify how maternal and gap gene products act in patterning the embryo of basal hemimetabolous insects, we analyzed the dynamic segmentation process in transgenic embryos of an intermediate-germ insect species, the cricket, Gryllus bimaculatus. Our data based on live imaging of fluorescently labeled embryonic cells and nuclei suggest that the positional specification of the cellular blastoderm may be established in the syncytium, where maternally derived gradients could act fundamentally in a way that is similar to that of Drosophila, namely throughout the egg. Then, the blastoderm cells move dynamically, retaining their positional information to form the posteriorly localized germ anlage. Furthermore, we find that the anterior head region of the cricket embryo is specified by orthodenticle in a cellular environment earlier than the gnathal and thoracic regions. Our findings imply that the syncytial mode of the early segmentation in long-germ insects evolved from a dynamic syncytial-to-cellular mode found in the present study, accompanied by a heterochronic shift of gap gene action.