Intracranial volumetric evaluation in postnatally repaired myelomeningocele infants.

INTRODUCTION: Most myelomeningocele (MMC) cases present with ventriculomegaly or hydrocephalus, yet a comprehensive volumetric assessment of MMC intracranial structures is lacking. This study aimed to provide baseline data on intracranial structural volumes immediately after birth in MMC infants who underwent repair surgeries after birth (postnatal repair). METHODS: In this retrospective single-center study, we analyzed 52 MMC infants undergoing postnatal repair, utilizing head computed tomography scans at birth for volumetric assessment. Intracranial volume (ICV), lateral ventricles volume (LVV), choroid plexus volume (CPV), and posterior cranial fossa volume (PCFV) were measured. Hydrocephalus was classified into no hydrocephalus, progressive hydrocephalus, and hydrocephalus at birth. Comparative analysis employed the Wilcoxon rank-sum test. Receiver operating characteristic (ROC) analysis discriminated cases with and without ventriculoperitoneal shunt (VPS). RESULTS: The median values were 407.50 mL for ICV, 33.18 mL for LVV, 0.67 mL for CPV, and 21.35 mL for PCFV. Thirty-seven cases (71.15%) underwent VPS. ROC analysis revealed an LVV cut-off value of 6.74 mL for discriminating cases with and without VPS. Progressive hydrocephalus showed no significant difference in ICV but significantly larger LVV compared to no hydrocephalus. Hydrocephalus at birth demonstrated statistically larger ICV and LVV compared to the other two types. CONCLUSION: Baseline volumetric data were provided, and volumetric analysis exhibited statistical differences among three hydrocephalus types. These findings enhance our understanding of intracranial volumetric changes in MMC, facilitating more objective assessments of MMC cases.

Growth patterns and ratios of posterior cranial fossa structures in the Japanese pediatric population: a study utilizing CT scans.

PURPOSE: The changes in the proportion of posterior cranial fossa structures during pediatric development remain unclear. This retrospective study aimed to investigate the growth patterns and ratios of these structures using CT scans. METHODS: Head CT scans of pediatric patients with minor head trauma from Osaka Women's and Children's Hospital between March 2006 and May 2023 were analyzed. The study segmented the intracranial volume (ICV), posterior cranial fossa volume (PCFV), cerebellum volume (CBMV), and brainstem volume (BSV). Correlation coefficients were calculated among the parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean and standard deviation values were measured. Growth curves were created by plotting mean values sequentially. Ratios such as PCFV/ICV and (CBMV + BSV)/PCFV were examined. Statistical analyses, including unpaired t tests and logarithmic curve fitting, were performed. RESULTS: A total of 234 CT scans (97 from females, 115 from infants under 1 year of age) were analyzed. Positive correlations were observed among the parameters, with the strongest between PCFV and CBMV. The growth curves for ICV, PCFV, CBMV, and BSV exhibited a two-phase process, with rapid growth until approximately 4 years of age, followed by stabilization. The ratios PCFV/ICV and (CBMV + BSV)/PCFV showed increasing trends from birth onwards, stabilizing by 4 and 1 years of age, respectively. CONCLUSION: This study provides insights into the growth patterns and ratios of posterior cranial fossa structures in the pediatric population. The findings demonstrate a two-phase growth process and increasing trends in the examined ratios.

Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy.

We have previously revealed the overexpression of Wilms' tumor gene 1 (WT1) in malignant glioma and developed WT1 peptide vaccine cancer immunotherapy. A phase II clinical trial indicated the clinical efficacy of the WT1 peptide vaccine for recurrent malignant glioma. Here, we aimed to investigate the immunological microenvironment in glioma tissues before and after WT1 peptide vaccine treatment. Paired tissue samples were obtained from 20 malignant glioma patients who had received the WT1 peptide vaccine for > 3 months and experienced tumor progression, confirmed radiographically and/or clinically, during vaccination. We discovered that the expression of WT1 and HLA class I antigens in the tumor cells significantly decreased after vaccination. Maintenance of WT1 expression, which is the target molecule of immunotherapy, in tumor cells during the vaccination period was significantly associated with a longer progression-free and overall survival. A high expression of HLA class I antigens and low CD4+/CD8+ tumor-infiltrating lymphocytes (TIL) ratio in pre-vaccination specimens, were also associated with a good prognosis. No statistically significant difference existed in the number of infiltrating CD3+ or CD8+ T cells between the pre- and post-vaccination specimens, whereas the number of infiltrating CD4+ T cells significantly decreased in the post-vaccination specimens. This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy.

[Distraction Osteogenesis for Craniosynostosis].

Distraction osteogenesis is the standard surgical procedure for cranioplasty in children over 6 months of age. This technique carries a risk of detachment of the extender and infection during the course, but such troubles can be reduced by accumulating surgical experience. In addition, furing distraction osteogenesis, the cranium can be sufficiently expanded by slowly stretching the scalp, while adjustment ensures that the facial appearance does not change too much. In this paper, I will explain the surgical technique and postoperative management, focusing on FOA(Fronto-orbital advancement)for trigonocephaly or brachycephaly and BPE(Bilateral parietal expansion)for scaphocephaly. The point of surgery in FOA is the osteotomy of the orbital bar. The osteotomy can be performed safely and easily using a wire saw. The aim of surgery in BPE is to extend an osteotomy up to the front of the coronal suture and down to the part near the cranial floor. This allows improvements of the cranial shape while sufficiently increasing the cranial volume.

Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.

We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3 . WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients.

Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response.

To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.

Clinical and radiological features of endodermal cyst in the oculomotor nerve: A case report.

We present a 9-year-old girl with an endodermal cyst of the oculomotor nerve in the left interpeduncular cistern, who had a history of left ptosis. We suggest that a cyst localized at the exit of the oculomotor nerve from the midbrain associated with oculomotor palsy may suggest this rare entity.

Unexpected Cerebral Hyperperfusion after Transient Hypoperfusion Associated with Stroke-like Migraine Attacks after Radiation Therapy Syndrome.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome, a delayed sequela of cranial radiotherapy encountered rarely, occurs due to transient neurological deficits coupled with migraine episodes. This case report describes an occurrence of SMART syndrome in an individual 8 years after receiving medulloblastoma treatment. The subject, a 21-year-old male, experienced abrupt aphasia and right-sided hemiparesis. Arterial spin labeling (ASL) revealed initial cerebral hypoperfusion in the left temporal and parietal regions, with no tumor resurgence or notable ischemic alterations. Two days later, the symptoms disappeared completely; nevertheless, at that time, ASL presented cerebral hyperperfusion in the same lobule. The subject experienced a pulsating headache and nausea the next day. In the context of SMART syndrome, this fluctuation in cerebral blood flow indicated by ASL is a unique finding. The significance of this case lies in the documentation of the dynamic evolution of cerebral perfusion in SMART syndrome via ASL, thereby elucidating its underlying pathophysiology. As hemiplegic migraine shows a similar cerebral perfusion pattern to SMART syndrome, we inferred an unexplored but shared pathophysiology among hemiplegic migraine and SMART syndrome. Through this successful capture of these distinct cerebral blood flow alterations, from hypoperfusion to hyperperfusion, our understanding of the pathophysiological intricacies inherent to SMART syndrome will be enhanced.

Normal growth curve of choroid plexus in children: implications for assessing hydrocephalus due to choroid plexus hyperplasia.

OBJECTIVE: Pediatric hydrocephalus requires evaluation while accounting for growth of the intracranial structures, but information on choroid plexus growth in children is lacking. This study aimed to create normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Additionally, the authors aimed to objectively assess the degree of hydrocephalus caused by choroid plexus hyperplasia (CPH) and to examine the impact of surgical procedures. METHODS: This retrospective study analyzed the head CT scans of pediatric patients with minor head trauma treated at Osaka Women's and Children's Hospital between March 2006 and May 2023. The study segmented and calculated intracranial, choroid plexus, and lateral ventricles volumes. The study also calculated the correlation coefficients among these 3 parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean ± SD values were calculated for each cluster. Growth curves were created by plotting mean values sequentially. Volume obtained from patients with CPH were z-normalized using mean and SD values and compared. RESULTS: A total of 229 CT scans (94 from females) were analyzed, and positive correlations were observed among intracranial volume, choroid plexus volume, and lateral ventricles volume, with the strongest correlation between the choroid plexus and lateral ventricles volumes. The growth rate of intracranial volume was rapid until approximately 20 months of age, while those of choroid plexus volume and lateral ventricles volume increased rapidly until approximately 1 year of age. Subsequently, choroid plexus volume and lateral ventricles volume plateaued at 1.5 ml and 10 ml, respectively. Three patients with CPH were enrolled and quantitatively evaluated on the basis of the z-normalized volume. Notable abnormal volumes of the choroid plexus (range z-normalized values 24.11-51.17) and lateral ventricles (46.78-122.36) were observed. In 2 patients, improvements in the z-normalized values of intracranial volume and lateral ventricles volume were observed after surgical interventions. Additionally, in 1 patient, choroid plexus volume was reduced by approximately 24% (range z-normalized values 51.17-38.93) after bilateral endoscopic plexus coagulation. CONCLUSIONS: This study provides normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Knowledge of these normal values holds the potential for objective assessment of abnormal values associated with hydrocephalus and choroid plexus diseases such as CPH.

Six-month survival of a monochorionic monoamniotic twin with sirenomelia.

BACKGROUND: Sirenomelia is a congenital malformation of the lower body characterized by a single midline lower limb and severe urogenital and gastrointestinal malformations. Sirenomelia is rare (estimated incidence of approximately 1/100,000) and usually lethal in the perinatal period. CASE: A 2,042 g Japanese male infant, one of monochorionic monoamniotic twins, was born at 34 weeks of gestation by elective caesarean section. Sirenomelia was prenatally diagnosed. Single midline lower limb, bilateral dysplastic kidneys, an omphalomesenteric fistula, colon atresia, imperforate anus, indiscernible genital structures, and myelomeningocele were detected at birth. The amniotic fluid volume was normal throughout the pregnancy course, which led to appropriate lung maturation of the twin with sirenomelia. Although renal replacement therapy was initiated soon after birth, stable peritoneal dialysis was difficult because of the limited intraperitoneal space, and the infant frequently developed peritonitis. He died of sudden cardiorespiratory arrest at 6 months of age. Postmortem examination showed bilateral dysplastic kidneys, agenesis of the ureters and urinary bladder, abnormal branching and agenesis of the distal colon, bilateral inguinal hernias, and small testes. CONCLUSION: Infants with sirenomelia, even those with end-stage kidney disease at birth, may survive if they have a stable cardiorespiratory status at birth and renal replacement therapy is appropriately initiated.