Effects of superficial temporal artery to middle cerebral artery bypass on postoperative infarction rates among young children (≤ 5 years old) with moyamoya disease.

Revascularization surgery for young children with moyamoya disease (MMD) is challenging. Although indirect revascularization is preferred because of the technical difficulty in direct anastomosis, higher risks of postoperative infarction remain a problem. We aimed to investigate the effect of superficial temporal artery to middle cerebral artery (STA-MCA) bypass on postoperative outcomes during the acute postoperative period in young children ≤ 5 years old with MMD. This retrospective study included consecutive young children with MMD who underwent surgical revascularization of the anterior cerebral circulation. Groups were determined according to the procedures performed, namely, the combined (STA-MCA bypass with indirect revascularization) and the indirect revascularization groups. The incidences of radiological or symptomatic infarction, transient neurological events, and new neurological deficits that remained at discharge were compared between groups. Of 38 surgical procedures, there were 23 combined and 15 indirect revascularizations. The median age of the patients was 3.0 years, which was significantly different between groups (P < .01). When comparing the postoperative outcomes between groups, the incidences of radiological and symptomatic infarction and new neurological deficits that remained at discharge were significantly lower in the combined revascularization group (P < .05). Logistic regression analysis adjusted for potential confounders found that surgical modality was a statistically significant independent risk factor associated with radiological and symptomatic infarctions (indirect/combined, odds ratio: 10.2; 95% confidence interval: 1.30-79.7; P < .05). STA-MCA bypass combined with indirect revascularization can reduce the incidence of postoperative infarction in young children with MMD and might lead to better neurological outcomes.

Long-Term Effects on Preventing Stroke after Endovascular Treatment or Bypass Surgery for Intracranial Arterial Stenosis.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of ischemic stroke worldwide due to its higher risk of recurrence with medical therapy. Although some large randomized studies failed to show the superiority of surgical treatment compared with medical therapy, the results of medical therapy are not sufficient. There are patients who still benefit from surgical treatment. This retrospective analysis aimed to evaluate the long-term efficacy of surgical therapy with percutaneous transluminal angioplasty and/or stenting (PTA/PTAS) or extracranial-intracranial (EC/IC) bypass surgery for patients with ICAS. METHODS: Between October 2005 and December 2016, 55 ICAS patients were treated with PTA/PTAS or EC-IC bypass surgery. Their electronic medical records were retrospectively reviewed and analyzed. The primary outcome was all adverse events beyond 30 days after a revascularization procedure. RESULTS: We performed 21 cases (35%) of PTA, 4 cases (7%) of PTAS, and 34 cases (58%) of EC-IC bypass surgery and the median follow-up duration was 66 months (range 1-144 months). The occurrence rate of the primary outcome was 10.2% and only 1 patient (1.8%) experienced ipsilateral disabling ischemic stroke beyond 30 days. The long-term functional independent survival rate was 83.6%. CONCLUSIONS: We demonstrated a long-term favorable outcome of combined surgical intervention for ICAS patients with PTA/PTAS and EC-IC bypass surgery, and the result was better than previously reported outcomes of medical therapy. Additional multicenter studies are required to draw firm conclusions on the efficacy of reduction of recurrent stroke in patients with ICAS.

Tumor Volume Decrease via Feeder Occlusion for Treating a Large, Firm Trigone Meningioma.

Trigone meningiomas are considered a surgical challenge, as they tend to be considerably large and hypervascularized at the time of presentation. We experienced a case of a large and very hard trigone meningioma that was effectively treated using initial microsurgical feeder occlusion followed by surgery in stages. A 19-year-old woman who presented with loss of consciousness was referred to our hospital for surgical treatment of a brain tumor. Radiological findings were compatible with a left ventricular trigone meningioma extending laterally in proximity to the Sylvian fissure. At initial surgery using the transsylvian approach, main feeders originating from the anterior and lateral posterior choroidal arteries were occluded at the inferior horn; however, only a small section of the tumor could initially be removed because of its firmness. Over time, feeder occlusion resulted in tumor necrosis and a 20% decrease in its diameter; the mass effect was alleviated within 1 year. The residual meningioma was then totally excised in staged surgical procedures after resection became more feasible owing to ischemia-induced partial softening of the tumor. When a trigone meningioma is large and very hard, initial microsurgical feeder occlusion in the inferior horn can be a safe and effective option, and can lead to necrosis, volume decrease, and partial softening of the residual tumor to allow for its staged surgical excision.

Development of Pyriform Sinus Suctioning Programs for Aspiration Pneumonia Prevention During the Acute Stroke.

Aspiration due to dysphagia is a factor associated with pneumonia during acute stroke. In such cases, it is likely that secretions in the pyriform sinuses enter the laryngeal inlet. The present study was based on the idea that it is possible to reduce aspiration pneumonia by periodically suctioning and removing such secretions (pyriform sinus suctioning), a study was conducted in a single facility. The incidence of pneumonia as a dependent variable was compared between before (control) and after (intervention group) intervention with pyriform sinus suctioning as an independent variable. With a view of unifying the quality and frequency of intervention, two programs to: initially confirm the safety of such suctioning; subsequently enhance/evaluate knowledge and skills related to the procedure (educational); and specify conditions for the implementation and criteria for determining its appropriateness (practical), were developed. The study involved 33 (mean age: 74.6 ± 12.4) and 30 (80.0 ± 8.8) control and intervention group members, respectively, 25 (83.3%) of the latter were treated with pyriform sinus suctioning for 5 days after a stroke. Pneumonia developed in 7 (21.2%) and 2 (6.7%) of the former and latter, respectively. As individuals with a Japan Coma Scale (JCS) score of III or a midline shift on head CT tend to develop pharyngeal dysphagia, the patients were also divided into 2 groups to compare the incidence of pneumonia based on the risk level: low: Japan Coma Scale scores of I-II without a midline shift on head CT; and high: scores of II-III with it. In the latter, the incidence after intervention was markedly lower (p = 0.06, φ = 0.326), while the former did not show changes (p = 0.574, φ = 0.066), supporting the effectiveness of pyriform sinus suctioning to prevent aspiration pneumonia among patients with a low risk level.

Ruptured partially thrombosed anterior inferior cerebellar artery aneurysms: two case reports and review of literature.

Aneurysms arising from the distal anterior inferior cerebellar artery (AICA) are very rare. When the parent artery is an AICA-posterior inferior cerebellar artery (PICA) variant, occlusion of the artery, even distal to the meatal loop, leads to a significant area of cerebellar infarction. We report two cases of ruptured partially thrombosed distal AICA aneurysms. In both cases, the parent artery was an AICA-PICA variant. The aneurysms were clipped in one case and trapped following occipital artery (OA)-AICA anastomosis in another case. It is important to keep the OA as a donor artery for revascularization in the treatment of the AICA-PICA variant aneurysms, especially when the absence of intra-aneurysmal thrombus is not comfirmed preoperatively.

Fungal Internal Carotid Artery Aneurysm Treated by Trapping and High-Flow Bypass: A Case Report and Literature Review.

We report a case of unruptured fungal internal carotid artery (ICA) aneurysm and review the pertinent literature. A 79-year-old man presented with decreased visual acuity on the right side, and he was diagnosed with retrobulbar optic neuritis. Medical treatment with steroids resulted in Aspergillus meningoencephalitis spreading to the bottom of bilateral frontal lobes, caused by an intracranial extension of sphenoid sinusitis. Magnetic resonance imaging (MRI) performed 26 days after the start of antifungal therapy showed a denovo right ICA aneurysm projecting anteriorly into the sphenoid sinus. As the aneurysm grew rapidly, it was trapped surgically after establishing a high-flow bypass from the external carotid artery to the middle cerebral artery. The patient's postoperative course was uneventful. Anti-fungal medication was continued until plasma concentrations of beta-D-glucan decreased to within normal limits. Although fungal ICA aneurysm carries a high mortality rate, early detection and prompt treatment by trapping and high-flow bypass can lead to good clinical outcome.

Outcomes in two Japanese adenosine deaminase-deficiency patients treated by stem cell gene therapy with no cytoreductive conditioning.

OBJECTIVE: We here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical trials, its results provide insights into SCGT for ADA deficiency. PATIENTS AND METHODS: Pt 1 was treated at age 4.7 years, whereas pt 2, who had previously received T-cell gene therapy, was treated at age 13 years. Bone marrow CD34(+) cells were harvested after enzyme replacement therapy (ERT) was withdrawn; following transduction of ADA cDNA by the γ-retroviral vector GCsapM-ADA, they were administered intravenously. No cytoreductive conditioning, at present considered critical for therapeutic benefit, was given before cell infusion. Hematological/immunological reconstitution kinetics, levels of systemic detoxification, gene-marking levels, and proviral insertion sites in hematopoietic cells were assessed. RESULTS: Treatment was well tolerated, and no serious adverse events were observed. Engraftment of gene-modified repopulating cells was evidenced by the appearance and maintenance of peripheral lymphocytes expressing functional ADA. Systemic detoxification was moderately achieved, allowing temporary discontinuation of ERT for 6 and 10 years in pt 1 and pt 2, respectively. Recovery of immunity remained partial, with lymphocyte counts in pts 1 and 2, peaked at 408/mm(3) and 1248/mm(3), approximately 2 and 5 years after SCGT. Vector integration site analyses confirmed that hematopoiesis was reconstituted with a limited number of clones, some of which were shown to have myelo-lymphoid potential. CONCLUSIONS: Outcomes in SCGT for ADA-SCID are described in the context of a unique protocol, which used neither ERT nor cytoreductive conditioning. Although proven safe, immune reconstitution was partial and temporary. Our results reiterate the importance of cytoreductive conditioning to ensure greater benefits from SCGT.

Determination of the deletion breakpoints in two patients with contiguous gene syndrome encompassing CYBB gene.

X-linked chronic granulomatous disease is a primary immunodeficiency caused by mutations in CYBB. Although large deletions involving CYBB are known to cause contiguous gene syndrome (CGS), only a few patients have been studied precisely at the molecular levels. Our study determined the deletion breakpoints in two patients with CGS involving CYBB by array comparative genomic hybridization and the following PCR and DNA walking studies. The deletion size was 3.5 Mb in Patient 1 and 0.8 Mb in Patient 2. There were no homologous architectural features between the telomeric and centromeric breakpoint junctions in the deletions of either patient. However, the telomeric breakpoint of Patient 2 was embedded in a stretch of low-copy repeats and the centromeric breakpoint was also embedded in a stretch of short segments with significant sequence homology. These findings suggest the potential involvement of genome architecture in stimulating genomic rearrangements in Patient 2.

A 5-year-old boy with unicentric Castleman disease affecting the mesentery: utility of serum IL-6 level and (18)F-FDG PET for diagnosis.

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology. It is quite difficult to diagnose CD without typical localized signs or symptoms. We present a 5-year-old boy with unicentric plasma cell CD in the mesentery, which was too small to be detected by any conventional imaging. (18)F-fluorodeoxyglucose positron emission tomography image and a serum cytokine profile prompted us to perform a curative surgical excision, confirming his diagnosis. Our case also supported an important role of interleukin-6 in the pathophysiology of plasma cell CD.

Stem cell transplantation in primary immunodeficiency disease patients.

BACKGROUND: Primary immunodeficiency diseases (PID) are rare but have a high associated risk of death from overwhelming infection in early childhood. Stem cell transplantation (SCT) can be curative for PID, but standardized protocols for each disease have not yet been established. METHODS: Between May 1995 and May 2005, nine patients diagnosed with a PID received SCT at the Department of Pediatrics, Hokkaido University Hospital. The median age of the patients (eight boys and one girl) was 1.0 year (range: 6 months-4 years). Five patients had Wiskott-Aldrich syndrome (WAS), three had severe combined immunodeficiency (SCID), and one had X-linked hyper-IgM syndrome (X-HIGM). Four patients received bone marrow transplantation (BMT), and five received cord blood stem cell transplantation (CBSCT). All patients, including those with SCID, received a conditioning regimen: six (WAS and X-HIGM) received a myeloablative conditioning regimen, and three (SCID) received a reduced-intensity conditioning regimen. RESULTS: All the patients are alive and have stable, complete chimerism, based on a median follow-up period of 4 years. Moreover, all patients have good immune reconstitution, and none required immunoglobulin replacement therapy. Two patients had significant acute graft-versus-host disease (GVHD), and three patients had chronic GVHD. Four of the nine patients developed cytomegalovirus (CMV) infection after SCT. CONCLUSION: The transplantation procedures appear to have provided a permanent cure in nine PID patients. Early diagnosis and prompt performance of SCT with an optimal donor and conditioning regimen contributed to the favorable outcomes.

Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome.

A 14-year-old Japanese girl with a progressing combined immunodeficiency had developed non-Hodgkin's diffuse large B cell lymphoma. Her molecular analysis showed a compound heterozygote of novel mutations in the LIG4 gene, M249V substitution and a five nucleotides deletion from nucleotide position 1,270-1,274. She had also a set of characteristic clinical features of LIG4 syndrome. Mutations in the LIG4 gene, which plays a critical role in the repair of DNA double-strand breaks, imply a correlation with malignancies and several cases with leukemia or lymphoma have already been reported. We report here on a case of LIG4 syndrome complicated with distinct EBV-associated B-cell lymphoma.

Epitope mapping of anti-alpha-fodrin autoantibody in juvenile Sjögren's syndrome: difference in major epitopes between primary and secondary cases.

OBJECTIVE: Juvenile Sjögren's syndrome (SS) is an early-onset type of SS. Autoantibody against the N-terminal 120 kDa form of a-fodrin is a specific and sensitive disease marker for both juvenile and adult SS. We investigated the initial and major determinants of a-fodrin in SS. METHODS: Sera were obtained from patients with juvenile SS, 10 with primary SS and 10 with secondary SS. Epitope specificities of IgG antibodies were examined by dot-blot analyses using overlapping fusion proteins of the N-terminal part (561 amino acid residues) of a-fodrin as antigens. RESULTS: All sera from patients with primary SS reacted with amino acid residues 1 to 98 and 36 to 150, but not with 91 to 199. Epitope mapping using fusion proteins with subfragments, each consisting of about 50 amino acid residues, showed reactivity with amino acid residues 27-80 and 79-132, suggesting that at least 2 epitopes are contained in the first 150 amino acid residues. All 3 cases with neurological complications had additional epitope specificities. Sera from patients with secondary SS showed more diversified specificities and strongly reacted with amino acid residues 1-98 and 334-432, whereas the reactivities to 36-150, a major epitope in primary SS, were minimal. CONCLUSION: Major and initial B cell epitopes specifically reside in N-terminal amino acids 36-132 and could be used as a diagnostic tool for primary SS. The epitope subsequently expands to other regions of a-fodrin in association with the development of neurological complications or disease progression. Secondary SS has distinct epitope specificities.