Differences in Scalp Tension Associated With Craniosynostosis Among Patients of Different Races.

BACKGROUND: Fronto-orbital advancement (FOA) is the gold standard treatment for craniosynostosis. Although FOA by gradual distraction has been practiced in Asia, it has not yet been accepted in Western countries. This may be attributable to differences in scalp tension among patients. PATIENTS AND METHODS: The extent of skin advancement was intraoperatively measured as skin tension among 12 European (France) and 16 Asian (Japan) patients older than 6 months (age, 9.63±3.78 y) who underwent cranioplasty. Skin tension was measured at 3 points (left, right, and middle) after a zigzag bicoronal incision was made. RESULTS: The skin tension measurements of European patients were as follows: left, 23.1±6.37 mm; middle, 18.5±3.85 mm; and right, 23.3±6.31 mm. Tension in the middle was significantly lower than that on the left and right (P<0.05). In contrast, the skin tension measurements of Asian patients were as follows: left, 12.8±1.49 mm; middle, 14.4±3.60 mm; and right, 13.0±1.74 mm. Tension in the middle was significantly higher than that on the left and right (P<0.05). In addition, skin tension was higher among European patients than among Asian patients. CONCLUSIONS: Scalp tension differed according to race. This should be considered when selecting appropriate treatment.

Geometric Morphometric Study on Distinguishing Metopic Craniosynostosis from Metopic Ridging.

Background: Craniosynostosis, a common congenital anomaly, results from premature fusion of the cranial sutures. One of the forms of craniosynostosis is premature fusion of the metopic suture, referred to as trigonocephaly, but the diagnosis of metopic suture synostosis remains controversial. The purpose of this study was to clarify, using geometric morphometric analysis, if a metopic ridge alone observed in cases of mild trigonocephaly represents a pathological phenomenon. Methods: Three different cranial morphologies were compared among patients up to 2 years old who were categorized into the true group, the mild group, and the normal group, based on the presence or absence of specific symptoms, history of cranioplasty for trigonocephaly, or lack of any abnormality on computed tomography. Using the obtained computed tomography images, 235 anatomical landmarks and semi-landmarks were plotted on the entire cranial surface for analysis of neurocranial morphology, and the cranial shapes represented by landmarks were analyzed using geometric morphometrics. Principal components of shape variations among specimens were then computed, based on the variance-covariance matrix of the Procrustes residuals of all specimens, and statistically analyzed. Results: The principal component analyses of the variations in endocranial shape, frontal bone shape, and occipital bone shape did not show any significant differences in cranial morphology between mild trigonocephaly and normal skulls; however, true trigonocephaly was found to differ significantly from mild trigonocephaly and normal skulls. Conclusions: These findings suggest that in assessments of cranial morphology, the presence of a ridge alone cannot be diagnosed as fundamentally pathological, and may represent normal morphology.

Delayed Stent Infection after Deployment of a Carotid Dual Layer Stent in Dialysis Cases.

Objective: Infection after carotid artery stenting (CAS) is rare. We report two dialysis cases of delayed stent infection associated with a carotid dual-layer stent (DLS), which occurred several months after deployment of the stent. Case Presentations: Case 1: A 74-year-old man receiving dialysis underwent CAS with DLS. Three months after CAS, the patient developed a high fever, neck pain, and neck swelling. Neck CT and carotid ultrasonography (CUS) indicated an abscess around the inserted DLS. The patient was treated with antibiotic agents and fully recovered. Case 2: A 73-year-old man receiving dialysis underwent CAS with DLS. Two months after CAS, this patient also developed a high fever, neck pain, and neck swelling. Contrast-enhanced neck CT indicated inflammatory effusion with an abscess and a giant infectious pseudoaneurysm. Endovascular stent graft reconstruction was employed urgently under antibiotic therapy to prevent its rupture. However, intracranial hemorrhage occurred postoperatively and left hemiparesis remained. Conclusion: Delayed carotid stent infection is a rare but severe complication. The use of a DLS might be avoided during CAS for dialysis cases.

Sulfonium Salt Reagents for the Introduction of Deuterated Alkyl Groups in Drug Discovery.

The pharmacokinetics of pharmaceutical drugs can be improved by replacing C-H bonds with the more stable C-D bonds at the α-position to heteroatoms, which is a typical metabolic site for cytochrome P450 enzymes. However, the application of deuterated synthons is limited. Herein, we established a novel concept for preparing deuterated reagents for the successful synthesis of complex drug skeletons with deuterium atoms at the α-position to heteroatoms. (dn -Alkyl)diphenylsulfonium salts prepared from the corresponding nondeuterated forms using inexpensive and abundant D2 O as the deuterium source with a base, were used as electrophilic alkylating reagents. Additionally, these deuterated sulfonium salts were efficiently transformed into dn -alkyl halides and a dn -alkyl azide as coupling reagents and a dn -alkyl amine as a nucleophile. Furthermore, liver microsomal metabolism studies revealed deuterium kinetic isotope effects (KIE) in 7-(d2 -ethoxy)flavone. The present concept for the synthesis of deuterated reagents and the first demonstration of a KIE in a d2 -ethoxy group will contribute to drug discovery research based on deuterium chemistry.

Comparative study of internal device vs. external device in Le Fort III distraction for syndromic craniosynostosis.

BACKGROUND: Le Fort III distraction for syndromic craniosynostosis is performed using internal or external devices. We compared the results of both devices. PATIENTS AND METHODS: We retrospectively evaluated 60 patients with syndromic craniosynostosis treated with Le Fort III distraction (internal or external device) between 2001 and 2021. We verified demographic data, surgery-related data, and complications using medical records. For each of the two devices, we compared the various factors associated with the device to each other. RESULTS: External deviceThirty-two patients with syndromic craniosynostosis were included. The mean age at surgery was 11.7 years, and the mean elongation length was 20.0mm. Class-III occlusion reoccurred in 11 patients and was significantly associated with age at surgery. Seven complications (device problems and others) were noted. Cranial pin slippage was significantly related to the elongation length.Internal deviceTwenty-eight patients with syndromic craniosynostosis were included. The mean age at surgery was 10.4 years, and the mean elongation length was 18.7mm. There were 15 complications, including device problems, zygomatic-maxillary fractures, and infections. Elongation length was significantly related to these complications. Class-III occlusion reoccurred in nine patients and was significantly related to age at surgery. CONCLUSION: This study found that complications are significantly more likely to occur in internal devices than in external devices, especially device infection. Our findings identified several factors that may assist surgeons in selecting between external and internal devices. The relationship between the amount of extension and device-related problems found in this study will be beneficial for solving these problems.

Long-Term Clinical Results of Two-Stage Total Ear Reconstruction of Microtia Using Autologous Cell-Engineered Chondrocytes.

BACKGROUND: Microtia repair requires a large volume of reconstruction material.In pediatric patients, the collectable volume of autologous cartilage is limited, and the impact of surgical invasion and donor-site morbidity can be particularly severe. The authors developed a new treatment method using cultured autologous human auricular chondrocytes that provides a sufficiently large volume of reconstruction material. METHODS: Approximately 1 cm2 of auricular cartilage was collected from the affected site. Chondrocytes were isolated and cultured with autologous serum to accelerate cell proliferation. The cells were subcultured and formed a gel-form mass without a scaffold. In our two-stage implantation, the cultured chondrocytes were first injected into the patient's lower abdomen, where the cells grew into a large, newly generated cartilage in 6 months. Thereafter, this cartilage was sculpted into an ear framework and subcutaneously reimplanted into the new ear location. Clinical outcomes were assessed over a long-term follow-up. RESULTS: Eight patients underwent surgery using cultured autologous auricular chondrocytes from 2002 to 2008. The patients' ages ranged from 6 to 10 years. The follow-up period ranged from 11 to 18 years. None of the patients experienced absorption of cultured chondrocytes after the second stage. Complications included one case of absorption and one case of allergic reaction in the first stage. CONCLUSIONS: The authors' patients represent the first successful cases of regenerative surgery for microtia using cultured chondrocytes. No malignant transformation, change in size, deformation, or other abnormalities were observed during the long-term follow-up, demonstrating the safety of cultured cartilage. No major complications occurred. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Factors Affecting Optic Nerve Damage in Le Fort III Osteotomy: A Retrospective Study.

The causes of visual impairment following Le Fort osteotomy for syndromic craniosynostosis have not been completely elucidated. The authors investigated the potential causes and means of prevention of optic nerve damage, with particular emphasis on intraoperative blood transfusion volume and operating time. This retrospective study evaluated patients who underwent Le Fort III osteotomy for syndromic craniosynostosis between 2000 and 2020. Data on pupillary reflex, pupil size, operating time, blood transfusion, age at time of surgery, sex, and syndrome type were obtained from medical records. Univariate analysis and multivariate analysis with the level of statistical significance set at P <0.05. For the 86 patients included, the mean values of operating time, amount of blood transfusion based on body weight, amount of blood transfusion per body weight per hour, and age were 6.0 hours (range: 3.5-12.3 h), 30.5 mL/kg (range: 0-322 mL/kg), 5.14 mL/kg/h (range: 0-35.7 mL/kg/h), and 10.0 years (range: 4-38 y), respectively. Crouzon, Apert, and Pfeiffer syndromes were observed in 49, 29, and 8 patients, respectively. Abnormal pupillary findings were observed in 27 patients of whom 25 showed no abnormalities in subsequent visual function and 2 developed blindness. Abnormal pupillary findings correlated with the amount of blood transfused per body weight ( P =0.0082) and amount of blood transfused per body weight per hour ( P =0.0052). As demonstrated in this study, increased intraoperative bleeding and amount of blood transfused were associated with optic nerve damage, particularly during acute bleeding. Prompt inspection of the pupils following surgery is therefore warranted.

[A case of cerebral embolism treated with early surgical intervention for aneurysm of sinus of Valsalva as embolic source].

The patient was a 78-year-old man. He was transferred to the emergency room presenting with aphasia and right hemiplegia. Head CT and CT angiography demonstrated a narrow territory of early ischemic signs and occlusion of the horizontal segment of the left middle cerebral artery (MCA), respectively. Endovascular thrombectomy was performed and complete recanalization of MCA was achieved. After admission, transthoracic echocardiography revealed a cystic mass near the left coronary apex of the aortic valve, which was diagnosed as an aneurysm of the sinus of Valsalva (ASV) by contrast-enhanced chest computed tomography. Transesophageal echocardiography showed a severe smoke-like echo within ASV, despite being in sinus rhythm. Intravenous anticoagulant therapy was started, and patch closure was performed by cardiovascular surgeons on the 13th day despite of early period after stroke onset. During the operation, no thrombus was seen around the inlet of ASV. On the two days after the operation, paroxysmal atrial fibrillation was detected and anticoagulant therapy was continued. In this patient, ASV was regarded as the embolic source of cerebral embolism, and anticoagulant therapy and surgical intervention were selected in the early period after stroke onset to prevent embolism recurrence, resulting in a favorable clinical course.

[Anti-myelin oligodendrocyte glycoprotein antibody-positive unilateral cerebral cortical encephalitis occurring first as general convulsion after meningitis symptoms and second after headache].

The case was a 30-year-old man. He had generalized convulsion after preceding meningitis symptoms and transferred to our emergency department. He was tentatively diagnosed with meningoencephalitis and Todd paralysis based on elevation of cell counts in cerebrospinal fluid and abnormal high signals in the right cerebral cortex on brain FLAIR-MRI, and admitted on the same day. After admission, treatment with antibiotics, dexamethasone, antiviral drug and anticonvulsants was started. Both his clinical symptoms and findings on MRI improved steadily, and then he was discharged on day 19. Subsequently, headache exacerbated again and an additional examination for his serum sample taken on first admission day revealed presence of anti myelin oligodendrocyte glycoprotein (MOG)-antibody, resulting in his diagnosis of anti-MOG antibody unilateral cerebral cortical encephalitis (MOG-UCCE) on day 42. Rehospitalization was planned for introduction of steroid therapy, but generalized convulsion recurred on day 44 and he was hospitalized again. MRI image revealed no FLAIR high signal and cerebrospinal fluid was almost normal, but his headache and mild hemiparesis and numbness on the left side deteriorated again. Therefore, he was treated with intravenous high dose methylprednisolone followed by oral steroids. His clinical symptoms gradually improved, and he was discharged with slight headache on day 71. After discharge, there has been no recurrence under continuation of low dose oral steroids for two years. This case shows the need to measure anti-MOG antibody and introduce steroid therapy in the early phase in a case of suspected MOG-UCCE in a young patient with meningoencephalitis accompanied by generalized convulsion and characteristic abnormal findings on FLAIR-MRI.

[A case of genetic Creutzfeldt-Jakob disease that required differential diagnosis of acute encephalopathy associated with Sjogren's syndrome].

An 86-year-old female was admitted to our hospital with acute progressive gait disturbance and cognitive impairment. Brain MR diffusion weighted imaging revealed abnormal high signal intensities in the bilateral hemispheres, dominantly in the frontal lobe. We first suspected acute encephalopathy due to Creutzfeldt-Jakob disease (CJD) from her clinical information. At the same time, we could not negate the possibility of Sjögren's syndrome (SjS) -related encephalopathy based on the abnormal findings on brain MRI and positive anti-SS-A antibody in the serum. After consulting with an otorhinolaryngologist and a pathologist, biopsy of the salivary gland was performed with a strict precaution against infection of prion virus. Pathological examination of the biopsy specimen showed accumulation of many lymphocytes around the gland, which satisfied grade 4 in the Greenspan classification. A definite diagnosis of SjS was made based on the pathological findings, and intravenous high dose methylprednisolone followed by oral prednisolone were administered for suspected SjS-related encephalopathy. However, the neurological symptoms did not improve and we judged that SjS-related encephalopathy was unlikely. The poor response to steroid therapy and the presence of tau protein, strongly positive 14-3-3 protein and a codon 180: Val/Ile mutation in the cerebrospinal fluid finally led to a clinical diagnosis of genetic CJD. In-hospital cooperation in terms of infection prevention is important when performing invasive procedure in the case of suspected CJD to distinguish treatable encephalopathy.

[A case of febrile infection-related epilepsy syndrome requiring prolonged intensive care management: a trial of intravenous ketamine and intrathecal dexamethasone therapy].

A 16-year-old male was brought to the emergency room with fever and status epilepticus, and was diagnosed with febrile infection-related epilepsy syndrome (FIRES). Seizure control was not achieved and the patient developed multiple complications. Ketamine infusion therapy and intrathecal dexamethasone therapy were administered, in addition to other anti-seizure treatment and immunotherapy for super-refractory status epilepticus (SRSE). The patient was weaned from the ventilator on day 170 and was able to live at home, although he continued to experience monthly focal motor seizures and moderate motor impairment. This case suggests that more aggressive treatment might be an option in FIRES with prolonged SRSE.

Present State of the Infection Protection System and Effects of a Change in the In-Hospital System in Endovascular Treatment for Large Vessel Occlusion in Acute Stroke Patients at a Single Institution.

Objective: Endovascular treatment (EVT) for large vessel occlusion in acute ischemic stroke patients during the SARS-CoV-2 epidemic requires the implementation of an in-hospital system to guard against infection. Changes to this system may be needed upon aggravation of the epidemic in a particular region. The objective of this study was to clarify the present state of infection protection and the effects of a change in the in-hospital system in EVT at a single institution. Methods: The subjects were consecutive patients treated by EVT under the protocol of infection protection using medical history and chest CT at our hospital between April 2020 and February 2021. For the subjects, background factors, time metrics, including door-to-puncture time (D2P), clinical outcome, and success of infection protection for medical staff were examined. The patients were divided into a group of those with PCR measurement after EVT (Group C; from April 2020 to November 2020) and a group of all with PCR measurement before EVT (Group P; from December 2020 to February 2021). Time metrics and clinical outcome were compared between the groups. Results: There were 69 subjects, including 40 and 29 patients in groups C and P, respectively. The median age was 82, which was higher in group P. The median D2P was 70 min, which did not differ significantly between the two groups, but it was slightly longer in group P than in group C by multivariate analysis. A favorable outcome (modified Rankin Scale 0-2 at 3 months) was observed in 23 patients (38%), which did not differ significantly between the two groups, but the rate of a favorable outcome was slightly lower in group P than in group C by multivariate analysis. Although medical staff wearing full personal protection equipment were needed for 15 patients (22%), 12 of whom were suspected of being positive and three (4%) were confirmed positive for SARS-CoV-2 by PCR, no staff member who participated in EVT was infected. Conclusion: The median D2P was 70 min and 38% had a favorable outcome of EVT under the present state of infection protection. After a change in the in-hospital system for clinical settings during the SARS-CoV-2 epidemic, the D2P increased and the rate of a favorable clinical outcome slightly decreased, but both were not significantly affected and infection protection for medical staff was effective. Therefore, the effects of a change were acceptable considering the circumstances.

[Eosinophilic granulomatosis with polyangiitis presenting with Guillain-Barré syndrome-like acute course. A case report].

A 57-years-old man with a history of bronchial asthma and pansinusitis developed acute progressive muscle weakness and sensory disturbance of the distal limbs after upper respiratory infection. On day 15 after onset of sensory disturbance and muscle weakness, the patient admitted to our hospital. A neurological examination revealed asymmetry weakness of both proximal and distal muscles, "glove and stocking type" hypoesthesia, and paresthesia without obvious pain. Blood tests and a nerve conduction study demonstrated eosinophilia and elevation of MPO-ANCA, axonal multiple mononeuropathy, respectively. The cerebrospinal fluid was normal. Eosinophilic granulomatosis with polyangiitis (EGPA) or Guillain-Barré syndrome (GBS) were suspected. So intravenous immunoglobulin therapy (IVIg) and high dose methylprednisolone pulse therapy (HDMP) followed by oral prednisolone were started. However, neurological symptoms did not improve. Sural nerve biopsy on day 31 revealed varying myelinating fiber loss at every nerve bundle and perivascular lymphocytic infiltration. The results did not fulfill the pathologic criteria for EGPA, but supported the changes of vasculitis. Cyclophosphamide (CPA) pulse therapy was administered for the additional therapy. Neurological symptoms did not improve and worsened again after decreasing oral prednisolone; therefore, combined therapy with IVIg, HDMP, and CPA was administered. Neurological symptoms then diminished gradually and the MPO-ANCA level and number of eosinophils normalized. This case suggests the importance of early nerve biopsy to obtain pathological findings supportive of EGPA diagnosis to allow introduction of aggressive immunosuppressive therapy such as CPA in a case with acute progressive motor-sensory neuropathy due to EGPA mimicking GBS.

Clinical Trial of the New Stent Retriever Tron FX for both Proximal and Distal Intracranial Large Vessel Occlusions.

BACKGROUND: In all of randomized controlled trials of mechanical thrombectomy, the target vessels were proximal. Herein we report a clinical trial of the Tron FX stent retriever, including the smallest size of 2/15 mm for distal intracranial large vessel occlusion (LVO). OBJECTIVE: Eligible patients presented within 8 h of onset with proximal or distal LVOs, and the Tron FX 4/20 mm or 2/15 mm were used as the first-line device. METHODS: The primary endpoints were rate of modified Thrombolysis in Cerebral Infarction (mTICI) grade 2a-3 immediately after using Tron FX only, and mortality rate 90 d. We compared the outcomes between sizes 4/20 and 2/15 mm. RESULTS: The clinical trial was conducted in 50 cases, of which 44% presented with distal LVO and 15 cases were treated using only Tron FX 2/15 mm. The overall rate of mTICI grade 2a-3 was 80.0% (75.8% with Tron FX 4/20 mm, and 86.7% with 2/15 mm), and a 90-day modified Rankin Scale ≤ 2 or improvement of National Institute of Health Stroke Scale after thrombectomy ≥ 10 was achieved in 66.7% of cases (61.3% with Tron FX 4/20 mm, and 80.0% with 2/15 mm). The overall 90-day mortality rate was 8.0%, and symptomatic intracranial hemorrhage within 24 h occurred in 2.0% of cases. CONCLUSION: In this clinical trial using the Tron FX, which included the size of 2/15 mm for distal LVO, its efficacy was similar and its safety was superior compared with previous studies.

Complications Due to Cranial Distraction for Craniosynostosis.

BACKGROUND: Complications of cranial distraction techniques can arise perioperatively. This study assessed long-term clinical outcomes following cranial distraction for craniosynostosis. We analyzed factors involved in those complications. METHODS: We retrospectively assessed outcomes from 120cases treated with cranial distraction for craniosynostosis between 1997 and 2019. Age at surgery, type of craniosynostosis, length of advancement, and complications were reviewed. We analyzed cases in which clinical characteristics and medical data appeared to increase the risk of complications. RESULTS: Of the 120 patients (65 males, 55 females), 79 had syndromic craniosynostosis and 41 had nonsyndromic craniosynostosis. Type of craniosynostosis was scaphocephaly in 17 patients, trigonocephaly in 4, plagiocephaly in 15, brachycephaly in 57, oxycephaly in 14, cloverleaf in 10, and others in 3. Mean age at surgery was 18.6 months (range, 3-525 months). Mean total length of advancement was 32.3 mm (range, 5.5-62.0 mm). No deaths were encountered. Complications included cerebrospinal fluid leaks in 5 patients, epidural abscess in 1, local infections in 33, device problems in 20, erosions and/or ulcers in 23 and decubitus ulcers in 8.Comparisons of complications and factors: Local infection showed no significant correlation with type of craniosynostosis, nor with the total length of advancement. Plate displacement showed significant relationships with total length of advancement, or with age at surgery (P < 0.01). CONCLUSION: These results suggested that local infection occurred independent of the type of craniosynostosis. Plate displacement and ulcers appear to occur more easily among patients with longer lengths of advancement or with surgery at a younger age, due to the weakness of the cranial bones.

Novel Suturectomy Using Absorbable Plates in Early Surgery for Craniosynostosis.

BACKGROUND: In craniosynostosis patients under 3 months of age, suturectomy is a valuable early treatment improving their outcomes. However, conventional suturectomy might not be in severe patients. The efficacy of our developed suturectomy using absorbable plates was examined. METHODS: Our method was indicated for craniosynostosis patients under 3 months old who had severe intracranial hypertension, scaphocephaly, plagiocephaly, or trigonocephaly between September 2011 and March 2018. All patients underwent suturectomy, and the bone edges on both sides of the cuts were covered with absorbable plates. Evaluation was conducted with 3-dimensional computed tomography and photographs, and cephalic index, distance from dorsum sellae to forehead on computed tomography were analyzed. RESULTS: Twenty-one of the 25 patients were evaluated. The preoperative cranial shapes were 4 brachycephaly, 6 scaphocephaly, 5 oxycephaly, 2 clover-leaf deformity, and 4 plagiocephaly. There were 9 syndromic and 12 nonsyndromic patients. The mean age at the time of surgery was 52.3 days (7-89), and the mean follow-up period was 3.5 years (1-8).The cephalic index and cranial definition improved in 18 patients. The secondary surgery was not required in four syndromic and none of the 12 nonsyndromic patients. There were no major complications. CONCLUSION: Placement of absorbable plates was able to prevent bone formation during the early postoperative period, and yet also promote bone formation after plate absorption. The authors believe syndromic craniosynostosis patients with severe deformities and nonsyndromic ones with scaphocephaly or plagiocephaly, successfully avoided secondary surgeries. This approach is less invasive for craniosynostosis and is expected to be highly effective.

[Autopsy case of cerebral embolism with lung cancer and atrial fibrillation in which the left atrium may have become an incubator for a tumor embolus].

An 82-year-old man with advanced lung cancer who had declined aggressive therapy was transferred to our hospital due to sudden-onset consciousness disturbance, global aphasia, and right hemiplegia. An electrocardiogram showed atrial fibrillation, and brain MRI and MRA revealed acute ischemic lesions of the left hemisphere and occlusion of the left internal carotid artery (ICA), respectively. We diagnosed acute ischemic stroke due to left ICA occlusion and performed endovascular thrombectomy, which resulted in complete recanalization of the left ICA after retrieval of the culprit embolus. Pathological examination of the retrieved thrombus revealed the presence of tumor tissue, as well as fibrin or red blood cells. Treatment was continued after admission, but the patient died of respiratory failure on day 40 of hospitalization. Autopsy revealed invasion of the tumor in the pulmonary vein, but not in the wall of the left atrium where thrombi were present. However, pathological examination of these thrombi in the left atrium revealed tumor tissue, along with fibrin or red blood cells. These findings suggest that the wall of the left atrium, in which lung cancer had not invaded, may be an incubator of a mixed embolus containing tumor tissue and thrombi in a case of cerebral embolism associated with both lung cancer and atrial fibrillation.