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.

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.

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.

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.

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.

Rare Median Cleft-Lip Repair With Novel Surgical Procedures Using Bilateral Cleft Margin Flaps.

Reports of median cleft lip with nasal anomalies are few, and descriptions of concomitant surgical repair of a median cleft lip and bifid nose deformity are similarly rare. These surgical repair techniques mainly involve the use of normal neighboring structures. Reconstruction of the columella and nasal base is especially important. A new surgical procedure was examined using bilateral cleft margin flaps for patients with a rare median cleft lip. Two patients with a rare median cleft lip were indicated for the procedure. One patient was 3 months old at surgery, and the other patient was 6 months old. These patients underwent single-stage reconstruction of the lip and nose. The new surgical procedure is characterized by the reconstruction of the columella, which involves creating a supportive structure using a cleft margin flap; subsequently, an anterior covering is created using a hinge flap from the nasal tip. Upper lip formation is performed by repair of the orbicularis oris muscle and rotation advancement of a cutaneous and mucosal flap from the lateral segments. The postoperative follow-up period was 4 to 5 years. The postoperative appearance was satisfactory in both patients. Furthermore, no significant complications were observed postoperatively. In conclusion, the surgical procedure with bilateral cleft margin flaps described in this report allows for successful reconstruction of a median cleft lip. This procedure is effectively tissue saving and results in satisfactory outcomes, which are maintained over a long term.

Repair of the Nasal Floor by the Cleft Margin Flap in Bilateral Complete Cleft Lip.

Bilateral complete cleft lip deformity has been the most challenging to plastic surgeons, and lots of methods of repair have been described in the literature. The basic principles are to achieve continuity of the orbicularis oris muscle, a balanced Cupid's bow with nasal ala, and a complete reconstruction of the nasal floor. The last one is, however, easily neglected. A well-reconstructed nasal floor serves as a good support of the nasal cartilage, which minimizes secondary deformity. In addition, a nasal floor with sufficient soft tissue and minimal contracture makes bone grafting easier in the future. The cleft margin flap was first introduced by Tajima in 1983 and used for the nasal floor repair in the unilateral complete cleft lip. The authors have used this technique in bilateral complete cleft lip repair, and from our practice, tension-free repairs of the nasal floors could easily be achieved by the cleft margin flaps. The results were satisfying and no significant scar contracture or deformity of the nasal floor was observed during follow-up. The authors conclude that the cleft margin flaps are viable and alternative choices for the repair of the nasal floors in bilateral complete cleft lip without major complications.

Frontal Hyperostosis in the Patients of Craniosynostosis After Cranial Distraction Osteogenesis.

BACKGROUND: Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors' practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon. MATERIALS AND METHODS: From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor. RESULTS: A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction. CONCLUSION: Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.

Cosmetic Comparison Between the Modified Uchida Method and the Mustarde Method for Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome.

PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare, congenital, surgically challenging disease. We undertook an objective, functional, and cosmetic comparison between the modified Uchida procedure and the Mustarde procedure on Asian patients with BPES. DESIGN: This is a retrospective, comparative, interventional case series with the description of 2 surgical techniques. PARTICIPANTS: Twenty consecutive Japanese patients with BPES were studied. METHODS: The patients were assigned to either the modified Uchida or the Mustarde procedure on the basis of preoperative intercanthal distance (ICD) ratio (ICD/palpebral fissure width). Intercanthal distance and margin reflex distance were measured from photographs before and after surgery. Classifications were made according to epicanthal fold score and cosmetic score using a visual analog scale (VAS). MAIN OUTCOME MEASURES: The main outcome measures were postoperative improvement in ICD ratio and the VAS. RESULTS: Of the 20 patients, 5 underwent the modified Uchida procedure and the other 15 underwent the Mustarde procedure. The preoperative median ICD ratio was 2.0 (range, 1.9-2.5) and 2.5 (range, 2.0-3.4) for the modified Uchida and Mustarde procedures, respectively, and decreased to 1.5 (range, 1.5-1.7) and 1.6 (range, 1.5-1.8) postoperatively. The mean ICD reduction rate was 35.7% (SD, 1.0%) in the Mustarde group and 22.1% (SD, 1.3%) in the modified Uchida group (P < 0.001).The mean VAS for the modified Uchida and Mustarde procedures was 5.9 (SD, 1.3) and 2.8 (SD, 1.1), respectively, which was statistically significant (P = 0.0166). CONCLUSIONS: Both the modified Uchida and Mustarde procedures could effectively shorten the ICD; however, cosmetic results were significantly superior using the modified Uchida method.

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.

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema: part 2.

Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although our previous compound 1 showed potent VAP-1 inhibitory activity, the activity differed between humans and rats. This issue was overcome by a hybrid design using human VAP-1 specific inhibitor 2, which was found by high-throughput screening (HTS), a docking study of a human VAP-1 homology model, and an analysis of sequence information for humans and rats. As a result, we identified compound 35c, which showed strong VAP-1 inhibitory activity (human IC(50) of 20 nM; rat IC(50) of 72 nM) and significant inhibitory effects in the ex vivo test.

Preoperative and postoperative orbital volume in patients with Crouzon and Apert syndrome.

Crouzon and Apert syndromes are frequently complicated by ocular abnormalities and patients with these syndromes often present with abnormal ocular morphology. The present study assesses orbital volume and ocular complications in patients associated with Crouzon and Apert syndromes.During an 8-year period starting in 2002, fronto-orbital advancement was used for cranial expansion on 23 cases of syndromic craniosynostosis. Of those, it was possible to evaluate 5 Crouzon and eight Apert syndrome cases. Orbital volume was measured using multislice CT scans. Both preoperative and postoperative orbital volumes were compared with normal orbital volume.Preoperative orbital volume was 5.8 to 10.0 cm (mean, 7.1 cm) in patients with Crouzon syndrome and 7.2 to 10.8 cm (mean, 9.1 cm) in patients with Apert syndrome. Postoperative intraorbital volume was 9.4 to 11.2 cm (mean, 10.4 cm) in patients with Crouzon syndrome and 11.6 to 13.2 cm (mean, 12.4 cm) in patients with Apert syndrome. The mean of orbital volume relative to the normal volume was 58% preoperatively and 74% postoperatively in patients with Crouzon syndrome and 69% (56-81%) preoperatively and 88% (81-95%) postoperatively in patients with Apert syndrome.In conclusion, orbital volume was smaller in the Crouzon syndrome group than in the Apert syndrome group, and symptoms, such as exophthalmos and exotropia, were noted in the Crouzon syndrome group. Orbit expansion did not fully restore normal orbital volume, but in most cases, it was useful for alleviation of preoperative symptoms (exophthalmos/eyeball prolapse, corneal erosion, conjunctivitis).

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.

Influences of pyrexia and age on theophylline clearance in young children with asthma.

Fifty hospitalized children with asthmatic bronchitis and bronchial asthma were treated with a continuous intravenous drip infusion of aminophylline. To investigate the pharmacokinetics of theophylline in the presence of pyrexia, patients were divided into two groups based on body temperature: a pyrexia group (> or = 38 degrees C) and a non-pyrexia group (< 38 degrees C). Theophylline clearance was 0.064 +/- 0.017 liters/kg/hr in the non-pyrexia group and 0.049 +/- 0.010 liters/kg/hr in the pyrexia group. Theophylline clearance in the non-pyrexia and pyrexia groups was 0.044 +/- 0.007 liters/kg/hr and 0.030 +/- 0.009 liters/kg/hr (< or = 6 months), 0.071 +/- 0.011 liters/kg/hr and 0.047 +/- 0.008 liters/kg/hr (6 to < or = 12 months), 0.084 +/- 0.012 liters/kg/hr and 0.055 +/- 0.006 liters/ kg/hr (1 to < or = 2 years), and 0.065 +/- 0.007 liters/kg/hr and 0.051 +/- 0.001 liters/kg/hr (2 to < or = 3 years), respectively. In all age groups, theophylline clearance of the pyrexia group was significantly less than that of the non-pyrexia group (p < 0.01), showing that there was a significant pharmacokinetic difference in theophylline clearance between the groups. Multivariate statistical analysis showed that theophylline clearance was affected by pyrexia and age. This study showed that the presence of pyrexia decreases theophylline clearance, and that it affects theophylline clearance in an age-dependent manner. Based on the results of this study, dosages should be designed based on the clearance at the time of pyrexia.

[Endovascular trapping using a tandem balloon technique for a spontaneous vertebrovertebral fistula associated with neurofibromatosis type 1].

We report a rare case of a young man who had spontaneous left vertebrovertebral fistula associated with neurofibromatosis Type 1. His complaints were severe pain in the left neck and numbness in the left upper extremity. Cervical MR images showed a large abnormal flow void to the left of the spinal canal. An angiogram demonstrated a fusiform aneurysm and a high flow arteriovenous fistula in the left vertebral artery that drained into the internal vertebral plexus and formed a large venous varix. The occipital artery, the thyrocervical artery and the contralateral vertebral artery were associated with the fistula. The arteriovenous fistula was treated by endovascular coil embolization, using a tandem balloon technique. For this fistula, exhibiting the combination of high flow and multiple associated arteries, the flow control technique during the coil embolization, using tandem balloons in both the subclavian artery and the distal portion of the fistula of the vertebral artery, was safe and feasible for preventing coil migration.

[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.