Multiple encephalopathy syndrome: a case of a novel radiological subtype of acute encephalopathy in childhood.

INTRODUCTION: This report presents the case of a novel subtype of acute encephalopathy syndrome in childhood found in a patient with influenza type A infection; the patient exhibited evident magnetic resonance imaging (MRI) findings. CASE REPORT: A 4-year-old boy was transferred to our hospital for prolonged (lasting 60 min) status epilepticus with influenza encephalopathy. Mild brain hypothermia therapy was applied for 72 h, followed by targeted temperature management for 96 h with mechanical ventilation in the intensive care unit. Moreover, methylprednisolone pulse therapy and immunoglobulin therapy were administered. One month after the treatment, his physical status recovered such that he was able to run, take food orally, communicate verbally, and successfully return to kindergarten. Interestingly, serial MRI studies revealed findings that were compatible with 1) acute necrotizing encephalopathy (ANE), 2) mild encephalitis/encephalopathy with a reversible splenial lesion (MERS type II), 3) acute cerebellitis, and 4) acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) on days 2, 4, 7, and 16, respectively. CONCLUSIONS: To the best of our knowledge, these significant MRI findings associated with acute encephalopathy have never been reported. Thus, herein, we propose the new term radiological "multiple encephalopathy syndrome (MES)" based on our case of acute encephalopathy in childhood.

Appropriateness of surgical antimicrobial prophylaxis in Japanese university hospitals.

BACKGROUND: Surgical antimicrobial prophylaxis (SAP) is one of the major purposes of antimicrobial use. AIM: To determine the adherence to the Japanese SAP guidelines in Japanese university hospitals. METHODS: This was a retrospective cohort study including 15 general hospitals and one dental university hospital. Up to three cases of 18 designated surgeries were evaluated regarding adherence to Japanese SAP guidelines: selection of antibiotics, timing of administration, re-dosing intervals, and duration of SAP. When all items were appropriate, surgery was defined as 'appropriate'. FINDINGS: In total, 688 cases (22-45 cases per surgery) were included. The overall appropriateness was 46.8% (322/688), and the appropriateness of each surgery ranged from 8.0% (2/25, cardiac implantable electronic device implantation) to 92.1% (35/38, distal gastrectomy). The appropriateness of each item was as follows: pre/intraoperative selections, 78.5% (540/688); timing of administrations, 96.0% (630/656); re-dosing intervals, 91.6% (601/656); postoperative selection, 78.9% (543/688); and duration of SAP, 61.4% (423/688). The overall appropriateness of hospitals ranged from 17.6% (9/51) to 73.3% (33/45). The common reasons for inappropriateness were the longer duration (38.5%, 265/688) and choice of antibiotics with a non-optimal antimicrobial spectrum before/during, and after surgery (19.0%, 131/688 and 16.9%, 116/688, respectively), compared to the guideline. CONCLUSIONS: Adherence to the guidelines differed greatly between the surgeries and hospitals. Large-scale multi-centre surveillance of SAP in Japanese hospitals is necessary to identify inappropriate surgeries, factors related to the appropriateness, and incidences of surgical site infections.

Anti-fibrotic effect of adipose-derived mesenchymal stem cell conditioned medium in muscle fibrosis.

OBJECTIVE: Recent investigations have demonstrated that the administration of MSC in mouse model of diseases provided beneficial effects. On the other hand, human adipose-derived MSC condition medium (ADSC-CM) is reported as containing beneficial secreted factors, but its role in muscle fibrosis has not been identified. The aim of this study was to investigate the inhibitory effects of MSC-CM in muscle fibrosis in vitro using the C2C12 murine muscle, myoblast cell line. MATERIALS AND METHODS: C2C12 cells were cultured overnight in 0.1% albumin-Dulbecco's Modifies Eagle's Medium (DMEM). The cells were then pre-incubated in ADSC-CM for 20 min, treated with 2.5-10 ng/mL human TGFß1 for 8-72 hours and analyzed using RT-qPCR, Western blot and immunofluorescent staining. RESULTS: Treatment with 20% ADSC-CM for 3 days suppressed αSMA protein expression in TGFß1 treated C2C12 cells. ADSC-CM stimulated the proliferation of C2C12 cells in a dose-dependent manner. Furthermore, TGFß1 induced Acta2/αSMA mRNA expression which was inhibited by ADSC-CM treatment for 8 hours. Decorin, one of the dermatan sulfate proteoglycans and an endogenous inhibitor of TGFß1, was expressed in ADSC-CM, but not in TGFß1 pre-incubated ADSC-CM. CONCLUSIONS: Our studies provide useful information for establishing anti-fibrotic mechanism(s) of ADSC-CM, thus facilitating potential application to prevent muscle fibrosis.

An infantile late-onset case Group of B Streptococcus meningitis diagnosed with a rapid latex kit.

Globally, vaccination has reduced the prevalence of meningitis caused by Streptococcus pneumoniae Neisseria meningitidis, and Haemophilus influenzae. However, neonatal Group B Streptococcus (GBS) meningitis continues to remain a problematic infection of the central nervous system. Here, we report a case of bacterial meningitis in a 34-day old male baby who presented with fever. A cerebrospinal fluid (CSF) test on the day of admission showed an increase in cell count with decreased glucose level. A rapid latex test of the CSF using a commercial kit diagnosed the causative pathogen as GBS. We administered the antibiotics ampicillin, cefotaxime, gentamicin and panipenem/betamipron to the patient for over 14 days. Partial seizures were frequently observed during the course and were well-controlled with midazolam and phenobarbital. Brain magnetic resonance imaging on day 17 showed subdural hygroma in the frontal region, and 99mTc ethyl-cysteinate dimer-single photon emission computed tomography confirmed a decreased cerebral blood flow predominantly in the left frontal region. After three years of follow-up, the condition of the patient improved without any neurological sequelae. Our report highlights that rapid identification of the causative organism is essential in infantile late-onset meningitis. In addition, we consider that the latex kit-based rapid testing of CSF is beneficial for identifying the causative agent of bacterial meningitis.

Immature ovarian teratoma with anti-NMDA-receptor encephalitis in a 13-year-old Japanese female patient.

We report a 13-year-old Japanese female with ovarian teratoma due to anti-NMDAR encephalitis. The patient was admitted with psychiatric symptoms, including memory impairment, insomnia, binge eating and mouth and hand twisting, associated with constipation. Serum alphafetoprotein and neopterin levels were elevated 102 ng/mL and 19 pmol/mL, respectively. Electroencephalography showed epileptic spikes in frontal and temporal regions. Cerebrospinal fluid (CSF) examination exhibited a pleocytosis. Thereafter, her consciousness level immediately worsened. Brain magnetic resonance imaging (MRI) noted hyper intense lesions in bilateral hippocampi, she was diagnosed with limbic encephalitis. Abdominal echogram showed a solid right ovarian tumour. and also confirmed as a tumour by abdominal MRI. The next day, right ovariectomy was performed and she treated two courses of methyl-prednisolone steroid pulse with high-dose immunoglobulins. Later days, CSF analysis revealed anti- NMDAR antibodies. Pathological diagnosis of the tumour was immature round shaped grade 3 ovarian teratoma, measuring 11cm. Two years follow up after admission, she completely recovered and no neurological sequelae.

Successful mild brain hypothermia therapy followed by targeted temperature management for pediatric hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is the most severe form of acute encephalopathy that progresses rapidly, often resulting in death or severe neurological sequelae. We report the case of a 4-year-old girl with HSES with shock and impaired consciousness. PATIENT AND METHODS: Blood test results showed hypercytokinemia, and the 4-year-old patient was immediately admitted to the intensive care unit. Within 4 h of symptom onset, she received mild brain hypothermia therapy with a target body temperature of 35°C. Methylprednisolone pulse, high dose immunoglobulin, and large doses of circulatory drugs were administered. RESULTS: After 72 h of brain hypothermia therapy, targeted temperature management with a target body temperature between 36°C and 37°C was continued for 96 h. The patient was diagnosed with HSES based on acute encephalopathy with shock, hypercytokinemia, low platelet count, coagulation disorder, renal damage, and intestinal bleeding. Magnetic resonance imaging results revealed no signs of any specific acute encephalopathy. She was discharged without neurological sequelae 28 days after symptom onset. CONCLUSIONS: Mild brain hypothermia therapy initiated in the early stages followed by targeted temperature management may be an effective way to improve neurological outcomes in children suffering from HSES.

A girl with acute encephalitis followed by acute cerebellitis/cerebellopathy.

OBJECTIVE: The purpose of this study is to bring attention to a case of acute encephalitis not concurrent with acute cerebellitis. CASE PRESENTATION: Five days after onset of common cold symptoms, a 17-months-old girl suffered convulsions, vomiting and respiratory arrest. On exam, she had pharyngeal inflammation, brisk deep tendon reflexes, respiratory acidosis, leukocytosis, negative rapid antigen tests, and segmental pneumonia. Brain CT and MRI/MRA were negative, and EEG was consistent with acute encephalitis. Following hypothermic therapy, methylprednisolone pulse therapy and cefotaxime, she recovered. Four days after discharge, she sustained limb and truncal ataxia associated with normal EEG, followed by bilateral intention tremor. Blood and CSF chemistry and cell counts were normal. Brain MRI revealed high intensity signals in the dentate nuclei and enhancement in the cerebellar white matter, suggestive of acute cerebellitis/cerebellopathy. SPECT imaging showed reduced blood flow in the cerebellum, right thalamus and brain stem. Following short-term administration of g-globulin and prednisolone, she regained her ability to sit and, eventually, to walk. Four months after initial presentation, her brain MRI was normal. No relapse has occurred in 5 years. CONCLUSIONS: The uncommon sequential development of acute encephalitis followed by acute cerebellitis suggests an immune-mediated cerebellar ataxia.

Long-term survival of a patient with acute neonatal-onset metabolic encephalopathy with carbamoyl phosphate synthetase 1 deficiency.

OBJECTIVE: Long-term survival of patients with neonatal-onset carbamoyl-phosphate synthetase 1 deficiency (CPS1D), an autosomal recessive disorder characterized by repeated, life-threatening hyperammonemia, is rare. We describe the diagnosis and clinical management of a teenager with neonatal-onset CPS1D who did not undergo therapeutic liver transplantation. CASE REPORT: Following emergent neonatal therapy, the patient was diagnosed with CPS1D based on clinical, radiological, biochemical and genetic analyses. Her clinical course, neurobehavioral development and therapeutic interventions are presented and discussed. RESULTS: Born from nonconsanguineous parents, the proband underwent phototherapy for neonatal jaundice, associated with acute encephalopathy, apnea and cerebral edema. Based on blood and urinary biochemical abnormalities, neonatal-onset CPS1D was diagnosed. Her hyperammonemia was corrected by hemodialysis, followed by sodium benzoate, L-arginine, levocarnitine and protein-free diet therapy. Because of a relapse and persistent neurobehavioral regression by age 1, a planned liver transplantation was cancelled. At age 10, sodium phenylbutyrate was substituted as ammonia scavenger. Genetic testing revealed compound heterozygote c.2359C>T (R787X) and c.236+6T>C variants of CPS1, confirming her diagnosis. Despite severe neurological sequelae, the patient is 16 and in stable condition. CONCLUSIONS: Our case suggests that early hemodialysis and pharmacologic interventions for acute neonatal hyperammonemia can improve the prognosis of patients with neonatal-onset CPS1D.

Craniofacial penetration by a wooden stick.

INTRODUCTION: Penetrating craniofacial injuries caused by stick-like foreign bodies occur as a result of accidents particularly in children, and often lead to significant morbidity. CASE SUMMARY: We describe a 5-year-old boy who sustained facial trauma after falling on a wooden stick which penetrated his left cheek. At the initial visit, his vital and neurological signs were normal. However, the stick had penetrated the frontal lobe to a depth of 3cm via the orbital cavity and the anterior skull base. The stick was successfully removed while visualizing the anterior skull base in an endoscopic transethmoidal approach. A follow-up examination one year after the accident demonstrated normal visual acuity and ocular motility, with no diplopia, tearing or pain. DISCUSSION: Penetrating facial injuries caused by stick-like objects carry a significantly higher risk of serious neurological involvement. Even if penetrating facial injuries sometimes appear trivial, the external injury site is often insufficient to determine the position of the object within the head. Although the cheek is a rare entry site for intracranial injuries, the extent of damage should be assessed fully before attempting removal.

The first multi-centre point-prevalence survey in four Japanese university hospitals.

BACKGROUND: The Japanese government adopted a national action plan on antimicrobial resistance, which aims to reduce drug-resistant pathogens and antimicrobial use. A point-prevalence survey (PPS) is a useful surveillance method to gain information about hospital epidemiology; however, no multi-centre PPS has previously been performed in Japan. AIM: To investigate general information about hospital epidemiology, healthcare-associated infections (HCAIs), and antimicrobial use in multiple Japanese university hospitals. METHODS: In July 2016, a multi-centre PPS was conducted using a standardized protocol at four university hospitals in Japan. FINDINGS: A total of 3199 patients were included. Median age and duration of hospital stay were 64 years and 10 days, respectively. A total of 246 (7.7%; 95% confidence interval (CI): 6.8-8.7) patients had 256 active HCAIs, and 933 (29.2%; 95% CI: 27.6-30.8) patients received 1318 antimicrobials. Pneumonia and gastrointestinal system infection were the most common HCAIs (N = 42, 16.4%), and Enterobacteriaceae (N = 49, 30.8%) were the predominant causative organisms. Carbapenems (N = 52, 17.8%), anti-MRSA medications, and cephems with antipseudomonal activity were the most frequently prescribed antimicrobials for HCAIs. As surgical prophylaxis, 46 of 278 antimicrobials (16.5%) were administered orally. Proportions of HCAI and antimicrobial use in each hospital ranged from 4.8% to 9.5% and 19.3%-35.0%, respectively. CONCLUSION: This multi-centre PPS recorded detailed HCAI data and distinct antimicrobial use in Japanese university hospitals. Further surveillance is necessary to reduce HCAIs and formulate feasible plans to achieve the national action plan on antimicrobial resistance.

Sociological histories on epilepsy as "causes for disqualification" stipulated in the Japanese Road Traffic Act of 1960 and Revised Road Traffic Act of 2001.

In the wake of successive cases of fatal accidents caused by patients behind the wheel whose driving was likely to be hindered due to paroxysmal diseases, including epilepsy, there has been an outcry from victims demanding stricter criminal penalties against the perpetrators due to negligence. As a result of this action, a revised Road Traffic Act was put into effect in Japan on June 14, 2013. This act established new penal provisions against any person who provides false statements on his/her medical condition(s) when acquiring or renewing a driver's license. In this paper, the social circumstances will be introduced regarding road traffic in Japan when the Road Traffic Act, the origin of today's revised Road Traffic Act, was enacted in 1960. An overview of the reasons behind the enactment of the original act will be provided. Additionally, the handling of patients with "provisions for disqualification," whose driving is likely to be hindered due to paroxysmal diseases, including "epilepsy," will be reviewed. This handling attracted repeated controversy during the enactment of the original act and will also be reviewed. One significant change in wording from "absolute causes for disqualification" in the Road Traffic Act of 1960 to "relative causes for disqualification" in the Revised Road Traffic Act of 2001 also will be discussed from a medical sociology perspective. Finally, the social status and socio-economic position of drivers with paroxysmal diseases, as it pertains to influences on lawmakers, will be discussed.

Endoscopic endonasal excision of nasal chondromesenchymal hamartoma with intracranial extension.

INTRODUCTION: Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign hamartoma of the sinonasal tract, predominantly involving infants and young children. METHODS: We report the case of a 3-year-old boy of NCMH with extension to anterior skull base. RESULTS: The tumor was completely resected piece by piece via an endonasal endoscopic approach. There is no recurrence 3 years after operation. CONCLUSIONS: We reported the case of NCMH extending to skull base was successfully resected by endonasal endoscopic approach.

Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids.

BACKGROUND: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. OBJECTIVES: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 µg/day) and fluticasone propionate (100 µg/day), in infants and preschool children with asthma. METHODS: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 µg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). RESULTS: Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs. CONCLUSIONS: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children.

Del(18)(q12.2q21.1) syndrome: a case report and clinical review of the literature.

The terminal deletion of the long arm of chromosome 18 is relatively common among cytogenetic abnormalities, which occur incidentally in approximately 1 in 40,000 live births. Proximal interstitial deletions of the long arm of chromosome 18 are less frequent. The critical region on chromosome 18 of this syndrome is del(18)(q12.2q21.1) and has recently been recognized as a new clinical entity. We describe a 8-year-old boy with developmental delay, obesity, and epilepsy, with characteristic facial anomalies in whom G-banding chromosome analysis revealed a unique karyotype of 46, XY, del(18)(q12.2q21.1). The patient was diagnosed with interstitial deletion chromosome 18q-syndrome. He received weight control therapy from a medical dietitian. For his epilepsy, he was administered oral carbamazepine at 4 mg/kg/day. At age six, he entered a special needs elementary school. After entering school, he often showed hyperkinesis, and was diagnosed with attention deficit hyperactivity disorder with mild mental retardation. Because patients with only del(18)(q12.2q21.1) have no serious associated malformations, physicians should be aware that even adult patients may have 18q-syndrome. Therefore, if epilepsy occurs in patients with minor facial anomalies, psychomotor retardation, obesity, and the possibility of 18q-syndrome with del(18)(q12.2q21.1) should be kept in mind, and chromosome testing should be performed.

Tumour necrosis factor inhibitor-associated sinusitis.

AIM: To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors. METHODOLOGY: A retrospective review of the medical records between 2003 and 2011 revealed that five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment. RESULTS: The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor. CONCLUSION: Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.

Frequency of CD4(+)FOXP3(+) regulatory T-cells at early stages after HLA-mismatched allogeneic hematopoietic SCT predicts the incidence of acute GVHD.

Acute GVHD (aGVHD) is a major obstacle to allogeneic hematopoietic SCT (alloHSCT). Although it is thought that aGVHD is initiated in secondary lymphoid organs at a very early stage of alloHSCT, whether CD4(+)FOXP3(+) regulatory T-cells (Tregs) have an impact on aGVHD development during this period remains unclear. Here, we measured Tregs in peripheral blood as early as possible after HLA-mismatched alloHSCT, and assessed the incidence of aGVHD. Flow cytometric analyses revealed that at the second week after HSCT, patients with aGVHD had significantly (P=0.018) lower Treg:CD4(+)T-cell ratios than those without aGVHD. As these differences were seen before the development of aGVHD, these ratios can predict the incidence of aGVHD. The cumulative incidence of aGVHD in patients with ratios of <9% was significantly higher than that in patients with ratios of 9% (P=0.0082, log-rank test). Additionally, the specific ratio of Tregs:CD4(+)T-cells was the most significant value among all other possible lymphocyte-associated ratios and absolute cell counts. These findings suggest that the ratio of Tregs:CD4(+)T-cells at the second week post HLA-mismatched alloHSCT might be a potent predictor of aGVHD in these patients. The practical efficacy of this finding should be verified in further interventional studies.

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

The role of HLA antibodies in allogeneic SCT: is the 'type-and-screen' strategy necessary not only for blood type but also for HLA?

The role of HLA antibodies in SCT has drawn increasing attention because of the significantly increased number of patients who receive HLA-mismatched SCT, including cord blood transplantation, haploidentical SCT and unrelated SCT. Technical advancements in the methods of HLA Ab testing have realized rapid, accurate and objective identification, as well as quantification of specific HLA antibodies. Recent clinical studies have suggested that the presence of donor-specific HLA antibodies (DSA) in patients is associated with graft failure in HLA-mismatched SCT when the above-listed stem cell sources are used and results in different impacts. Of note, most of the 'HLA-matched' unrelated SCT actually involve HLA mismatches in HLA-DP and the presence of antibodies against this locus has been reported to be associated with graft failure. Thus, HLA Ab should be examined as a work-up for all patients who undergo SCT from 'alternative donors.' The simplest route for preventing HLA Ab-mediated graft failure in Ab-positive patients is to avoid donors who possess the target Ag of HLA antibodies. If SCT from such donors must be performed, treatment for DSA before SCT may improve the chances of successful donor engraftment.