Lacrimal sac massage for congenital nasolacrimal duct obstruction: a multicentre randomised controlled trial.

AIM: Congenital nasolacrimal duct obstruction (CNLDO) is the most common cause of epiphora and mucous discharge in the newborn. We conducted a multicentre randomised controlled trial to determine whether Crigler massage promotes the resolution of CNLDO in infants under 1 year of age. METHODS: A total of 102 infants aged 3-11 months with unilateral CNLDO were enrolled in the study. Patients were randomly assigned to the massage and non-massage groups (n=51/group). As an allocation adjustment factor, the patients were divided into age groups of 3-5, 6-8 and 9-11 months. In the massage group, the guardian performed 10 strokes two times per day for each day until resolution or 1 month. The primary endpoint was a comparison of the 1-month resolution rate in the massage and non-massage groups. RESULTS: This study included 49 male and 53 female patients with a mean age of 6.4±2.4 months. Overall, in this study, the resolution rate was not significantly different between the massage and non-massage groups (31.4% and 33.3%, respectively). However, the resolution rate was higher in the massage group in the 3-5 months age group among the protocol-compliant patients after excluding those with insufficient massage frequency (the massage group, 68.8% and the non-massage group, 28.6%, p=0.022). CONCLUSIONS: There was no increase in the resolution rate after 1 month of lacrimal sac massage in patients 3-11 months old with unilateral CNLDO. However, in protocol-compliant younger age groups, Crigler massage may be effective. TRIAL REGISTRATION NUMBER: UMIN Clinical Trial Registry (UMIN000032840; www.umin.ac.jp/).

Comparing the effectiveness of two surgical techniques for treating lower lid epiblepharon in children: a randomized controlled trial.

A multicenter randomized controlled trial was conducted to compare the effectiveness of incisional and nonincisional surgical techniques for treating lower lid epiblepharon in children. The study included 89 eyes from 50 children aged 3-15 years (mean, 7.5 ± 2.4 years) with moderate lower lid epiblepharon. Patients were randomly assigned to either incisional (modified Hotz procedure with lid margin splitting; 45 eyes of 25 patients) or nonincisional (44 eyes of 25 patients) surgery groups. Treatment outcomes and changes in astigmatism were evaluated 6 months after surgery. Incisional surgery provided a significantly higher percentage (77.8%) of well-corrected treatment results (P = 0.026; odds ratio, 2.88; 95% confidence interval, 1.07-8.22) than nonincisional surgery (55.4%). The mean change in astigmatism 6 months after surgery was - 0.24 ± 0.42 and - 0.01 ± 0.47 D in the incisional and nonincisional surgery groups, respectively. The improvement in astigmatism was significantly higher in the incisional surgery group than in the nonincisional surgery group (P = 0.008). The incisional surgical treatment for moderate epiblepharon in children resulted in a higher number of well-corrected patients, indicating an absence of both ciliary touch and superficial keratitis as well as statistically significant improvements in astigmatism correction.

Bilateral Incomplete Atypical Femur Fractures with Severe Bowing Treated Using Elastic Intramedullary Nails: A Case Report.

CASE: A 77-year-old woman with bilateral symptomatic atypical femoral fractures (AFFs) and severe anterolateral bowing due to long-term bisphosphonate administration was treated using stainless elastic intramedullary nails. Weight-bearing pain disappeared immediately after surgery. Radiographs obtained 1 year postoperatively showed fracture healing. CONCLUSION: Although intramedullary nail insertion has been recommended for symptomatic incomplete AFFs, in cases of severe bowing, rigid nail insertion was often challenging, and the complication rates were higher than those with mild bowing. The advantage of our method is easy insertion, suggesting effective treatment.

Persistent Hyperplastic Primary Vitreous with Microphthalmia and Coloboma in a Patient with Okur-Chung Neurodevelopmental Syndrome.

Okur-Chung neurodevelopmental syndrome is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1, which encodes the alpha 1 catalytic subunit of -casein kinase II. This syndrome is characterized by intellectual disability, developmental delay, and multisystemic -abnormalities including those of the brain, extremities, and skin as well as cardiovascular, gastrointestinal, and immune systems. In this study, we describe a 5-year-old boy with a de novo novel nonsense variant in CSNK2A1, NM_001895.3:c.319C>T (p.Arg107*). He showed bilateral persistent hyperplastic primary vitreous with microphthalmia, lens dysplasia, and coloboma. Ocular manifestations are very rare in this syndrome, and this study expands the spectrum of the clinical presentations of this syndrome.

Impaired neural reward processing in children and adolescents with reactive attachment disorder: A pilot study.

Reactive attachment disorder (RAD) is characterized by markedly disturbed and developmentally inappropriate social relatedness due to parental maltreatment. RAD patients often display a high number of comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, and certain RAD symptoms are difficult to discriminate from ADHD. One of the core characteristics of ADHD is a decrease in neural reward processing due to dopamine dysfunction. The aim of the present study was to determine whether the brain activity involved in reward processing in RAD patients is impaired in comparison with ADHD patients and typically developed controls. Five RAD patients, 17 typically developed (TD) controls and 17 ADHD patients aged 10-16 years performed tasks with high and low monetary reward while undergoing functional magnetic resonance imaging. ADHD patients were tested before and after 3 months treatment with osmotic release oral system-methylphenidate. Before treatment, ADHD patients showed that striatal and thalamus activities only in the tasks with low monetary reward were lower than TD controls. RAD patients showed decrease in activity of the caudate, putamen and thalamus during both the high and low monetary reward conditions in comparison with all the other groups. In RAD patients, the activity of the putamen was associated with the severity of posttraumatic stress and overt dissociation. Reward sensitivity was markedly decreased in children and adolescents with RAD, as evidenced by a diminished neural response during reward perception. This suggests that dopaminergic dysfunction exists in these patients, and may inform future dopaminergic treatment strategies for RAD.

Distinguishing between autism spectrum disorder and attention deficit hyperactivity disorder by using behavioral checklists, cognitive assessments, and neuropsychological test battery.

Children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share many common symptoms, including attention deficit, behavioral problems, and difficulties with social skills. The aim of this study was to distinguish between ASD and ADHD by identifying the characteristic features of both the disorders, by using multidimensional assessments, including screening behavioral checklists, cognitive assessments, and comprehensive neurological battery. After screening for comorbid disorders, we carefully selected age-, sex-, IQ-, and socio-economic status-matched children with typical development (TD). In the Wechsler Intelligence Scale for children, a lower score was observed for the ASD group than for the TD group in Picture concept, which is a subscale of perceptual reasoning. A lower score was shown by the ADHD group than by the TD group in the spatial working memory test in the Cambridge Neuropsychological Test Automated Battery (CANTAB(®)). Although ASD and ADHD have many similar symptoms, they can be differentiated by focusing on the behavioral and cognitive characteristics of executive function.

Default mode network in young male adults with autism spectrum disorder: relationship with autism spectrum traits.

BACKGROUND: Autism spectrum traits are postulated to lie on a continuum that extends between individuals with autism and individuals with typical development (TD). Social cognition properties that are deeply associated with autism spectrum traits have been linked to functional connectivity between regions within the brain's default mode network (DMN). Previous studies have shown that the resting-state functional connectivities (rs-FCs) of DMN are low and show negative correlation with the level of autism spectrum traits in individuals with autism spectrum disorder (ASD). However, it is unclear whether individual differences of autism spectrum traits are associated with the strength of rs-FCs of DMN in participants including the general population. METHODS: Using the seed-based approach, we investigated the rs-FCs of DMN, particularly including the following two core regions of DMN: the anterior medial prefrontal cortex (aMPFC) and posterior cingulate cortex (PCC) in 19 young male adults with high-functioning ASD (mean age = 25.3 ± 6.9 years; autism-spectrum quotient (AQ) = 33.4 ± 4.2; full scale IQ (F-IQ) = 109.7 ± 12.4) compared with 21 age- and IQ-matched young male adults from the TD group (mean age = 24.8 ± 4.3 years; AQ = 18.6 ± 5.7; F-IQ = 109.5 ± 8.7). We also analyzed the correlation between the strength of rs-FCs and autism spectrum traits measured using AQ score. RESULTS: The strengths of rs-FCs from core regions of DMN were significantly lower in ASD participants than TD participants. Under multiple regression analysis, the strengths of rs-FCs in brain areas from aMPFC seed showed negative correlation with AQ scores in ASD participants and TD participants. CONCLUSIONS: Our findings suggest that the strength of rs-FCs in DMN is associated with autism spectrum traits in the TD population as well as patients with ASD, supporting the continuum view. The rs-FCs of DMN may be useful biomarkers for the objective identification of autism spectrum traits, regardless of ASD diagnosis.

Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification.

BACKGROUND: Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. CASE: We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. CONCLUSION: In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state.

Effects of methylphenidate in children with attention deficit hyperactivity disorder: a near-infrared spectroscopy study with CANTAB®.

BACKGROUND: A wide range of evidence supports the methylphenidate (MPH)-induced enhancement of prefrontal cortex (PFC) functioning and improvements in behavioral symptoms in patients with attention deficit hyperactivity disorder (ADHD). Although working memory (WM) has been hypothesized to be impaired in patients with ADHD, no pharmacological studies have examined visuospatial WM (VSWM) with near-infrared spectroscopy (NIRS). STUDY AIM: The present study was designed to investigate the acute effects of MPH on neuropsychological performance and hemodynamic activation in children with ADHD during VSWM tasks. METHODS: The subject group included 10 boys and 1 girl previously diagnosed with ADHD. Two VSWM tasks of differing degrees of difficulty were conducted. This is the first study on the pharmacological effects of MPH in children with ADHD to evaluate hemodynamic responses in the PFC with simultaneous NIRS. RESULTS: No significant differences were found in the scores for both spatial working memory (SWM) and score of spatial span (SSP) tasks between the MPH-off and MPH-on conditions. However, a significant MPH-effect on changes in oxy-hemoglobin levels in the PFC was found only in the SWM task. CONCLUSION: These findings suggest that PFC activation might be affected by MPH, depending on the degree of difficulty of the particular task. Although the MPH-induced change on behavior may or may not be obvious, NIRS measurements might be useful for assessing the psychological effects of MPH even when performance changes were not observed in the cognitive tasks.

Effectiveness and tolerability of switching to aripiprazole from risperidone in subjects with autism spectrum disorders: a prospective open-label study.

BACKGROUND: Subjects with autism spectrum disorders (ASDs) often exhibit behavioral symptoms such as aggressiveness and irritability. The purpose of this study was to examine the efficacy and the tolerability of aripiprazole switched from risperidone in children and adolescents with ASD. METHODS: This prospective, 12-week, open-label study included 9 male subjects with ASD (age range, 9-22 years; mean ± SD age, 14.8 ± 4.0 years) followed up for 12 weeks after switching to aripiprazole from risperidone. The primary outcome measures were the Clinical Global Impression-Improvement scales and the irritability subscale of the Aberrant Behavior Checklist. RESULTS: The mean ± SD maintenance dosages of risperidone and aripiprazole were 0.6 ± 0.4 mg/d and 4.8 ± 4.0 mg/d, respectively. The mean ± SD scores of the irritability subscale of the Aberrant Behavior Checklist before switching to aripiprazole (baseline) and 12 weeks after switching to aripiprazole (end point) were 14.8 ± 7.6 and 13.1 ± 8.0, respectively. The mean ± SD Clinical Global Impression-Improvement score, a comparison from baseline to end point, was 2.4 ± 0.7. Mild somnolence was observed only in 1 subject. No significant changes in vital signs, weight, electrocardiogram, or laboratory measures occurred during switching to aripiprazole. Serum prolactin levels decreased significantly from 17.3 ± 9.4 ng/mL (baseline) to 2.3 ± 1.7 ng/mL (end point). CONCLUSIONS: The results show that aripiprazole might be generally well tolerated and might constitute an alternative treatment of subjects with ASD who experience poor efficacy or tolerability issues with risperidone treatment. Additional long-term controlled studies are needed to evaluate the efficacy and the safety of switching to aripiprazole from other antipsychotics in subjects with ASD.

Effect of dietary zinc deficiency on ischemic vulnerability of the brain.

Deficiency of zinc, which modulates glutamate release, might increase ischemic vulnerability of the brain. We examined effects of dietary zinc deficiency for 2 weeks on ischemic vulnerability in several brain regions using dynamic positron autoradiography technique and [18F]2-fluoro-2-deoxy-d-glucose with rat brain slices. In the normal diet group, the cerebral glucose metabolic rate (CMRglc) was not significantly different from that of the ischemia-unloaded control even after the loading of ischemia for 45 min. However, in the zinc-deficient diet group, CMRglc was significantly lower than that of the ischemia-unloaded control after loading of ischemia for 45 min. With treatment of MK-801 (NMDA receptor antagonist) from the start of ischemia loading, CMRglc was not significantly different from that of the ischemia-unloaded control. These findings, obtained for all analyzed brain regions, suggest that dietary zinc deficiency increased ischemic vulnerability in the brain, and that glutamate might contribute to this effect through activation of the NMDA receptor.

Long-term oxytocin administration improves social behaviors in a girl with autistic disorder.

BACKGROUND: Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. CASE PRESENTATION: We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. CONCLUSION: This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

Switching to aripiprazole in subjects with pervasive developmental disorders showing tolerability issues with risperidone.

BACKGROUND: Subjects with Pervasive Developmental Disorders (PDD) often exhibit behavioral symptoms such as aggressiveness and irritability, which are targets of psychopharmacologic intervention. This retrospective study was designed to examine children and adolescents with PDD experiencing tolerability issues with risperidone treatment, and thereby assess the efficacy and tolerability of switching to aripiprazole. METHODS: This naturalistic study included 23 subjects with PDD (16 males, 7 females, age range 9-24 years, mean age 15.1±3.9 years) diagnosed according to DSM-IV criteria and followed up for 14.9±8.4 weeks after switching to aripiprazole from risperidone. Outcome measures were the Clinical Global Impression-Severity (CGI-S) and CGI Improvement (CGI-I) scales. RESULTS: The mean CGI-S scores of pre-aripiprazole treatment and post-aripiprazole treatment were, respectively 4.7±1.4 and 4.6±1.3. Mean maintenance dosages of risperidone and aripiprazole were, respectively, 0.7±0.5mg/day and 2.8±1.3mg/day. The mean CGI-I score, which shows the difference induced by switching from risperidone to aripiprazole, was 3.4±0.8 for the whole sample, suggesting that the efficacy of risperidone for treating behavioral problems of PDD was maintained by aripiprazole. Some improvement of safety/tolerability issues such as increased appetite, somnolence, hyperprolactinemia, and amenorrhea occurred after switching to aripiprazole. CONCLUSION: Results show that switching to aripiprazole might be generally well tolerated and might constitute an alternative treatment for subjects with PDD who experience tolerability issues with risperidone treatment. Additional long-term controlled studies of PDD subjects should be undertaken to evaluate the efficacy and safety of switching to aripiprazole from other antipsychotics.