Secondary metopic craniosynostosis after posterior cranial decompression in cloverleaf skull deformity.

Cloverleaf skull deformity or Kleeblattschadel syndrome is a severe condition where multiple cranial sutures are absent and prematurely fused, leading to a trilobate head shape. The remaining open sutures or fontanelles compensate for rapid brain expansion, while the constricted fused calvarium restricts brain growth and results in increased intracranial pressure. Recent data show that early posterior cranial and foramen magnum decompression positively affects infants with cloverleaf skulls. However, long-term sequelae are still rarely discussed. We hereby report a child who developed secondary metopic craniosynostosis after posterior cranial decompression, which required a front-orbital advancement and cranial remodelling as a definitive procedure.

Birk-Barel Intellectual Disability Dimorphism and KCNK9 Imprinting Syndrome: Craniofacial Surgery Considerations for an Exceedingly Rare Syndrome.

Birk-Barel intellectual disability dimorphism syndrome, also referred to as KCNK9 imprinting syndrome, is an exceedingly rare condition described in under 20 cases that presents with intellectual disability, hypotonia, scoliosis, dysphonia, dysphagia, and craniofacial dysmorphic features. The condition follows an autosomal dominant pattern of inheritance in the maternally expressed KCNK9 gene on chromosome 8. Due to the complexity of presentation, patients with Birk-Barel syndrome are optimally managed by a multidisciplinary team including a craniofacial surgeon. Previously described craniofacial dysmorphic features include micrognathia, cleft palate, dolichocephaly, broad nasal tip, and broad philtrum, among others. Here the authors describe a genetically confirmed case that has been managed in our institution's multidisciplinary cleft and craniofacial clinic. The authors aim to discuss Birk-Barel syndrome for a surgical and craniofacial audience with considerations for operative management in the context of a multidisciplinary team.

Deep Brain Stimulation for Severe and Intractable Aggressive Behavior.

Aggressive behavior in patients with intellectual disability can be resistant to pharmacological treatment and have detrimental consequences to themselves, family members, and caregivers. Hypothalamic deep brain stimulation (DBS) has been used to improve this type of behavior in severe and refractory cases. Here, we present the description and analysis of DBS of the posteromedial hypothalamus (PMH) and its long-term impact as treatment to improve severe and refractory aggressive behaviors, even with previous bilateral hypothalamotomy without improvement in patients with intellectual disability. Eleven patients underwent bilateral DBS of the PMH. Their medical records were reviewed, and the impact on behavior was measured using preoperative and postoperative Modified Overt Aggression Scale (MOAS) during the last follow-up medical visit. Nine of 11 patients presented a significant decrease in the severity of aggressive behavior, with a preoperative and postoperative MOAS average value of 50.5 and 18.7, respectively. An overall improvement of 63% was seen with a mean follow-up time of 4 years. A patient who previously underwent a bilateral hypothalamotomy via radiofrequency was included in this group. During follow-up, 3 patients presented deterioration of symptoms subsequent to pulse generator depletion but made a full clinical recovery after battery replacement. We posit that DBS of the PMH may be a safe and effective in improving severe and refractory aggressive behavior in patients with long-term intellectual disability.

Comparison of seizure outcomes and ADL recovery period after total or anterior corpus callosotomy in adolescent and young adults with drop attacks and severe mental retardation.

PURPOSE: The aim of this study was to evaluate seizure outcomes and postoperative neurologic complications, with an emphasis on the recovery period of activities of daily living (ADL) between anterior partial corpus callosotomy (ACC) and total corpus callosotomy (TCC) in adolescent and young adults with drop attacks and severe mental retardation. METHODS: We retrospectively reviewed the clinical records of consecutive patients with intractable epilepsy who underwent corpus callosotomy (CC) for drop attacks between 2010 and 2019 in the Department of Neurosurgery, Hiroshima University hospital, with a minimum follow-up of one year. Inclusion criteria of this study were 1) age at surgery: 11-39 years, 2) preoperative intelligence quotient <35, and 3) preoperative Barthel index (BI) ≥30. Postoperative full ADL recovery was defined as complete recovery to the preoperative BI score. We compared the postoperative days required for 1) recovery of oral intake ability, 2) discharge from our hospital, 3) returning home from any hospital, 4) returning home with full ADL recovery, and 5) seizure outcomes in patients with ACC versus those with one-stage TCC. RESULTS: Ten patients with ACC and 14 patients with one-stage TCC met the inclusion criteria. The period for returning home with full ADL recovery was a median of 15 days (range 9-45 days) after ACC, while the median was 21.5 days (range 10-62 days) after one-stage TCC (p = 0.2904). Although there was a tendency for the ADL recovery period to be longer after one-stage TCC, there were no statistically significant differences in any category of ADL recovery period. Eleven of 14 (78.6 %) patients who received a one-stage TCC showed favorable seizure outcomes, with drop attack cessation, which was significantly better than 1 of 10 (10 %) patients with ACC (p = 0.0009). CONCLUSIONS: From the viewpoint of postoperative seizure outcomes and ADL recovery period, one-stage TCC is preferred to ACC for adolescent and young adults with severe mental retardation.

Anaesthesia and orphan disease: management of a case of Nicolaides-Baraitser syndrome undergoing cleft palate surgery.

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by mutations in the SMRCA2 gene, which affects chromatin remodelling and leads to a wide range of symptoms including microcephaly, distinct facial features, recurrent seizures, and severe mental retardation. Until now, less than 100 cases have been reported. CASE PRESENTATION: A 22-month old male infant with NCBRS underwent elective cleft palate surgery. The anaesthetists were challenged by the physiological condition of the patient: narrow face, very small mouth, mild tachypnea, slight sternal retractions, physical signs of partial monosomy 9p, and plagiocephalus, midface hypoplasia, V-shaped cleft palate, enhanced muscular hypotension, dysplastic kidneys (bilateral, estimated GFR: approx. 40 ml/m2), nocturnal oxygen demand, and combined apnea. In addition, little information was available about interaction of the NCBRS displayed by the patient and anaesthesia medications. CONCLUSIONS: The cleft palate was successfully closed using the bridge flap technique. Overall, we recommend to perform a trial video assisted laryngoscopy in the setting of spontaneous breathing with deep inhalative anaesthesia before administration of muscle relaxation to detect any airway difficulties while remaining spontaneoues breathing and protective reflexes.

A proposal of rehabilitative approach in the rare disease "De Barsy Syndrome": case report.

De Barsy syndrome is an autosomal recessive condition characterized by an progeroid appearance with distinctive facial features and cutis laxa. Ophthalmological, orthopedic, and neurological anomalies are generally also present. This syndrome is rare and the complex therapeutic management, from a surgical but also rehabilitative point of view, has not been recognized. The aim of this paper is to describe a possible rehabilitative protocol, after an orthopedic surgical treatment, in a child with De Barsy Syndrome. A 6-year-old boy was born with a congenital bilateral hip dysplasia associated with bilateral congenital foot deformity (vertical talus). Moreover, he showed stereotypic dyskinetic movements and psychomotor delay with cognitive impairment and absent language; the sitting position was maintained with orthoses to support the trunk control and the standing position was not acquired. He was treated with pinstripe knee-highs for the foot and double nappy for the hips. At 19 months old, he underwent a two stage surgical approach for a bilateral pronated valgus foot with severe talonavicular subluxation. Satisfactory hip range of motion was achieved by conservative treatment alone. Afterwards, for the foot laxity and the flat-pronated foot corrective shoes were prescribed. The main rehabilitative goals were: attention improvement, visual exploration for foot-eye and hand-eye coordination, encourage the essential prerequisites of language, controlling the upright position using support, improving hip-knee-foot relationship, improving load transfer between the right and left sides of the body, and bimanual coordination. The rehabilitation process lasted six months, three times a week, for a time from 30 minutes to 60 minutes per session. The results were encouraging and the patient acquired the possibility of sitting with the indicated postural system, the possibility of assuming an upright position and taking a few steps with the aid of rollator with a postural stabilization system for the pelvis.

Shortening Scarf Osteotomy for Macrodactyly and Valgus of the Hallux in Acrodysostosis Lesser Toes Brachydactyly.

LEVELS OF EVIDENCE: Level V: Case report.

Mowat Wilson syndrome and Hirschsprung disease: a retrospective study on functional outcomes.

AIM OF THE STUDY: Mowat Wilson syndrome (MWS) is a complex genetic disorder due to mutation or deletion of the ZEB2 gene (ZFHX1B), including multiple clinical features. Hirschsprung disease is associated with this syndrome with a prevalence between 43 and 57%. The aim of this study was to demonstrate the severe outcomes and the high complication rates in children with MWS, focusing on their complicated follow-up. METHODS: A retrospective comparative study was conducted on patients referred to Robert-Debré Children's Hospital for MWS from 2003 to 2018. Multidisciplinary follow-up was carried out by surgeons, geneticists, gastroenterologists, and neurologists. Data regarding patient characteristics, surgical management, postoperative complications, and functional outcomes were collected. RESULTS: Over this period of 15 years, 23 patients were diagnosed with MWS. Hirschsprung disease was associated with 10 of them (43%). Of these cases, two patients had recto-sigmoïd aganglionosis (20%), three had aganglionic segment extension to the left colic angle (30%), two to the right colic angle (20%), and three to the whole colon (30%). The median follow-up was 8.5 years (2 months-15 years). All patients had seizures and intellectual disability. Six children (60%) presented with cardiac defects. At the last follow-up, three patients still had a stoma diversion and 7 (70%) were fed orally. One patient died during the first months. Eight (80%) of these children required a second surgery due to complications. At the last follow-up, three patients reported episodes of abdominal bloating (42%), one recurrent treated constipation (14.3%), and one soiling (14.3%). Genetic analysis identified three patients with heterozygous deletions, three with codon mutations, and three with frameshift mutations. CONCLUSIONS: MWS associated with Hirschsprung disease has a high rate of immediate surgical complications but some patients may achieve bowel function comparable with non-syndromic HD patients. A multidisciplinary follow-up is required for these patients. LEVEL OF EVIDENCE: Retrospective observational single cohort study, Level 3.

Children With Intellectual and Developmental Disabilities as Organ Transplantation Recipients.

The demand for transplantable solid organs far exceeds the supply of deceased donor organs. Patient selection criteria are determined by individual transplant programs; given the scarcity of solid organs for transplant, allocation to those most likely to benefit takes into consideration both medical and psychosocial factors. Children with intellectual and developmental disabilities have historically been excluded as potential recipients of organ transplants. When a transplant is likely to provide significant health benefits, denying a transplant to otherwise eligible children with disabilities may constitute illegal and unjustified discrimination. Children with intellectual and developmental disabilities should not be excluded from the potential pool of recipients and should be referred for evaluation as recipients of solid organ transplants.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders.

INTRODUCTION: Little is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. METHODS: A total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. RESULTS: Nineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). CONCLUSION: Epilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

Dental management of a child with ectrodactyly ectodermal dysplasia cleft lip/palate syndrome: A case report.

Ectrodactyly ectodermal dysplasia with clefting is a rare syndrome resulting from TP63 gene mutations. It is inherited in autosomal dominant manner or as a de novo transfiguration. It is characterized by a triad of ectodermal dysplasia, ectrodactyly, and facial clefts. This report represents a clinical case of 5 years and 6 months-old male child with ectrodactyly ectodermal dysplasia cleft lip and palate syndrome requiring treatment of his carious teeth. After history taking and clinical examination, the necessary treatment was provided under general anesthesia due to the definitely negative behavior of the child. The treatment outcomes had a positive impact on the behavior and acceptance to dental treatment. This was evidenced by completion of the prosthetic and space management appliances on the dental chair. The child's quality of life was consequently improved. This was evidenced by the reduced response scores of the child perception questionnaire (CPQ11-14 ) after treatment. This report highlighted the value of proper diagnosis and fulfillment of the unmet dental needs for patients with orofacial syndromes to improve their quality of life.

Mowat-Wilson Syndrome Presenting With Purpura Fulminans.

Purpura fulminans is a rapidly progressive syndrome of intravascular thrombosis and hemorrhagic infarction of the skin. The most common infectious etiology is Neisseria meningitidis sepsis, and less commonly it has been documented as a complication of invasive Streptococcus pneumoniae In children who are otherwise healthy, splenic dysfunction is a significant predisposing factor for invasive pneumococcal infection. We present the case of a 10-month-old girl with a history of developmental delay, who developed an overwhelming infection complicated by purpura fulminans and was found to have previously undiagnosed Mowat-Wilson syndrome with anatomic asplenia. We propose screening patients with clinical features suggestive of Mowat-Wilson syndrome for asplenia to evaluate the need for additional preventive care.

Epidemiology of gastrostomy insertion for children and adolescents with intellectual disability.

The largest group of recipients of pediatric gastrostomy have neurological impairment with intellectual disability (ID). This study investigated trends in first gastrostomy insertion according to markers of disadvantage and ID etiology. Linked administrative and health data collected over a 32-year study period (1983-2014) for children with ID born between 1983 and 2009 in Western Australia were examined. The annual incidence rate change over calendar year was calculated for all children and according to socioeconomic status, geographical remoteness, and Aboriginality. The most likely causes of ID were identified using available diagnosis codes in the linked data set. Of 11,729 children with ID, 325 (2.8%) received a first gastrostomy within the study period. The incidence rate was highest in the 0-2 age group and there was an increasing incidence trend with calendar time for each age group under 6 years of age. This rate change was greatest in children from the lowest socioeconomic status quintile, who lived in regional/remote areas or who were Aboriginal. The two largest identified groups of ID were genetically caused syndromes (15.1%) and neonatal encephalopathy (14.8%).Conclusion: Gastrostomy is increasingly used in multiple neurological conditions associated with ID, with no apparent accessibility barriers in terms of socioeconomic status, remoteness, or Aboriginality. What is Known: • The use of gastrostomy insertion in pediatrics is increasing and the most common recipients during childhood have neurological impairment, most of whom also have intellectual disability (ID). What is New: • Nearly 3% of children with ID had gastrostomy insertion performed, with the highest incidence in children under 3 years of age. • Gastrostomy use across different social groups was equitable in the Australian setting.

Johanson-Blizzard syndrome with associated urogenital anomalies.

We present a case of a child with pancreatic insufficiency and facial defects typical of Johanson-Blizzard syndrome (JBS), along with the more facultative anomalies of the JBS, such as those of the urogenital system including persistent urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth revealed a phallic structure with urethral meatus, non-palpable gonads, two orifices in close proximity in the perineum, with the anterior being a common urogenital channel and the posterior, the rectum. A voiding cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and a common urogenital sinus extending 1.5 cm before dividing into three channels: the native urethra, an accessory urethra directed anteriorly towards the clitoris and a septate vagina with uterus didelphys. JBS was suspected by clinical presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty.

Impact of resective epilepsy surgery on health-related quality of life in children with and without low intellectual ability.

OBJECTIVE: The current study examined pre- and postoperative health-related quality of life (HRQL) across children with and without low intellectual ability. We also aimed to clarify the literature on postsurgical change by assessing domain-specific HRQL pre- and postoperatively in children with drug-resistant epilepsy. METHOD: All patients (n=111) underwent resective epilepsy surgery between 1996 and 2016 at the Hospital for Sick Children in Toronto, comparing baseline and 1-year follow-up HRQL with the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-76). At the group-level, postsurgical change in HRQL was examined through linear mixed-effects modeling. Clinically important change in HRQL at the individual level was quantified using a standard error of measurement (SEM)-based criterion, and estimates were stratified by intellectual ability. RESULTS: Children with epilepsy and low intellectual ability had lower overall HRQL compared with those with normal intelligence (b=-10.45, SE=4.89, p=.035). No differences in change in HRQL related to intellectual level were found. In the broader sample, significant postoperative improvements were found for HRQL related to physical activity (b=8.28, SE=1.79, p<.001), social activity (b=15.81, SE=2.76, p<.001), and behavior (b=4.34, SE=1.35, p=.001). Postoperative improvements in physical and social HRQL were associated with better seizure control (p=.011). Conversely, cognitive and emotional domains of HRQL did not improve one year postoperatively, even in the presence of improved seizure control. SIGNIFICANCE: Results suggest that children with low intellectual ability can expect to achieve similar improvements in HRQL after epilepsy surgery compared with those with normal intelligence. Further, while overall HRQL is shown to improve in children following epilepsy surgery, domain-specific change is nuanced and has important implications for health practitioners aiming to monitor treatment progress of patients.

Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation.

OBJECTIVE: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT. METHODS: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulinlike growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT. RESULTS: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without shortterm therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05). CONCLUSION: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.

A neuropsychologist's view: Outcome after RF-ablation for mTLE.

Concern about postoperative worsening of cognitive functions after temporal lobe epilepsy surgery is an important issue. In this article we review our data on neuropsychological outcome after radiofrequency (RF) ablation of amygdalohippocampal complex (AHC). On a group level we found initial improvement in intelligence domains and unchanged memory scores one year after the surgery. During longitudinal follow-up, we found improvement in both intellectual and memory domains. This improvement was most pronounced up to two years after surgery. On an individual level, no patient worsened in any intellectual domain and most patients improved in memory. We hypothesize that this favorable outcome may be a consequence of minimization of collateral damage and incomplete destruction of target structures. We also summarize our experience with psychiatric complications of the procedure.

Bilateral cochlear implantation in a child with Johanson Blizzard Syndrome.

Sensorineural hearing loss (SNHL) occurs in more than 80% of cases of Johanson Blizzard Syndrome (JBS). However, limited knowledge exists in medical literature of cochlear implantation (CI) outcomes in children with JBS. We report the case of a 5 year-old male with JBS and bilateral CI. While minimal progress in spoken language scores was noted after 4 years of bilateral CI use, substantial improvements in discrimination of speech sounds and audibility of spoken language and environmental sounds were documented. Cochlear implantation is an available treatment option of profound SNHL in children with JBS even if spoken language outcomes are marginal.

The characteristics of salivary pepsin in patients with severe motor and intellectual disabilities.

PURPOSE: The aim of the present study was to determine the utility of measuring the salivary pepsin level (SPL) as an objective assessment of gastroesophageal reflux disease (GERD) in severe motor and intellectual disabilities (SMID) patients. SUBJECTS AND METHODS: This prospective study included 26 SMID patients who underwent simultaneous 24-h multichannel intraluminal impedance pH measurement (pH/MII) and SPL evaluation. The enrolled patients were divided into GERD (+) or GERD (-) groups according to the pH/MII findings. The age, gender and pH/MII parameters were compared between the two groups. A correlation analysis was also conducted for the SPL following early-morning fasting and post-enteral feeding and the age, gender, presence of gastrostomy and tracheostomy and pH/MII parameters. The SPL was compared between the two sampling groups. RESULTS: Fifteen patients were classified as GERD (+), and 11 patients were classified as GERD (-). The mean SPL following early-morning fasting and post-enteral feeding among all patients were 104.3 (median: 38, 25th and 75th percentile: 12, 361) ng/ml and 222.2 (median: 152:0, 500) ng/ml, respectively. Regarding positivity, 76.9% and 73.1% of SPL values in early-morning fasting and post-enteral feeding SMID patients, respectively, were positive (≧16ng/ml). The SPL following early-morning fasting demonstrated a weak but significant positive correlation with age. In contrast, we noted no correlation between the pH/MII parameters and the SPL for either the early-morning fasting or post-enteral feeding patients, and no significant difference in the SPL was observed between the GERD (+) and (-) patients. CONCLUSIONS: The present study showed that a high proportion of SMID patients had a relatively high SPL, regardless of the presence of GERD. The SPL in SMID patients might be affected by several distinctive factors in addition to gastroesophageal reflux.