Development of Calvarial Bone Osteomyelitis in a Noonan Syndrome Patient Following Fronto-Orbital Advancement of Craniosynostosis: A Novel Technique of Treatment Using Povidone and Hydrogen Peroxide Solutions.

This is a case of a pediatric patient with Noonan syndrome (NS) and craniosynostosis who developed calvarial bone osteomyelitis following corrective surgery. Despite complications, such as postoperative bleeding and infections, including osteomyelitis, multidisciplinary management strategies were employed, including antibiotics, debridement, and novel use of hydrogen peroxide and povidone solutions due to bone thinning. The discussion highlights challenges in managing syndromic craniosynostosis, emphasizing the importance of tailored approaches and prophylactic antibiotics. The innovative treatment approach using hydrogen peroxide and povidone presents a potential alternative for bone infections and osteomyelitis post-cranial reconstruction, offering insights for future management strategies. Lessons learned regarding infection rates and novel treatment modalities contribute to evolving approaches in managing complications in syndromic craniosynostosis.

Intracranial Volume in Relation to Parent Satisfaction and Expert Opinion: A Novel Look at Surgical Outcomes.

Factors like parent satisfaction and expert opinion have been proposed as outcome measures related to craniosynostosis (CS) surgery. However, there is no real tangible score for CS surgery outcomes. In our study, we aimed to explore different factors considered as a tangible outcome measure of CS surgery. Methods: A retrospective cohort study of 23 patients with CS who were operated on in a tertiary care university hospital. Parents were interviewed to assess their satisfaction of aesthetic outcome. This was correlated to two expert opinions and to the amount of skull expansion. Results: The mean follow-up duration was 2.24 ± 1.12 years. Twelve of the 23 fathers were satisfied, whereas 11 of the 23 mothers were satisfied. The overall combined satisfaction rate of both parents was on the higher side with no difference in between. There was a significant association between expansion rate of 7.65 ± 4.99% and the overall parent's satisfaction (P = 0.002). Additionally, there was a good correlation between both experts with statistically significant association (P = 0.004). No correlation was found between the parents' satisfaction and the experts' opinions. Conclusions: The study is valuable, as it investigates the relationship between the expansion rate, parents' satisfaction, and expert opinion as predicted values of craniosynostosis surgery. The overall satisfaction correlated significantly well with the expansion rate. However, such numerical assessment is not a real guide for assessing clinical outcomes' as no association was found between expansion rate, satisfaction rate, and expert opinion.

A case of postoperative cerebellar mutism with hyperphagia in a child following gross total resection of medulloblastoma occupying the cerebellar vermis.

INTRODUCTION: Cerebellar mutism syndrome is a well-known complication following posterior fossa tumor resection. Its incidence is markedly increased among patients with medulloblastoma. Patients typically present with an inability to communicate verbally due to disruption of the dentato-thalamocortical pathway. CASE DESCRIPTION: We present a unique case of cerebellar mutism in a three-year-old girl who underwent gross total resection of medulloblastoma occupying the cerebellar vermis. In addition to mutism, the patient developed hyperphagia. DISCUSSION: This case report aims to contribute to current understanding of the role of cerebello-hypothalamic connections in cerebellar mutism and their clinical significance.

Ceftazidime-avibactam for the Treatment of Multidrug-resistant Pseudomonas aeruginosa Central Nervous System Infection in Pediatric Patient: A Case Report.

Very limited experimental and clinical data are currently available regarding the cerebrospinal fluid (CSF) penetration of ceftazidime-avibactam in adults. Nevertheless, up to our knowledge, there are no data of ceftazidime-avibactam use in central nervous system infections in pediatric patients. For that, here we describe our experience with the use of ceftazidime-avibactam in addition to intraventricular colistin in a pediatric patient diagnosed with ventriculoperitoneal shunt infection due to multidrug-resistant P. aeruginosa. A 2-year-old boy known to pre-term, delivered at 26 weeks with hydrocephalus that required ventriculoperitoneal shunt which was infected due to P. aeruginosa. He was treated with multiple antipseudomonal agents; however, cultures remained persistently positive. On day 54 of admission, the isolate was reported as multidrug-resistant P. aeruginosa and he was switched to ceftazidime-avibactam and intraventricular colistin. CSF cultures became sterile 3 days after initiation of this antibiotic regimen, and subsequent CSF cultures had no growth. No recurrent episode of central nervous system infections due to P. aeruginosa occurred up to 2 years of follow-up.

Clinical and Genetic Characterization of Craniosynostosis in Saudi Arabia.

Background: Craniosynostosis (CS) is defined as pre-mature fusion of one or more of the cranial sutures. CS is classified surgically as either simple or complex based on the number of cranial sutures involved. CS can also be classified genetically as isolated CS or syndromic CS if the patient has extracranial deformities. Currently, the link between clinical and genetic patterns of CS in the Saudi population is poorly understood. Methodology: We conducted a retrospective cohort study among 28 CS patients, of which 24 were operated and four were not. Clinical and genetic data were collected between February 2015 and February 2019, from consenting patient's families. The electronic chart data were collected and analyzed including patient demographics, craniofacial features, other anomalies and dysmorphic features, operative data, intra cranial pressure (ICP), parent consanguinity and genetic testing results. Results: The most common deformity in our population was trigonocephaly. The most performed procedure was cranial vault reconstruction with fronto-orbital advancement, followed by posterior vault distraction osteogenesis and suturectomy with barrel staving. Genetics analysis revealed pathogenic mutations in FGFR2 (6 cases), TWIST1 (3 cases), ALPL (2 cases), and TCF12 (2 cases), and FREM1 (2 case). Conclusion: Compared to Western countries, our Saudi cohort displays significant differences in the prevalence of CS features, such as the types of sutures and prevalence of inherited CS. The genomic background allows our phenotype-genotype study to reclassify variants of unknown significance. Worldwide, the sagittal suture is the most commonly affected suture in simple CS, but in the Saudi population, the metopic suture fusion was most commonly seen in our clinic. Further studies are needed to investigate the characteristics of CS in our population in a multicenter setting.

Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome.

Latent transforming growth factor ß (TGFß)-binding proteins (LTBPs) are microfibril-associated proteins essential for anchoring TGFß in the extracellular matrix (ECM) as well as for correct assembly of ECM components. Variants in LTBP2, LTBP3, and LTBP4 have been identified in several autosomal recessive Mendelian disorders with skeletal abnormalities with or without impaired development of elastin-rich tissues. Thus far, the human phenotype associated with LTBP1 deficiency has remained enigmatic. In this study, we report homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families. Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly). In vitro studies on proband-derived dermal fibroblasts indicate distinct molecular mechanisms depending on the position of the variant in LTBP1. C-terminal variants lead to an altered LTBP1 loosely anchored in the microfibrillar network and cause increased ECM deposition in cultured fibroblasts associated with excessive TGFß growth factor activation and signaling. In contrast, N-terminal truncation results in a loss of LTBP1 that does not alter TGFß levels or ECM assembly. In vivo validation with two independent zebrafish lines carrying mutations in ltbp1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. In addition, one of the mutant zebrafish lines shows voluminous and hypo-mineralized vertebrae. Overall, our findings in humans and zebrafish show that LTBP1 function is crucial for skin and bone ECM assembly and homeostasis.

The longitudinal impact of COVID-19 pandemic on neurosurgical practice.

OBJECTIVE: This observational cross-sectional multicenter study aimed to evaluate the longitudinal impact of the coronavirus disease 2019 (COVID-19) pandemic on neurosurgical practice. METHODS: We included 29 participating neurosurgeons in centers from all geographical regions in the Kingdom of Saudi Arabia. The study period, which was between March 5, 2020 and May 20, 2020, was divided into three equal periods to determine the longitudinal effect of COVID-19 measures on neurosurgical practice over time. RESULTS: During the 11-week study period, 474 neurosurgical interventions were performed. The median number of neurosurgical procedures per day was 5.5 (interquartile range [IQR]: 3.5-8). The number of cases declined from 72 in the first week and plateaued at the 30's range in subsequent weeks. The most and least number of performed procedures were oncology (129 [27.2 %]) and functional procedures (6 [1.3 %]), respectively. Emergency (Priority 1) cases were more frequent than non-urgent (Priority 4) cases (178 [37.6 %] vs. 74 [15.6 %], respectively). In our series, there were three positive COVID-19 cases. There was a significant among-period difference in the length of hospital stay, which dropped from a median stay of 7 days (IQR: 4-18) to 6 (IQR: 3-13) to 5 days (IQR: 2-8). There was no significant among-period difference with respect to institution type, complications, or mortality. CONCLUSION: Our study demonstrated that the COVID-19 pandemic decreased the number of procedures performed in neurosurgery practice. The load of emergency neurosurgery procedures did not change throughout the three periods, which reflects the need to designate ample resources to cover emergencies. Notably, with strict screening for COVID -19 infections, neurosurgical procedures could be safely performed during the early pandemic phase. We recommend to restart performing neurosurgical procedures once the pandemic gets stabilized to avoid possible post pandemic health-care system intolerable overload.

Neurosurgical Procedures and Safety During the COVID-19 Pandemic: A Case-Control Multicenter Study.

OBJECTIVE: Quantitative documentation of the effects of outbreaks, including the coronavirus disease 2019 (COVID-19) pandemic, is limited in neurosurgery. Our study aimed to evaluate the effects of the COVID-19 pandemic on neurosurgical practice and to determine whether surgical procedures are associated with increased morbidity and mortality. METHODS: A multicenter case-control study was conducted, involving patients who underwent neurosurgical intervention in the Kingdom of Saudi Arabia during 2 periods: pre-COVID-19 and during the COVID-19 pandemic. The surgical intervention data evaluated included diagnostic category, case priority, complications, length of hospital stay, and 30-day mortality. RESULTS: A total of 850 procedures were included, 36% during COVID-19. The median number of procedures per day was significantly lower during the COVID-19 period (5.5 cases) than during the pre-COVID-19 period (12 cases; P < 0.0001). Complications, length of hospital stay, and 30-day mortality did not differ during the pandemic. In a multivariate analysis comparing both periods, case priority levels 1 (immediate) (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.24-2.67), 1 (1-24 h) (OR, 1.63; 95% CI, 1.10-2.41), and 4 (OR, 0.28; 95% CI, 0.19-0.42) showed significant differences. CONCLUSIONS: During the early phase of the COVID-19 pandemic, the overall number of neurosurgical procedures declined, but the load of emergency procedures remained the same, thus highlighting the need to allocate sufficient resources for emergencies. More importantly, performing neurosurgical procedures during the pandemic in regions with limited effects of the outbreak on the health care system was safe. Our findings may aid in developing guidelines for acute and long-term care during pandemics in surgical subspecialties.

Pediatric intracranial hypertension. Experience from 2 Tertiary Centers.

OBJECTIVE: To review the experience of 2 tertiary centers in Saudi Arabia with intracranial hypertension (IH) in the pediatric population. METHODS: We retrospectively reviewed and analyzed pediatric patients diagnosed with IH from June 2002 to May 2017 in 2 institutes. RESULTS: We identified 53 patients (30 females and 23 males) with a mean age of 7 years at the time of presentation. Among them, 41 patients were younger than 12 years, and 12 were older. Obese and overweight patients constituted 27.00% (n = 14) of all cases, 8 (66.7%) of whom were older than 12 years. The most common presenting feature was papilledema followed by headache. Vitamin D deficiency, which constituted the most common associated condition, was identified in 12 (22.6%) patients. Acetazolamide was the treatment option in 98.11% of patients, and only 5.7% underwent surgical interventions. The length of follow-up ranged from 6 months to 8 years. CONCLUSION: Intracranial hypertension is rare in children and commonly seen in overweight females older than 12 years similar to adults. Patients younger than 12 years tend to develop secondary IH. More studies are needed to characterize the clinical presentation and guide the management plan.

Low-Cost Desktop-Based Three-Dimensional-Printed Patient-Specific Craniofacial Models in Surgical Counseling, Consent Taking, and Education of Parent of Craniosynostosis Patients: A Comparison With Conventional Visual Explanation Modalities.

BACKGROUND: Craniosynostosis is a complex craniofacial deformity. Surgical decision, if needed, is always hard on the parent and requires the use of multimodalities of explanation. To the authors' knowledge, there have been no studies tackling family counseling about the deformity and surgical decision-making process with the use of low-cost patient-specific three-dimensional (3D)-printed models. METHODS: A cross-sectional study investigating the utility of patient-specific 3D-printed models using a desktop-based 3D printer. Questionnaire was constructed and validated screening the demographics, knowledge, expectation, and surgical decision-making process supplied using Likert. Data were collected consecutively from each parent first after explanation with conventional 3D computed tomography (CT) images, and then repeated after the 3D-printed model has been presented. RESULTS: Fourteen parents were screened. Majority of parents considered the pathology to have a potential effect of child's functional and aesthetic outcomes. After using the 3D-printed models, the participants had a clear vision and needed not to read any more about the condition (P = 0.05, P = 0.019, respectively). Agreement for surgical management was in favor of the 3D-printed models compared with CT images (P = 0.028). Explanation with CT images yielded higher mean score in knowledge about potential complications compared with 3D models (P value = 0.007). For the 3D models, average printing time was 26 hours, and a mean cost of 5.2$. CONCLUSION: The utility of desktop 3D printing is an affordable modality to provide adequate information about craniosynostosis and can assist surgical decision-making. Knowledge and adaptation of such cheap technology represents a great skill aiding clinical practice.

The genetic landscape of familial congenital hydrocephalus.

OBJECTIVE: Congenital hydrocephalus is an important birth defect, the genetics of which remains incompletely understood. To date, only 4 genes are known to cause Mendelian diseases in which congenital hydrocephalus is the main or sole clinical feature, 2 X-linked (L1CAM and AP1S2) and 2 autosomal recessive (CCDC88C and MPDZ). In this study, we aimed to determine the genetic etiology of familial congenital hydrocephalus with the assumption that these cases represent Mendelian forms of the disease. METHODS: Exome sequencing combined, where applicable, with positional mapping. RESULTS: We identified a likely causal mutation in the majority of these families (21 of 27, 78%), spanning 16 genes, none of which is X-linked. Ciliopathies and dystroglycanopathies were the most common etiologies of congenital hydrocephalus in our cohort (19% and 26%, respectively). In 1 family with 4 affected members, we identified a homozygous truncating variant in EML1, which we propose as a novel cause of congenital hydrocephalus in addition to its suggested role in cortical malformation. Similarly, we show that recessive mutations in WDR81, previously linked to cerebellar ataxia, mental retardation, and disequilibrium syndrome 2, cause severe congenital hydrocephalus. Furthermore, we confirm the previously reported candidacy of MPDZ by presenting a phenotypic spectrum of congenital hydrocephalus associated with 5 recessive alleles. INTERPRETATION: Our study highlights the importance of recessive mutations in familial congenital hydrocephalus and expands the locus heterogeneity of this condition. Ann Neurol 2017;81:890-897.

Idiopathic intracranial hypertension in children: Diagnostic and management approach.

Idiopathic intracranial hypertension (IIH) is a rare neurological disorder in children. It is characterized by raised intracranial pressure (ICP) in the absence of brain parenchymal lesion, vascular malformations, hydrocephalus, or central nervous system (CNS) infection. The diagnosis is usually confirmed by high opening pressure of cerebrospinal fluid (CSF) with exclusion of secondary causes of intracranial hypertension. If not treated properly, it may lead to severe visual dysfunction. Here we review the etiology, clinical presentation, diagnostic criteria and management of IIH in children through illustration of the clinical and radiological presentation of a 13-year-old overweight girl who presented with severe headache, diplopia and bilateral papilledema. Otherwise, she had unremarkable neurological and systemic examinations. Lumbar puncture showed a high CSF opening pressure (360-540 mmH2O). Her investigations showed normal complete blood count (CBC), normal renal, liver, and thyroid function tests. Cerebrospinal fluid (CSF) and blood chemistry were unremarkable. Magnetic resonant image (MRI) of the brain demonstrated empty sella turcica, tortuous optic nerves, and flattening of the posterior sclera. Magnetic resonant venography (MRV) showed focal narrowing of the distal transverse sinuses and absence of venous sinus thrombosis. She required treatment with acetazolamide and prednisolone. With medical treatment, weight reduction, and exercise, our patient had a remarkable improvement in her symptoms with resolution of papilledema in two months. This review highlights the importance of early recognition and management of IIH to prevent permanent visual loss.