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Purpose: To describe the rate, characteristics, and outcomes of rhegmatogenous retinal detachment (RD) in patients with Knobloch syndrome., Design: A single-center retrospective cohort study., Participants: Fifty patients with Knobloch syndrome diagnosed clinically, with or without molecular confirmation of recessive pathogenic COL18A1 variants., Methods: A retrospective chart review of all patients diagnosed with Knobloch syndrome from November 1, 1983 to March 31, 2023. Demographic data, ophthalmic evaluation at baseline and follow-up, interventions, and final anatomic and visual outcomes were collected., Main Outcome Measures: Rate, time of onset, characteristics, and treatment outcomes of RD., Results: Fifty patients with Knobloch syndrome were included. Males constituted 56% of cases. The diagnosis was confirmed with molecular genetic testing in 37 (74%) patients. Twenty-two patients (44%) had documented occipital bony defects or scalp lesions. Forty-eight of 100 eyes (48%) developed RD at a mean (standard deviation [SD]) age of 6.5 (6.1) years. The mean (SD) follow-up was 7.7 (5.6) years (range, 6 months to 24.3 years). Macular hole-related RD comprised 33% of RD cases. The overall single-surgery success rate was 36% and the final anatomic success rate was 70%. Macular hole-related RD carried a slightly worse prognosis with a 58% final anatomic success rate. Vitrectomy with adjunct scleral buckle and silicone oil tamponade provided the highest single-surgery success (62.2%). In eyes with measurable best-corrected visual acuity (BCVA), the mean preoperative BCVA was 1.2 logarithm of the minimum angle of resolution (Snellen equivalent, 20/320). After successful repair, mean visual acuity was 1.3 logarithm of the minimum angle of resolution (Snellen equivalent, 20/500)., Conclusions: Retinal detachment in Knobloch syndrome is frequent and occurs in young children. Macular hole-related RD comprises one third of RD cases and requires careful macular evaluation. Vitrectomy, combined with scleral buckling and silicone oil tamponade, appears to provide the best anatomic outcomes., Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Objective: To explore the influencing factors of adult spontaneous meningoencephalocele, which occurs in the lateral recess of sphenoid sinus, in order to improve the level of clinical diagnosis and treatment. Methods: The clinical data of 27 adults with spontaneous meningoencephalocele in lateral recess of sphenoid sinus in Department of the Otorhinolaryngology, the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2022 were retrospectively analyzed. Preoperative sinus CT and MRI were performed to confirm the diagnosis and location of meningoencephalocele. Results: ①There were 0 cases of lateral recess of sphenoid sinus type Ⅰ, 8 cases of lateral recess of sphenoid sinus type Ⅱ and 19 cases of lateral recess of sphenoid sinus type Ⅲ. ②Among the 27 adult patients with spontaneous meningoencephalocele, 9 were male and 18 were female, and the onset age was 19-72 years old, with an average age of（50.7±12.4） years old. 18 cases were complicated with cerebrospinal fluid leakage, 11 cases with headache and dizziness, 3 cases with recurrent meningitis（complicated with cerebrospinal fluid leakage）, and 2 cases with epilepsy. ③There were 20 patients with intracranial hypertension, 17 patients with body mass index（BMI） ≥25 kg/m², and 8 patients with empty sella. Conclusion: Type Ⅲ of lateral recess of sphenoid sinus is the most common type in adult spontaneous meningoencephalocele, and intracranial hypertension and obesity are the influencing factors of this disease. Puncture, biopsy or operation should not be performed for patients suspected of spontaneous meningoencephalocele, and imaging examination should be performed to identify the source of the tumor., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Purpose: Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is the primary treatment, transitioning from frontal craniotomy to endoscopic methods, offering improved outcomes. Yet, more studies are needed. A comprehensive review on trans-sellar trans-sphenoidal encephalocele (TSTSE) is missing. Our study aims to fill this gap, offering a comprehensive perspective for physicians., Methods: This review adhered to the PRISMA guideline. Eligible studies focused on human subjects, specifically trans-sellar encephaloceles, and provided comprehensive treatment details. English language articles published up to April 11th, 2023, were considered. Two trained researchers conducted article screening using consistent criteria. Data extraction covered various aspects, including clinical presentation, surgical methods, and outcomes, with results presented descriptively in two tables. Due to the rarity of this congenital anomaly, meta-analysis and publication bias assessment were not feasible. Data extraction was independently conducted by two reviewers, with subsequent cross-verification., Results: A total of 36 patients were identified from 14 studies, the most frequently observed clinical presentation was dyspnea (41.67%) and the most frequently observed accompanying anomaly was cleft lip/palate (55.56%). CT and MRI were adopted in nearly all the cases, and trans-nasal approach was the most often used surgical approach (57.14%) with the 'soft material combination' the most commonly used method for cranial base repairment (35.71%). A total of two deaths occurred and diabetes insipidus was the most common perioperative complication which occurred in six surgery patients (21.43%)., Conclusion: TSTSE predominantly affects males and presents with dyspnea, visual deficits, pituitary insufficiency, and cranial base-related symptoms. Early diagnosis is critical, with advanced imaging playing a key role. Endocrine assessment is vital for hormone management. Surgery offers symptom relief but entails risks, including reported fatalities and complications. The choice between surgery and conservative management requires careful deliberation. The trans-nasal approach is favored for its reduced trauma, yet further research is necessary to validate this preference., (© 2024. The Author(s).)

A cerebrospinal-fluid-related (CSF-related) problem occurred in 25-30% of frontoethmoidal encephalocele (FEE) cases. Since there was no algorithm or guideline, the judgment to treat the CSF-related problem often relies upon the surgeon's experience. In our institution, the early shunt was preferable to treat the problem, but it added risks to the children. We developed an algorithm, "Shunt Algorithm for Frontoethmoidal Encephalocele" (SAFE), to guide the surgeon in making the most reasonable decision. To evaluate the SAFE's efficacy in reducing unnecessary early shunting for FEE with CSF-related intracranial abnormality. Medical records of FEE patients with CSF-related abnormalities treated from January 2007 to December 2019 were reviewed. The patients were divided into two groups: before the SAFE group as group 1 (2007 - 2011) and after the SAFE group as group 2 (2012 - 2019). We excluded FEE patients without CSF-related abnormalities. We compared the number of shunts and the complications between the two groups. One hundred and twenty-nine patient's medical records were reviewed. The males were predominating (79 versus 50 patients) with an average age of 58.2±7.1 months old (6 to 276 months old). Ventriculomegaly was found in 18 cases, arachnoid cysts in 46 cases, porencephalic cysts in 19 cases, and ventricular malformation in 46 cases. Group 1, with a score of 4 to 7 (19 cases), received an early shunt along with the FEE repair. Complications occurred in 7 patients of this group. Group 2, with a score of 4-7, received shunts only after the complication occurred in 3 cases (pseudomeningocele unresponsive with conservative treatment and re-operation in 2 cases; a sign of intracranial hypertension in 1 case). No complication occurred in this group. Groups 1 and 2, with scores of 8 or higher (6 and 8 cases, respectively), underwent direct shunt, with one complication (exposed shunt) in each group. The SAFE decision algorithm for FEE with CSF-related intracranial abnormalities has proven effective in reducing unnecessary shunting and the rate of shunt complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We highlight an under-recognized epileptic pathology in a 56-year-old left-handed female with progressive right facial numbness and weekly focal seizures characterized by episodic aphasia. She was found to have a left frontoparietal intradiploic meningoencephalocele (IDME). Her only epilepsy risk factor was minor head trauma 10 years prior to presentation. She underwent craniotomy for encephalocele resection and mesh cranioplasty without residual neurological deficits and excellent seizure outcome: at 3-year follow-up, she was still seizure-free since surgery, except for an isolated breakthrough seizure at 7 postoperative months when she discontinued her preoperative regimen of Lacosamide monotherapy. Traumatic IDME is a rare condition and rarely presents with seizures. Symptoms may arise up to decades following minor head trauma and are progressive in nature. The likely definitive treatment is cranioplasty and dural repair with or without resecting the protruding parenchyma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Neural tube defects (NTDs) are one of the most common congenital anomalies and a cause of chronic disability. The study was done to study outcomes of neural tube defects admitted at a tertiary level neonatal intensive care unit (NICU) from 2018 to 2022, a period of 4 years that also coincided with the COVID pandemic. The secondary outcome was to study the clinical presentation, associated anomalies and epidemiological features., Methods: It was a retrospective observational study; data of infants was obtained from medical records and analysis was done., Results: Thirty-four neonates were enrolled, of which there were 16 (47%) males and 18 (53%) females. History of pre-pregnancy maternal folate intake was present in 4 (11.7%) cases. 33 (97%) babies were diagnosed with meningomyelocele (MMC) and one each had anencephaly, iniencephaly and encephalocele, of which one had frontal and two had occipital encephalocele. The median age of surgery was 16 days of life with primary repair being the most common procedure followed by MMC repair with VP shunt. Twenty babies (58.8%) were discharged successfully, while 9 (26.5%) expired and 5 (14.7%) were discharged against medical advice; which can be attributed to the financial problems of the patients in a developing country. The overall deaths in our series were four (26.5%) which is slightly higher than other studies which may be due to the fact that this study was conducted during the COVID era with lesser rates of folate supplementation, reduced access to prenatal diagnosis coupled with poor follow-up and compliance of patients post-surgical repair., Conclusion: This study emphasizes the importance of periconceptional folic acid supplementation, prenatal diagnosis, early surgery and meticulous follow-up as being pivotal to improving outcomes in children with NTDs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors report no conflicts of interest.

Post-traumatic orbital meningoencephaloceles related to orbital roof fractures are a challenging clinical entity because of their rarity and difficult differential diagnosis. We report a case of post-traumatic intra-orbital meningoencephalocele in a 69-year-old man, secondary to a likely trapdoor mechanism, treated with a modified one-piece orbitozygomatic craniotomy. We also performed an extensive literature review of traumatic Intra-Orbital Encephalocele related to Orbital Roof Fracture focused on adult patients on electronic databases including Scopus, MEDLINE/PubMed, and Google Scholar. Patient well recovered after surgery with immediate exophthalmos resolution and discharged without visual or neurological deficits. The literature review included 22 papers with a total of 28 patients: 22 males (78.6%) and 6 females (21.4%), with a median age of 34.7 years. Twenty-six patients (92.9%) reported ocular injuries, with associated intracranial complications in 16 cases (61.5%). Twenty-seven patients (96.4%) were surgically treated, 18 of those underwent unilateral or bilateral frontal approach. Most orbital roof fractures can be managed nanoperatively if asymptomatic. Indeed, when the intra-orbital volume decreases, for example due to an encephalocele, the intra-orbital pressure could increase and determine an orbital compartment syndrome. In our case, we performed a one-piece modified orbitozygomatic approach, which has several advantages in comparison to the frequent unilateral or bilateral frontal craniotomy like the better exposure of the brain and orbit and a minimum brain retraction., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Although rare, temporal encephalocele is an important causative agent in surgically remediable drug-refractory epilepsy. The ideal treatment for temporal encephalocele remains unclear with a variety of resective surgeries recommended. Here, we analyse patient data on temporal encephalocele with a view to highlighting diagnostic clues and management strategies., Methods: Comprehensive databases at Deenanath Mangeshkar Hospital, Pune from January 2015 to June 2019 were reviewed for this observational study. Of 107 temporal lobe epilepsy surgery patients, nine individuals with temporal encephalocele were identified, who formed the study cohort. Their clinical, neuropsychological, EEG, imaging and long-term outcome data were analysed., Results: The study cohort consisted of seven males and two females with a mean age of 22 years. Epilepsy onset age varied from 4.5 to 19 years. Seven patients had focal non-motor seizures with impaired awareness, while two patients had focal motor seizures. Temporal encephalocele detection by MRI was reported in only two patients, and was missed in seven individuals. Three patients underwent standard anterior temporal lobectomy while the remaining six underwent resection of the temporal encephalocele with surrounding temporal pole. Eight patients showed Engel Class I outcome and one showed Class IIa outcome after a mean follow-up duration of 27 months (17-44 months). Histopathology confirmed gliosis in seven, hippocampal sclerosis type I in one and suspicious dyslamination with prominent gliosis in one patient. Six of eight patients reported an improvement in their psychological state (mood, anxiety and motivation) over time., Significance: A careful review of MRI in patients with temporal lobe epilepsy is necessary, followed by investigations for the presence of an encephalocele. When temporal lobe epilepsy is associated with encephalocele, tailored resection of the encephalocele and the surrounding temporal pole, sparing mesial temporal structures, demonstrates excellent long-term clinical and neuropsychological outcome.

Background: Antenatally detected occipital encephalocele and polycystic kidneys are a common presentation of ciliopathies like Joubert syndrome and Meckel Gruber syndrome which have considerable genetic and phenotypic overlap. Case reports: We describe 3 cases of antenatally diagnosed occipital encephalocele and enlarged kidneys with fetal autopsy, histopathology & exome sequencing results. A novel nonsense variant in the CEP290 gene was reported in first case (Meckel syndrome). The second case shows the importance of fetal exome where the parents were carriers for 2 ciliopathy genes (TMEM138 & SDCCAG8). Diagnosis in this case was confirmed by fetal exome sequencing (Joubert syndrome). Multiexon deletion in TMEM67 and KIF14 present in trans was identified in the third case (Meckel syndrome), likely resulting in digenic inheritance. Conclusion: We report 2 cases of Meckel syndrome with a novel variant and multiexon deletion, and 1 case of Joubert syndrome which depicts the limitations of preconceptional carrier screening in ciliopathies due to overlapping phenotypes.

Meckel syndrome (MKS, OMIM:249000) is a severe multiorgan dysplastic lethal ciliopathy with extreme genetic heterogeneity. Defects in RPGRIP1L are the cause of MKS type 5 (MKS5, OMIM:611561). However, only six different variants have been reported in eight MKS5 cases with biallelic variants. Here, we describe the case of a Chinese family with recurrent fetal malformations. The proband was a 14-week gestation fetus with occipital encephalocele, polycystic kidneys, polydactyly, and single ventricular heart. Trio whole-exome sequencing was performed, and two novel compound heterozygous variants of RPGRIP1L (c.427C > T, p.Gln143Ter and c.1351-11A > G) were identified. cDNA studies of the splicing variant demonstrated a reading-frame shift with a subsequent premature stop codon (p.Glu451Serfs*6). After the proband was diagnosed with MKS5, the couple chose preimplantation genetic testing for monogenic disorders (PGT-M) and prenatal genetic diagnosis (PND) to prevent the transmission of pathogenic variants, which led to a successful pregnancy recently. In summary, we have identified two novel variants of RPGRIP1L in a Chinese family, which expand the variant spectrum of MKS5. Furthermore, we have described the successful application of PGT-M and PND in this family. These techniques could assist couples with a genetic predisposition in avoiding the transmission of genetic diseases to their offspring., (© 2022. Society for Reproductive Investigation.)

A 5-year-old girl came to the Tianjin Medical University Eye Hospital in May 2021 because of her poor eyesight after birth. The physical examination showed that she had high myopia, esotropia, horizontal tremor, and high myopia retinopathy of both eyes. After inquiring about her medical history, we found that the baby's occipital cystic mass swelled after birth, and CT examination showed that the occipital skull plate defect with meningocele, but without treatment, at present, the occipital mass had subsided by itself. Considering the eye manifestations and skull changes of the child, it may be conformed to Knobloch syndrome, after the detection of V4 by full exon gene, it was found that the child had the compound heterozygous variation of pathogenic gene COL18A1, and Knobloch syndrome was definite, Knobloch syndrome is a rare autosomal recessive hereditary disease with typical features of high myopia, retinal detachment and occipital encephalocele. At present, there is no clear treatment plan, and gene therapy may be an effective treatment for Knobloch syndrome in the future.

Background: To establish the molecular diagnosis in two brothers presenting with the ocular features of Knobloch Syndrome using whole genome sequencing (WGS)., Methods: Clinical examination and ophthalmological phenotyping were completed under general anaesthesia. DNA samples were tested on a targeted retinal dystrophy next-generation sequencing panel. Subsequently, WGS was performed to identify additional variants., Results: Clinical examination confirmed the diagnosis of Knobloch Syndrome. Targeted sequencing identified a novel heterozygous frameshift pathogenic variant in COL18A1 , c.2864dupC; p.(Gly956ArgfsX20), inherited from their mother. A second paternally inherited heterozygous missense variant was identified in both brothers, c.5014 G > A; p.(Asp1672Asn), which was initially considered to have too high frequency to be pathogenic (MAF 8.8%). This led to an in-depth analysis of the COL18A1 locus using WGS data, which confirmed that Asp1672Asn is a likely pathogenic hypomorphic allele., Conclusion: To date, all confirmed genetic diagnoses of Knobloch syndrome are attributable to variants in COL18A1 . The family described here has a heterozygous novel loss of function variant. Detailed analysis of WGS data combined with family segregation studies concluded that although Asp1672Asn has a high population frequency, it is the most likely second pathogenic variant in our family. This supports the hypothesis that this is a hypomorphic allele, which, in combination with a loss of function pathogenic variant, leads to Knobloch syndrome.To our knowledge, this is the first time that WGS has been used to confirm a molecular diagnosis of Knobloch syndrome in this way and has provided further insight into the molecular mechanisms in this rare disorder.

The analysis of the state of two patients with congenital cerebral hernias was carried out, which made it possible to establish differences in the effect of hernias on the state of the body. In the first case, the hernia is localized in the nasal cavity, and after its removal, the postoperative cerebrospinal fluid (CSF) leakage was stopped by a flap of the mucous membrane from the opposite side of the nasal septum. In the second case clinical analysis and computed tomography made it possible to state that the hernia was in the retromaxillary space and did not affect the patient's condition. Computed tomography shows signs of moderate blood pressure on the adjacent formations, and removal of the hernia and stopping the subsequent CSF leakage were impossible. The presented observations demonstrate an ambiguous approach to resolving the issue of surgical intervention in such cases.

Knobloch syndrome is an autosomal recessive phenotype mainly characterized by retinal detachment and encephalocele caused by biallelic pathogenic variants in the COL18A1 gene. However, there are patients clinically diagnosed as Knobloch syndrome with unknown molecular etiology not linked to COL18A1. We studied an historical pedigree (published in 1998) designated as KNO2 (Knobloch type 2 syndrome with intellectual disability, autistic behavior, retinal degeneration, encephalocele). Whole exome sequencing of the two affected siblings and the normal parents resulted in the identification of a PAK2 non-synonymous substitution p.(Glu435Lys) as a causative variant. The variant was monoallelic and apparently de novo in both siblings indicating a likely germ-line mosaicism in one of the parents; the mosaicism, however, could not be observed after deep sequencing of blood parental DNA. PAK2 encodes a member of a small group of serine/threonine kinases; these P21-activating kinases (PAKs) are essential in signal transduction and cellular regulation (cytoskeletal dynamics, cell motility, death and survival signaling and cell cycle progression). Structural analysis of the PAK2 p.(Glu435Lys) variant that is located in the kinase domain of the protein predicts a possible compromise in the kinase activity. Functional analysis of the p.(Glu435Lys) PAK2 variant in transfected HEK293T cells results in a partial loss of the kinase activity. PAK2 has been previously suggested as an autism-related gene. Our results show that PAK2-induced phenotypic spectrum is broad and not fully understood. We conclude that the KNO2 syndrome in the studied family is dominant and caused by a deleterious variant in the PAK2 gene., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele. Our aim is to report the clinical and genetic findings of four Israeli children affected by Knobloch syndrome., Methods: Retrospective study of four patients diagnosed with Knobloch syndrome, who underwent full ophthalmic examination, electroretinography, and neuroradiologic imaging. Genetic analysis included whole exome sequencing (WES) and Sanger sequencing., Results: The four patients included in this study had high myopia and nystagmus at presentation. Ocular findings included vitreous syneresis, macular atrophy, macular coloboma, and retinal detachment. One child had iris transillumination defects and an albinotic fundus, initially leading to an erroneous clinical diagnosis of albinism. Electroretinography revealed a marked cone-rod pattern of dysfunction in all four children. Brain imaging demonstrated none to severe occipital pathology. Cutaneous scalp changes were present in three patients. WES analysis, confirmed by Sanger sequencing revealed COL18A1 biallelic null mutations in all affected individuals, consistent with autosomal recessive inheritance., Conclusions: This report describes variable features in patients with Knobloch syndrome, including marked lack of eye pigment similar to albinism in one child, macular coloboma in two children as well as advanced cone-rod dysfunction in all children. One patient had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of this syndrome, with its variable phenotype may aid early diagnosis, monitoring for potential complications, and providing appropriate genetic counseling.

A full-term female baby presented at 24 hours of life at the emergency department with occipital encephalocele, bilateral cleft lip, and cleft palate. She was born to a second gravida mother with no consanguinity between the parents. On examination, encephalocele was 10centimeters x 7centimeters in size with bilateral cleft lip and palate. It presents the opportunity for healthcare professionals to learn about a group of congenital neurological disorders in the content of a rare case presentation and highlights the importance of ultrasonography in the antenatal period for the detection of neural tube defects in the early stage for proper counselling and management. A compulsory prenatal diagnosis of the suspected family should be done by the intervention of the public sector of any country so that we can prevent and avoid abnormal birth.

Objectives: Cerebrospinal fluid (CSF) leaks and meningoencephaloceles originating in the lateral recess of the sphenoid sinus can be challenging. The traditional transpterygoid approach through the pterygopalatine fossa (PPF) is time consuming and places important structures at risk, which can lead to significant morbidity. We report a multi-institutional experience using a simplified, endoscopic modified transpterygoid approach (MTPA), which spares the PPF contents in the management of lateral sphenoid sinus meningoencephaloceles and CSF leaks., Study Design: Multi-Institutional, Retrospective Case Series., Methods: Patients with lateral sphenoid recess CSF leaks and meningoencephaloceles between 2014 and 2020 who underwent the MTPA at two academic medical centers were identified. Repair techniques and outcomes were evaluated., Results: Thirty-three patients underwent the MTPA for management. Skull base reconstruction was performed using a free mucosal graft (24/33, 72.7%), nasoseptal flap (4/33, 12.1%), bone grafts (3/33, 9.1%), and abdominal fat grafts (2/33, 6.1%). Lumbar drains and perioperative intracranial pressure measurements were routinely employed. Postoperative complications were uncommon and included three patients (9.7%) with temporary V2 anesthesia, one patient (3.2%) with prolonged V2 anesthesia, and one patient (3.2%) with subjective dry eye, all of which resolved at 9 months postoperatively. There were no recurrent CSF leaks resulting in a 100% success rate. Average follow-up was 13 months., Conclusion: The MTPA reduces morbidity and greatly simplifies access to the lateral sphenoid sinus for the management of CSF leaks and meningoencephaloceles, without compromising exposure. This technique avoids the need for extensive PPF dissection and should be considered for the management of benign lesions involving the lateral sphenoid sinus., Level of Evidence: 4 Laryngoscope, 131:2224-2230, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

Objectives: This study investigates a unique case of multiple osteochondromas (MO) comorbid with enlarged parietal foramina and correlates the findings with the existing literature. The aim of this study is to provide a deeper understanding of anatomic variation for physicians., Methods: A 66-year-old White male donor was examined during a routine cadaveric dissection performed by medical students in an anatomy laboratory. Detailed exploration of the skeleton and organs was performed, and photographs were taken. Tissue samples were obtained from multiple outgrowths, and histopathologic examination was done., Results: Bilateral bony growths were noted rising from the long bones of the upper and lower extremities (femur, tibia, fibula, and radius). An accessory muscle was found to be associated with the left radial bony growth. Histopathologic examination was positive for osteochondroma. Inspection of the skull revealed enlarged parietal foramina. Other findings included tibiofibular synostosis, abnormally shaped vertebral bodies and ribs, and elongated styloid processes of the skull., Conclusions: In combination with the histopathologic examination, the case report and literature review elucidate a more precise clinical picture for those affected with MO or similar disorders. This report also emphasizes the necessity of further investigation of the pathogenesis of MO and Potocki-Shaffer syndrome., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: The authors report no conflicts of interest.

Background: Aspiration pneumonitis is an inflammatory disease of the lungs which is difficult to diagnose accurately. Large-volume aspiration of oropharyngeal or gastric contents is essential for the development of aspiration pneumonitis. The role of cerebrospinal fluid (CSF) rhinorrhea is often underestimated as a rare etiological factor for aspiration in the diagnosis process of aspiration pneumonitis., Case Presentation: We present a case of a patient with 4 weeks of right-sided watery rhinorrhea accompanied by intermittent postnasal drip and dry cough as the main symptoms. Combined with clinical symptoms, imaging examination of the sinuses, and laboratory examination of nasal secretions, she was initially diagnosed as spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, and intraoperative endoscopic findings and postoperative pathology also confirmed this diagnosis. Her chest computed tomography showed multiple flocculent ground glass density shadows in both lungs on admission. The patient underwent endoscopic resection of meningoencephalocele and repair of skull base defect after she was ruled out of viral pneumonitis. Symptoms of rhinorrhea and dry cough disappeared, and pneumonitis was improved 1 week after surgery and cured 2 months after surgery. Persistent CSF rhinorrhea caused by spontaneous sphenoid sinus meningoencephalocele was eventually found to be a major etiology for aspiration pneumonitis although the absence of typical symptoms and well-defined risk factors for aspiration, such as dysphagia, impaired cough reflex and reflux diseases., Conclusions: We report a rare case of aspiration pneumonitis caused by spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, which can bring more attention and understanding to the uncommon etiology for aspiration, so as to make more accurate diagnosis of the disease and early surgical treatment., (© 2021. The Author(s).)

Renal cystic diseases are characterized by genetic and phenotypic heterogeneity. Congenital renal cysts can be classified as developmental disorders and are commonly diagnosed prenatally using ultrasonography and magnetic resonance imaging. Progress in molecular diagnostics and availability of exome sequencing procedures allows diagnosis of single-gene disorders in the prenatal period. Two patients with a prenatal diagnosis of polycystic kidney disease are presented in this article. TMEM67 mutations were identified in both fetuses using a whole-exome sequencing (WES) study. In one of them, the phenotypic syndrome diagnosed prenatally was different from that diagnosed in the postnatal period.

Objective: Late surgical correction of meningoencephalocele is a rare scenario that remains challenging for surgeons. Three-dimensional models can mimic the correct anatomical relationships, and technological systems have brought advances to medicine. This study aims to present a novel preoperative planning modality that combines augmented reality with a hybrid model for complex malformation associated with late correction., Methods: The present report describes a case of frontoethmoidal encephalocele of a 10-year-old girl. Two different methods for planning the approach were developed: 1) a hybrid hands-on model and 2) augmented reality, using a cell phone app and headset display. The customized hybrid model was created based on patient's imaging. The augmented reality app was developed with a real-time interface., Results: The hybrid model recreated anatomic alterations, thereby allowing a multidisciplinary team to determine an appropriate surgical approach. All aspects of the surgical procedure were simulated. A pre- to postoperative comparison was made, which emphasized benefit of tridimensional anatomical relationships using augmented reality tool and its role in preoperative planning., Conclusions: The authors believe this new multimodality preoperative platform could be a useful method to improve multidisciplinary discussion as well as a powerful tool for teaching and planning., (Copyright © 2021. Published by Elsevier Inc.)

Background: Meckel-Gruber syndrome (MKS; OMIM No. 249000) is a rare, in utero lethal disease characterized by occipital encephalocele, polycystic kidneys, and polydactyly. Methodology and Results: In this study, two fetuses diagnosed as having MKS in the prenatal period were evaluated on the basis of ultrasonographic findings, postmortem autopsy findings, and molecular genetic analyses. Using exome sequencing analyses a novel homozygous frameshift variant (NM_015631: c.530delA, p.Lys177Argfs*47) was detected at exon 4 of TCTN3 gene in case 1, and a novel homozygous synonymous variant (NM_025114: c.180G>A, p Lys60Lys) was detected at exon 3 of CEP290 gene in case 2. Case 1 is the first reported case in the literature, which showed the typical MKS clinical feature with a novel frameshift variation in the TCTN3 gene. The variant in case 2 is the first reported synonymous variant of CEP290 gene in the literature, which has been shown to affect splicing in a functional study at the RNA level. Conclusion: TCTN3 gene variants that were rarely associated with the typical MKS phenotype and all cases with these variations have been discussed in the context of genotype-phenotype. The detection of the first synonymous variant of CEP290 gene and the demonstration of its effect on splicing by a functional study are likely to contribute to the molecular etiology of MKS.

This article introduces the basic concepts of intracranial physiology and pressure dynamics. It also includes discussion of signs and symptoms and examination and radiographic findings of patients with acute cerebral herniation as a result of increased as well as decreased intracranial pressure. Current best practices regarding medical and surgical treatments and approaches to management of intracranial hypertension as well as future directions are reviewed. Lastly, there is discussion of some of the implications of critical medical illness (sepsis, liver failure, and renal failure) and treatments thereof on causation or worsening of cerebral edema, intracranial hypertension, and cerebral herniation., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Skull base cephaloceles (SBCs) are defined as herniation of intracranial content through the skull base and are classified based on composition, etiology, and topographic location. Anterior SBCs frequently protrude in the sinonasal cavity, and consequently are at potential risk of infection. Therefore, the current recommendation is to treat SBCs with the primary intent of preventing meningitis, and surgery represents the mainstay of treatment. Anterior SBCs may display a wide spectrum of severity and complexity, and in each case the risks and benefits of surgical approaches are to be carefully weighted based on thorough assessment of symptoms, age, general conditions, location and size of the lesion, as well as expertise of the surgeon. In the last 30 years, the evolution and diffusion of transnasal endoscopic surgery have substantially changed the surgical management of the majority of SBC. In the past, they were treated exclusively with open transcranial approaches that may be burdened by relevant morbidity and risk for severe complications. The transnasal endoscopic corridor now provides easy access to the lesion and different reconstructive strategies using endonasal pedicled flaps, without any external incision, cranioplasty or brain manipulation. However, there are still scenarios in which an exclusive transnasal endoscopic route is contraindicated. The aim of the present review was to provide an overview on the comprehensive management of anterior SBC, with a particular focus on lesions suitable for endoscopic surgery. Furthermore, special aspects of SBC management in children and adults will be highlighted.

An otherwise healthy two-month-old female C57BL/6J mouse presented with a left-sided head tilt. Differential diagnoses included idiopathic necrotizing arteritis, bacterial otitis media/interna ( Pasteurella pneumotropica , Pseudomonas aeruginosa , Streptococcus sp. , Mycoplasma pulmonis and Burkholderia gladioli ), encephalitis, an abscess, neoplasia, a congenital malformation and an accidental or iatrogenic head trauma. Magnetic resonance imaging (MRI) revealed a large space-occupying right olfactory lobe intra-axial lesion with severe secondary left-sided subfalcine herniation. Following imaging, the animal was euthanized due to poor prognosis. Histopathologic examination revealed a unilateral, full-thickness bone defect at the base of the cribriform plate and nasal conchae dysplasia, resulting in the herniation of the olfactory bulb into the nasal cavity. There was also a left midline-shift of the frontal cortex and moderate catarrhal sinusitis in the left mandibular sinus. The MRI and histopathologic changes are consistent with a congenital malformation of the nasal cavity and frontal aspect of the skull known as an ethmoidal meningoencephalocele. Encephaloceles are rare abnormalities caused by herniation of contents of the brain through a defect in the skull which occur due to disruption of the neural tube closure at the level anterior neuropore or secondary to trauma, surgical complications, cleft palate or increased intracranial pressure. The etiology is incompletely understood but hypotheses include genetics, vitamin deficiency, teratogens, infectious agents and environmental factors. Ethmoidal encephaloceles have been reported in multiple species including humans but have not been reported previously in mice. There are multiple models for spontaneous and induced craniofacial malformation in mice, but none described for ethmoidal encephaloceles.

Different cellular constituents of the central nervous system occurring in encephaloceles or neuroglial heterotopias (NGHs) have been reported, but the ependymal morphology has rarely been described in the previous literature, let alone the related histological images. To determine the ependymal morphology in encephaloceles or NGHs, we report a rare case of encephalocele with numerous ependymal components. Radiological examination showed that a 6.2 × 3.1 cm nasal dorsum mass-forming encephalocele in a 24-year-old woman, who had an intracranial connection through a frontal bone defect. This patient underwent a resection of the encephalocele under nasal endoscopy and a reconstruction of the cranial base. The patient had a good prognosis with no postoperative complications during follow-up. Microscopically, the ependymal components entrapped in a collagenized background showed numerous slit-like spaces lined by columnar cells with abundant palely eosinophilic cytoplasm and apical surface microvilli. With immunohistochemistry, in addition to the expression of EMA along with the slit-like spaces, GFAP and S100 were diffusely expressed in the slit-like spaces. In conclusion, the ependymal component in either encephaloceles or NGHs may present slit-like spaces arranged in an anastomosing pattern. The unusual morphology of ependyma continues to be underrecognized by pathologists and is easily misdiagnosed; therefore, an awareness of the morphological change in ependyma is necessary.

Objective: To investigate the etiology and longitudinal clinical, neuropsychological, psychosocial, and surgical outcome profile of patients with medication refractory epilepsy and temporal encephaloceles with a view to highlight diagnostic clues and management strategies., Methods: The comprehensive epilepsy program databases at two surgical epilepsy centers from January 2000 to October 2018 were reviewed for this observational study, to identify patients with encephaloceles causing temporal lobe epilepsy (TLE) and treated with surgical resection. Their clinical, radiological, neuropsychological, psychiatric, and surgical data were obtained. Body mass index (BMI) data were also reviewed due to possible correlation between idiopathic intracranial hypertension and encephaloceles., Results: Thirteen patients (eight female) were identified; only three were recognized on initial magnetic resonance imaging (MRI) report. Temporal encephaloceles were identified on the left in eight patients, on the right in three patients, and bilaterally in two patients. One patient had a strong family history of encephaloceles. The median BMI for patients with seizure onset ≤20 years of age was 22.4, whereas for patients with onset >20 years median BMI was 32.6 (P = .06). Five patients underwent a focal lesionectomy, three patients had limited temporal lobectomy, and five patients had standard anterior temporal lobectomy. Median postoperative follow-up was 5.5 years. All but one patient were free of disabling seizures. Nine of ten neuropsychologically tested patients had no discernable cognitive decline postoperatively. Postoperative psychosocial adjustment features were present in four patients., Significance: Genetic factors and a possible association with idiopathic intracranial hypertension (given female predominance and elevated BMI) may contribute to the causation of temporal lobe encephaloceles. It is notable that a targeted surgical approach in the management of patients with TLE associated with encephaloceles has an excellent long-term clinical and neuropsychological outcome. Subtle encephaloceles should be actively searched for in patients with drug-resistant TLE because they significantly change surgical strategy and prognostication., (© 2020 International League Against Epilepsy.)

Objective: Nasal meningoencephalocele (encephalocele or cephalocele) is a rare condition with congenital, traumatic, or spontaneous origins. We investigated the clinicopathological characteristics of nasal encephaloceles to improve pathologists' and clinicians' understanding of this disease., Methods: Sixteen patients with nasal encephaloceles were enrolled in this retrospective study investigating the condition's clinical and morphological features., Results: Patients' average age was 37.8 (±20.8) years. The ratio of men to women was 2.2:1, patients' mean age was 47.4 (±11.8) years, and 10/16 patients had spontaneous encephaloceles. All patients with traumatic and spontaneous encephaloceles presented with cerebrospinal fluid leak. In 9/16 patients, the skull defect site occurred on the lateral wall of the sphenoid sinus. Both congenital patients experienced nasal obstruction. Histopathology, herniated tissues were brain and/or meningeal tissue, and the brain tissue was almost mature glial tissue., Conclusion: Nasal meningoencephalocele is a rare condition that can be challenging to diagnose. In patients with recurrent clear nasal discharge or in children with a unilateral nasal mass, a high index of suspicion for encephalocele is essential. In this study, spontaneous cases were most common in adults, and the lateral wall of the sphenoid sinus was the most common location., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite the well documented increased risk of thrombosis in patients with cancer and during chemotherapy, cerebral venous sinus thrombosis (CVT) remains a rare entity. We present a rare case of cerebrospinal fluid (CSF) rhinorrhoea secondary to a left transverse sinus thrombus which occurred 2 years previously during chemotherapy for breast cancer. The patient underwent a three-layer repair using Neuro-Patch, septal cartilage and middle turbinate pedicle flap and was started on acetazolamide. There was no recurrence at 1-year follow-up. Raised intracranial pressure secondary to cerebral venous occlusion can erode the base of skull and predispose to CSF leaks. Despite the theoretical risk, there have been no cases reported where CSF leaks have occurred following chemotherapy induced CVT. We describe the first case and discuss pathophysiology and management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the findings and the management of macular hole (MH)-related retinal detachment (RD) in children with Knobloch syndrome., Design: Retrospective interventional case series., Participants: Patients with Knobloch syndrome who presented with MH-related RD., Methods: Retrospective chart review of patients with Knobloch syndrome who presented with MH-related RD from January 2012 to December 2018. Interventions included pars plana vitrectomy and silicone oil tamponade with or without scleral buckle, drainage retinotomy, or relaxing retinectomy., Main Outcome Measures: MH characteristics and surgical anatomical outcome., Results: The study included 9 eyes of 5 patients (age range 2 months to 5 years; median age 5.5 months). Presenting symptoms were poor fixation and nystagmus. The fellow eye of 1 patient had RD due to peripheral breaks. The MH was clinically visible in 8 eyes and detected only by OCT in 1 eye. The RD was shallow and extended to the anterior equator in 7 eyes and localized to a punched-out atrophic lesion in 1 eye. Seven eyes underwent surgical repair. At the last follow-up examination (follow-up range 11 to 42 months; mean 24 months, standard deviation 11.8 months), retinal reattachment with MH closure was achieved in 5 eyes along with marked improvement in fixation., Conclusion: Patients with Knobloch syndrome may develop MH-related RD as early as infancy. The condition may be easily overlooked in children but should be suspected in the setting of high myopia, vitreoretinal degeneration, and encephalocele., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective case series., Objective: Anterior sacral meningocele (ASM) is a rare disorder. We reviewed 11 cases of congenital ASM and classified them into three types based on the anatomy and relationship between the cyst and sacral nerve roots., Summary of Background Data: The cohort with ASM is relatively large; the classification is novel and has not been previously reported., Methods: Eleven consecutive patients with ASM who underwent surgery between February 2014 and January 2019 were retrospectively analyzed. They included four males and seven females. The dorsal transsacral approach was adopted in all cases. The follow-up time was at least 3 months., Results: We attempted to classify ASM into three types. Of the 11 cases, six were caudal type, two were paraneural type, and three were nerve-root type. The meningocele was ligated after exploring no nerve involvement, in Type I and II. For Type III, the herniating sac and involved nerve roots were ligated when the nerve roots were indicated as nonfunctional on neurophysiological monitoring; otherwise, the sacral nerve roots were protected and imbricated on the residual sac like a hand-in-glove, and sutured to reconstruct the nerves sleeve. Eight cases were accompanied by tethered cord syndrome (TCS); spinal cord detethering was done with one-stage operation. Ten patients' presenting symptoms improved at 3 to 6 months' follow-up; notably, constipation significantly improved. Only one case accompanied by an epidermoid cyst had a second laparoscopic surgery by a general surgeon., Conclusion: Aim of surgical treatment is to obliterate the communication between the subarachnoid space and herniated sac, detether the spinal cord, and resect the congenital tumor. The new classification helps to recognize the relationship between the meningocele and sacral nerve roots, and subsequently adopt different surgical strategies. We consider the dorsal transsacral approach relatively feasible, safe, and with lower complication., Level of Evidence: 4.

Objectives: Congenital encephaloceles provide unique diagnostic and reconstructive challenges for the pediatric rhinologist. The objectives of the current study were to evaluate contemporary treatment strategies for congenital encephaloceles focusing on presentation, surgical technique, and outcomes., Methods: Multi-institutional retrospective chart review of congenital encephaloceles (2003-2019). Data regarding demographics, presenting symptoms, associated abnormalities, surgical technique, size, location, and complications were collected., Results: Fourteen patients with 15 congenital encephaloceles were treated using endoscopic techniques (avg 6.0 years, range 2 months-22 years) with mean follow up of 23 months. The majority presented with nasal obstruction (n = 13); only one child had cerebrospinal fluid (CSF) rhinorrhea. Associated anomalies included nasal deformities, congenital hypopituitarism, and Morning Glory syndrome. Average encephalocele size was 2.44 cm (range 0.5-3.6 cm) with mean skull base defect size of 8.6 x 7.7 mm. Locations included the foramen cecum (n = 9), central sphenoid (n = 3), midline anterior cranial fossa (n = 1), orbital plate of frontal bone (n = 1), and ethmoid roof (n = 1). Because of favorable expansion from encephaloceles, it was unnecessary to postpone surgeries to allow nasal cavity growth. Three individuals had prior operations, including surgeries for "nasal polyp" or "adenoid cyst". Two patients had post-operative complications (meningitis and CSF leak) effectively treated with no further sequelae., Conclusions: In the current study, congenital encephaloceles in children as young as 2 months were successfully repaired using endoscopic techniques. Endoscopic approaches remain a safe and effective intervention for management of these lesions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To determine the frequency of genetic and additional structural abnormalities as well as pregnancy outcomes in fetuses with prenatally diagnosed cephalocele., Methods: A retrospective analysis of data retrieved from ultrasound examinations and genetic testing in fetuses with cephalocele diagnosed between 2006 and 2018 in a tertiary referral hospital along with a systematic literature search in the PubMed database on fetuses with prenatally diagnosed cephalocele., Results: Twenty-one out of 36 fetuses were found to have additional structural anomalies (58.3%). In four fetuses, anomalies were consistent with limb-body wall complex, in five with Meckel-Gruber syndrome, and in one with amniotic band syndrome. Genetic abnormalities were present in 11.1% of fetuses (trisomy 6; microdeletion 22q11.21; microduplication 16p13.11; pathogenic variant in gene CC2D2A). Twenty-eight pregnancies were terminated (77.8%; 28/36); two were miscarried (5.6%; 2/36). All six children from pregnancies that continued were liveborn but only two survived the surgery and developed neurological sequence. Overall survival rate was 25% (2/8) with 0% intact survival., Conclusions: Additional structural anomalies are common in fetuses with cephalocele. A significant number of fetuses have genetic abnormalities, and a detailed genetic testing should be performed in all cases. The prognosis is poor with high mortality rate and 0% intact survival., (© 2020 John Wiley & Sons, Ltd.)

The diagnostic deployment of massively parallel short-read next-generation sequencing (NGS) has greatly improved genetic test availability, speed, and diagnostic yield, particularly for rare inherited disorders. Nonetheless, diagnostic approaches based on short-read sequencing have a poor ability to accurately detect gene conversion events. We report on the genetic analysis of a family in which 3 fetuses had clinical features consistent with the autosomal recessive disorder Meckel-Gruber syndrome (MKS). Targeted NGS of 29 known MKS-associated genes revealed a heterozygous TMEM231 splice donor variant c.929+1A>G. Comparative read-depth analysis, performed to identify a second pathogenic allele, revealed an apparent heterozygous deletion of TMEM231 exon 4. To verify this result we performed single-molecule long-read sequencing of a long-range polymerase chain reaction product spanning this locus. We identified four missense variants that were absent from the short-read dataset due to the preferential mapping of variant-containing reads to a downstream TMEM231 pseudogene. Consistent with the parental segregation analysis, we demonstrate that the single-molecule long reads could be used to show that the variants are arranged in trans. Our experience shows that robust validation of apparent dosage variants remains essential to avoid the pitfalls of short-read sequencing and that new third-generation long-read sequencing technologies can already aid routine clinical care., (© 2019 Wiley Periodicals, Inc.)

The authors describe a rare case of recurrent ectopic meningioma associated with sphenoid encephalocele in the medial anterior orbit of a 52-year-old man with a history of a resected intracranial meningioma. Typical features of ectopic meningioma are reviewed as well as potential etiologies of this very rare recurrence of intracranial meningioma in the orbit. Treatment is typically surgical excision.The authors report a rare case of recurrent orbital ectopic meningioma in the right medial canthus of a 52-year-old man.

Background: Schizencephaly is a neuronal migration anomaly characterized by presence of a cleft between ependymal layer of the ventricle and pia mater of the cerebral cortex. It may be associated with additional cerebral abnormalities, including polymicrogyria, pachygyria, gray matter heterotopy, ventriculomegaly and corpus callosum agenesis. Case Report: We present a female fetus with schizencephaly accompanied by occipital encephalocele, polymicrogyria, agenesis of the corpus callosum, dysmorphic facies and cardiac muscular ventricular septal defect. Array comparative genomic hybridization (array-cGH) analysis revealed a deletion of chromosome 22q13.32 including FAM19A5 gene that is a member of TAFA family. Conclusions: Schizencephaly may be accompanied by unexpected structural and genetic anomalies as in our case with occipital encephalocele, dysmorphic facies, cardiac ventricular septal defect and chromosome 22q13.32 deletion.